The Histone Deacetylase Inhibitor Trichostatin-A Modifies the Expression of Trichothecene Mycotoxin Regulatory Gene in .

Background: is the causal agent of Fusarium Head Blight (FHB) on wheat and produces deoxynivalenol (DON), known to cause extreme human and animal toxicosis. This species' genome contains genes involved in plant-pathogen interactions and regulated by chromatin modifications. Moreover, histone deacetylase inhibitors (HDACIs), including trichostatin A (TSA), have been employed to study gene transcription regulation because they can convert the structure of chromatin.

Rivaroxaban population pharmacokinetic and pharmacodynamic modeling in Iranian patients.

What Is Known And Objective: Although predictable pharmacokinetic and pharmacodynamic of rivaroxaban allow fixed dosing regimens without routine coagulation monitoring, there is still the necessity to monitor and predict the effects of rivaroxaban in specific conditions and different populations. The current study was designed and conducted to analyze the rivaroxaban population pharmacokinetics in Iranian patients and establish a pharmacokinetic/pharmacodynamic model to predict the relationship between rivaroxaban concentration and its anticoagulant activity.

Methods: A sequential nonlinear mixed effect pharmacokinetic/pharmacodynamic modeling method was used to establish the relation between rivaroxaban concentration and anti-factor Xa activity, prothrombin time, and activated partial thromboplastin time (aPTT) as pharmacodynamic biomarkers in a population of sixty-nine Iranian patients under treatment with oral rivaroxaban.

Oral delivery of indinavir using mPEG-PCL nanoparticles: preparation, optimization, cellular uptake, transport and pharmacokinetic evaluation.

Indinavir (IDV) is a potent HIV protease inhibitor used in the treatment of human immunodeficiency virus (HIV). IDV is a weak base with limited aqueous solubility in its unprotonated form; therefore, solubility of IDV in the gastrointestinal tract fluids is the rate-limiting step of its absorption and onset of action. However, in many cases, drugs are not absorbed well in the gastrointestinal tract; polymer nanoparticles were recognized as an effective carrier system for drug encapsulation and are now studied as a vehicle for oral delivery of insoluble compounds.

Magnetic brain targeting of naproxen-loaded polymeric micelles: pharmacokinetics and biodistribution study.

The blood brain barrier is a major obstacle to the entry of the majority of CNS-active agents. In the present research, the potential of magnetic polymeric micelles (MPMs) for brain-targeting of naproxen was evaluated. The MPMs were made of methoxy poly(ethyleneglycol)-poly (caprolactone) copolymer and super paramagnetic iron oxide nanoparticles (SPIONs).

Neuropharmacokinetic evaluation of lactoferrin-treated indinavir-loaded nanoemulsions: remarkable brain delivery enhancement.

Objective: Indinavir (IDV), an antiretroviral protease inhibitor used in treatment of HIV infection, has limited entry into brain due to efflux by the P-glycoprotein presented in blood-brain barrier. The aim of present study was to develop lactoferrin-treated nanoemulsion containing indinavir (Lf-IDV-NEs) for delivery to brain.

Methods: Indinavir-loaded nanoemulsions (IDV-NEs) were prepared by high-speed homogenization method, and then lactoferrin was coupled to IDV-NEs by water soluble EDC method.

Silencing the tobacco gene for RNA-dependent RNA polymerase 1 and infection by potato virus Y cause remodeling of cellular organelles.

RNA-dependent RNA polymerase 1 (RDR1) has been shown to be involved in DNA methylation, RNA silencing and regulating expression of other genes. RDR1 gene expression is stimulated by infection with potato virus Y° (PVY). Transgenic Nicotiana tabacum plants silenced for RDR1 gene expression showed morphological changes in mesophyll cells, associated with remodeling of the nuclei, chloroplasts and mitochondria.

Naproxen conjugated mPEG-PCL micelles for dual triggered drug delivery.

A conjugate of the NSAIDs drug, naproxen, with diblock methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) copolymer was synthesized by the reaction of copolymer with naproxen in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The naproxen conjugated copolymers were characterized with different techniques including (1)HNMR, FTIR, and DSC. The naproxen conjugated mPEG-PCL copolymers were self-assembled into micelles in aqueous solution.

Predictive performance of Vancomycin population pharmacokinetic models in Iranian patients underwent hematopoietic stem cell transplantation.

Objective: Many hematopoietic stem cell transplantation (HSCT) patients receive vancomycin empirically during febrile neutropenia. There are several models for estimation of vancomycin pharmacokinetic parameters and calculation of initial dosing regimen accordingly. However, the performance of these methods in HSCT patients remained to be evaluated.

