Effect of novel alpha-conotoxins on nicotine-stimulated [3H]dopamine release from rat striatal synaptosomes

Nicotine's action on the midbrain dopaminergic neurons is mediated by nicotinic acetylcholine receptors (nAChRs) that are present on the cell bodies and the terminals of these neurons. Previously, it was suggested that one of the nAChR subtypes located on striatal dopaminergic terminals may be an alpha3beta2 subtype, based on partial inhibition of nicotine-stimulated [(3)H]dopamine release by alpha-conotoxin MII, a potent inhibitor of heterologously expressed alpha3beta2 nAChRs. More recent studies indicated that alpha-conotoxin MII also potently blocks alpha6-containing nAChRs. In the present study, we have examined the nAChR subtype(s) modulating [(3)H]dopamine release from striatal terminals by using novel alpha-conotoxins that have 37- to 78-fold higher selectivity for alpha6-versus alpha3-containing nAChRs. All of the peptides partially (20-35%) inhibit nicotine-stimulated [(3)H]dopamine release with IC(50) values consistent with those obtained with heterologously expressed rat alpha6-containing nicotinic acetylcholine receptors. These results, together with previous studies by others, further support the idea that alpha6-containing nicotinic receptors modulate nicotine-stimulated dopamine release from rat striatal synaptosomes.     

Hepatitis C prevalence and elimination planning in Pakistan,a bottom-up approach accounting for provincial variation

In Pakistan, substantial changes to hepatitis C virus (HCV) programming and treatment have occurred since the 2008 nationwide serosurvey estimated a 4.8% anti-HCV prevalence. In the absence of an updated national study, this analysis uses provincial data to estimate a national prevalence and the interventions needed to achieve elimination. Using a Delphi process, epidemiologic HCV data for the four provinces of Pakistan (accounting for 97% of the population) were reviewed with 21 subject-matter experts in Pakistan. Province-level estimates were inputted into a mathematical model to estimate the national HCV disease burden in the absence of intervention (Base), and if the World Health Organization (WHO) elimination targets are achieved by 2030 (80% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage, and 65% reduction in mortality: WHO Elimination). An estimated 9,746,000 (7,573,000–10,006,000) Pakistanis were living with viraemic HCV as of January 1, 2021; a viraemic prevalence of 4.3% (3.3–4.4). WHO Elimination would require an annual average of 18.8 million screens, 1.1 million treatments, and 46,700 new infections prevented anually between 2022 and 2030. Elimination would reduce total infections by 7,045,000, save 152,000 lives and prevent 104,000 incident cases of hepatocellular carcinoma from 2015 to 2030. Blood surveys, programmatic data, and expert panel input uncovered more HCV infections and lower treatment numbers in the provinces than estimated using national extrapolations, demonstrating the benefits of a bottom-up approach. Screening and treatment must increase 20 times and 5 times, respectively, to curb the HCV epidemic in Pakistan and achieve elimination by 2030.     

Alteration in CD8+ T cell subsets in enterovirus-infected patients: An alarming factor for type 1 diabetes mellitus

Type 1 diabetes is a multi-factorial disease that can develop due to the combination of genetic and environmental factors. Viruses, particularly enteroviruses, are major environmental candidates in the pathogenesis of type 1 diabetes, even though the mechanisms of pathogenicity of these viruses and their effects on the immune system have not been understood very well yet. Previous studies show that any imbalance in the population of different lymphocyte subsets could develop autoimmune diseases. Our theory is that enteroviral infection causes an impairment in the distribution of lymphocyte subtypes and consequently results in the diabetes onset in some individuals. Therefore, in this project, we evaluated the distribution of T CD8+ lymphocytes and their subsets in type 1 diabetes patients. This study was conducted to investigate the relationship between enteroviral infection and type 1 diabetes mellitus in an Iranian population, and suggestion a predicting approach for susceptible subjects.     

Sildenafil protective effects on high glucose-induced neurotoxicity in PC12 cells: the role of oxidative stress,apoptosis, and inflammation pathways in an in vitro cellular model for diabetic neuropathy

Objectives Diabetic neuropathy (DN) induces lifetime disability and there is currently no effective therapy to treat or to minimize patients suffering, so it is thereby imperative to develop therapeutic strategies for this disease. Since oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation are crucial mechanisms in development and progression of DN, it is important to explore tools by which one can reduce factors related to these pathways. Herein, the understandings of the sildenafil neuroprotective effect through increase of cGMP level and the mediation of oxidative stress, apoptosis, and inflammation pathways on neurotoxicity induced by high glucose (HG) in PC12 cells as an in vitro cellular model for DN were investigated.

