The Tyrphostin Agent AG490 Prevents and Reverses Type 1 Diabetes in NOD Mice

<div><h3>Background</h3><p>Recent studies in the NOD (non-obese diabetic) mouse model of type 1 diabetes (T1D) support the notion that tyrosine kinase inhibitors have the potential for modulating disease development. However, the therapeutic effects of AG490 on the development of T1D are unknown.</p> <h3>Materials and Methods</h3><p>Female NOD mice were treated with AG490 (i.p, 1 mg/mouse) or DMSO starting at either 4 or 8 week of age, for five consecutive week, then once per week for 5 additional week. Analyses for the development and/or reversal of diabetes, insulitis, adoptive transfer, and other mechanistic studies were performed.</p> <h3>Results</h3><p>AG490 significantly inhibited the development of T1D (p = 0.02, p = 0.005; at two different time points). Monotherapy of newly diagnosed diabetic NOD mice with AG490 markedly resulted in disease remission in treated animals (n = 23) in comparision to the absolute inability (0%; 0/10, p = 0.003, Log-rank test) of DMSO and sustained eugluycemia was maintained for several months following drug withdrawal. Interestingly, adoptive transfer of splenocytes from AG490 treated NOD mice failed to transfer diabetes to recipient NOD.<em>Scid</em> mice. CD4 T-cells as well as bone marrow derived dendritic cells (BMDCs) from AG490 treated mice, showed higher expression of Foxp3 (p<0.004) and lower expression of co-stimulatory molecules, respectively. Screening of the mouse immune response gene arrary indicates that expression of costimulaotry molecule Ctla4 was upregulated in CD4+ T-cell in NOD mice treated with AG490, suggesting that AG490 is not a negative regulator of the immune system.</p> <h3>Conclusion</h3><p>The use of such agents, given their extensive safety profiles, provides a strong foundation for their translation to humans with or at increased risk for the disease.</p> </div

Homocysteine, vitamin B12 and folate levels in premature coronary artery disease

BACKGROUND: Hyperhomocysteinemia is known as an independent risk factor of atherosclerosis, but the probable role of hyperhomocysteinemia in premature Coronary Artery Disease (CAD) is not well studied. The aim of this study was to assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the development of premature CAD. METHODS: We performed an analytical case-control study on 294 individuals under 45 years (225 males and 69 females) who were admitted for selective coronary angiography to two centers in Tehran. RESULTS: After considering the exclusion criteria, a total number of 225 individuals were enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3 years (40.1 +/- 4.2 years in males and 39.4 +/- 4.8 years in females). Compared to the control group, the level of homocysteine measured in the plasma of the male participants was significantly high (14.9 +/- 1.2 versus 20.3 +/- 1.9 micromol/lit, P = 0.01). However there was no significant difference in homocysteine level of females with and without CAD (11.8 +/- 1.3 versus 11.5 ± 1.1 micromol/lit, P = 0.87). Mean plasma level of folic acid and vitamin B12 in the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin B12 deficiency. Logistic regression analysis for evaluating independent CAD risk factors showed hyperhomocysteinemia as an independent risk factor for premature CAD in males (OR = 2.54 0.95% CI 1.23 to 5.22, P = 0.01). Study for the underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12 deficiency had significant influence on incidence of hyperhomocysteinemia. CONCLUSION: We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (bellow 45 years old) – especially in men -and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia

Therapeutic effects of Lavandula angustifolia

Several medicines are used in the nervous system disorders. Since there are several adverse effects of neurological medicines are reported, traditional and complementary medicine itself as new alternative regiment, which require further knowledge about the herbal medicine which the core center of complementary medicine. Lavandula angustifolia with the formal name of Lavandula Officinalis has many effects including widespread effect on central and peripheral nervous system, including anti-inflammatory, anti-apoptosis, antioxidant, antimutant, and neuroprotective effects. It shows analgesic effects and can alleviate pain, tolerance and dependency similar to morphine. Lavandula angustifolia has anti - inflammatory effect. Also this plant affects on cellular mechanisms like oxidative reactions (decrease of oxidative stress), apoptosis (anti - apoptosis), and nitric oxide production decrease of no production), anti - mutation and anti - cancer by this plant is reportd. It seems that effects of Lavandula are mediated through Calcium-Calmodulin and its kinase dependent

