Different effects of adenylyl cyclase activators and phosphodiesterases inhibitors on cervical cancer (HeLa) and breast cancer (MCF-7) cells proliferation

Breast and cervical cancers are the most common cancers in Iran and worldwide. Hormonal stimulation of cyclic adenosine mono phosphate (cAMP) and the cAMP-dependent protein kinase PKA regulates cell growth by different mechanism. cAMP can stimulate cell growth in many cell types while inhibiting cell growth in others. In some cell lines have been shown that the proliferation of tumor cells is reduced by increasing cAMP in cells. In this study, we evaluate growth arrest of selective PDE3 and non-selective PDE inhibitors, which lead to increase level of cAMP in cervical (HeLa) and breast cancer (MCF7) cell lines have been studied. Cells were incubated with different concentrations of selective, non-selective PDE inhibitors, beta adrenergic receptor agonist and direct stimulator of adenylyl cyclase. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). Result showed that selective PDE inhibitors decreased cell viability in HeLa and MCF-7 cells as a time-dependent manner. Non-selective inhibitor and beta-adrenergic receptor agonist also decrease cell viability but they are less powerful than selective PDE3 inhibitors. Forskolin had no effect in viability of cells. Analysis of DNA fragmentation by flow cytometry showed apoptosis involved in selective PDE3 inhibitors induced toxicity in HeLa cell. Thus, the growth inhibitory effects of selective PDE3 inhibitors are more effective than non-selective inhibitor. Further studies are needed to investigate the mechanism of action is on the field.     

Study motives and career choices of Iranian medical and dental students

To compare the study motives and career choices of senior undergraduate medical and dental students in Iran. A cross-sectional questionnaire-based survey study involving final year medical and dental students from 4 dental and medical schools was conducted in 2010. The questionnaire was designed in three sections (Demographic details, motivational items and career choice items) and after confirming the validity and reliability of the questions, it was distributed among the students. Data were entered into SPSS; statistical analysis included logistic regression and multiple linear regression. The response rate was 62% (n=219) for medical and 64% (n=300) for dental students. The factor analysis identified six motivational items: "Social and professional status", "Health care and people", "Others' recommendation", "personal interest and nature of occupation", "Occupational experience" and "Personal life". Medical students were more influenced by "Playing a role in community health" and "Personal interest". "Work independence" and "Social factors" however were two major influential factors among dental students. There were significant differences in important influences by age (Social and professional status, Others' recommendation), Parents' education (Social and professional status, Health care and people, Personal life) and marital status (single >married: Occupational experience, married > single: Personal life). Engaging in postgraduate studies was the first career preference among 90.9% and 89.8% of dental and medical students respectively. Medical and dental students report a wide range of motivational factors in studying medicine/dentistry and future career plans which is affected by age, parents' education and marital status.     

Change in general and central adiposity measures in prediction of incident dysglycemia; Tehran Lipid and Glucose Study

ObjectivesTo examine the change in general and central adiposity measures as a predictor of incident dysglycemia during a 6-year follow-up.SubjectsA total of 4029 (2333 women and 1696 men) non-dysglycemic Iranians aged ≥ 20 years, underwent standard fasting and 2-h post-challenge plasma glucose tests at baseline and follow-up.ResultsDuring follow-up, 458 new cases of dysglycemia occurred. In multivariable models including baseline values of each anthropometric measure, odds ratios (ORs) for dysglycemia incidence corresponding to a 1-SD increase in changes of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and hip circumference (HC), were 1.32, 1.56, 1.39, 1.51 and 1.39 for men and 1.59, 1.50, 1.37, 1.47, and 1.38, for women, respectively (all P < 0.05). After controlling for weight change and WC change among men and women, respectively, HC change did not remain as a predictor. Using the paired homogeneity test, there was no superiority for changes in central obesity measures compared to changes in BMI to predict dysglycemia.ConclusionThe association between HC changes and incident dysglycemia was dependent upon changes in central and general adiposity measures, where the former did not have higher predictability than the latter in prediction of dysglycemia.     

