Modulating the cyclic guanosine monophosphate substrate selectivity of the phosphodiesterase 3 inhibitors by pyridine, pyrido[2,3-d]pyrimidine derivatives and their effects upon the growth of HT-29 cancer cell line.

Analogues with the scaffolds of 3-cyano-4-alkoxyphenyl-6-bromoaryl-2-pyridone and 2-amino-3-cyano-4-alkoxyphenyl-6-bromoarylpyridine were synthesized. Cyclization of the 2-amino derivatives with formic acid and formamide gave the corresponding pyrido[2,3-d]pyrimidin-4(3H)-one and the pyrido[2,3-d]-pyrimidin-4-amine derivatives, respectively. Active phosphodiesterase 3 (PDE3) inhibitors were identified from each of the four aforementioned scaffolds.

Association of inducible nitric oxide synthetase genotype and Helicobacter pylori infection gastric cancer risk may be due to faulty primer design.

Rafiei et al recently described an association between the presence of the C150T polymorphism of the inducible nitric oxide synthase (iNOS) gene and Helicobacter pylori (H. pylori) induced gastric cancer. When we used primer-BLAST to find the polymerase chain reaction (PCR) product that would be generated by the primers used by these authors no products against any of the sequences present in the GenBank database were found.

Improvement in visual acuity and contrast sensitivity in patients with central serous chorioretinopathy after macular subthreshold laser therapy.

Purpose: The purpose of the study was to measure the improvement in vision and contrast sensitivity in patients with central serous chorioretinopathy after macular subthreshold laser therapy.

Methods: Cases included in this clinical trial were patients diagnosed with acute central serous chorioretinopathy less than 1 month in duration. Each patient was randomized to either observation group or treatment group with subthreshold argon laser.

Design of novel β-carboline derivatives with pendant 5-bromothienyl and their evaluation as phosphodiesterase-5 inhibitors.

New derivatives with the tetrahydro-β-carboline-imidazolidinedione and tetrahydro-β-carboline-piperazinedione scaffolds and a pendant bromothienyl moiety at C-5/C-6 were synthesized and tested for their ability to inhibit PDE5 in vitro. The following SAR can be concluded: The tetracyclic scaffold is essential for PDE5 inhibition; the ethyl group is the most suitable among the adopted N-substituents on the terminal ring (hydantoin/piperazinedione); the appropriate stereochemistry of C-5/C-6 derived from the aldehyde rather than C-11a/C-12a derived from tryptophan appears crucial for inhibition of PDE5; surprisingly, derivatives with the hydantoin terminal ring are more active than their analogs with the piperazinedione ring; the selectivity versus PDE5 relative to PDE11 with cGMP as a substrate is mainly a function of the substitution and stereochemistry pattern of the external ring, in other words of the interaction with the H-loop residues of the isozymes. Thirteen derivatives showed PDE5 inhibitory activity with IC(50) values in the range of 0.

Specific count model for investing the related factors of cost of GERD and functional dyspepsia.

Aim: The purpose of this study is to analyze the cost of GERD and functional dyspepsia for investing its related factors.

Background: Gastro-oesophageal reflux disease GERD and dyspepsia are the most common symptoms of gastrointestinal disorders. Recent studies showed high prevalence and variety of clinical presentation of these two symptoms imposed enormous economic burden to the society.

Phytase supplementation improves blood zinc in rats fed with high phytate Iranian bread.

Background: More than one third of energy intake in Iran is provided from bread. Therefore, improving bread mineral bioavailability through dephytinization can play an important role in decreasing the prevalence of many mineral deficiencies. In this study, effect of phytase supplementation on zinc, iron and calcium status in growing rats fed with a diet containing high phytate Iranian bread (Sangak) was assessed.

Comparison of real-time PCR and conventional PCR with two DNA targets for detection of Leishmania (Leishmania) infantum infection in human and dog blood samples.

Zoonotic visceral leishmaniasis (VL) is endemic in northwestern Iran. Real-time PCR, conventional PCR, and the direct agglutination test (DAT) were used to diagnose Leishmania infantum infection in blood samples from 100 domestic dogs and 100 humans. Based on clinical evaluation, 82 humans and 72 dogs from the endemic area were categorized as having asymptomatic infection, DAT positive with no clinical signs of VL, or symptomatic infection, DAT positive with at least one sign of VL.

Canine visceral leishmaniasis: a comparative study of real-time PCR, conventional PCR, and direct agglutination on sera for the detection of Leishmania infantum infection.