Effect of Hydro Alcoholic Extract of Citrullus Colocynthis Fruit on Caspase 3 Gene Expression in MCF-7 Breast Cancer Cell Line

Introduction: Breast cancer is regarded as one of the most common female cancers in the world. Many efforts have been made to treat the breast cancer, among which surgery, radiation, and chemotherapy can be mentioned. There is an increasing interest regarding using herbal preparations as a promising source of new anti-cancer drugs because of their safety profile and efficient pharmaceutical potentials. Since citrullus colocynthis proposes some cytotoxic effects against cancer, the present study aimed to explore the effect of hydro alcoholic extract of C. colocynthis fruit on the viability and expression level of Caspase-3 in MCF-7 cell line. Methods: In this laboratory study, the MCF-7 breast cancer cells were treated by different concentrations of Citrullus Colocynthis ethanol extract for 24, 48 and 72 h. The extract effect on cell viability was assessed by trypan blue staining. The RNA extraction was performed, and after the construction of cDNA, expression of Caspase 3 was analyzed via Real-Time PCR. Results: The obtained results revealed a noticeable dose and time dependent reduction in viability of C. colocynthis in the treatment group compared to the control samples. Moreover Real-Time PCR results demonstrated that the expression of Caspase3 gene at 48 and 72 hours after extract treatment significantly increased compared to the control cells. Conclusion: It can be concluded that citrullus colocynthis fruit extract can destroy cancer MCF-7 cells, which is resulted from an increase in caspase 3 gene expression

Incident Reporting in Mashhad Hospitals

Objectives: In this study, our aim was to evaluate and classify the voluntary error reports in the hospitals of Mashhad University of Medical Sciences. Patients have the right to receive health care in accordance to the best standards. Health care carries a risk of harm for patient safety, and with respect to today’s stressful systems with a large number of patients, it would be inevitable. The meaning of risk management is to predict adverse events and reduce their occurrence.Materials and Methods: A voluntary medical error reporting form was designed and approved by the clinical governance team of Mashhad Medical University. They were then distributed inside hospitals in the way in which everyone (health providers and patients) could access them easily. The forms were collected and classified monthly in all wards. Classification was performed on the base of type, outcome and reporter. Data gathering took place from spring to autumn 2012. The data was analyzed by the SPSS software. Results: 2500 errors were extracted from 1000 voluntary error reporting forms of the 12 hospitals of Mashhad Medical University. The most frequent error type was treatment errors (36%) related to drug administration, standard procedures and surgical events. Conclusions: Error reporting as a basic activity has an important role in discovering pitfalls of the health care system. To promote the reporting culture, its non punitive base must become clear for all professors and staff members, because this kind of reporting could lead to fewer medical errors and higher staff awareness about probable errors

Efficacy of Evidence Based Care on Care Quality of Mother and Infant in 3 Teaching Hospitals: A Protocol

Introduction: Reducing infant mortality rate during delivery is a priority in the world. Even with the existing activities that take place in hospitals, due to a lack of simple and effective methods, this mortality reduction trend is slow. The objects of this study were to apply and investigate the effects of WHO evidence-based guidelines for safe delivery on the quality of maternal and neonatal support. Materials and Methods: This is a semi-experimental study with external control. After forward and backward translation of WHO safe childbirth checklist, in an expert meeting irrelevant/infeasible items in the checklist were omitted or modified. Personnel performance on checklist items was evaluated by researchers who were present in the whole period of mother and neonate hospitalization in two phases. Intervention was done in two hospitals and one hospital was considered as control. At first, the instructions were provided for all the collaborating personnel in forms of pamphlets, posters and booklets and after two weeks second phase began by arranging an educational session for personnel. The data of these two phases is being compared. Discussion: If our prior assumption be proved, we anticipate improvements in some items of checklist .Some of these items are skin contact, breast feeding rate in first hour postpartum, hand hygiene, and mother's knowledge regarding the parturition during the time in which they are hospitalized together with a decrease in episiotomy infection/dehiscence prevalence. These changes can be regarded as an overall promotion in maternal/neonatal support