Docking, synthesis, and pharmacological evaluation of isoindoline derivatives as anticonvulsant agents

Eleven analogs of N-arylisoindoline pharmacophore were synthesized and evaluated for their anticonvulsant activities. The in vivo screening data acquired indicate that all the analogs have the ability to protect against pentylenetetrazole-induced seizure. Compounds 2, 6, and 11 elevated clonic seizure thresholds at 30 min which were more active than reference drug phenytoin, and compounds 2, 7, and 11 showed marked anticonvulsant activity on tonic seizure. The most potent compounds were 2 and 11 which had comparative activity to the phenytoin. Using a model of the open pore of the Na channel, we have docked all compounds. Docking studies have revealed that these compounds interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and have additional hydrophobic interactions with other domains in the channel’s inner pore.     

Inheritance Pattern and Clinical Aspects of 93 Iranian Patients with Chronic Granulomatous Disease

Background

Chronic granulomatous disease (CGD) is a rare immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. We studied CGD inheritance forms (autosomal recessive (AR) or X-linked (XL)) and AR-CGD subtypes in Iran.

Methods

Clinical and functional investigations were conducted in 93 Iranian CGD patients from 75 families.

Results

Most of the patients were AR-CGD (87.1%). This was related to consanguineous marriages (p?=?0.001). The age of onset of symptoms and diagnosis were lower in XL-CGD compared with AR-CGD (p?phox defect was the predominant subtype (55.5%). The most common clinical features in patients were lymphadenopathy (65.6%) and pulmonary involvement (57%). XL-CGD patients were affected more frequently with severe infectious manifestations.

Conclusions

Although XL-CGD is the most common type of the disease worldwide, only 12 patients (12.9%) were XL-CGD in our study. The relatively high frequency of AR-CGD is probable due to widely common consanguineous marriages in Iran.     

Current status of the anger superiority hypothesis: A meta‐analytic review of N2pc studies

Numerous investigators have tested contentions that angry faces capture early attention more completely than happy faces do in the context of other faces. However, syntheses of studies on early event‐related potentials related to the anger superiority hypothesis have yet to be conducted, particularly in relation to the N200 posterior‐contralateral (N2pc) component which provides a reliable electrophysiological index related to orienting of attention suitable for testing this hypothesis. Fifteen samples (N = 534) from 13 studies featuring the assessment of N2pc amplitudes during exposure to angry‐neutral and/or happy‐neutral facial expression arrays were included for meta‐analysis. Moderating effects of study design features and sample characteristics on effect size variability were also assessed. N2pc amplitudes elicited by affectively valenced expressions (angry and happy) were significantly more pronounced than those elicited by neutral expressions. However, the mean effect size difference between angry and happy expressions was ns. N2pc effect sizes were moderated by sample age, number of trials, and nature of facial images used (schematic vs. real) with larger effect sizes observed when samples were comparatively younger, more task trials were presented and schematic face arrays were used. N2pc results did not support anger superiority hypothesis. Instead, attentional resources allocated to angry versus happy facial expressions were similar in early stages of processing. As such, possible adaptive advantages of biases in orienting toward both anger and happy expressions warrant consideration in revisions of related theory.     

The effect of hydroalcoholic extract of <Emphasis Type="Italic">Mangifera indica</Emphasis> on induced osteoarthritis of knee in male guinea pigs

Osteoarthritis (OA) is one of the top six diseases for which complementary and alternative medicine is used. Among the herbal products, mango could be regarded as a potential natural remedy for OA due to its anti-inflammatory characteristics. The aim of the present study was to evaluate the healing effect of mango on OA of the knee. Eighteen male guinea pigs were chosen, and anterior cruciate ligament transection was performed for them to induce OA for the animal models. Then, they were recruited in four treatment groups (n = 5): (a) oral treatment, (b) intra-articular injection treatment, (c) prevention, and (d) control. After 18 weeks, the outcomes were evaluated by radiologic and histopathologic assessments. Histopathological assessment of the articular cartilages showed smooth and continuous articular surface with columnar cell distribution in the injection group which were improved better than the others while the surface in the control group has an irregularity. The radiological assessment of the knee joints shows that they were improved during the second 4 weeks after treatment. Radiological findings were similar to histopathologic assessment in which the improvement of the articular cartilage was better in the injection group compared with the oral and prevention group. The control group did not change remarkably. It seems that Mangifera fruit can be regarded as an effective complementary and alternative treatment for OA of the knee.