Canine visceral leishmaniasis (CVL) is endemic in northwestern Iran. This study aimed to compare real-time PCR, conventional PCR, and the direct agglutination test (DAT) for the diagnosis Leishmania infantum infection in 167 serum samples of domestic dog. Bone marrow was used for parasitological examination (smears and/or culture) in symptomatic visceral leishmaniasis, and serum was used for detection of L.

Exploring the PDE5 H-pocket by ensemble docking and structure-based design and synthesis of novel β-carboline derivatives.

By studying the co-crystal information of interactions between PDE5 and its inhibitors, forty new tetrahydro-β-carbolines based-analogues were synthesized, and tested for their PDE5 inhibition. Some compounds were as active as tadalafil in inhibiting PDE5 and of better selectivity profile particularly versus PDE11A, the nature of the terminal ring and its nitrogen substituent are the main determinants of selectivity. Ensemble docking confirmed the role of H-loop closed conformer in activity versus its occluded and open forms.

Breast Cancer Survival Analysis: Applying the Generalized Gamma Distribution under Different Conditions of the Proportional Hazards and Accelerated Failure Time Assumptions.

Background: The goal of this study is to extend the applications of parametric survival models so that they include cases in which accelerated failure time (AFT) assumption is not satisfied, and examine parametric and semiparametric models under different proportional hazards (PH) and AFT assumptions.

Methods: The data for 12,531 women diagnosed with breast cancer in British Columbia, Canada, during 1990-1999 were divided into eight groups according to patients' ages and stage of disease, and each group was assumed to have different AFT and PH assumptions. For parametric models, we fitted the saturated generalized gamma (GG) distribution, and compared this with the conventional AFT model.

Association between serum levels of MASP-2 and neutropenic febrile attacks in children with leukemia.

Background: Infectious complications are a major etiology of morbidity and mortality in febrile neutropenic patients. Low serum mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) concentration may represent a risk factor for infection in leukemia patients receiving chemotherapy. This study evaluates the relationship between serum levels of MASP-2 with neutropenic febrile attacks in children with leukemia.

Associations of Demographic and Socioeconomic Factors with Complete Treatment and Follow-up of Colon Cancer.

Background: Cancer is the second cause of death in the world, and colon cancer is the third cause of death and is one of the most common cancers which will cure with early diagnosis, treatment and sufficient follow up. Assessing factors which affect this cancer is important for prolonging patient survival. Socioeconomic factors are among effective factors of cancer morbidity and mortality.

The knowledge and attitudes of a female at-risk population towards the prevention of AIDS and sexually transmitted infections in Tehran.

Background: The female at-risk population represents a subgroup that is both a crucial determining factor in acquired immune deficiency syndrome (AIDS) transmission and a gap in the existing literature in Iran. The objective of this study was to evaluate the level of sex workers' knowledge towards to safe procedures of sexually transmitted infection and AIDS prevention as well as attitudes towards AIDS.

Methods: A sample of 256 female sex workers working in Tehran was obtained by a variety of methods.

Applying conventional and saturated generalized gamma distributions in parametric survival analysis of breast cancer.

Background: The generalized gamma distribution statistics constitute an extensive family that contains nearly all of the most commonly used distributions including the exponential, Weibull and log normal. A saturated version of the model allows covariates having effects through all the parameters of survival time distribution. Accelerated failure-time models assume that only one parameter of the distribution depends on the covariates.

New NSAID targets and derivatives for colorectal cancer chemoprevention.

Clinical and preclinical studies provide strong evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent numerous types of cancers, especially colorectal cancer. Unfortunately, the depletion of physiologically important prostaglandins due to cyclooxygenase (COX) inhibition results in potentially fatal toxicities that preclude the long-term use of NSAIDs for cancer chemoprevention. While studies have shown an involvement of COX-2 in colorectal tumorigenesis, other studies suggest that a COX-independent target may be at least partially responsible for the antineoplastic activity of NSAIDs.

Research priorities in medical education in the Eastern Mediterranean Region.

Ways are needed to effect quality improvement in medical education research in the Eastern Mediterranean Region (EMR). This study aimed to determine the principle themes and to draw up a list of priorities in medical education research in EMR. Using the nominal group technique with a group of 30 experts, a list of major themes in medical education research was prepared.

The modifying effects of fish oil on fasting ghrelin mRNA expression in weaned rats.

Ghrelin expression and secretion seem to be influenced by the fat content of the diet. However, data on the probable adverse effect of high fat diet (HFD) with different dietary fats and saturation level of fatty acids is inconclusive. This study aimed at investigating the effects of HFDs on fasting total and acyl-ghrelin plasma levels, gastric fundus and duodenum ghrelin mRNA expressions.

