2-Aminopyridine Analogs Inhibit Both Enzymes of the Glyoxylate Shunt in .

is an opportunistic pathogen responsible for many hospital-acquired infections. can thrive in diverse infection scenarios by rewiring its central metabolism. An example of this is the production of biomass from C nutrient sources such as acetate via the glyoxylate shunt when glucose is not available.

The Multiple Sclerosis Self-Management Scale-Revised (MSSM-R): Persian Version and Psychometric Analysis.

Background: Self-management is the most important component in the treatment of chronic diseases, including multiple sclerosis (MS). The Bishop and Frain Multiple Sclerosis Self-Management Scale-Revised (MSSM-R) is one of the valid tools available for self-management assessment. The purpose of this study was to evaluate the psychometric properties of the MSSM-R in Iranian people with MS.

Effect of Islam-based religious program on spiritual wellbeing in elderly with hypertension.

Background: Lack of spiritual health in patients with hypertension leads to many mental, social, and physical effects, On the other hand, considering the prevalence of hypertension among the elderly, interventions to enhance their spiritual wellbeing is essential. Therefore, the aim of this study was to examine the effect of religious programs based on Islam on spiritual wellbeing in elderly patients with hypertension who referred to the health centers of Isfahan in 2014.

Materials And Methods: This study was a randomized clinical trial.

Effects of Omega-3 Fatty Acid Supplementation on Serum Biomarkers, Inflammatory Agents, and Quality of Life of Patients on Hemodialysis.

Introduction: Patients on long-term hemodialysis are at a higher risk of cardiovascular disease and premature mortality. It is generally believed that omega-3 supplementation can prevent cardiovascular events due to its anti-inflammatory and anti-atherosclerotic effects.

Materials And Methods: Fifty-two hemodialysis patients were divided into 2 groups to receive omega-3 and placebo for 6 six months.

Does Omega-3 supplementation decrease carotid intima-media thickening in hemodialysis patients?

Objective: A randomized, double-blind, placebo-controlled clinical trial was performed to assess the effect of omega-3 supplementation (3 g/day) on atherosclerosis progression by measuring carotid intima-media thickness (cIMT) in hemodialysis (HD) patients.

Methods: A total of 54 HD patients were randomized into two groups: Intervention group ( = 27), in which patients were given 3 g/day omega-3 for 6 months and placebo group ( = 27), in which patients received placebo using the same administration protocol. All patients underwent a carotid artery ultrasound scan to measure cIMT at baseline and at 6 months.

1,2,4-Triazolyl 5-Azaspiro[2.4]heptanes: Lead Identification and Early Lead Optimization of a New Series of Potent and Selective Dopamine D3 Receptor Antagonists.

A novel series of 1,2,4-triazolyl 5-azaspiro[2.4]heptanes with high affinity and selectivity at the dopamine (DA) D3 receptor (D3R) is described. Some of these compounds also have high selectivity over the hERG channel and were characterized with respect to their pharmacokinetic properties both in vitro and in vivo during lead identification and early lead optimization phases.

Ketamine administration makes patients and physicians satisfied during gastro-enteric endoscopies.

Background: A suitable sedative status during gastro-enteric endoscopies results in better physicians' approach and more stable view of internal organs. Therefore, we evaluated the effect of ketamine for sedation in endoscopic procedures of adult patients.

Materials And Methods: Patients who were candidates for gastro-enteric endoscopy during the years 2014-2015 were included into the study and divided into two groups of case (administered 5 mg/kg of oral ketamine half an hour before initiation of the procedure) and control (administered placebo in a same pattern).

Effect of hope therapy on the hope of diabetic patients.

Background: Hope is the most important factor in diabetic patients' life. The level of hope may be changing among these individuals as a result of chronic nature of diabetes and its complications. When the level of hope increases among these patients, they can resist against physical and psychological complications of diabetes more, accept the treatment better, enjoy life more, and adapt with their situations more efficiently.

Contribution of rat intestinal metabolism to the xenobiotics clearance.

