Methods and findings in experimental and clinical pharmacology最新文献

O(6)-Benzylguanine; (-)-Gossypol; Abatacept, AC-2592, Adalimumab, AIDSVAX gp120 B/E, Alemtuzumab, Aliskiren fumarate, ALVAC E120TMG, Ambrisentan, Amlodipine, Anakinra, Aripiprazole, Armodafinil, Atomoxetine hydrochloride, Avotermin; Bevacizumab, BIBW-2992, Bortezomib, Bosentan, Botulinum toxin type B; Canakinumab, CAT-354, Ciclesonide, CMV gB vaccine, Corifollitropin alfa, Daptomycin, Darbepoetin alfa, Dasatinib, Denosumab; EndoTAG-1, Eplerenone, Esomeprazole sodium, Eszopiclone, Etoricoxib, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; F-50040, Fesoterodine fumavate, Fondaparinux sodium, Fulvestrant; Gabapentin enacarbil, Golimumab; Imatinib mesylate, Inhalable human insulin, Insulin glargine, Ivabradine hydrochloride; Lercanidipine hydrochloride/enalapril maleate, Levosimendan, Liposomal vincristine sulfate, Liraglutide; MDV-3100, Mometasone furoate/formoterol fumavate, Multiepitope CTL peptide vaccine, Mycophenolic acid sodium salt, Nabiximols, Natalizumab, Nesiritide; Obeticholic acid, Olmesartan medoxomil, Omalizumab, Omecamtiv mecarbil; Paclitaxel-eluting stent, Paliperidone, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ ribavirin, Pemetrexed disodium, Polymyxin B nonapeptide, PORxin-302, Prasugrel, Pregabalin, Pridopidine; Ranelic acid distrontium salt, Rasagiline mesilate, rDEN4delta30-4995, Recombinant human relaxin H2, rhFSH, Rilonacept, Rolofylline, Rosiglitazone maleate/metformin hydrochloride, Rosuvastatin calcium, Rotigotine; Salcaprozic acid sodium salt, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, Sitaxentan sodium, Sorafenib, Sunitinib malate; Tadalafil, Tapentadol hydrochloride, Temsirolimus, Tenofovir, Tenofovir disoproxil fumarate, Teriparatide, Tiotropium bromide, Tocilizumab, Tolvaptan, Tozasertib, Treprostinil sodium; Ustekinumab; Vardenafil hydrochloride hydrate, Varenicline tartrate, Vatalanib succinate, Voriconazole, Vorinostat; Zotarolimus-eluting stent.

Pentylenetetrazol (PTZ)-induced oxidative stress results in disturbance of the antioxidant enzyme status accompanied by neuronal injury and the development of epilepsy in rats. The present study evaluated the antioxidant effects of curcumin against PTZ-induced convulsions. Over a period of 30 days, i.p. injections of subconvulsive doses of PTZ on alternate days resulted in the development of a well-known kindling model of epilepsy. Spectrophotometric analysis revealed a markedly elevated activity of the antioxidant enzymes malondialdehyde (MDA), catalase and glutathione S-transferase (GST) in the cerebrum and cerebellum of epileptic rats due to PTZ-induced oxidative stress. Oral supplementation of curcumin at a dose of 2 g/kg for 30 days resulted in a transient decrease in MDA, catalase and GST levels in the rat cerebrum and cerebellum. Piperine (20 mg/kg orally) was administered along with curcumin to enhance the bioavailability of the latter up to 20-fold more. Combined treatment with curcumin and carbamazepine (3.6 mg/kg orally) also gave similar results, indicating that the potent antioxidant curcumin can be used as an adjuvant in antiepileptic therapy.

