MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Basic and Clinical Pharmacology and Toxicology' source. Wed, 08 Feb 2012 14:04:00 +0100 http://www.medworm.com/index.php?rid=5667557&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2012.00862.x In conclusion, despite limitations in drawing definitive conclusions due to a relatively small sample size and variability in renal impairment among patients, our findings suggest that a teicoplanin loading dose of 12 mg/kg bodyweight results in a safe and rapid attainment of therapeutic trough plasma concentrations. This regimen may enhance treatment efficacy. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5667557 Mon, 06 Feb 2012 05:00:00 +0100 5667557 http://www.medworm.com/index.php?rid=5667556&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2012.00861.x AbstractOseltamivir is widely used for the treatment and prophylaxis of influenza. Renewed interest in the central nervous system (CNS) tolerability profile of oseltamivir has been triggered by reports of neuropsychiatric adverse events in influenza patients. In addition, a recent preclinical study in rodents suggested a hypothermic effect of oseltamivir. The current studies investigated the CNS effects, body temperature effect and toxicokinetic profile of oseltamivir in rats. The CNS/temperature study included three groups receiving oseltamivir (500, 763 and 1,000 mg/kg free base by oral gavage), one vehicle/control group and one reference group (D‐amphetamine, 10 mg/kg). CNS parameters (behaviour, motor activity and co‐ordination, and sensory/motor reflex responses) and rectal temper... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5667556 Mon, 06 Feb 2012 05:00:00 +0100 5667556 http://www.medworm.com/index.php?rid=5667555&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2012.00863.x AbstractEnd‐stage kidney disease (ESKD) is a major health problem associated with very high morbidity and mortality secondary to cardiovascular complications, especially in ESKD patients on dialysis. Therefore, exploring key mechanisms underlying cardiovascular alterations associated with ESKD may offer reasonable pharmacological targets that may benefit these patients. Imbalanced matrix metalloproteinases (MMP) activities have been implicated in many cardiovascular diseases, and growing evidence now indicates that excessive MMP activities contribute to cardiovascular complications in ESKD patients. However, there is no study on the effects of MMP inhibitors (MMPIs) in such patients. MMPIs may prevent against the vascular and cardiac changes associated with ESKD. In this MiniReview, we a... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5667555 Wed, 01 Feb 2012 05:00:00 +0100 5667555 http://www.medworm.com/index.php?rid=5660251&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2012.00860.x AbstractAcute morphine administration decreases cardiac responses to ischaemic injury. This project has determined whether induction of morphine dependence in rats by gradually increasing morphine doses for 21 days induces structural and functional changes in the cardiovascular system due to mineralocorticoid receptor activation, since morphine increases plasma corticosterone concentrations. Morphine‐dependent rats showed ventricular hypertrophy, increased collagen deposition in the left ventricle together with an increased ventricular stiffness and increased plasma malondialdehyde concentrations without changes in systolic blood pressure or thoracic aortic responsiveness. These parameters were attenuated or normalized in morphine‐dependent rats treated with spironolactone (50 mg/kg/da... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5660251 Wed, 01 Feb 2012 05:00:00 +0100 5660251 http://www.medworm.com/index.php?rid=5620601&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2012.00857.x AbstractNumerous studies have demonstrated that BPA can cause reproductive toxicity. Ginseng has wide range of pharmacological actions and, more importantly, has proven its worth with respect to reproductive function in several reports. We hypothesized that ginsenosides, the main active components of ginseng, may protect against BPA‐induced cell damage. Therefore, an in vitro culture model of 15P‐1 Sertoli cells was employed to investigate whether ginsenosides have protective effects on BPA‐stimulated 15P‐1 Sertoli cells. The results revealed that ginsenosides (75 μg/ml) significantly inhibited BPA‐induced decreases in cell viability and increases in apoptosis. Immunofluorescence staining showed that BPA exposure‐induced collapse of vimentin intermediate filaments was prevente... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5620601 Mon, 23 Jan 2012 18:36:44 +0100 5620601 http://www.medworm.com/index.php?rid=5620602&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2012.00856.x AbstractThe cytoprotective properties of carbon monoxide (CO) gas and CO‐releasing molecules (CORMs) are well established. Despite promising pre‐clinical results, little attention has been paid to the toxicological profile of CORMs. The effects of CORM‐2 and its CO‐depleted molecule (iCORM‐2) (20‐400μM), were compared in primary rat cardiomyocytes and two cell lines (HeK and MDCK). Cells were assessed for cell viability, apoptosis, necrosis, cytology, mitochondrial energetics, oxidative stress and cell cycle arrest markers. In separate experiments, the anti‐apoptotic effects of CORM‐2 and i‐CORM‐2 treatment were compared against CO gas treatment in HeK and MDCK lines. H2O2 induced cellular damage, measured by lactate dehydrogenase (LDH) release from primary cardiomyocy... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5620602 Mon, 23 Jan 2012 05:00:00 +0100 5620602 http://www.medworm.com/index.php?rid=5609395&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00848.x In this study, we investigated the therapeutic effects of simvastatin administered in combination with bone marrow stromal cells (BMSCs) following experimentally induced embolic stroke in rats. Effects on infarct volume, brain oedema and neurological deficits were examined. Focal ischaemic brain injury was induced by emblazing a preformed clot into the middle cerebral artery in rats. Animals were administered simvastatin (40 mg/kg) at 1 hr after stroke, or BMSCs (3 × 106) at 24 hr after stroke or a combination of these two treatments. Rats receiving a dose of simvastatin in combination with BMSC administration demonstrated a significant reduction in neurological deficits, a significant reduction in infarct volume and a significant decrease in brain oedema. Our data show that combinin... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5609395 Fri, 20 Jan 2012 18:34:17 +0100 5609395 http://www.medworm.com/index.php?rid=5572509&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00855.x AbstractThe ATP‐sensitive K+ channels opener (KATPCO), P1075 [N‐cyano‐N’‐(1,1‐dimethylpropyl)‐N”‐3‐pyridylguanidine], has been shown to cause relaxation of various isolated animal and human blood vessels by opening of vascular smooth muscle ATP‐sensitive K+ (KATP) channels. In addition to the well‐known effect on the opening of KATP channels, it has been reported that vasorelaxation induced by some of the KATPCOs includes some other K+ channel subtypes. Given that there is still no information on other types of K+ channels possibly involved in the mechanism of relaxation induced by P1075, the present study was designed to examine the effects of P1075 on the rat renal artery with endothelium and with denuded endothelium, and to define the contribution of different K+... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5572509 Sun, 01 Jan 2012 05:00:00 +0100 5572509 http://www.medworm.com/index.php?rid=5552727&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00854.x In conclusion, TUDCA had a nephroprotective effect on IR‐induced AKI by inhibiting ERS and by blocking GRP78 and CHOP expression, reducing Caspase 12 activation, and inhibiting cell apoptosis. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5552727 Sat, 31 Dec 2011 08:04:04 +0100 5552727 http://www.medworm.com/index.php?rid=5609396&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00854.x In conclusion, TUDCA had a nephroprotective effect on IR‐induced AKI by inhibiting ERS and by blocking GRP78 and CHOP expression, reducing Caspase 12 activation and inhibiting cell apoptosis. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5609396 Wed, 28 Dec 2011 05:00:00 +0100 5609396 http://www.medworm.com/index.php?rid=5538363&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00852.x Abstract:  Increased oxidative stress in the brain has consistently been implied in ageing and in several degenerative brain disorders. Acting as a pivotal antioxidant in the brain, vitamin C is preferentially retained during deficiency and may play an essential role in neuroprotection during ageing. Thus, a lack of vitamin C could be associated with an increase in redox imbalance in the ageing brain. The present study compared oxidative stress of ageing to that of a long‐term non‐scorbutic vitamin C deficiency in guinea pigs. Adults (3‐9 months old) were compared to old (36‐42 months old) animals during a six‐month dietary intervention by assessing vitamin C transport and redox homeostasis in the brain. In contrast to our hypothesis, chronic vitamin C deficiency did not affect... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5538363 Sun, 25 Dec 2011 06:58:34 +0100 5538363 http://www.medworm.com/index.php?rid=5538364&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00853.x In this study, depressive or anti‐depressive effects of B[α]P were investigated. Here, we report that a sub‐acute B[α]P oral exposure (0.02–0.2 mg/kg) increases mobility behaviour in female adult mice in the tail suspension test, but not in the forced swimming test, without altering locomotion, suggesting that the tail suspension test was a more sensitive indicator of B[α]P‐induced neurobehavioural disturbance. This might be due to differences in neurochemical substrates and pathways, mediating the performance in these behavioural models of depression. The effect of B[α]P on female adult mice in the tail suspension test was similar to that obtained with sub‐acute treatment of the antidepressant reference drug imipramine (10 mg/kg). Therefore, B[α]P at 0.02 mg/kg and 0.2 mg... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5538364 Sat, 24 Dec 2011 05:00:00 +0100 5538364 http://www.medworm.com/index.php?rid=5525332&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00851.x AbstractQuaternary ammonium compounds (QAC) constitute a family of widely used chemical substances. The QAC benzalkonium chloride (BAC) has caused bronchoconstriction in human beings by poorly understood mechanisms and lung damage at high concentration as shown in a single rat study. The present study evaluates acute airway effects in mice after inhalation of aerosols of the QACs, BAC, hexadecyl trimethyl ammonium bromide (HTA), cetyl pyridinium chloride (CPC) and dimethyl dioctadecyl ammonium bromide (DDA). The QACs gave rise to concentration‐dependent decreases in the tidal volume (VT) and a concomitant increase in respiratory rate indicating pulmonary irritation. The potencies of the QAC to induce these effects were in the order: BAC > HTA = CPC > DDA. Furthermore, inhalation of... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5525332 Thu, 22 Dec 2011 06:58:26 +0100 5525332 http://www.medworm.com/index.php?rid=5525335&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00850.x AbstractMechanisms of transcellular transport of 4‐chloro‐2‐methylphenoxyacetic acid (MCPA) across the small intestine were investigated using Caco‐2 cells cultured on permeable membranes. The cell monolayers were incubated with MCPA, either from apical side at pH 6.0 or 7.4, or basolateral side at pH 7.4. The accumulation and apical‐to‐basolateral transport of MCPA was markedly stimulated by the acidic pH on the apical side (inwardly directed H+‐gradient), dependent on metabolic energy and inhibited by co‐incubation with acetic acid or benzoic acid. Without the H+‐gradient, on the other hand, the basolateral‐to‐apical transport of MCPA (secretory transport) was higher than the apical‐to‐basolateral transport (absorptive transport), although the secretory transpor... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5525335 Mon, 19 Dec 2011 05:00:00 +0100 5525335 http://www.medworm.com/index.php?rid=5525334&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00848.x In this study, we investigated the therapeutic effects of simvastatin administered in combination with bone marrow stromal cells (BMSCs) following experimentally induced embolic stroke in rats. Effects on infarct volume, brain oedema and neurological deficits were examined. Focal ischaemic brain injury was induced by emblazing a preformed clot into the middle cerebral artery in rats. Animals were administered simvastatin (40 mg/kg) at 1 hr after stroke, or BMSCs (3×106) at 24 hr after stroke or a combination of these two treatments. Rats receiving a dose of simvastatin in combination with BMSC administration demonstrated a significant reduction in neurological deficits, a significant reduction in infarct volume and a significant decrease in brain oedema. Our data show that combining simva... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5525334 Mon, 19 Dec 2011 05:00:00 +0100 5525334 http://www.medworm.com/index.php?rid=5525333&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00849.x This study assessed the analgesic effect of remifentanil in 20 healthy Korean men using three pain models to investigate whether these models can be used in Asians. The study was a double‐blind, placebo‐controlled, 2‐way cross‐over study. The subjects received intravenous remifentanil with doses starting at 0.01 μg/kg/min and increasing by 0.01 μg/kg/min up to 0.10 μg/kg/min in one session; they received placebo in another session. Heat pain thresholds were assessed at dose levels of 0.02, 0.05, 0.08 and 0.10 μg/kg/min. Pressure pain threshold and tolerance and mechanical pain threshold were assessed at 0.08 μg/kg/min. Remifentanil dose‐dependently increased the heat pain threshold. The differences (95% confidence interval) between remifentanil and placebo were 1.54°C (0.78... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5525333 Mon, 19 Dec 2011 05:00:00 +0100 5525333 http://www.medworm.com/index.php?rid=5495116&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00832.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5495116 Tue, 13 Dec 2011 07:10:26 +0100 5495116 http://www.medworm.com/index.php?rid=5495115&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00837.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5495115 Tue, 13 Dec 2011 07:10:01 +0100 5495115 http://www.medworm.com/index.php?rid=5495114&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00835.