Michaelis-Menten constants K m and V max values were determined by product formation and substrate depletion at several substrate concentrations of 4-methylumbelliferone using rat intestinal microsomes. K m and V max values determined by measuring product formation were in good agreement with substrate depletion approach. We also investigated hepatic and intestinal in vitro intrinsic clearance (CLint) in the liver and intestinal microsomes and compare with reports in the literature using nine test compounds, atorvastatin, 7-ethoxycoumarin, indomethacin, 4-methylumbelliferone, midazolam, nifedipine, testosterone, terfenadine and verapamil, in rats.

Recognition of the kind of stress coping in patients of multiple sclerosis.

Background: Investigations have shown that some factors like stress can increase the recurrence and severity of multiple sclerosis (MS). Considering the direct influences of depression and anxiety on our body immunity system, and also the relation between stress and factors, such as Insulin Growth Factor (IGF-1), involved in neurogenesis and myelin repairing, it is an essential issue to identify the most common method used in relieving stress by such patients.

Objective: To identify the type of common coping methods for stressful situation.

Evaluation of different approaches to identifying a higher throughput assay for time-dependent inhibition (TDI).

The availability of a reliable in vitro assay to evaluate time-dependent inhibition (TDI) of cytchrome P450 enzymes by novel compounds is essential for the identification of candidate medicines. We have evaluated three assay methods, making use of 59 marketed compounds and 28 novel GSK compounds. Recombinant bactosomes expressing the CYP3A4 isozyme were used with two fluorescence-based methods: a "Re-addition" assay and a "30 min" assay.

A comparative study of the CYP450 inhibition potential of marketed drugs using two fluorescence based assay platforms routinely used in the pharmaceutical industry.

Semi-automated high throughput screening for the inhibition of major human cytochrome P450 enzymes (1A2, 2C9, 2C19, 2D6 and 3A4) expressed in Escherichia Coli (Cypex bactosomes) or human lymphoblastoid cells (Gentest cDNA microsomes) using fluorescent probes has been evaluated using 68 marketed drugs. In general lower IC50 values were obtained with Cypex bactosomes compared with Gentest cDNA microsomes. This could be due to use of higherconcentration of protein and also the lower activity of Gentest cDNA microsomes.

Evaluation of cytochrome P450 inhibition assays using human liver microsomes by a cassette analysis /LC-MS/MS.

In vitro inhibition assays are used to screen new chemical entities (NCEs) for inhibition studies by using human liver microsomes. High-throughput inhibition assays using pooling methods have been developed to keep pace with screening requirements at the lead ADME stage. This method can determine IC(50) NCEs using microsomes from various organs from any species.

Identifying a higher throughput assay for metabolism dependent inhibition (MDI).

A higher throughput method of screening for the metabolism dependent inhibition of 56 marketed drugs was evaluated and compared data from the PHLM assay (using midazolam as probe) with Cypex assay (using diethoxyfluoresin (DEF) as probe) for CYP3A4 by using 96 well plate. Also 27 marketed drugs were selected to evaluate the reproducibility of Cypex assay using 7-benzyloxyquinoline (7-BQ) as second probe substrate for CYP3A4. Furthermore Cypex CYP2D6 was used to evaluate the reproducibility of this system using 4-methylaminomethyl-7-methoxycoumarin (MMC) as probe substrate with 15 marketed drugs.

Pharmacokinetics, metabolism and excretion of the glycine antagonist GV150526A in rat and dog.

1. The pharmacokinetics, metabolic fate and excretion of 3-[-2(phenylcarbamoyl) ethenyl-4,6-dichloroindole-2-carboxylic acid (GV150526), a novel glycine antagonist for stroke, in rat and dog following intravenous administration of [C14]-GV150526A were investigated. 2.

Identification of UDP-glucuronosyltransferases involved in the human hepatic metabolism of GV150526, a novel glycine antagonist.

The major metabolic pathway for elimination of GV150526 is by glucuronidation exerted by glucuronosyl transferases (UGTs). Potential exists for the modification of GV150526 pharmacokinetics by drugs capable of inhibiting the glucuronidation of GV150526. Using human liver microsomes, 44 compounds were screened for inhibition of GV150526 glucuronidation.

In vivo metabolism of a novel cholecystokinin B (CCK-B) antagonist in rat and dog plasma and rat faeces.