Inappropriate drug combinations occur frequently and may lead to serious adverse events. In Iran, drug overdose and interactions are relatively common but rarely reported and are mainly derived from admitted subjects. The aim of this study was to determine the prevalence of possible drug-drug interactions via a population database survey in Mashhad, Iran. In this survey all prescriptions paid by insurance companies in the period 21rst March 2006 to 20th March 2008 were studied retrospectively. Data were gathered from the Division of Rational Use Drug, Food and Drug Vice Chancellor of Mashhad University of Medical Sciences, Iran. Drug interactions were categorized based on severity, onset and dynamic/kinetic nature. Incidence was calculated based on the number of interactions/1000 prescriptions. In total 11,562,808 prescriptions were studied, among which 5% showed interactions. Two hundred and four types of potential interactions were detected. Belladonna, phenytoin sodium, cimetidine, propranolol hydrochloride, gentamicin, acetylsalicylic acid (ASA), Antacid, theophylline and carbamazepine were the most common medications. Among them, 54% showed dynamic and 34% kinetic interactions, 11% were categorized to be both and 76% displayed rapid-onset interactions. Moderate interactions were the most dominant (70%) phenomenon. Dynamic and kinetic interactions significantly differed with respect to the onset of interactions (P < 0.001). A rather different pattern of drug-drug interaction exists in Iran, highlighting the need for a nationwide program on related education and a stronger focus on severe and rapid-onset interactions. Further studies warrant the need to explore high-risk patients.

In the present study the effect of mycophenolate mofetil (MMF), an immunosuppressant, on mercuric chloride (HgCl(2))-induced nephrotoxicity in male Wistar rats was investigated. Animals (200-250 g) were divided into five groups and were subjected to a 6-day treatment schedule. The first (control) group received only vehicle without any active drug. The second to fifth groups were administered HgCl(2) challenge (single dose of 5 mg/kg, s.c.) on the fourth day. Additionally, the second group received distilled water (DW) on all 6 days and the third group was administered DW the initial 3 days and MMF (10 mg/kg b.i.d. by oral gavage) on days 4-6. The fourth group was given DW the initial 2 days and MMF on days 3-6 and the fifth group received MMF all 6 days. All animals were euthanized on the sixth day. It was found that HgCl(2) administration caused significant nephrotoxicity, as indicated by a rise in serum creatinine, blood urea and soluble intercellular adhesion molecule 1 (sICAM-1) concentrations, histopathological injury and increased oxidative stress (altered malondialdehyde and glutathione levels) as compared to the control group. Administration of MMF significantly ameliorated HgCl(2)-induced nephrotoxicity. The results suggest the potential of MMF in preventing the acute nephrotoxicity of HgCl(2).

Iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) combined with laser Doppler fluximetry (LDF) is a tool used to determine microvascular endothelial function. Our aim was to study the reproducibility of different parameters of this technique using iontophoresis with low current strength on the forearm skin of healthy subjects. Baseline skin perfusion was done before application of five current pulses with 1 min of current-free interval. Current strength of 0.007 mA, current density of 0.01 mA/cm(2) and charge density of 6 mC/cm(2) were used, along with 1% ACh and 1% SNP. The absolute maximum change in perfusion (max), percent change in perfusion (% change), peak change in perfusion (peak) and area under the curve during iontophoresis (AUC) at the anodal and cathodal leads were recorded. Measurements were performed in three sessions for 2 days. The coefficient of variation (CV) was calculated for each parameter. Among the parameters studied, maximum change in perfusion and peak flux were the most reproducible parameters.

Squamous cell carcinoma of the head and neck (SCCHN) have been reported to be related to both genetic and environmental factors, including alcohol consumption and alcohol-metabolizing enzymes such as alcohol dehydrogenase (ADH). We conducted a hospital-based, case-control study including 50 cases with diagnosed SCCHN and 100 controls with non-neoplastic conditions such as upper respiratory tract infection. The genomic DNA was isolated from peripheral blood leukocytes. The ADH1C*1 wild-type and ADH1C*2 variant alleles were analyzed with an RFLP method by using SspI as restriction enzyme. The ADH1C*1 allele frequencies were 0.89 (CI95% = 0.84-0.91) in controls and 0.77 (CI95% = 0.71-0.83) in cases, and respective frequencies of the ADH1C*2 allele were 0.11 (CI95% = 0.07-0.14) and 0.23 (CI95% = 0.17-0.29) among controls and cases (P = 0.01). The ADH1C*1/*1 genotype frequency was significantly higher in the control group (77%) compared to that of the cases (58%) (P = 0.02).These findings suggest that a lower presence of ADH1C*1 allele is associated with SCCHN, but larger numbers are needed to more precisely estimate the interaction, if any, with ADH1C. Interestingly, the ADH1C allele and genotype frequencies in our control group living in Denizli were significantly different compared to a previously published report from healthy volunteers living in Ankara (P < 0.0001).

Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, AMA1-C1/alhydrogel, Amlodipine besylate/atorvastatin calcium, Aripiprazole, Artesunate/amodiaquine, Asenapine maleate; Bosentan, Brivaracetam; Carisbamate, Clevudine, Clofarabine, Corticorelin acetate; Dasatinib; Elinogrel potassium, Entecavir, Erlotinib hydrochloride, Eslicarbazepine acetate, Etazolate; Fampridine, Fluarix, Fondaparinux sodium, Fulvestrant; Gabapentin enacarbil, GDC-0941, GI-5005, Golimumab; Imatinib mesylate, Lacosamide, Lapatinib ditosylate, Levetiracetam, Liraglutide, LOLA; Mecasermin, Morphine hydrochloride; Natalizumab, Nilotinib hydrochloride monohydrate; Olmesartan medoxomil, Omacetaxine mepesuccinate; Paclitaxel-eluting stent, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Poly I:CLC, Pralatrexate, Pregabalin; Ranolazine, Rasagiline mesilate, Retigabine hydrochloride, Rhenium Re-186 etidronate, Rosuvastatin calcium, Rotigotine, RTL-1000, Rufinamide; Sirolimus-eluting coronary stent, Sirolimus-eluting stent, Sorafenib, Stiripentol; Tiotropium bromide; Valsartan/amlodipine besylate, Varenicline tartrate; XL-184; Zoledronic acid monohydrate.

The present study was conducted to investigate the reactivity of the corpus cavernosum smooth muscle after unilateral cavernous nerve neurotomy in rabbits. Rabbits (18) were randomly divided into two groups: sham-operated (n = 9) and those subjected to unilateral neurotomy of a 5-mm segment of the cavernous nerve (n = 9). The reactivity of the corpus cavernosum tissue from the neurotomized and sham groups was studied in organ chambers at 4 weeks postoperation. In the neurotomized group, endothelium-dependent relaxation of the corpus cavernosum smooth muscle to carbachol was significantly increased when compared to the sham group. In addition, the sensitivity (i.e., pD(2)) of neurotomized strips to carbachol was also increased when compared to controls. Electrical field stimulation-induced neurogenic relaxation was significantly reduced in the neurotomized group. Relaxation to the nitric oxide (NO) donor sodium nitroprusside and to papaverine was similar in the cavernosal tissue of both groups. There was no change in agonist potency. Furthermore, neurotomy had no effect on KCl-induced contractile responses. When tissue contraction was induced with phenylephrine to study relaxation to various stimuli, the tension induced was similar in the neurotomized and the sham control groups. We conclude that unilateral, chronic cavernous nerve neurotomy causes significant functional changes to the penile erectile tissue of rabbits, which may contribute to the development of impotence.

Cantharidin (CA) is partially water-soluble. Solid dispersion of CA (CA-SD) in polyethylene glycol 4000 (PEG 4000) was carried out by a solvent-fusion method to increase its dissolution rate and oral bioavailability. The physicochemical properties of this solid dispersion (SD) were evaluated immediately after preparation by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM), and the oral in vivo bioavailability was studied. In in vitro experiments CA was analyzed by high-pressure liquid chromatography (HPLC) and by gas chromatography-mass spectrometry (GC-MS) in in vivo experiments. The solubility and dissolution rate of CA were improved by the SD technique. A comparison of the pharmacokinetics between CA-SD and free CA was performed in rats. The results showed that CA-SD had a higher bioavailability than free CA after oral dosing. By comparing the AUC(0-t) of CA and CA-SD, the relative bioavailability of CA-SD to free CA was 295.4%. From these observations it could be concluded that the CA-SD has a higher absorption than pure CA and this corresponds with the dissolution result in vitro.