Methods We reported that the PC12 cells pre-treatment with sildenafil (0.008 μM) for 60 min and then exposing the cells to HG (25 mM for 72 h) or normal glucose (NG) (5 mM for 72 h) condition, show:

Results (1) significant attenuation in reactive oxygen species, MDA and TNF-a levels, Bax/Bcl-2 ratio, expression of caspase 3 and UCP2 proteins; (2) significant increase in viability, GSH/GSSG ratio, mitochondrial membrane potential, and ATP levels.

Conclusion All these data together led us to propose neuroprotective effect of sildenafil is probably through its antioxidant, antiapoptotic, and anti-inflammatory activities. Of course, further studies are required to explain the underlying mechanism of the sildenafil effects.     

Enabling informed policymaking for chronic kidney disease with a registry: Initiatory steps in Iran and the path forward

Objectives

Chronic kidney disease (CKD) registries have been used for more than half a century. Iran lacks a comprehensive registry to capture data of all CKD patients for an informed care planning and policy making. We aimed to identify the objectives and possible challenges for developing a CKD registry and also to define its minimum data set (MDS) in our healthcare context.

The effects of maternal exposure to second-hand smoke on breast-feeding duration: A prospective cohort study

Aim

Encouraging exclusive breastfeeding up to 6 months is one of the main priorities for public health. However, the rate of exclusive breastfeeding is decreasing in Iran. Moreover, there have been few studies conducted on the effects of maternal exposure to cigarette smoke on breastfeeding duration in Iran. Considering the importance of breast milk for infant development, the future health of the baby and ultimately the family, this study was designed to assess the effect of maternal exposure to second-hand smoke on exclusive breastfeeding duration.

Subjects and methods

The effect of smoke exposure on exclusive breastfeeding was investigated in a prospective cohort study. The study included 170 mothers in the exposed group and 170 mothers in the non-exposed group. There were losses to follow-up (12 %), so a statistical analysis was carried out on a total of 299 women. Breastfeeding duration and maternal exposure to second-hand smoke were recorded in three follow-up interviews, including 3–5 days, 3 months and 6 months after delivery. Maternal exposure to second-hand smoke was assessed by self-reports. A Kaplan-Meier survival analysis and Cox regression model were used for data analysis.

Results

Maternal exposure to second-hand smoke during the postpartum period can cause a significant reduction in exclusive breastfeeding during a 6-month period (p?<?0.001). According to the Cox regression model, heavily exposed (hazard ratio?=?2.22, 95 % confidence interval: 1.45–3.39) and lightly exposed mothers (hazard ratio?=?1.65, 95 % confidence interval: 1.25–2.42) were more likely to stop exclusive breastfeeding earlier compared with non-exposed women.

Conclusion

Maternal exposure to second-hand smoke is associated with an increased risk of discontinuation of exclusive breastfeeding before 6 months. A stance of no smoking at home and avoidance of passive smoking could possibly improve the rate of breastfeeding in Iran.     

Intracranial neurenteric cyst with post-operative chemical meningitis and vagal nerve palsy

Intracranial neurenteric cysts are rare congenital lesions that, though benign, are difficult to diagnose radiologically given their similar imaging appearance to other intracranial cystic lesions. We present a case of a 21-year-old female with a pathologically proven, symptomatic neurenteric cyst in the premedullary cistern. Superimposed on this uncommon diagnosis were also rare post-operative complications of chemical meningitis and vagal nerve injury. We review the current literature surrounding intracranial neurenteric cysts, their imaging characteristics, differential diagnosis, therapeutic options, and potential complications related to their resection.     

Maternal death due to COVID‐19 and high BMI: A case report from Hamadan,Iran

Pregnant women suffering chronic illness or obstetric complications such as obesity are prone to severe pneumonia and COVID‐19. Obesity in pregnancy is associated with many complications for both mother and fetus. Here, we report the death of an obese mother with COVID‐19.