Population Pharmacokinetic Analysis of the Oral Absorption Process and Explaining Intra-Subject Variability in Plasma Exposures of Imatinib in Healthy Volunteers.

Background And Objective: Imatinib mesylate is presently the first-line treatment for chronic myeloid leukemia (CML). The aim of this study was to investigate the absorption and distribution kinetics of imatinib in healthy Iranian volunteers using nonlinear mixed effects modeling (NLMEM) to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters after oral administration.

Methods: This analysis was based on data from 24 healthy subjects who participated in a bioequivalence study after administering a single dose of 200 mg of each formulation.

Rotylenchus castilloi n. sp. (Nematoda: Hoplolaimidae), a new species with long stylet from northern Iran.

Rotylenchus castilloi n. sp., a new bisexual species is described and illustrated based on morphological, morphometric and molecular data.

Influence of flocculating agents and structural vehicles on the physical stability and rheological behavior of nitrofurantoin suspension.

Background: Nitrofurantoin is a nitrofuran antibiotic that has been used for treatment of urinary tract against positive and negative bacteria.

Objectives: The aim of this study was to evaluate the effect of structural vehicles and flocculating agents on physical stability and rheological behavior of nitrofurantoin suspension.

Materials And Methods: To formulate the suspensions, the effect of glycerin and polysorbate 80 as wetting agents was evaluated and their particle sizes were determined using the sieve method.

Population pharmacokinetics of imatinib in Iranian patients with chronic-phase chronic myeloid leukemia.

Purpose: We evaluated the population pharmacokinetics (PPK) and exposure-response relationship of imatinib mesylate in Iranian patients with chronic myeloid leukemia (CML).This study was designed to assess steady state (SS) imatinib trough concentrations (Cmin) and pharmacokinetics parameters of imatinib in patients with CML in chronic phase after at least 12-month treatment.

Methods: Plasma concentrations from a randomized controlled trial consist of 61 patients who received oral imatinib at doses ranged between 300 and 800 mg in various dosing interval, which were quantified using a validated reversed-phase high-performance liquid chromatographic method with UV detection method on different occasions at SS and evaluated using PPK model.

Development and Validation of a High-Performance Liquid Chromatography Method With UV Detection for Determination of 1-(2-phenylethyl)-5- (quinaldin-4-yl) Biuret in Rat Plasma.

Background: Recently, biuret derivatives have been reported as showing moderate to good cytotoxic effect against certain cancer cell lines. In this study, a high-performance liquid chromatography method was developed for determination of 1-(2-phenylethyl)-5-(quinaldin-4-yl) biuret (PEQB) in rat plasma to use in future studies on this compound and related derivatives.

Objectives: In this study, we describe a simple and sensitive high-performance liquid chromatography method with UV detection for determination of 1-(2-phenylethyl)-6-(quinaldin-4-yl) biuret (PEQB) in rat plasma.

Antinociceptive effect of some biuret derivatives on formalin test in mice.

Purpose: The current study was designed to investigate the antinociceptive effects of several biuret derivatives with N, N`-diphenyl, N-phenyl-N`-alkylphenyl, N,N`-bis alkylphenyl, 2-methylquinoline-4-yl, benzo[d]thiazol-2-ylthio and (1-phenyl-1H-tetrazol-5-yl)thio substituents on the formalin-evoked pain in mice.

Methods: Antinociceptive activity of the nine biurets derivatives were assessed at different doses in mice using formalin test and the results were compared with those of indomethacin(20 mg/kg) and vehicle of the compounds. Area under the pain score curve against time (AUEC) up to 60 minutes was used as the measure of pain behavior.

Vancomycin Pharmacokinetic Parameters in Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT).

Background: Vancomycin is used abundantly in patients undergoing HSCT, especially during neutropenic fever. Despite its widespread use little is known about vancomycin pharmacokinetics in HSCT patients. We conducted this study to investigate vancomycin pharmacokinetic parameters in our HSCT patients and to evaluate current dosing regimen based on trough vancomycin concentrations measurement.

Percutaneous absorption of salicylic Acid after administration of trolamine salicylate cream in rats with transcutol(®) and eucalyptus oil pre-treated skin.

Purpose: This study was conducted to assess the effect of skin pre-treatment with Transcutol(®) and eucalyptus oil on systemic absorption of topical trolamine salicylate in rat.

Methods: Pharmacokinetic parameters of salicylic acid following administration of trolamine salicylate on rat skin pre-treated with either Transcutol(®) or eucalyptus oil were determined using both non-compartmental and non-linear mixed effect modeling approaches and compared with those of control group.