PP006. The comparison of serum VEGF and sFlt-1 on preeclampsia and eclampsia pregnant woman before and after delivery at Ulin Hospital, Banjarmasin, Indonesia.

Introduction: Preeclampsia is the main cause of maternal morbidity and mortality at Indonesia. In 2010, 228 maternal deaths occur in 100,000 live birth. Ulin Hospital, Banjarmasin, a tertiary care hospital has high prevalence of preeclampsia and eclampsia (22%).

A novel sulindac derivative that potently suppresses colon tumor cell growth by inhibiting cGMP phosphodiesterase and β-catenin transcriptional activity.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely reported to inhibit tumor growth by a COX-independent mechanism, although alternative targets have not been well defined or used to develop improved drugs for cancer chemoprevention. Here, we characterize a novel sulindac derivative referred to as sulindac benzylamine (SBA) that does not inhibit COX-1 or COX-2, yet potently inhibits the growth and induces the apoptosis of human colon tumor cells. The basis for this activity appears to involve cyclic guanosine 3',5',-monophosphate phosphodiesterase (cGMP PDE) inhibition as evident by its ability to inhibit cGMP hydrolysis in colon tumor cell lysates and purified cGMP-specific PDE5, increase intracellular cGMP levels, and activate cGMP-dependent protein kinase G at concentrations that suppress tumor cell growth.

CoMFA and CoMSIA studies of 1,2-dihydropyridine derivatives as anticancer agents.

Taking advantage of our in-house experimental data on 3-cyano-2-imino-1, 2-dihydropyridine and 3-cyano-2- oxo-1,2-dihydropyridine derivatives as inhibitors of the growth of the human HT-29 colon adenocarcinoma tumor cell line, we have established a highly significant CoMFA and CoMSIA models (q2cv=0.70/0.639).

Four-component synthesis of 1,2-dihydropyridine derivatives and their evaluation as anticancer agents.

Two series of compounds with the general formula of 4,6-diaryl-2-oxo-1,2 dihydropyridine-3-carbonitriles and their isosteric imino derivatives were synthesized through a one pot reaction of acetophenone, aldehyde and ammonium acetate with ethyl cyanoacetate or malononitrile, respectively. The synthesized compounds were evaluated for tumor cell growth inhibitory using the human HT-29 colon and MDA-MB-231 breast tumor cell lines. Compound 4-(2- Ethoxyphenyl)-2-imino-6-(4-fluorophenyl)-1,2-dihydropyridine-3 carbonitrile (6) showed IC50 value of 0.

Fish oil and olive oil can modify insulin resistance and plasma desacyl-ghrelin in rats.

Background: Evidence exists for reciprocal effects of insulin and desacyl-ghrelin (DAG) concentration, but the association between different fatty acid saturation in high fat diet (HFD) and these hormones remain to be established. To evaluate the impact of different sources of dietary fat and the level of fatty acid saturation on plasma insulin and DAG levels and also the association of DAG with insulin action this study was carried out.

Methods: Male weaning Wistar rats were randomly divided into four groups of HFDs, high fat butter (HF-B), high fat soy (HF-S), high fat olive (HF-O), high fat fish (HF-F), and a group of standard diet (SD).

Synthesis and binding study of certain 6-arylalkanamides as molecular probes for cannabinoid receptor subtypes.

Tetrahydrocannabinol and other mixed cannabinoid (CB) receptors CB(1)/CB(2) receptor agonists are well established to elicit antinociceptive effects and psychomimetic actions, however, their potential for abuse have dampened enthusiasm for their therapeutic development. In an effort to refine a semi-rigid structural framework for CB(2) receptors binding, we designed novel compounds based on aromatic moiety and flexible linker with various amides mimicking the outlook of the endogenous anandamide which could provide as CB(2) receptor ligand. In this direction, we developed and synthesized new aryl or arylidene hexanoic acid amides and aryl alkanoic acid diamide carrying different head groups.

Bayesian correction for mortality trend of oral cavity cancer.

Aim: The aim of this study is to estimate oral cavity cancer mortality for Iranian population, using Bayesian approach in order to revise this misclassification.

Background: Mortality is a familiar projection to address the burden of cancers, but according to Iranian death registry, about 20% death statistics were still recorded in misclassified categories.

Patients And Methods: We analyzed national death statistic reported by the Iranian Ministry of Health and Medical Education from 1995 to 2004 stratified by age group, sex, and cause of death are included in this analysis.