1. The in vivo metabolism of a novel CCK-B antagonist ((+)-N-[1-(adamantane-1-methyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H -1,5-benzodiazepin-3-yl]-N'-phenylurea, GV150013X) was investigated using rat and dog plasma (male and female) and rat faeces samples after administration of GV150013X. 2.

Metabolism of a novel CCK-B antagonist in rat, dog and human liver microsomes.

1. The in vitro metabolism of a novel CCK-B antagonist ((+)-N-[1-adamantane-1-methyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H- 1, 5-benzodiazepin-3-yl]N'-phenyl-urea; GV150013X) was investigated using rat, dog and human liver microsomes. 2.

In vitro metabolism of GV150013X by using liver microsomes and liver tissue slices from different species.

The metabolism of GV150013X was studied in vitro using washed liver microsomes and liver tissue slices from different species. This work was carried out in order to compare the metabolite profiles resulting from incubation of GV150013X with human, rat, dog and rabbit liver microsomes and those from rat, rabbit and human liver tissue slices. This compound was found to be converted to at least 8 metabolites by rat and human liver microsomes.

In vitro studies on the metabolic fate of mifentidine, a novel histamine H2-receptor antagonist.

The in vitro metabolism of mifentidine and several of its metabolites was studied using hepatic microsomes from seven animal species. The effects of potential enzyme inducers, inhibitors and activators were also studied. Mifentidine metabolites identified and characterised were: 4-imidazolylphenylamine (amine), 4-imidazolylphenyl-formamide (formamide), the urea derivative of mifentidine (urea) and the imidazole-hydroxylated derivative of the amine (i-OH-amine), along with three unidentified metabolites, M1, M2 and M3.

Characterization of 2-amino-1-benzylbenzimidazole and its metabolites using tandem mass spectrometry.

We have investigated the in vitro hamster hepatic microsomal metabolism of the amino-azaheterocycle, 2-amino-1-benzylbenzimidazole (ABB). Three major metabolites were isolated and structurally characterized, using a combination of off-line HPLC, in conjunction with both electron ionization and fast atom bombardment ionization tandem mass spectrometry. ABB was shown to be debenzylated to afford 2-aminobenzimidazole (AB), as well as N- and C-oxidized to give 1-benzyl-N2-hydroxyaminobenzimidazole (BHB) and 2-amino-1-benzyl-hydroxybenzimidazole, respectively.

Characterization of N-benzylcarbazole and its metabolites from microsomal mixtures by tandem mass spectrometry.

The metabolism of N-benzylcarbazole (NBC) was studied in vitro using hamster hepatic microsomes to establish whether the corresponding amide is formed. This work was carried out in order to see if the extremely low pka characteristic of such a benzylic amine would allow the formation of the carbonyl derivative. No amide formation was observed.

The influence of local antichlamydial antibody on the acquisition and persistence of human ocular chlamydial infection: IgG antibodies are not protective.

In order to study the effect of antichlamydial antibodies in ocular secretions on resistance to ocular chlamydial infection and clearance of this infection, we have performed linked longitudinal studies in a Gambian village in which trachoma is endemic. We have measured IgG and IgA antibody levels to a local serotype B isolate of Chlamydia trachomatis by amplified enzyme immunoassay, and chlamydial antigen levels in conjunctival swabs using a commercially available immunoassay which detects chlamydial glycolipid. Having previously demonstrated that sharing a bedroom with a case of active trachoma is a risk factor for acquisition of the disease, we have analyzed the effect of IgG and IgA antibody on the acquisition and persistence of clinical trachoma after controlling for age, sex, exposure to infection and for the presence of chlamydial antigen using a Poisson regression model.

An evaluation of tandem mass spectrometry in drug metabolism studies.

The use of precursor ion and constant neutral loss scanning as a means of rapidly detecting drug metabolites is evaluated. Four clinically useful drugs, namely (i) cyclophosphamide, (ii) mifentidine, (iii) cimetropium bromide and (iv) haloperidol, were subjected to microsomal incubations to afford phase I metabolites. Aside from a minor clean-up procedure involving zinc sulfate precipitation of microsomal proteins and solid-phase extraction of metabolites using a Sep-pak C-18 cartridge, the mixtures were analysed directly by fast atom bombardment tandem mass spectrometry.