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5495114 Tue, 13 Dec 2011 07:09:59 +0100 5495114 http://www.medworm.com/index.php?rid=5495113&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00844.x AbstractFatty acid synthase (FASN), a multi‐enzyme complex, is involved in lipid biosynthesis. FASN is over‐expressed in different types of cancers and is being widely investigated for its role in cancer progression, diagnosis and therapy. Here, three inhibitors targeting different domains of FASN — cerulenin, triclosan and orlistat — were evaluated for their anti‐proliferative efficacy in ocular cancer, retinoblastoma (RB) cells and their toxicity (if any) in normal cells. FASN inhibitors were tested in cultured retinoblastoma Y79 cells, normal fibroblast (3T3) and Müller glial (MIOM1) cells. Cell viability was determined by MTT‐based assay, and IC50 (50% inhibitory concentration) of the FASN inhibitors was calculated in neoplastic and non‐neoplastic cells. The IC50 after 4... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5495113 Tue, 13 Dec 2011 07:08:29 +0100 5495113 http://www.medworm.com/index.php?rid=5598250&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00844.x Abstract:  Fatty acid synthase (FASN), a multi‐enzyme complex, is involved in lipid biosynthesis. FASN is over‐expressed in different types of cancers and is being widely investigated for its role in cancer progression, diagnosis and therapy. Here, three inhibitors targeting different domains of FASN – cerulenin, triclosan and orlistat – were evaluated for their anti‐proliferative efficacy in ocular cancer, retinoblastoma (RB) cells and their toxicity (if any) in normal cells. FASN inhibitors were tested in cultured retinoblastoma Y79 cells, normal fibroblast (3T3) and Müller glial (MIOM1) cells. Cell viability was determined by MTT‐based assay, and IC50 (50% inhibitory concentration) of the FASN inhibitors was calculated in neoplastic and non‐neoplastic cells. The IC50 af... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5598250 Mon, 12 Dec 2011 05:00:00 +0100 5598250 http://www.medworm.com/index.php?rid=5487536&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00841.x AbstractPrevious studies on animals have revealed that garlic (Allium sativum) is effective in reducing blood and tissue lead concentrations. The aim of this study was to investigate therapeutic effects of garlic and compare it with D‐penicillamine in patients with chronic lead poisoning. After coordination and obtaining informed consent, clinical examinations and blood lead concentration (BLC) of 117 workers at a car battery industry were investigated. BLC was determined by heated graphite atomization technique of an atomic absorption spectrometer. The workers were randomly assigned into two groups of garlic (1200 micrograms allicin, 3 times daily) and D‐penicillamine (250 milligrams, 3 times daily) and treated for 4 weeks. BLC was determined again 10 days post‐treatment. Clinical s... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5487536 Fri, 09 Dec 2011 05:00:00 +0100 5487536 http://www.medworm.com/index.php?rid=5487535&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00842.x AbstractWe evaluated the pharmacokinetics of clindamycin and the dose of clindamycin phosphate necessary to treat peritonitis after intraperitoneal administration of clindamycin phosphate to patients on CAPD. This was an open‐label, prospective, single‐dose study conducted at the two levels of institutional clinical care in South Korea. Twelve patients (six male, six female; all older than 25 years), mean CAPD duration of 38.2 months with various origins without peritonitis received 600 mg clindamycin phosphate mixed with only the first 2‐L dialysate (1.5% dextrose). The 1.5, 1.5, 2.5 and 1.5% dextrose dialysates were serially exchanged every 6 hr. If patients were non‐anuric, 24‐hr urine samples were also collected. Clindamycin phosphate was incompletely activated to clindamycin... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5487535 Fri, 09 Dec 2011 05:00:00 +0100 5487535 http://www.medworm.com/index.php?rid=5476968&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00839.x In conclusion, the estimated MEC, 20‐35 ng/mL, and MEAC, 45‐50 ng/mL, values of P‐oxycodone in patients after laparoscopic cholecystectomy were significantly higher than those proposed previously. Early pain after LCC appeared to be a feasible method to estimate the analgesic efficacy of oxycodone in acute pain management. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5476968 Sun, 04 Dec 2011 05:00:00 +0100 5476968 http://www.medworm.com/index.php?rid=5487534&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00843.x AbstractCadmium is a heavy metal that is known to cause toxicity to cells and at low concentrations can initiate apoptosis. The present study was undertaken with the aim of defining the role of phospholipase C (PLC) in mediating cadmium‐induced apoptosis in human embryonic kidney HEK 293 cells. We have shown that intracellular Ca2+ levels increased significantly in HEK 293 cells after 24 hr exposure to Cd. The activity of the calcium‐dependent protease calpain rose by 4‐fold. The phospholipase C specific inhibitor, U73122, prevented the Cd‐dependent increase in Ca2+ levels and also abolished Cd‐dependent calpain and caspase 3 activation as well as Cd‐dependent mitochondrial Bax accumulation. Inhibition of PLC also leads to an increased cell viability following exposure to Cd. T... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5487534 Thu, 01 Dec 2011 05:00:00 +0100 5487534 http://www.medworm.com/index.php?rid=5476967&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00840.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5476967 Thu, 01 Dec 2011 05:00:00 +0100 5476967 http://www.medworm.com/index.php?rid=5469384&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00838.x Abstract:  The frequency distribution of SNPs and haplotypes in the ABCB1, SLCO1B1 and SLCO1B3 genes varies largely among continental populations. This variation can lead to biases in pharmacogenetic studies conducted in admixed populations such as those from Brazil and other Latin American countries. The aim of the present study was to evaluate the influence of self‐reported colour, geographical origin and genomic ancestry on distributions of the ABCB1, SLCO1B1 and SLCO1B3 polymorphisms and derived haplotypes in admixed Brazilian populations. A total of 1039 healthy adults from the North, Northeast, Southeast and South of Brazil were recruited for this investigation. The c.388A>G (rs2306283), c.463C>A (rs11045819) and c.521T>C (rs4149056) SNPs in the SLCO1B1 gene and c.334T&g... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5469384 Thu, 01 Dec 2011 05:00:00 +0100 5469384 http://www.medworm.com/index.php?rid=5449910&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00836.x AbstractMonoisoamyl DMSA (MiADMSA), a lipophillic chelating agent has emerged as a promising drug for treatment of arsenic. The present study aimed at exploring the optimum dose and route of administration for achieving maximum arsenic elimination with minimal side effects. We also carried out a pharmacokinetic analysis of this drug to support arsenic chelation. Rats were exposed to arsenic (25ppm) for 6 months and later received MiADMSA (50 or 100 mg/kg) orally and via i.p. route for 5 days. Oxidative stress parameters and arsenic levels in soft tissues, liver function test and histopathology of liver and kidney was done. Plasma kinetic of MiADMSA (plasma free drug and total drug) at 50 and 100 mg/kg p.o. was done. Arsenic exposure resulted in significant oxidative stress and hepatotoxici... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5449910 Mon, 28 Nov 2011 07:01:50 +0100 5449910 http://www.medworm.com/index.php?rid=5609397&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00836.x Abstract:  Monoisoamyl DMSA (MiADMSA), a lipophilic chelating agent has emerged as a promising drug for the treatment of arsenic. The present study aimed at exploring the optimum dose and route of administration for achieving maximum arsenic elimination with minimal side effects. We also carried out a pharmacokinetic analysis of this drug to support arsenic chelation. Rats were exposed to arsenic (25 ppm) for 6 months and later received MiADMSA (50 or 100 mg/kg) orally and via i.p. route for 5 days. Oxidative stress parameters and arsenic levels in soft tissues, liver function test and histopathology of liver and kidney were performed. Plasma kinetic of MiADMSA (plasma‐free drug and total drug) at 50 and 100 mg/kg p.o. was carried out. Arsenic exposure resulted in significant... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5609397 Sat, 26 Nov 2011 05:00:00 +0100 5609397 http://www.medworm.com/index.php?rid=5441461&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00834.x AbstractExcessive and sustained increases in oxidative stress and apoptosis have been implicated in the pathogenesis of many diseases. In the present study, we demonstrated that 4‐hydroxynonenal (4‐HNE), a product of lipid peroxidation in a range of concentration (0.1‐50 μM) showed cytotoxic effects on SH‐SY5Y cell culture at a concentration > 5μM at 4 hr of exposure. 4‐HNE dose‐dependently decreased cell viability and significantly promoted reactive oxygen species formation and enhanced oxidative stress as reflected in the increased level of lipid peroxidation and catalase activity and decreased glutathione peroxidase activity as well as glutathione levels. 4‐HNE–induced oxidative stress was associated with increased transcriptional and translational expressions of Ba... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5441461 Fri, 25 Nov 2011 06:49:41 +0100 5441461 http://www.medworm.com/index.php?rid=5432114&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00833.x AbstractAnacardic acid (AA) is a bioactive phytochemical found in nutshell of Anacardium occidentale. Chemically, it is a mixture of several closely related organic compounds, each consisting of salicylic acid substituted with an alkyl chain. The traditional Ayurveda depicts nutshell oil as a medicinal remedy for alexeritic, amebicidal, gingivitis, malaria and syphilitic ulcers. However, the enduring research and emerging evidence suggests that AA could be a potent target molecule with bactericide, fungicide, insecticide, anti‐termite and molluscicide properties and as a therapeutic agent in the treatment of the most serious pathophysiological disorders like cancer, oxidative damage, inflammation and obesity. Furthermore, AA was found to be a common inhibitor of several clinically ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5432114 Tue, 22 Nov 2011 06:53:10 +0100 5432114 http://www.medworm.com/index.php?rid=5476970&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00830.x This study aimed to analyse medication errors committed by health care professionals leading to toxicological consultations at the Czech Toxicological Information Centre and to identify the categories of special concern for further interventions of health care quality experts. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5476970 Fri, 11 Nov 2011 05:00:00 +0100 5476970 http://www.medworm.com/index.php?rid=5401026&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00830.x This study aimed to analyse medication errors committed by health care professionals leading to toxicological consultations at the Czech Toxicological Information Centre (TIC), and to identify the categories of special concern for further interventions of health care quality experts.From the TIC database, 44,344 calls concerning drug application were studied retrospectively over the period of 2000‐2010. The calls regarding medication errors caused by mistakes of the health care personnel were identified and analysed.From 215 calls regarding medication errors, 130 involved children (90 below 5 years of age) and 85 adults (30 over 60 years of age). Out of 25 patients with severe drug intoxications, 60.0% were children under 5 years of age with parenteral administration of the pharmaceutica... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5401026 Fri, 11 Nov 2011 05:00:00 +0100 5401026 http://www.medworm.com/index.php?rid=5476969&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00829.x This study aimed to evaluate the effect of sibutramine and zinc on FR production. Female Wistar rats (about 250 g) were used in this study. The animals received 400 μg/kg of zinc and 10 mg/kg of sibutramine intraperitoneally every 36 hr for 15 days. At the end of the study, the rats were killed and their brains used for the measurement of lipid peroxidation thiobarbituric acid‐reactive substances (TBARS), reduced glutathione (GSH), hydrogen peroxide (H2O2), calcium and 5‐hydroxyindole acetic acid (5‐HIAA) levels, all by means of validated methods. Corporal weight and food consumption were found to be decreased in the zinc/sibutramine group. TBARS decreased in cortex, hemispheres and medulla oblongata. GSH decreased in cortex, hemispheres and cerebellum in the sibutramine g... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5476969 Mon, 07 Nov 2011 05:00:00 +0100 5476969 http://www.medworm.com/index.php?rid=5469385&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00824.x Abstract:  The fact that there is a complex and bidirectional communication between the immune and nervous systems has been well demonstrated. Lipopolysaccharide (LPS), a component of gram‐negative bacteria, is widely used to systematically stimulate the immune system and generate profound physiological and behavioural changes, also known as ‘sickness behaviour’ (e.g. anhedonia, lethargy, loss of appetite, anxiety, sleepiness). Different ethological tools have been used to analyse the behavioural modifications induced by LPS; however, many researchers analysed only individual tests, a single LPS dose or a unique ethological parameter, thus leading to disagreements regarding the data. In the present study, we investigated the effects of different doses of LPS (10, 50, 200 and 500 ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5469385 Mon, 07 Nov 2011 05:00:00 +0100 5469385 http://www.medworm.com/index.php?rid=5387790&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00829.x This study aimed to evaluate the effect of sibutramine and zinc on FR production.Female Wistar rats (about 250 g) were used. The animals received 400μg/kg of zinc and 10mg/kg of sibutramine intraperitoneally every 36 hr for 15 days. At the end of the study, the rats were killed and their brains used for measurement of lipid peroxidation (TBARS), reduced glutathione (GSH), hydrogen peroxide (H2O2), calcium and 5‐hydroxyindole acetic acid (5‐HIAA) levels, all by means of validated methods. Corporal weight and food consumption were found to be decreased in the zinc/sibutramine group. TBARS decreased in cortex, hemispheres and medulla oblongata. GSH decreased in cortex, hemispheres and cerebellum in the sibutramine group. Zinc given alone and in combination with sibutramine decreased H2O2... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5387790 Mon, 07 Nov 2011 05:00:00 +0100 5387790 http://www.medworm.com/index.php?rid=5387791&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00828.x This study was conducted to investigate the efficacy of RA on DN and to elucidate the potential mechanism. High glucose (HG) stimulated cultured human renal proximal tubular epithelial cells (HK‐2) analysed CTGF expression by western blotting, and it was investigated whether extracellular signal‐regulated kinase (ERK) signaling pathway was involved. Using streptozotocin (STZ)‐induced rat animal models, diabetic rats were randomized to receive intragastric (i.g.) doses of RA. Renal tissue, blood and urine samples were collected to determine biochemical index and analyze protein expression. In vitro study, RA reduced CTGF excretion in HG‐induced HK‐2 cells through the ERK signaling pathway. In an in vivo study, I.g. of RA 7.5 mg/kg or 15 mg/kg significantly ameliorated renal functi... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5387791 Fri, 04 Nov 2011 04:00:00 +0100 5387791 http://www.medworm.com/index.php?rid=5387792&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00827.x AbstractRecent studies have demonstrated that nuclear factor‐κB (NF‐κB) and high‐mobility group box1 (HMGB1) are associated with the pathophysiology of sepsis. The present study was carried out to investigate the effects of Protocatechuic aldehyde (PA) on an experimental model of sepsis induced by caecal ligation and puncture (CLP) in rats, and to elucidate the potential mechanism in the cultured murine macrophage cell line, RAW264.7 cells. Treatment of RAW 264.7 cells with PA blocked TNF‐α‐induced NF‐κB phosphorylation and decreased HMGB1 expression. Septic rats received doses of 50 mg of PA alone or plus Imipenem by intravenous bolus injection into the tail vein. The results showed that PA reduced serum levels of HMGB1 and triggering the receptor expressed on myeloid cell... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5387792 Wed, 02 Nov 2011 04:00:00 +0100 5387792 http://www.medworm.com/index.php?rid=5401025&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00831.x AbstractImazalil, cypermethrin and carbendazim are detected in plants for human nutrition. To explore if their combinations, applied orally in low doses, would induce changes in metabolic patterns and hepatotoxicity, a subchronic in vivo experiment was conducted. Doses of 10 mg kg−1 of imazalil (im) and cypermethrin (cy) and 20 mg kg−1 of carbendazim (car) and their combinations (im, 10 mg kg−1 + cy, 10 mg kg−1; im, 10 mg kg−1 + car, 20 mgkg−1; car, 20 mg kg−1 + im, 10 mg kg−1) were given to Swiss mice daily over 28 days. After 24 hr from the last dose, the relationships of cytotoxicity biomarkers were analysed: serum lactate dehydrogenase, aspartate transaminase, alanine transferase, amylase, alkaline phosphatase, creatine kinase, creatinine and total proteins. Individual ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5401025 Tue, 01 Nov 2011 04:00:00 +0100 5401025 http://www.medworm.com/index.php?rid=5387789&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00824.x AbstractThe fact that there is a complex and bidirectional communication between the immune and nervous systems has been well demonstrated. Lipopolysaccharide (LPS), a component of gram‐negative bacteria, is widely used to stimulate the immune system systemically and generate profound physiological and behavioural changes, also known as “sickness behaviour” (e.g. anhedonia, lethargy, loss of appetite, anxiety, sleepiness). Different ethological tools have been used to analyse the behavioural modifications induced by LPS; however, many researchers analysed only individual tests, a single LPS dose or a unique ethological parameter, thus leading to disagreements regarding the data. In the present study, we investigated the effects of different doses of LPS (10, 50, 200 and 500 μg/kg, i... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5387789 Tue, 01 Nov 2011 04:00:00 +0100 5387789 http://www.medworm.com/index.php?rid=5348033&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00826.x In conclusion, a marked entrapment of amitriptyline by intravenous lipid emulsion was observed but this did not improve the pigs’ haemodynamic recovery from severe amitriptyline intoxication. Care should be exercised in the antidotal use of lipid emulsion until controlled human studies indicate its efficacy and safety. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5348033 Wed, 26 Oct 2011 13:07:58 +0100 5348033 http://www.medworm.com/index.php?rid=5422544&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00825.x Abstract:  There has been recent interest in combining antiplatelets, angiotensin‐converting enzyme inhibitors (ACEIs) and statins in primary and secondary ischaemic stroke prevention. This observational study was performed to evaluate the impact of adding ACEIs and/or statins to antiplatelets on post‐stroke in‐hospital mortality. Ischaemic stroke patients attending a hospital in Malaysia over an 18‐month period were evaluated. Patients were categorized according to their vital status at discharge. Data included demographic information, risk factors, clinical characteristics and previous medications with particular attention on antiplatelets, ACEIs and statins. In‐hospital mortality was compared among patients who were not taking antiplatelets, ACEIs or statins before stroke on... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5422544 Tue, 25 Oct 2011 04:00:00 +0100 5422544 http://www.medworm.com/index.php?rid=5348034&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00825.x AbstractThere has been recent interest in combining antiplatelets, angiotensin‐converting enzyme inhibitors (ACEIs) and statins in primary and secondary ischaemic stroke prevention.This observational study was performed in order to evaluate the impact of adding ACEIs and/or statins to antiplatelets on post‐stroke in‐hospital mortality.Ischaemic stroke patients attending a hospital in Malaysia over an 18‐month period were evaluated. Patients were categorized according to their vital status at discharge. Data included demographic information, risk factors, clinical characteristics and previous medications with particular attention on antiplatelets, ACEIs and statins. In‐hospital mortality was compared among patients who were not taking antiplatelets, ACEIs or statins before stroke ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5348034 Tue, 25 Oct 2011 04:00:00 +0100 5348034 http://www.medworm.com/index.php?rid=5336601&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00823.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5336601 Sat, 22 Oct 2011 05:55:37 +0100 5336601 http://www.medworm.com/index.php?rid=5336602&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00817.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5336602 Fri, 21 Oct 2011 04:00:00 +0100 5336602 http://www.medworm.com/index.php?rid=5336603&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00821.x Abstract:  The hybrid created from the crossbreeding of European and African bees, known as the Africanised bee, has provided numerous advantages for current beekeeping. However, this new species exhibits undesirable behaviours, such as colony defence instinct and a propensity to attack en masse, which can result in serious accidents. To date there is no effective treatment for cases of Africanised bee envenomation. One promising technique for developing an efficient antivenom is the use of phage display technology, which enables the production of human antibodies, thus avoiding the complications of serum therapy, such as anaphylaxis and serum sickness. The aim of this study was to produce human monoclonal single‐chain Fv (scFv) antibody fragments capable of inhibiting the toxic effect... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5336603 Thu, 20 Oct 2011 04:00:00 +0100 5336603 http://www.medworm.com/index.php?rid=5324274&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00820.x Abstract:  Erythropoietin (EPO) belongs to a group of pharmacological agents with multifunctional effects. EPO was originally acknowledged as the main regulator of erythropoiesis but it also exhibits several extra haematopoietic properties, such as promoting the maintenance of homeostasis of cells under stress. These pleiotropic effects have been extensively investigated in preclinical models including models of ischaemic‐reperfusions injuries, inflammation, neuroprotection, neovascularisation and wound healing. Promising effects of EPO have especially been reported in models of ischaemic‐reperfusions injuries. The mechanisms by which EPO exerts these organ‐protective effects are not completely understood, although anti‐apoptotic, anti‐inflammatory and anti‐oxidative properti... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5324274 Tue, 18 Oct 2011 06:57:35 +0100 5324274 http://www.medworm.com/index.php?rid=5336604&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00822.x AbstractConsiderable evidence supports the presence of oxidative stress in cystic fibrosis (CF). The disease has long been associated with both increased production of reactive oxygen species (ROS) as well as impaired antioxidant status, in particular during the chronic pulmonary infection with P. aeruginosa, which is the main cause of morbidity and mortality in CF.Guinea pigs are unable to synthesize ascorbate (ASC) or vitamin C, a major antioxidant of the lung, and thus like human beings rely on its presence in the diet. On this basis, guinea pigs receiving ASC deficient diet have been used as a model of oxidative stress.The aim of our study was to investigate the consequences of a 7‐day biofilm‐grown P. aeruginosa lung infection in 3‐month‐old guinea pigs receiving either ASC su... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5336604 Tue, 18 Oct 2011 04:00:00 +0100 5336604 http://www.medworm.com/index.php?rid=5387793&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00820.x Abstract:  Erythropoietin (EPO) belongs to a group of pharmacological agents with multifunctional effects. EPO was originally acknowledged as the main regulator of erythropoiesis, but it also exhibits several extra haematopoietic properties, such as promoting the maintenance of homeostasis of cells under stress. These pleiotropic effects have been extensively investigated in preclinical models including models of ischaemic‐reperfusions injuries, inflammation, neuroprotection, neovascularisation and wound healing. Promising effects of EPO have especially been reported in models of ischaemic–reperfusions injuries. The mechanisms by which EPO exerts these organ‐protective effects are not completely understood, although anti‐apoptotic, anti‐inflammatory and anti‐oxidative propert... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5387793 Mon, 17 Oct 2011 04:00:00 +0100 5387793 http://www.medworm.com/index.php?rid=5324275&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00819.x Abstract:  Prolonged consumption of ethanol produces prefrontal cortex (PFC) dysfunction in patients and this has been demonstrated using structural, physiological and psychological measurements. We therefore wanted to develop an animal model of PFC dysfunction to study whether this state changes sensitivity for ethanol or other behavioural/motivational measures. Adolescent Wistar rats were first screened in the novel object recognition task to establish a pre‐treatment baseline measure of locomotor activity, anxiety‐like behaviour and PFC function. Animals were divided into 4 treatment groups (Saline, 5 mg/kg PCP, 2.5g/kg ethanol, Ethanol + PCP) and injected i.p. for 5 days followed by a 2‐day washout. On the 8th day, animals were allowed to explore a Y‐maze for 10 min. and spon... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5324275 Mon, 17 Oct 2011 04:00:00 +0100 5324275 http://www.medworm.com/index.php?rid=5315009&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00818.x This article reviews the relationship between intracellular Ca2+ signalling and VSMC phenotype. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5315009 Sat, 15 Oct 2011 06:08:47 +0100 5315009 http://www.medworm.com/index.php?rid=5401027&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00816.x Abstract:  The effect of the natural product 3,3′‐diindolylmethane (DIM) on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells was explored. The Ca2+‐sensitive fluorescent dye fura‐2 was applied to measure [Ca2+]i. DIM at concentrations of 40–80 μM induced a [Ca2+]i rise in a concentration‐dependent manner. The response was reduced partly by removing Ca2+. DIM‐evoked Ca2+ entry was suppressed by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In the absence of extracellular Ca2+, incubation with the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin or 2,5‐di‐tert‐butylhydroquinone (BHQ) inhibited or abolished DIM‐induced [Ca2+]i rise. Incubation with DIM also inhibited thapsigargin or BHQ‐induced [... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5401027 Thu, 13 Oct 2011 04:00:00 +0100 5401027 http://www.medworm.com/index.php?rid=5387794&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00814.x In conclusion, depending on the speed of transfer between the plasma and the effect site as well as the participation of active metabolites, the time‐course of the analgesic effects can be close to the plasma concentrations (alfentanil and derivates) or observed with a prolonged delay (codeine, buprenorphine, morphine). These PK/PD data can be used to better characterize the differences between opioids, and partly explain the important observed variability among opioids in experimental conditions and should be systematically evaluated during drug development to better predict their selection in specific clinical conditions. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5387794 Thu, 13 Oct 2011 04:00:00 +0100 5387794 http://www.medworm.com/index.php?rid=5315012&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00815.x AbstractVascular networks are dynamic structures, adapting to changing conditions by structural remodelling of vessel diameters and by growth of new vessels and regression of existing vessels. The vast number of blood vessels in the circulatory system, more than 109, implies that vessels’ arrangement and structure are not under individual genetic control but emerge as a result of generic responses of each segment to the various stimuli that it experiences. To obtain insight into the types of response that are needed, a network‐oriented approach has been used, in which theoretical models are used to simulate structural adaptation in vascular networks, and the results are compared with experimental observations. With regard to the structural control of vessel diameters, this approach sho... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5315012 Thu, 13 Oct 2011 04:00:00 +0100 5315012 http://www.medworm.com/index.php?rid=5315011&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00816.x AbstractThe effect of the natural product 3,3’‐diindonylmethane (DIM) on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells was explored. The Ca2+‐sensitive fluorescent dye fura‐2 was applied to measure [Ca2+]i. DIM at concentrations of 40‐80 μM induced a [Ca2+]i rise in a concentration‐dependent manner. The response was reduced partly by removing Ca2+. DIM‐evoked Ca2+ entry was suppressed by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In the absence of extracellular Ca2+, incubation with the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin or 2,5‐di‐tert‐butylhydroquinone (BHQ) inhibited or abolished DIM‐induced [Ca2+]i rise. Incubation with DIM also inhibited thapsigargin or BHQ‐induced [Ca2+]i ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5315011 Thu, 13 Oct 2011 04:00:00 +0100 5315011 http://www.medworm.com/index.php?rid=5315010&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00814.x In conclusion, depending on the speed of transfer between the plasma and the effect site as well as the participation of active metabolites, the time‐course of the analgesic effects can be close to the plasma concentrations (alfentanil and derivates) or observed with a prolonged delay (codeine, buprenorphine, morphine). These PK/PD data can be used to better characterize differences between opioids and partly explain the important observed variability among opioids in experimental conditions and should be systematically evaluated during drug development to better predict their selection in specific clinical conditions. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5315010 Thu, 13 Oct 2011 04:00:00 +0100 5315010 http://www.medworm.com/index.php?rid=5401028&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00811.x In this study, we evaluated the effects of SP from the red seaweed Gracilaria cornea (Gc‐TSP) in nociceptive and inflammatory models. In mice, Gc‐TSP (3, 9 or 27 mg/kg) significantly reduced nociceptive responses, as measured by the number of writhes, at all tested doses. In a formalin test, Gc‐TSP significantly reduced licking time in both phases of the test at a dose of 27 mg/kg. In a hot‐plate test, the antinociceptive effect was observed only in animals treated with 27 mg/kg of Gc‐TSP, suggesting that the analgesic effect occurs through a central action mechanism at the highest dose. Gc‐TSP (3, 9 or 27 mg/kg) caused only a slight reduction in neutrophil migration in the rat peritoneal cavity. However, lower doses of Gc‐TSP (3 and 9 mg/kg) significantly inhibited... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5401028 Mon, 10 Oct 2011 04:00:00 +0100 5401028 http://www.medworm.com/index.php?rid=5387795&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00809.x Abstract:  The aim of the study was to evaluate the pentoxifylline administration on the foetal–placental circulation and neonatal outcome in women with threatened preterm labour. Pentoxifylline was given as a supplement to standard tocolytic therapy in a group of 43 patients (pentoxifylline group) as an intravenous infusion and oral supplementation in a total dosage of 800 mg/day. The drug was administered within 3 weeks after admission. No pentoxifylline was given in the control group (53 patients). Doppler velocimetry of pulsatility indices (PI) of the umbilical (UA) and middle cerebral (MCA) arteries as well as cerebro‐placental ratio (CPR) were calculated. Also, the neonatal outcome was estimated in both groups. From the second week of therapy with pentoxifylline, the PI dec... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5387795 Mon, 10 Oct 2011 04:00:00 +0100 5387795 http://www.medworm.com/index.php?rid=5304873&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00809.x Abstract:  The aim of the study was the evaluation of pentoxifylline administration on the foetal – placental circulation and neonatal outcome in women with threatened preterm labour. Pentoxifylline was given as a supplement to standard tocolytic therapy in a group of 43 patients (pentoxifylline group) as an intravenous infusion and oral supplementation in a total dosage of 800 mg/day. The drug was administered within three weeks after admission. No pentoxifylline was given in the control group (53 patients). Doppler velocimetry of pulsatility indices (PI) of the umbilical (UA) and middle cerebral (MCA) arteries as well as cerebro‐placental ratio (CPR) were calculated. Also, the neonatal outcome was estimated in both groups. From the second week of therapy with pentoxifylline, the pu... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5304873 Mon, 10 Oct 2011 04:00:00 +0100 5304873 http://www.medworm.com/index.php?rid=5304872&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00811.x In this study, we evaluated the effects of sulfated polysaccharides from the red seaweed G. cornea (Gc‐TSP) in nociceptive and inflammatory models. In mice, Gc‐TSP (3, 9 or 27 mg/kg) significantly reduced nociceptive responses, as measured by the number of writhes, at all tested doses. In a formalin test, Gc‐TSP significantly reduced licking time in both phases of the test at a dose of 27 mg/kg. In a hot‐plate test, the antinociceptive effect was observed only in animals treated with 27 mg/kg of Gc‐TSP, suggesting that the analgesic effect occurs through a central action mechanism at the highest dose. Gc‐TSP (3, 9 or 27 mg/kg) caused only a slight reduction in neutrophil migration in the rat peritoneal cavity. However, lower doses of Gc‐TSP (3 and 9 mg/kg) significantly inhib... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5304872 Mon, 10 Oct 2011 04:00:00 +0100 5304872 http://www.medworm.com/index.php?rid=5304871&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00810.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5304871 Mon, 10 Oct 2011 04:00:00 +0100 5304871 http://www.medworm.com/index.php?rid=5304870&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00812.x Abstract:  Up‐regulation of vascular endothelial growth factor (VEGF) is important to hepatocyte regeneration in the late stages of acetaminophen (APAP) toxicity in the mouse. The following study was conducted to examine the relationship of hypoxia inducible factor 1α (HIF‐1α) to VEGF and hepatocyte regeneration in APAP toxicity by using an inhibitor of HIF‐1α DNA‐binding activity, echinomycin (EC). B6C3F1 male mice were treated with APAP (200 mg/kg IP), followed by EC (0.15 mg IP) and killed at 4 hr. Serum ALT, necrosis, hepatic glutathione (GSH) and APAP protein adducts were comparable in the APAP/EC and the APAP/veh mice at 4 hr. Additional studies showed that high dose EC (0.3 mg) reduced hepatic VEGF but also lowered hepatic GSH. Subsequent studies were performed using th... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5304870 Mon, 10 Oct 2011 04:00:00 +0100 5304870 http://www.medworm.com/index.php?rid=5297354&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00807.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5297354 Thu, 06 Oct 2011 04:00:00 +0100 5297354 http://www.medworm.com/index.php?rid=5387796&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00805.x Abstract:  Markers of dopamine D1 receptor activation were determined to elucidate intracellular mechanisms associated with the combined effects of caffeine and 3,4 methylenedioxymethamphetamine (MDMA), reported previously to produce increased toxicity, when compared with either drug alone. Caffeine (10 mg/kg) and MDMA (15 mg/kg) were administered to male Sprague Dawley rats alone and in combination. One hour after drug administration, core body temperature and phosphorylation of the dopamine D1‐related intracellular markers, cAMP response element binding protein (CREB), the dopamine and c‐AMP‐regulated phosphoprotein of 32 kDa (DARPP‐32) and expression of the immediate early gene and cellular activation marker c‐fos were determined in the hypothalamus. Co‐administratio... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5387796 Tue, 04 Oct 2011 04:00:00 +0100 5387796 http://www.medworm.com/index.php?rid=5286178&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00805.x AbstractMarkers of dopamine D1 receptor activation were determined in order to elucidate intracellular mechanisms associated with the combined effects of caffeine and MDMA, reported previously to produce increased toxicity, when compared to either drug alone. Caffeine (10 mg/kg) and MDMA (15 mg/kg) were administered to male Sprague Dawley rats alone and in combination. One hour following drug administration, core body temperature and phosphorylation of the dopamine D1‐related intracellular markers, cAMP response element binding protein (CREB), the dopamine and c‐AMP‐regulated phosphoprotein of 32 kDa (DARPP‐32) and expression of the immediate early gene and cellular activation marker c‐fos were determined in the hypothalamus. Co‐administration of caffeine with MDMA increased co... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5286178 Tue, 04 Oct 2011 04:00:00 +0100 5286178 http://www.medworm.com/index.php?rid=5286179&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00804.x In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5286179 Mon, 03 Oct 2011 04:00:00 +0100 5286179 http://www.medworm.com/index.php?rid=5304869&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00813.x Abstract:  Arterioles are the blood vessels in the arterial side of the vascular tree that are located proximal to the capillaries and, in conjunction with the terminal arteries, provide the majority of resistance to blood flow. Consequently, arterioles are important contributors to the regulation of mean arterial pressure and tissue perfusion. Their wall consists of cellular and extracellular components that have been traditionally classified as conforming three layers: an intima containing endothelial cells sited on a basement membrane; a media made of an internal elastic lamina apposed by 1 or 2 layers of smooth muscle; and an adventitia composed mostly of collagen bundles, nerve endings and some fibroblasts. These components of the arteriolar wall are dynamically interconnected provi... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5304869 Sat, 01 Oct 2011 04:00:00 +0100 5304869 http://www.medworm.com/index.php?rid=5297353&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00808.x AbstractThe ability of three newly developed reversible inhibitors of acetylcholinesterase (K298, K344 and K474) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman‐poisoned mice was compared. Neither pyridostigmine nor new reversible inhibitors of acetylcholinesterase were able to decrease the LD50 value of soman. Thus, the pharmacological pre‐treatment with pyridostigmine or newly synthesized inhibitors of acetylcholinesterase was not able to protect mice against soman‐induced lethal acute toxicity. The pharmacological pre‐treatment with pyridostigmine alone or with K474 was able to slightly increase the efficacy of antidotal treatment (the oxime HI‐6 in combination with atropine) of ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5297353 Sat, 01 Oct 2011 04:00:00 +0100 5297353 http://www.medworm.com/index.php?rid=5286177&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00806.x AbstractCurcumin (diferuloylmethane), a phenolic compound obtained from the rhizome of Curcuma longa, has been found to inhibit cell proliferation in various human cancer cell lines, including non‐small cell lung cancer (NSCLC). Thymidine phosphorylase (TP) is considered an attractive therapeutic target, because increased TP expression can suppress cancer cell death induced by DNA damaging agents. Mitomycin C (MMC), a chemotherapeutic agent used to treat NSCLC, inhibits tumour growth through DNA cross‐linking and breaking. Whether MMC can affect TP expression in NSCLC is unknown. Therefore, in this study, we hypothesized that curcumin enhances the effects of MMC‐mediated cytotoxicity by decreasing TP expression and ERK1/2 activation. Exposure of human NSCLC cell lines H1975 and H1650... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5286177 Sat, 01 Oct 2011 04:00:00 +0100 5286177 http://www.medworm.com/index.php?rid=5261278&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00802.x Abstract:  The standard treatment for ovarian cancer in advanced stages is post‐surgery treatment with taxane‐platin chemotherapy. Despite an initial high response rate, most patients eventually relapse. The dose‐limiting toxicities of paclitaxel are neutropenia and neuropathy but the inter‐individual variability is large. The aim of this prospective study was to investigate the impact of genetic variants in key drug metabolizing/transporter genes on toxicity and compliance. CYP2C8*3 and three ABCB1 polymorphisms were chosen for primary analysis and a host of other candidate genes was explored in 92 prospectively recruited Scandinavian Caucasian women with primary ovarian cancer who were treated with paclitaxel and carboplatin. A single investigator assessed the clinical toxicity... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5261278 Thu, 29 Sep 2011 05:47:18 +0100 5261278 http://www.medworm.com/index.php?rid=5261279&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00803.x AbstractTransient receptor potential vanilloid‐1 (TRPV1) has been implicated as a mediator of itch in allergic rhinitis. To address this possibility, we synthesized a TRPV1 blocker (SB‐705498) for nasal administration in patients with seasonal allergic rhinitis. The pharmacological activity of SB‐705498 was confirmed on human TRPV1‐expressing HEK293 cells, using fluorometric calcium imaging, and in patients with allergic rhinitis subjected to nasal capsaicin challenges. The effect of SB‐705498 was studied in patients with seasonal allergic rhinitis subjected to daily allergen challenges for seven days, using a double‐blind, placebo‐controlled, randomized and cross‐over design. SB‐705498 was delivered by nasal lavage 10 min. before each allergen challenge. Primary end‐po... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5261279 Tue, 27 Sep 2011 04:00:00 +0100 5261279 http://www.medworm.com/index.php?rid=5251120&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00801.x AbstractRadial artery frequently develops spasm and requires vasodilator therapy during coronary artery bypass graft surgery. Levosimendan was recently shown to oppose 5‐hydroxytryptamine‐induced contraction of radial artery grafts. The aim of the present study was to explore whether levosimendan retains its vasodilatory capacity following in vitro pre‐incubation of radial artery segments with the inodilator. A possible cumulative effect of the drug in human platelets was also studied. Human isolated radial artery segments were pre‐incubated in 0.16 μmol L−1 levosimendan containing solution or in 0.9% NaCl, Bretschneider, 5% albumin and a 5% human serum protein solution (Biseko) as controls for 45 min. Contractions were induced by three consecutive administrations of 5‐h... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5251120 Sun, 25 Sep 2011 18:34:59 +0100 5251120 http://www.medworm.com/index.php?rid=5238398&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00800.x AbstractThe clinical benefit of implementing Bayesian approach for lithium drug monitoring was evaluated. Intervention group (N=42) and historical control group (N=55) patients were each divided into two groups: Dosage with immediate‐release lithium carbonate or a sustained release formulation, lithium citrate. Bayesian approach was performed in the intervention groups and estimation of lithium steady‐state trough concentration was obtained from non‐steady‐state blood sample, collected about 12 hr after the first lithium study dose. The estimate was compared with the actually measured steady‐state concentration. In the control group, lithium monitoring was traditionally performed as steady state blood sampling. Predicted and measured lithium concentrations were comparable. The de... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5238398 Thu, 22 Sep 2011 07:56:53 +0100 5238398 http://www.medworm.com/index.php?rid=5409058&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00800.x Abstract:  The clinical benefit of implementing Bayesian approach for lithium drug monitoring was evaluated. Intervention group (N = 42) and historical control group (N = 55) patients were each divided into two groups: Dosage with immediate‐release lithium carbonate or a sustained‐release formulation, lithium citrate. Bayesian approach was performed in the intervention groups, and estimation of lithium steady‐state trough concentration was obtained from non‐steady‐state blood sample, collected about 12 hr after the first lithium study dose. The estimate was compared with the actually measured steady‐state concentration. In the control group, lithium monitoring was traditionally performed as steady‐state blood sampling. Predicted and measured lithium concentrations... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5409058 Tue, 20 Sep 2011 04:00:00 +0100 5409058 http://www.medworm.com/index.php?rid=5226595&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00799.x Abstract:Essential hypertension (EH) is associated with structural changes of small arteries (SMASCH) in terms of wall thickening and lumen narrowing throughout the entire resistance circulation. This remodelling process occurs early in EH development and is an important contributor to the elevation of vascular resistance. SMASCH also decreases the vasodilatory capability leading to demand‐related organ dysfunction (e.g. microvascular angina) and later contributes to organ failure as seen in hypertensive heart‐ and renal failure. In large groups of patients, office blood pressure (BP) precisely predicts strokes and myocardial infarctions, but it is difficult to apply risk prediction equations based on studies of large numbers of patients in individual patients. Office BP may be a rathe... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5226595 Sun, 18 Sep 2011 23:37:04 +0100 5226595 http://www.medworm.com/index.php?rid=5336608&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00798.x Abstract:  This MiniReview is focused on the nature of intercellular signalling along the endothelium that helps to co‐ordinate blood flow control in vascular resistance networks. Vasodilation initiated by contracting skeletal muscle ascends from arterioles within the tissue to encompass resistance arteries upstream and thereby increase blood flow during exercise. In resistance vessels, acetylcholine microiontophoresis or intracellular current injection initiates hyperpolarization that conducts through gap junction channels (GJCs) along the vessel wall resulting in conducted vasodilation (CVD). Both ascending vasodilation and CVD are eliminated with endothelial cell (EC) disruption, pointing to common signalling events and mutual dependence upon EC integrity. As demonstrated by electri... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5336608 Wed, 14 Sep 2011 04:00:00 +0100 5336608 http://www.medworm.com/index.php?rid=5336605&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00796.x Abstract:  Microvessels live ‘a life under pressure’ in several ways. In a literal sense, vessels of the microcirculation are exposed to high levels of stress caused primarily by the intravascular pressure head. In a figurative sense, the individual vessel and the microvascular network as a whole must continuously strive to meet the changing demands of the surrounding tissue. The ‘principle of optimal operation’ as formulated by Y. C. Fung states that living tissues adapts structurally through remodelling and growth until a level of tensile and compressive stresses is reached at which tissue performance is optimal. This behaviour is characteristic for the microvascular wall. It is highly plastic by nature and meets sustained changes by structural adaptation so as to maintain func... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5336605 Wed, 14 Sep 2011 04:00:00 +0100 5336605 http://www.medworm.com/index.php?rid=5304874&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00797.x This study is the first to investigate the inhibitory effect of nonylphenol (NP) on human bronchial epithelial cell lines BEAS‐2B and HBE135‐E6E7 (HBE). The results show that NP inhibits bronchial epithelial proliferation via the Fas/Fas ligand apoptotic system. We also treated BEAS‐2B and HBE with NP and harvested the condition medium (CM), which was then added to bronchial smooth muscle cells (BSMC). Cultures of BSMC with NP‐BEAS‐2B‐CM and NP‐HBE‐CM increased BSMC proliferation and migration. Exposure of BEAS‐2B and HBE to NP caused epithelial cells to produce inflammatory cytokines IL‐6 and IL‐8, which subsequently induced BSMC proliferation and migration. Depleting both IL‐6 and IL‐8 completely reversed the effect of NP‐BEAS‐2B‐CM‐ and NP‐HBE‐CM‐... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5304874 Wed, 14 Sep 2011 04:00:00 +0100 5304874 http://www.medworm.com/index.php?rid=5226599&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00795.x Abstract:As a cancer chemotherapeutic agent, paclitaxel (Taxol®) causes dose‐related peripheral neuropathy in human beings. The mechanisms underlying this toxicity are currently unknown and there are no validated treatments for its prevention or control. To assess whether lithium as a pre‐treatment and at subtherapeutic dose could prevent the peripheral neuropathy produced by it, rats were treated with paclitaxel (2mg/kg i.p. every other day for a total of 16 times) and/or lithium chloride (300mg/l) via water supply. General toxicity and body weight were measured regularly during the experiment. To evaluate the sensory and motor neuropathy hot plate, open‐field test and nerve conduction velocity were used. In rats treated with only paclitaxel, there was behavioural, electrophysiolog... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5226599 Wed, 14 Sep 2011 04:00:00 +0100 5226599 http://www.medworm.com/index.php?rid=5226598&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00797.x This study is the first to investigate the inhibitory effect of nonylphenol (NP) on human bronchial epithelial cell lines BEAS‐2B and HBE135‐E6E7 (HBE). The results show that NP inhibits bronchial epithelium proliferation via the Fas/Fas ligand apoptotic system. We also treated BEAS‐2B and HBE with NP and harvested the condition medium (CM), which was then added to bronchial smooth muscle cells (BSMC). Cultures of BSMC with NP‐BEAS‐2B‐CM and ‐HBE‐CM increased BSMC proliferation and migration. Exposure of BEAS‐2B and HBE to NP caused epithelial cells to produce inflammatory cytokines IL‐6 and IL‐8, which subsequently induced BSMC proliferation and migration. Depleting both IL‐6 and IL‐8 completely reversed the effect of NP‐BEAS‐2B‐CM and NP‐HBE‐CM‐media... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5226598 Wed, 14 Sep 2011 04:00:00 +0100 5226598 http://www.medworm.com/index.php?rid=5226597&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00798.x AbstractThis MiniReview is focused on the nature of intercellular signaling along the endothelium that helps to coordinate blood flow control in vascular resistance networks. Vasodilation initiated by contracting skeletal muscle ascends from arterioles within the tissue to encompass resistance arteries upstream and thereby increase blood flow during exercise. In resistance vessels, acetylcholine microiontophoresis or intracellular current injection initiates hyperpolarization that conducts through gap junction channels (GJCs) along the vessel wall resulting in conducted vasodilation (CVD). Both ascending and conducted vasodilation are eliminated with endothelial cell (EC) disruption, pointing to common signaling events and mutual dependence upon EC integrity. As demonstrated by electrical ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5226597 Wed, 14 Sep 2011 04:00:00 +0100 5226597 http://www.medworm.com/index.php?rid=5226596&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00796.x Abstract:Micro‐vessels live “a life under pressure” in several ways. In a literal sense, vessels of the microcirculation are exposed to high levels of stress caused primarily by the intravascular pressure head. In a figurative sense, the individual vessel and the microvascular network as a whole must continuously strive to meet the changing demands of the surrounding tissue. The “principle of optimal operation” as formulated by Y.C. Fung states that living tissues adapts structurally through remodeling and growth until a level of tensile and compressive stresses is reached at which tissue performance is optimal. This behaviour is characteristic for the microvascular wall. It is highly plastic by nature and meets sustained changes by structural adaptation so as to maintain functio... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5226596 Wed, 14 Sep 2011 04:00:00 +0100 5226596 http://www.medworm.com/index.php?rid=5209453&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00769.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5209453 Mon, 12 Sep 2011 21:52:15 +0100 5209453 http://www.medworm.com/index.php?rid=5209447&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00794.x Abstract:Blood vessel structure and caliber is not static. Rather, vessels remodel continuously in response to their biomechanical environment. Vascular caliber is dictated by the amount, composition and organization of the elastic extracellular matrix. In addition, the amount and organization of contractile smooth muscle cells (SMC) also needs to be regulated. The SMC are organized such that maximum contractile force generally occurs at diameters slightly below the diameter at full dilation and physiological pressure. Thus, in a remodeling vessel, not only the matrix but also the SMC need to undergo structural adaptation. Surprisingly little is known on adaptation of SMC contractile properties in the vasculature. The purpose of this review is to explore this SMC plasticity in the context ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5209447 Mon, 12 Sep 2011 21:50:37 +0100 5209447 http://www.medworm.com/index.php?rid=5336607&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00793.x Abstract:  Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodelling of the entire maternal uterine vasculature. The main focus of this MiniReview is to provide information on upstream (pre‐placental) maternal uterine vascular remodelling that facilitates gestational increases in uterine blood flow. Consideration of the three‐dimensional pattern of remodelling (circumferential enlargement versus axial elongation), changes in vessel biomechanical properties, and underlying mechanisms [shear stress, nitric oxide, vascular endothelial growth factor (VEGF)/placental growth factor (PlGF), the renin–angiotensin system] and pathways (local versus systemic; venoarterial exchange) are provided using the rat a... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5336607 Thu, 08 Sep 2011 04:00:00 +0100 5336607 http://www.medworm.com/index.php?rid=5336606&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00794.x Abstract:  Blood vessel structure and calibre are not static. Rather, vessels remodel continuously in response to their biomechanical environment. Vascular calibre is dictated by the amount, composition and organization of the elastic extracellular matrix. In addition, the amount and organization of contractile smooth muscle cell (SMC) also need to be regulated. The SMCs are organized such that maximum contractile force generally occurs at diameters slightly below the diameter at full dilation and physiological pressure. Thus, in a remodelling vessel, not only the matrix but also the SMCs need to undergo structural adaptation. Surprisingly little is known on the adaptation of SMC contractile properties in the vasculature. The purpose of this review is to explore this SMC plasticity in th... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5336606 Thu, 08 Sep 2011 04:00:00 +0100 5336606 http://www.medworm.com/index.php?rid=5209451&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00790.x In this study, we focused on UGT1A isoforms broadly expressed in hepatic and extrahepatic tissues, and examined the expression and inducibility of UGT1As (UGT1A1 and UGT1A3–1A10) in MCF‐7 cells (human breast carcinoma cell line). Reverse transcription polymerase chain reaction (RT‐PCR) analysis demonstrated that UGT1A1, UGT1A6 and UGT1A9 mRNAs as well as the mRNAs of transcriptional regulators (aryl hydrocarbon receptor, AhR; AhR nuclear translocator, Arnt; oestrogen receptor α, ERα; ERβ; and glucocorticoid receptor, GR) are expressed in MCF‐7 cells. UGT1A6 mRNA level in MCF‐7 cells was significantly increased to 1.9‐fold by β‐naphthoflavone (BNF), whereas UGT1A1 and UGT1A9 mRNA levels were not affected by BNF. There were no significant changes in the mRNAs of UGT1A1, UGT... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5209451 Thu, 08 Sep 2011 04:00:00 +0100 5209451 http://www.medworm.com/index.php?rid=5209450&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00791.x In conclusion, Zingiber officinale suppressed markers of hepatic inflammation in HFD‐fed rats, as evidenced by decreased hepatic cytokine gene expression and decreased NF‐κB activation. The study demonstrates that the anti‐inflammatory effect of Zingiber officinale occurs at least in part through the NF‐κB signalling pathway. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5209450 Thu, 08 Sep 2011 04:00:00 +0100 5209450 http://www.medworm.com/index.php?rid=5209449&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00792.x Abstract:  Cholesterol 7α‐hydroxylase (CYP7A1) is the rate‐limiting enzyme of bile acid production in human beings, and organic anion transporting polypeptide 1B1 (OATP1B1) may influence bile acid hepatic uptake and cholesterol and bile acid synthesis rate. Our purpose was to investigate the effects of gender and CYP7A1 and SLCO1B1 polymorphisms on the fasting plasma concentrations of bile acids, bile acid synthesis marker and total cholesterol in a Finnish population. Fasting plasma concentrations of 16 endogenous bile acids, their synthesis marker (7α‐hydroxy‐4‐cholesten‐3‐one) and total cholesterol were measured in 243 samples from 143 healthy volunteers. The volunteers were genotyped for 6 haplotype‐tagging single nucleotide polymorphisms (SNPs) of CYP7A1 and two fu... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5209449 Thu, 08 Sep 2011 04:00:00 +0100 5209449 http://www.medworm.com/index.php?rid=5209448&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00793.x Abstract:Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire maternal uterine vasculature. The main focus of this MiniReview is to provide information on upstream (pre‐placental) maternal uterine vascular remodeling that facilitates gestational increases in uterine blood flow. Consideration of the three‐dimensional pattern of remodeling (circumferential enlargement versus axial elongation), changes in vessel biomechanical properties, and underlying mechanisms (shear stress, nitric oxide, Vascular endothelial growth factor (VEGF)/Placental growth factor (PlGF), the renin‐angiotensin system) and pathways (local versus systemic; venoarterial exchange) are provided using the rat as the p... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5209448 Thu, 08 Sep 2011 04:00:00 +0100 5209448 http://www.medworm.com/index.php?rid=5196680&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00779.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5196680 Wed, 07 Sep 2011 00:31:40 +0100 5196680 http://www.medworm.com/index.php?rid=5196679&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00778.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5196679 Wed, 07 Sep 2011 00:31:38 +0100 5196679 http://www.medworm.com/index.php?rid=5196678&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00777.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5196678 Wed, 07 Sep 2011 00:31:36 +0100 5196678 http://www.medworm.com/index.php?rid=5196677&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00776.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5196677 Wed, 07 Sep 2011 00:31:34 +0100 5196677 http://www.medworm.com/index.php?rid=5196676&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00775.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5196676 Wed, 07 Sep 2011 00:31:33 +0100 5196676 http://www.medworm.com/index.php?rid=5196674&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00789.x Conclusions:  The strongest determinants of VKA dose are well‐known pharmacogenetic variables and age. The variables describing health‐related behaviour and socio‐psychological factors are strongly inter‐correlated and not useful in dosing algorithms. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5196674 Wed, 07 Sep 2011 00:29:47 +0100 5196674 http://www.medworm.com/index.php?rid=5196675&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00765.x Abstract:  The effects of the Kv7 channel modulators retigabine (opener) and XE991 (blocker) on rat bladder function were investigated ex vivo and in vivo to assess the potential of Kv7 openers for the treatment of overactive bladder. In organ bath studies, capsaicin‐stimulated rat urinary bladder rings were exposed to retigabine and XE991 and the effect on tension and amplitude was evaluated. In anaesthetized rats, retigabine (0.01–1 mg/kg, i.v.) effects on bladder function, in which overactivity was induced by continuous infusion of 0.5% acetic acid, were assessed. The effect of retigabine (10 mg/kg, p.o.) on cystometric parameters was also measured in conscious rats with capsaicin‐induced irritated bladders. Localization of Kv7 subunits within bladder tissue was analysed by ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5196675 Mon, 05 Sep 2011 23:00:00 +0100 5196675 http://www.medworm.com/index.php?rid=5297355&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00789.x Abstract:  Vitamin K antagonists (VKA) are highly effective anticoagulants but their use is hampered by multiple interactions with food and medicine and a narrow therapeutic range. The large variation in dose requirements has led to the development of several dosing algorithms based on pharmacogenetic and clinical variables. In contrast, evidence about the influence of behavioural (i.e. diet and exercise) and socio‐psychological factors is sparse. To investigate the impact of pharmacogenetic, clinical, behavioural and socio‐psychological factors on maintenance dose of VKA. In a cross‐sectional study, we interviewed 250 consecutive patients from an anticoagulant clinic and subsequently measured pharmacogenetic and anthropometric variables. Statistical analyses were carried out using... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5297355 Mon, 05 Sep 2011 04:00:00 +0100 5297355 http://www.medworm.com/index.php?rid=5184591&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00787.x The objective of this study was to evaluate the ability of schisandrin A (SchA) to inhibit the P450 enzyme CYP3A in vivo. Male Sprague‐Dawley rats were intragastrically gavaged with varied doses of SchA (8 mg/kg or 16 mg/kg or 32 mg/kg) or 75mg/kg ketoconazole for 3 consecutive days. Ketoconazole, a chemical inhibitor of CYP3A, was used as positive control. Subsequently, changes of hepatic microsome CYP3A activity and the pharmacokinetic profiles of midazolam, a specific CYP3A substrate, were studied as indicators of rat hepatic microsomal activity of CYP3A. Differences in the plasma concentrations of midazolam and its related metabolites and the hepatic microsome concentrations of 1′‐hydroxy midazolam were analysed by high‐performance liquid chromatography (HPLC). The current resu... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5184591 Thu, 01 Sep 2011 23:00:00 +0100 5184591 http://www.medworm.com/index.php?rid=5184590&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00788.x In conclusion, bupropion add‐on can act as augmenting agent in patients of depression with partial response to SSRIs. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5184590 Wed, 31 Aug 2011 23:00:00 +0100 5184590 http://www.medworm.com/index.php?rid=5162601&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00786.x Abstract:  In cardiovascular and metabolic diseases, small resistance arteries may show the presence of structural alterations. In particular, in essential hypertension, an increased media‐to‐lumen ratio of subcutaneous small arteries with no change of the total amount of vascular wall tissue (eutrophic remodelling), has already been described several years ago. Similar alterations have been demonstrated also in patients with diabetes mellitus and obesity, in this case, however, a more evident contribution of vascular smooth muscle cell growth (hypertrophic remodeling) is present. The present review addresses the effects of obesity on small resistance artery structure. Similar to diabetic patients, obese patients show an increased media‐to‐lumen ratio of subcutaneous small arteri... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5162601 Sat, 27 Aug 2011 15:27:41 +0100 5162601 http://www.medworm.com/index.php?rid=5286180&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00786.x Abstract:  In cardiovascular and metabolic diseases, small resistance arteries may show the presence of structural alterations. In particular, in essential hypertension, an increased media‐to‐lumen ratio of subcutaneous small arteries with no change in the total amount of vascular wall tissue (eutrophic remodelling) has already been described several years ago. Similar alterations have been demonstrated also in patients with diabetes mellitus and obesity; in this case, however, a more evident contribution of vascular smooth muscle cell growth (hypertrophic remodelling) is present. This review addresses the effects of obesity on small resistance artery structure. Similar to diabetic patients, obese patients show an increased media‐to‐lumen ratio of subcutaneous small arteries, whi... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5286180 Thu, 25 Aug 2011 04:00:00 +0100 5286180 http://www.medworm.com/index.php?rid=5261281&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00784.x Abstract:  The monoterpene (−)‐borneol is present in essential oils of several medicinal plants. The aim of this study was to evaluate (−)‐borneol effects on rat thoracic aorta artery rings. The cumulative addition of (−)‐borneol (10−9–3 × 10−4 M) on a phenylephrine‐induced pre‐contraction (10−6 M) promoted a vasorelaxant effect in a concentration‐dependent manner and independent of vascular endothelium. A similar effect was obtained on KCl‐induced pre‐contractions (80 mM). (−)‐Borneol (10−5–3 × 10−4 M) inhibited contractions induced by cumulative addition of CaCl2 (10−6–3 × 10−2 M) in depolarizing medium without Ca2+ in a concentration‐dependent manner. On S‐(−) Bay K 8644‐induced pre‐contractions (10−7�... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5261281 Mon, 22 Aug 2011 04:00:00 +0100 5261281 http://www.medworm.com/index.php?rid=5261280&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00785.x Abstract:  The healthy endothelium prevents platelet aggregation and leucocyte adhesion, controls permeability to plasma components and maintains vascular integrity. Damage to the endothelium promotes endothelial dysfunction characterized by: altered endothelium‐mediated vasodilation, increased vascular reactivity, platelet aggregation, thrombus formation, increased permeability, leucocyte adhesion and monocyte migration. Molecular processes contributing to these phenomena include increased expression of adhesion molecules, synthesis of pro‐inflammatory and pro‐thrombotic factors and increased endothelin‐1 secretion. Decreased nitric oxide bioavailability and increased generation of reactive oxygen species (ROS) are among the major molecular changes associated with endothelial dy... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5261280 Mon, 22 Aug 2011 04:00:00 +0100 5261280 http://www.medworm.com/index.php?rid=5162603&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00784.x Abstract:  The monoterpene (‐)‐borneol is present in essential oils of several medicinal plants. The aim of this study was to evaluate (‐)‐borneol effects on rat thoracic aorta artery rings. The cumulative addition of (‐)‐borneol (10−9 ‐ 3 x 10−4 M) on a phenylephrine‐induced pre‐contraction (10−6 M) promoted a vasorelaxant effect in a concentration‐dependent manner and independent of vascular endothelium. A similar effect was obtained on KCl‐induced pre‐contractions (80 mM). (‐)‐Borneol (10−5 ‐ 3 x 10−4 M) inhibited contractions induced by cumulative addition of CaCl2 (10−6 ‐ 3 x 10−2 M) in depolarizing medium without Ca2+ in a concentration‐dependent manner. On S‐(‐) Bay K 8644‐induced pre‐contractions (10−7 M), (‐)‐borneol ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5162603 Sun, 21 Aug 2011 23:00:00 +0100 5162603 http://www.medworm.com/index.php?rid=5162602&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00785.x Abstract: The healthy endothelium prevents platelet aggregation and leukocyte adhesion, controls permeability to plasma components and maintains vascular integrity. Damage to the endothelium promotes endothelial dysfunction characterized by: altered endothelium‐mediated vasodilation, increased vascular reactivity, platelet aggregation, thrombus formation, increased permeability, leukocyte adhesion and monocyte migration. Molecular processes contributing to these phenomena include increased expression of adhesion molecules, synthesis of pro‐inflammatory and pro‐thrombotic factors and increased endothelin‐1 (ET‐1) secretion. Decreased nitric oxide (NO) bioavailability and increased generation of reactive oxygen species (ROS) are among the major molecular changes associated with end... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5162602 Sun, 21 Aug 2011 23:00:00 +0100 5162602 http://www.medworm.com/index.php?rid=5144396&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00783.x In conclusion, although decreased/lack of COMT activity did not robustly alter feeding behaviour of female rodents, we observed some alterations in the microstructure of feeding. However, these minor changes were highly dependent on the extent and fashion in which COMT is manipulated. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5144396 Sat, 20 Aug 2011 16:01:17 +0100 5144396 http://www.medworm.com/index.php?rid=5261282&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00783.x In conclusion, although decreased/lack of COMT activity did not robustly alter feeding behaviour of female rodents, we observed some alterations in the microstructure of feeding. However, these minor changes were highly dependent on the extent and fashion in which COMT was manipulated. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5261282 Thu, 18 Aug 2011 04:00:00 +0100 5261282 http://www.medworm.com/index.php?rid=5144397&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00782.x Abstract:  L‐dopa is still the gold standard in the symptomatic treatment of Parkinson’s disease (PD), and thus it is the most commonly used drug in the non‐clinical assessment of new drug therapies to PD, including those intended to improve the effect of L‐dopa. In unilaterally 6‐OHDA‐lesioned rat model of PD, the results from L‐dopa‐induced rotation tests are often unpredictable. While repeated administration of L‐dopa improves the rotation, the exact mechanisms underlying the extensive variability in rotation responses between rats and testing times are unclear. In the present study, we aimed to assess whether the route of administration (oral or intraperitoneal) or the form of L‐dopa (base or methyl ester) is associated with the extensive variation in rotation res... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5144397 Tue, 16 Aug 2011 23:00:00 +0100 5144397 http://www.medworm.com/index.php?rid=5144398&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00781.x We describe two contemporary cases of non‐consanguineous patients using the same quantity of substance during the same period demonstrating that both direct toxicity and secondary immune reaction may be involved in Teucrium chamaedrys L. hepatotoxicity. Probably, a key factor is played by contemporary weight‐losing diets as reported in almost all cases of hepatoxic reactions to Teucrium chamaedrys L. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5144398 Mon, 15 Aug 2011 23:00:00 +0100 5144398 http://www.medworm.com/index.php?rid=5120101&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00766.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5120101 Fri, 12 Aug 2011 17:21:16 +0100 5120101 http://www.medworm.com/index.php?rid=5109986&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00780.x Abstract:The aim of this exploratory study was to investigate in a homogeneous population of anti‐retroviral naïve HIV‐1‐infected adults, the relationships between genetic polymorphisms involved in nevirapine metabolism (CYP2B6 516G>T, 785A>G and 1459C>T; CYP3A5 6986A>G (CYP3A5*3)), transport (ABCB1 2677G>T/A, and 3435C>T), and antigen recognition (HLA‐DRB1*0101), and the hepatic and/or cutaneous toxicity occurring within the first 8 or 72 weeks of treatment, plasma trough concentrations (Ctrough) at week 8 and immuno‐virological response to nevirapine at week 24.Associations between genetic polymorphisms and toxicity, Ctrough and response to nevirapine were performed in a population of 72 HIV‐1 positive and nevirapine‐treated patients followed during 72 we... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5109986 Sun, 31 Jul 2011 23:00:00 +0100 5109986 http://www.medworm.com/index.php?rid=5040346&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00768.x Abstract:Recombinant human parathyroid hormone [rhPTH(1‐84)] represents a new class of anabolic agents for the treatment of osteoporosis. The present study was designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of rhPTH(1‐84) following single‐ and multiple‐dose subcutaneous administration in healthy Chinese subjects. Six cohorts of 32 subjects received a single dose of rhPTH(1‐84) at 0.5 to 5.0 μg/kg, and two cohorts of 12 subjects received 2.0 and 3.0 μg/kg of rhPTH(1‐84) once daily for 7 consecutive days to assess its safety and tolerability. The results indicated that rhPTH(1‐84) appeared to be safe and well tolerated. Additionally, pharmacokinetics of rhPTH(1‐84) and its active N‐terminal fragment rhPTH(1‐34) were investigated after... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5040346 Wed, 20 Jul 2011 17:00:58 +0100 5040346 http://www.medworm.com/index.php?rid=5144399&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00768.x Abstract:  Recombinant human parathyroid hormone [rhPTH(1–84)] represents a new class of anabolic agents for the treatment of osteoporosis. The present study was designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of rhPTH(1–84) after single‐ and multiple‐dose subcutaneous administration in healthy Chinese volunteers. Six cohorts of 32 volunteers received a single dose of rhPTH(1–84) at 0.5–5.0 μg/kg, and two cohorts of 12 volunteers received 2.0 and 3.0 μg/kg of rhPTH(1–84) once daily for 7 consecutive days to assess its safety and tolerability. The results indicated that rhPTH(1–84) appeared to be safe and well tolerated. Additionally, pharmacokinetics of rhPTH(1–84) and its active N‐terminal fragment rhPTH(1–34) were investiga... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5144399 Tue, 19 Jul 2011 23:00:00 +0100 5144399 http://www.medworm.com/index.php?rid=5040347&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00767.x The objective of this study was to determine if p‐aminophenol could be toxic for in vitro developing mouse cortical neurons as a first step in establishing a link between acetaminophen use and neuronal apoptosis. We exposed developing mouse cortical neurons to various concentrations of drugs for 24 hr in vitro. Acetaminophen itself was not toxic to developing mouse cortical neurons at therapeutic concentrations of 10 to 250 μg/ml. However, concentrations of p‐aminophenol from 1 μg/ml to 100 μg/ml produced significant (p<0.05) loss of mouse cortical neuron viability at 24 hr compared to the controls. The naturally occurring endocannabinoid anandamide also caused similar 24‐hr loss of cell viability in developing mouse cortical neurons at concentrations from 1 μg/ml to 100 μg/m... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5040347 Tue, 19 Jul 2011 23:00:00 +0100 5040347 http://www.medworm.com/index.php?rid=5030935&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00763.x Abstract  Recent investigations have postulated a link between oxidative stress and endoplasmic reticulum (ER) dysfunction in cerebral ischaemic/reperfusion (I/R) injury. Diabetes is common amongst elderly patients with stroke and has been postulated to aggravate brain I/R damage by triggering oxidative as well as ER stress. We investigated whether treatment with edaravone (1‐10 mg/kg), a potent free radical scavenger protects against cerebral I/R injury in rats associated with comorbid type 2 diabetes. Diabetic rats exposed to 2‐hr middle cerebral artery occlusion (MCAO) and 22 hr of reperfusion significantly had increased infarct, oedema volume and functional neurological deficits as compared to sham‐operated rats. Also, the massive DNA fragmentation accompanied by significant in... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5030935 Sat, 16 Jul 2011 16:34:13 +0100 5030935 http://www.medworm.com/index.php?rid=5021344&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00762.x In conclusion, quinpirole‐induced inhibition of the sympathetic vasopressor outflow is primarily mediated by activation of dopamine D2‐like receptors. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5021344 Wed, 13 Jul 2011 16:52:56 +0100 5021344 http://www.medworm.com/index.php?rid=5109988&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00761.x Abstract:  Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5109988 Sat, 09 Jul 2011 23:00:00 +0100 5109988 http://www.medworm.com/index.php?rid=5109987&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00762.x In conclusion, quinpirole‐induced inhibition of the sympathetic vasopressor outflow is primarily mediated by activation of dopamine D2‐like receptors. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5109987 Sat, 09 Jul 2011 23:00:00 +0100 5109987 http://www.medworm.com/index.php?rid=5021345&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00761.x Abstract:Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated by using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in humans. In particular, human transplacental transfer of the food carcinogens acrylamide, glycidamide and nitrosodimethylamine are in focus. Because the... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5021345 Sat, 09 Jul 2011 23:00:00 +0100 5021345 http://www.medworm.com/index.php?rid=5144401&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00760.x Abstract:  Low‐grade inflammation plays a role in cardiovascular disease. The innate and the adaptive immune responses participate in mechanisms that contribute to inflammatory responses. It has been increasingly appreciated that different subsets of lymphocytes and the cytokines they produce modulate the vascular remodelling that occurs in cardiovascular disease. Effector T cells such as T‐helper (Th) 1 (interferon‐γ‐producing) and Th2 lymphocytes (that produce interleukin‐4), as well as Th17 (that produce interleukin‐17), and T suppressor lymphocytes including regulatory T cells (Treg), which express the transcription factor forkhead box P3 (Foxp3), are involved in the remodelling of small arteries that occurs under the action of angiotensin II, deoxycorticosterone‐salt ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5144401 Thu, 07 Jul 2011 23:00:00 +0100 5144401 http://www.medworm.com/index.php?rid=5144400&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00759.x Abstract:  Breast cancer patients with positive epidermal growth factor receptor (EGFR) expression have significantly worse post‐relapse prognosis than patients with negative EGFR expression. Vinorelbine (NVB) is usually reserved as a salvage therapy after anthracyclines and taxanes in patients with breast cancer. To see whether EGFR expression has a predictive value in NVB‐mediated effect on human breast cancer cells, we examined 50 primary breast cancer samples. Of these, 42% were found to be NVB sensitive by ATP‐tumour chemosensitivity assay. Sensitivity was correlated with EGFR expression level (p = 0.001). To dynamically examine EGFR’s effect on NVB sensitivity in breast cancer cells, we used the real‐time cell electronic sensing system with EGFR‐positive and EGFR‐... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5144400 Thu, 07 Jul 2011 23:00:00 +0100 5144400 http://www.medworm.com/index.php?rid=5010328&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00759.x Abstract:Breast cancer patients with positive epidermal growth factor receptor (EGFR) expression have significantly worse post‐relapse prognosis than patients with negative EGFR expression. Vinorelbine (NVB) is usually reserved as a salvage therapy after anthracyclines and taxanes in breast cancer patients. To see whether EGFR expression has a predictive value in vinorelbine‐mediated effect on human breast cancer cells, we examined 50 primary breast cancer samples. Of these, 42% were found to be NVB‐sensitive by ATP‐tumour chemosensitivity assay (ATP‐TCA). Sensitivity was correlated with EGFR expression level (P=0.001). To dynamically examine EGFR’s effect on NVB sensitivity in breast cancer cells, we used the real‐time electronic sensing (RT‐CES) system with EGFR positive ... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5010328 Thu, 07 Jul 2011 23:00:00 +0100 5010328 http://www.medworm.com/index.php?rid=5109989&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00757.x Abstract:  The aim of this study was to explore the influence of simvastatin dosing time, variable compliance and circadian cholesterol production on the reduction of low‐density lipoprotein (LDL). A published pharmacokinetic–pharmacodynamic (PKPD) model for simvastatin was identified and evaluated. A model for circadian LDL production was incorporated into the PKPD model. Reduction in LDL from baseline was simulated stochastically from the full model at dose levels of 10, 20, 40 and 80 mg daily for 30 days. Simulated dosing times for each data set were morning (8.00 a.m.), evening (22.00 p.m.), evening with reduced compliance and evening for a hypothetical bioequivalent generic. Differences in LDL reduction from baseline between evening (33–43%) and morning dosing (31–43%) w... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5109989 Tue, 05 Jul 2011 23:00:00 +0100 5109989 http://www.medworm.com/index.php?rid=5010332&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00755.x Abstract:Benzo(a)pyrene (BaP) is a representative compound of polycyclic aromatic hydrocarbons (PAHs) exerting cytotoxity and genotoxity in the human liver, lung, stomach and skin. However, the toxic effect of BaP on cervical tissue remains unclear. The present study was carried out to investigate the toxic effects of BaP on the cervix of ICR mice. Female mice were treated with BaP by intraperitoneal injection and oral gavage at a dose of 2.5, 5 and 10mg/kg body weight, twice a week for 14 weeks. BaP treatment caused a significant increase in the levels of MDA and IL‐6 with significantly increased activity of CYP1A1, creatine kinase (CK) and aspartate aminotransferase (AST) and decreased activity of glutathione‐S‐transferase (GST) in the cervix and liver. The relative cervix weight w... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5010332 Tue, 05 Jul 2011 23:00:00 +0100 5010332 http://www.medworm.com/index.php?rid=5010331&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00756.x In this study, we established a brain ageing model by using D‐galactose and investigated the concentrations of oxidative stress markers on the hippocampus, parietal and frontal lobes of male Sprague‐Dawley rats. A mimetic ageing model was established by injecting D‐galactose (60 mg/kg/day/i.p.) in the experimental group for 42 days. At the end of this period, we tested spatial memory using the Morris Water Maze test. To investigate the magnitude of oxidative damage in proteins, lipids and DNA, we studied the concentrations of various oxidative stress parameters in the hippocampus, parietal and frontal lobes of the brain. Glial and neuronal cell oxidative damage was observed in each of the three anatomic regions. It was found that protein carbonyl groups and advanced oxidation product... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5010331 Tue, 05 Jul 2011 23:00:00 +0100 5010331 http://www.medworm.com/index.php?rid=5010330&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00757.x Abstract:The aim of this paper was to explore the influence of simvastatin dosing time, variable compliance and circadian cholesterol production on the reduction of low‐density lipoprotein (LDL). A published PKPD model for simvastatin was identified and evaluated. A model for circadian LDL production was incorporated into the PKPD model. Reduction in LDL from baseline was simulated stochastically from the full model at dose levels of 10, 20, 40 and 80 mg daily for 30 days. Simulated dosing times for each dataset were morning (8.00 a.m.), evening (22.00 p.m.), evening with reduced compliance and evening for a hypothetical bioequivalent generic. Differences in LDL reduction from baseline between evening (33‐43%) and morning dosing (31‐43%) were negligible across a range of doses. Any d... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5010330 Tue, 05 Jul 2011 23:00:00 +0100 5010330 http://www.medworm.com/index.php?rid=5010329&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00758.x Abstract:Increased blood pressure (essential hypertension) is associated with increased cardiovascular risk and the condition is treated primarily with a view to reducing this parameter. However, in the early stages, the main pathological changes are increased peripheral resistance and altered cardiovascular structure. The aim of this MiniReview was to trace the endeavours over the past several decades to translate these findings into answering the question whether normalization of resistance vessel structure should be a target for therapy. This MiniReview describes first the altered structure of the resistance vasculature in essential hypertension, where the vessels show increased media:lumen ratio due to inward eutrophic remodelling. Secondly, evidence is presented that altered small art... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5010329 Tue, 05 Jul 2011 23:00:00 +0100 5010329 http://www.medworm.com/index.php?rid=5080384&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00752.x Abstract:  Cardiovascular disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). We suggested that plasma osteoprotegerin (OPG), a strong, independent predictor of cardiovascular disease, could discriminate between anti‐diabetic treatments depending on their benefits regarding cardiovascular disease. The South Danish Diabetes Study, an investigator‐driven, randomized, controlled clinical trial lasting 2 years, was used to test this hypothesis in patient groups with different medication strategies (insulin aspart or NPH insulin, added either metformin/placebo or rosiglitazone/placebo). A total of 371 individuals were eligible for the study. Basic variables were analysed along with measurement of plasma OPG and HbA1c at the beginning and end of the st... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5080384 Mon, 04 Jul 2011 23:00:00 +0100 5080384 http://www.medworm.com/index.php?rid=4999562&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00750.x We present a 51‐year‐old woman with severe bupropion toxicity whose haemodynamic status transiently improved following intravenous fat emulsion. Serum analysis demonstrated an increase of serum concentration of hydroxybupropion, an active metabolite of bupropion, following IFE administration, lending support to one of the proposed mechanisms of IFE.Case report:  A 51‐year‐old woman presented to the emergency department with generalized tonic‐clonic convulsions lasting approximately 30 sec., and a wide complex rhythm on her ECG that was suggestive of myocardial sodium channel blockade. Despite sodium bicarbonate therapy, the patient developed profound hypotension refractory to high‐dose norepinephrine. Intravenous fat emulsion (IFE) was administered with haemodynamic improveme... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4999562 Mon, 04 Jul 2011 23:00:00 +0100 4999562 http://www.medworm.com/index.php?rid=4999561&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00749.x Abstract:  Rotundifolone is the major constituent of the essential oil of Mentha x villosa Hudson. In preliminary studies, rotundifolone induced significant hypotensive, bradycardic and vasorelaxant effects in rats. Thus, to gain more insight into the pharmacology of rotundifolone, the aim of this study was to characterize the molecular mechanism of action involved in relaxation produced by rotundifolone. The relaxant effect was investigated in rat superior mesenteric arteries by using isometric tension measurements and whole cell patch‐clamp techniques. Rotundifolone relaxed phenylephrine‐induced contractions in a concentration‐dependent manner. Pre‐treatment with KCl (20mM), charybdotoxin (10−7M) or tetraethylammonium (TEA 10−3 or 3x10−3 M) significantly attenuated the re... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4999561 Mon, 04 Jul 2011 23:00:00 +0100 4999561 http://www.medworm.com/index.php?rid=4999560&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00751.x Abstract:  Lornoxicam is extensively metabolized by CYP2C9 and a CYP2C9*13 is one of the principal variant alleles in East Asian populations. The aim of this study was to evaluate the effects of CYP2C9*1/*13 on the pharmacokinetic parameters of lornoxicam in healthy subjects. A single oral dose of 8 mg lornoxicam was given to 22 Korean subjects with different CYP2C9 genotypes (8, 8 and 6 carriers of CYP2C9*1/*1, *1/*3 and *1/*13 genotypes, respectively). Lornoxicam and 5′‐hydroxylornoxicam levels were analysed using HPLC‐UV in plasma samples collected up to 24 hr after taking the drug. In subjects with CYP2C9*1/*13, lornoxicam had a higher Cmax (p < 0.001), a longer half‐life (p < 0.001), a lower oral clearance (p < 0.001) and a higher area under the plasma‐concentrati... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4999560 Mon, 04 Jul 2011 23:00:00 +0100 4999560 http://www.medworm.com/index.php?rid=4999559&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00753.x Abstract:  The aim of this study was to evaluate systemic exposure to carboplatin and its haematological toxicity in advanced non‐small cell lung cancer patients both older and younger than 70 years when the target area under the curve (AUC) in elderly patients was reduced by 20%. For this purpose, a population pharmacokinetic model was developed and the haematological toxicity of the drug was assessed. A total of 33 patients received carboplatin on day 1 and gemcitabine (1250 mg/m2) on days 1 and 8. This schedule was repeated every 21 days. The Calvert‐Crokcoft‐Gault formula was employed to calculate a dose of carboplatin with a target AUC of 5 mg·min/mL in patients under 70 years and 4 mg·min/mL in patients aged 70 or older. The data of 24 patients were treated for population m... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4999559 Mon, 04 Jul 2011 23:00:00 +0100 4999559 http://www.medworm.com/index.php?rid=4999558&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00752.x Abstract:  Cardiovascular disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). We hypothesized that plasma osteoprotegerin (OPG), a strong, independent predictor of cardiovascular disease, could discriminate between anti‐diabetic treatments depending on their benefits regarding cardiovascular disease.The South Danish Diabetes Study, an investigator‐driven, randomised, controlled clinical trial lasting 2 years was used to test this hypothesis in patient groups with different medication strategies (insulin aspart or NPH insulin, added either metformin/placebo or rosiglitazone/placebo). A total of 371 individuals were eligible for the study. Basic variables were analysed along with measurement of plasma OPG and HbA1c at the beginning and end of the stu... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4999558 Mon, 04 Jul 2011 23:00:00 +0100 4999558 http://www.medworm.com/index.php?rid=5010327&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00760.x Abstract:Low‐grade inflammation plays a role in cardiovascular disease. The innate and the adaptive immune response participate in mechanisms that contribute to inflammatory responses. It has been increasingly appreciated that different subsets of lymphocytes and the cytokines they produce modulate the vascular remodeling that occurs in cardiovascular disease. Effector T cells such as T‐helper (Th) 1 (interferon‐γ‐producing) and Th2 lymphocytes (that produce interleukin‐4), as well as Th17 (that produce interleukin‐17), and T suppressor lymphocytes including regulatory T cells (Treg), which express the transcription factor forkhead box P3 (Foxp3) are involved in the remodeling of small arteries that occurs under the action of angiotensin II, deoxycorticosterone‐salt and aldo... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5010327 Thu, 30 Jun 2011 23:00:00 +0100 5010327 http://www.medworm.com/index.php?rid=4999557&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00754.x Abstract:  The UDP‐glucuronocyl transferases (UGTs) comprise a major excretion pathway for diverse endogenous and exogenous substrates. Relations are reported between polymorphisms of exon 1 of UGT1 and drug side effects or carcinogenesis, but few studies exist of common exon polymorphisms that exert influence throughout UGT1 isoforms. We analysed the polymorphism c.1091C>T, resulting in the amino acid substitution of p.P364L, found on common exon 4. We studied 187 healthy, adult Japanese volunteers. The allele frequency was 0.0053. We investigated the effect of p.P364L on glucuronidation of β‐estradiol, acetaminophen, propofol, lamotrigine, imipramine and cyproheptadine in an in vitro expression study. The Vmax values for β‐estradiol of p.P364L‐UGT1A1, ‐1A3, ‐1A7, ‐1A... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4999557 Thu, 30 Jun 2011 23:00:00 +0100 4999557 http://www.medworm.com/index.php?rid=4978039&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00748.x Abstract:  Doxorubicin (Dox) has been widely used as an anti‐cancer drug, but its use is limited by serious toxicity to the heart, kidney and liver. Mitochondrial dysfunction is one of the potential mechanisms of toxicity but not fully understood. Fenofibrate, one of peroxisome proliferator‐activated receptor‐alpha (PPARα) ligands, is involved in lipid metabolism which takes place primarily in the mitochondria, so mitochondrial function may be affected by fenofibrate. Therefore, we investigated the effects of DOX and fenofibrate on activities of both mitochondrial citrate synthase and NADH oxidase, which are marker enzymes in the tricarboxylic acid (TCA) cycle and a measure of the complex I‐III‐IV activity in electron transport chain, respectively. Dox (15mg/kg) and/or fenofib... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4978039 Wed, 29 Jun 2011 17:09:28 +0100 4978039 http://www.medworm.com/index.php?rid=4970872&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00747.x In conclusion, KYP‐2047 showed better brain penetration characteristics than JTP‐4819 both in vitro and in vivo. KYP‐2047 is a brain‐penetrating, potent and long‐acting PREP inhibitor; thus, it represents a convenient pharmacological tool for assessing the potential of PREP as a drug target. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4970872 Mon, 27 Jun 2011 18:25:43 +0100 4970872 http://www.medworm.com/index.php?rid=4961095&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00745.x Abstract:Maternal pulmonary exposure to ultrafine particles during pregnancy may affect the health of the child. Developmental toxicity of carbon black (Printex 90) nanoparticles was evaluated in a mouse model. Time‐mated mice were intratracheally instilled with Printex 90 dispersed in Millipore water on gestation days 7, 10, 15 and 18, with total doses of 11, 54 and 268 μg Printex 90/animal. The female offspring prenatally exposed to 268 μg Printex 90/animal displayed altered habituation pattern during the Open field test. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4961095 Thu, 23 Jun 2011 18:26:18 +0100 4961095 http://www.medworm.com/index.php?rid=5040348&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00745.x Abstract:  Maternal pulmonary exposure to ultrafine particles during pregnancy may affect the health of the child. Developmental toxicity of carbon black (Printex 90) nanoparticles was evaluated in a mouse model. Time‐mated mice were intratracheally instilled with Printex 90 dispersed in Millipore water on gestation days (GD) 7, 10, 15 and 18, with total doses of 11, 54 and 268 μg Printex 90/animal. The female offspring prenatally exposed to 268 μg Printex 90/animal displayed altered habituation pattern during the Open field test. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5040348 Wed, 22 Jun 2011 23:00:00 +0100 5040348 http://www.medworm.com/index.php?rid=4961098&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00743.x Abstract:The calcium sensitizer levosimendan has shown beneficial effects on cardiac remodelling in spontaneously diabetic Goto‐Kakizaki (GK) rats 12 weeks after experimental myocardial infarction (MI). However, the short‐term effects and the cellular mechanisms remain partially unresolved.The aim was to study the effects of oral levosimendan treatment on the myocardial gene expression profile in diabetic GK rats 4 weeks after MI/sham operation.Myocardial infarction was induced to diabetic Goto‐Kakizaki (GK) rats. Twenty‐four hours after surgery, rats were randomized into four groups: MI, MI +levosimendan (1 mg/kg/day), sham‐operated, sham‐operated +levosimendan. Cardiac function and histology were examined 1, 4 and 12 weeks post‐MI. The effects of levosimendan on cardiac gen... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4961098 Wed, 22 Jun 2011 23:00:00 +0100 4961098 http://www.medworm.com/index.php?rid=4961097&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00744.x This study evaluated the genotoxic/antigenotoxic and mutagenic effects of memantine in CF‐1 mice, following standardized protocols. Memantine was administered i.p. at 7.5, 15 or 30 mg/kg for three consecutive days. Blood and brain samples were collected to assess DNA damage using the alkaline comet assay. The mutagenic effect was assessed using the bone marrow micronucleus test. In addition, possible antioxidant effects were evaluated measuring the survival of Saccharomyces cerevisiae yeast strains (wild‐type and isogenic mutants lacking superoxide dismutase) to co‐treatment of memantine plus hydrogen peroxide. Memantine decreased DNA oxidative damage mainly in brain tissue. This antigenotoxic effect corroborated an increase observed in the survival of S. cerevisiae wild‐type strai... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4961097 Wed, 22 Jun 2011 23:00:00 +0100 4961097 http://www.medworm.com/index.php?rid=4961096&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00746.x This study demonstrated the antinociceptive and anti‐inflammatory activities of simvastatin in five models of tonic or phasic pain. These actions seem to be related to the inhibition of cytokine and prostanoid release and stimulation of nitric oxide synthesis. A possible clinical role of simvastatin could be related to the potentially beneficial effects in the neuropathic pain and by their pleiotropic properties, they could play a clinical role in anti‐inflammatory disease. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4961096 Wed, 22 Jun 2011 23:00:00 +0100 4961096 http://www.medworm.com/index.php?rid=4946697&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00742.x In conclusion, the antidepressant and increased locomotor activity relies on both R‐ and S‐phenotropil, but the memory‐improving activity is only characteristic of R‐phenotropil. These results may be important for the clinical use of optically pure isomers of phenotropil. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4946697 Mon, 20 Jun 2011 17:07:16 +0100 4946697 http://www.medworm.com/index.php?rid=5040349&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00742.x In conclusion, the antidepressant and increased locomotor activity relies on both R‐ and S‐phenotropils, but the memory‐improving activity is only characteristic of R‐phenotropil. These results may be important for the clinical use of optically pure isomers of phenotropil. (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=5040349 Sun, 19 Jun 2011 23:00:00 +0100 5040349 http://www.medworm.com/index.php?rid=4938135&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00741.x In this study, we evaluated the effectiveness of magnesium‐25, carrying porphyrin‐fullerene nanoparticles, on diabetes‐induced neuropathy. Previous studies have suggested that dorsal root ganglion (DRG) neurons comprise a specific target and may be responsible for the known complications of DN. Experimental DN was induced by intraperitoneal injection of streptozotocin (STZ) (45 mg/kg). Different forms of magnesium including 25Mg‐PMC16, 24Mg‐PMC16 and MgCl2 were administered intravenously in equal dose (0.5 LD50) at 48‐hr intervals before STZ injection. Peripheral nerves were studied after 2 months of diabetes in groups using qualitative approaches, morphometric analysis of DRG neurons and motor function tests. We showed that STZ‐induced DN caused morphological abnormalities i... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4938135 Sat, 18 Jun 2011 16:46:00 +0100 4938135 http://www.medworm.com/index.php?rid=4904406&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00738.x Abstract:  In this work, the effect of a single dose of diazepam was tested on different markers of oxidative damage in the striatum of rats in an acute model of immobilization (restraint) stress. In addition, the locomotor activity was measured at the end of the restraint period. Immobilization was induced to animals for 24 hr and then, lipid peroxidation, superoxide dismutase activity and content, and mitochondrial function were all estimated in striatal tissue samples. Corticosterone levels were measured in serum. Diazepam was given to rats as a pre‐treatment (1 mg/kg, i.p.) 20 min. before the initiation of stress. Our results indicate that acute stress produced enhanced striatal levels of lipid peroxidation (73% above the control), decreased superoxide dismutase activity (54% below... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4904406 Sun, 05 Jun 2011 23:00:00 +0100 4904406 http://www.medworm.com/index.php?rid=4914217&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00740.x (Source: Basic and Clinical Pharmacology and Toxicology) Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4914217 Tue, 31 May 2011 23:00:00 +0100 4914217 http://www.medworm.com/index.php?rid=4904405&cid=s_37574_13_f&fid=37574&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1742-7843.2011.00739.x Abstract:  Hydroquinone impairs several leukocyte cell functions, which alter the immune response. Although endothelial cell functions are important for the development of immune responses, hydroquinone actions on endothelial cell functions have not been shown. Therefore, the effect of hydroquinone exposure (10 or 100 μM for 2 hr) on primary culture of microvascular endothelial cells (PMECs) obtained from the cremaster muscle of Wistar rats incubated in the presence or absence of lipopolysaccharide (LPS, 2 μg/mL) was investigated. Hydroquinone treatment induced the membrane expression of cell adhesion molecules (CAMs) from the immunoglobulin superfamilies ICAM‐1 (intercellular), VCAM‐1(vascular) and PECAM‐1 (platelet‐endothelial) and induced the secretion of cytokines interleuk... Basic and Clinical Pharmacology and Toxicology journals http://www.medworm.com/rss/comments.php?id=4904405 Tue, 31 May 2011 23:00:00 +0100 4904405