Results: Median (% of interquartile range/median) of salicylic acid AUC0-8hr (ng/mL/hr) values in Transcutol(®) or eucalyptus oil treated rats were 2522(139%) and 58976(141%), respectively as compared to the 3023(327%) of the control group.

Rheological behavior and stability of ciprofloxacin suspension: Impact of structural vehicles and flocculating agent.

Ciprofloxacin is a fluoroquinolone and is used against a broad spectrum of gram-negative and gram-positive bacteria. The aim of the study is to investigate the effect of structural vehicles and other formulating factors on physical stability and rheological behavior of ciprofloxacin suspension. To formulate the suspensions, the effect of glycerin and polysorbate 80 as wetting agents was evaluated.

In silico and in vitro comparative activity of novel experimental derivatives against Leishmania major and Leishmania infantum promastigotes.

This in silico and in vitro comparative study was designed to evaluate the effectiveness of some biurets (K1 to K8) and glucantime against Leishmania major and Leishmania infantum promastigotes. Overall, eight experimental ligands and glucantime were docked using AutoDock 4.3 program into the active sites of Leishmania major and Leishmania infantum pteridine reductase 1, which were modeled using homology modeling programs.

Comparison of Valproic acid Clearance between Epileptic Patients and Patients with Acute Mania.

Objectives: The purpose of this study was assessment of the influence of acute manic phase on the steady state pharmacokinetics of valproic acid (VPA) in bipolar patients in comparison with those of epileptic patients.

Materials And Methods: Ninteen acutely manic and 25 epileptic patients who fulfilled inclusion and exclusion criteria were entered in this prospective study. Blood samples were collected at trough time in steady state and plasma concentrations were determined by fluorescence polarization immunoassay (FPIA).

Development and validation of limited sampling strategies for estimation of cyclosporine area under the concentration-time curve in hematopoietic stem cell transplant patients.

The aim of this study was to develop and validate limited sampling strategies for accurately predicting 12-hour area under the concentration-time curve (AUC(0-12 h)) to provide a practical method for more precise therapeutic drug monitoring of cyclosporine A in stem cell transplant patients. Steady-state cyclosporine blood concentrations were measured within a dosing interval (12 hours post administration) in 35 allogeneic bone marrow transplant patients receiving 238 mg (±117 mg) twice-daily dose of cyclosporine. Limited sampling strategies were developed by multiple linear regression analysis of relationship between cyclosporine A full AUC(0-12 h) values and different combinations of preselected blood concentrations.

Optimization of the simultaneous determination of imatinib and its major metabolite, CGP74588, in human plasma by a rapid HPLC method using D-optimal experimental design.

A simple, rapid and specific HPLC method has been developed and validated for the simultaneous determination of imatinib, a tyrosine kinase inhibitor, and its major metabolite, CGP74588, in human plasma. The optimization of the HPLC procedure involved several variables, of which the influences of each was studied. After a series of preliminary-screening experiments, the composition of the mobile phase and the pH of the added buffer solution were set as the investigated variables, while the resolution between imatinib and CGP74588 peaks, the retention time and the imatinib peak width were chosen as the dependent variables.

Spasmolytic effect of stachys lavandulifolia vahl. Crude methanolic extract and fractions on rat ileum.

The aim of this study was to investigate the effect of aerial parts of Stachys lavandulifolia Vahl. Extract on the rat ileum contractions. The crude extract was prepared by maceration method (90% methanol) followed by fractionating into chloroform, ethyl acetate, petroleum ether and water.

Incorporating in vitro information on drug metabolism into clinical trial simulations to assess the effect of CYP2D6 polymorphism on pharmacokinetics and pharmacodynamics: dextromethorphan as a model application.

In vitro-in vivo extrapolation of clearance, embedded in a clinical trial simulation, was used to investigate differences in the pharmacokinetics and pharmacodynamics of dextromethorphan between CYP2D6 poor and extensive metabolizer phenotypes. Information on the genetic variation of CYP2D6, as well as the in vitro metabolism and pharmacodynamics of dextromethorphan and its active metabolite dextrorphan, was integrated to assess the power of studies to detect differences between phenotypes. Whereas 6 subjects of each phenotype were adequate to achieve 80% power in showing pharmacokinetic differences, the power required to detect a difference in antitussive response was less than 80% with 500 subjects in each study arm.

Determination of theophylline clearance after cimetidine infusion in critically ill patients.

The potential for continuous infusion of cimetidine to affect the clearance of aminophylline was assessed in 18 critically ill patients treated for bronchospasm. This was a pharmacokinetic drug-drug interaction study in which the subjects were administered aminophylline as a continuous infusion at low doses (mean 10.8 mg/hr).