Memory impairment is one of the main complications of Alzheimer’s disease (AD). This condition can be induced by hyper-stimulation of N-Methyl-D-aspartate receptors (NMDARs) of glutamate in the hippocampus, which ends up to pyramidal neurons determination. The release of neurotransmitters relies on voltage-gated calcium channels (VGCCs) such as P/Q-types. Omega-lycotoxin-Gsp2671e (OLG1e) is a P/Q-type VGCC modulator with high affinity and selectivity. This bio-active small protein was purified and identified from the Lycosa praegrandis venom. The effect of this state-dependent low molecular weight P/Q-type calcium modulator on rats was investigated via glutamate-induced excitotoxicity by N-Methyl-D-aspartate. Also, Electrophysiological amplitude of field excitatory postsynaptic potentials (fEPSPs) in the input–output and Long-term potentiation (LTP) curves were recorded in mossy fiber and the amount of synaptophysin (SYN), synaptosomal-associated protein, 25 kDa (SNAP-25), and synaptotagmin 1(SYT1) genes expression were measured using Real-time PCR technique for synaptic quantification. The outcomes of the current study suggest that OLG1e as a P/Q-type VGCC modulator has an ameliorative effect on excitotoxicity-induced memory defects and prevents the impairment of pyramidal neurons in the rat hippocampus.

Background and purpose: Several studies have shown the effectiveness of screening programs in decreasing the costs and disutility of type-2 diabetes and related complications. As there is a growth in the incidence of type-2 diabetes amongst the Iranian population, the cost-effectiveness of performing type-2 diabetes screening tests in community pharmacies of Iran was evaluated in this study from the payer’s perspective. The target population consisted of two hypothetical cohorts of 1000 people 40 years of age without a prior diagnosis of diabetes, for the intervention (screening test) and no-screening groups. Experimental approach: A Markov model was developed to evaluate the cost-effectiveness and cost-utility of a type-2 diabetes screening test in community pharmacies in Iran. A 30-year time horizon was considered in the model. Three screening programs with 5-year intervals were considered for the intervention group. The evaluated outcomes were quality-adjusted life-years (QALYs) for cost-utility-analysis and life-years-gained (LYG) for cost-effectiveness-analysis. To examine the robustness of the results, one-way and probabilistic-sensitivity analyses were applied to the model. Findings/Results: The screening test represented both more effects and higher costs. The incremental effects in the base-case scenario (no-discounting) were estimated to be 0.017 and 0.0004 (approximately 0) for QALYs and LYG, respectively. The incremental cost was estimated to be 2.87 USD/patient. The estimated incremental-cost-effectiveness ratio was 164.77 USD/QALY. Conclusion and implications: This study indicated that screening for type-2 diabetes in community pharmacies of Iran could be considered highly cost-effective, as it meets the WHO criteria of the annual GDP per capita ($2757 in 2020).

Excitotoxicity is a common pathological process in Alzheimer’s disease (AD) which is caused by the over-activity of N-Methyl-D-Aspartate receptors (NMDARs). The release of neurotransmitters depends on the activity of voltage-gated calcium channels (VGCCs). Hyper-stimulation of NMDARs can enhance the releasement of neurotransmitters through the VGCCs. This malfunction of channels can be blocked by selective and potent N-type VGCCs ligand. Under excitotoxicity condition, glutamate has negative effects on the pyramidal cells of the hippocampus, which ends in synaptic loss and elimination of these cells. These events leads to learning and memory elimination through the hippocampus circuit’s dysfunction. A suitable ligand has a high affinity to receptor or channel and is selective for its target. The bioactive small proteins of venom have these characteristics. Therefore, peptides and small proteins of animal venom are precious sources for pharmacological applications. The omega-agatoxin-Aa2a was purified, and identified from Agelena labyrinthica specimens, as an N-type VGCCs ligand for this study. The effect of the omega-agatoxin-Aa2a on the glutamate-induced excitotoxicity in rats was evaluated through behavioral tests including Morris Water Maze, and Passive avoidance. The syntaxin1A (SY1A), synaptotagmin1 (SYT1), and synaptophysin (SYN) genes expression were measured via Real-Time PCR. The local expression of synaptosomal-associated protein, 25 k Da (SNAP-25) was visualized using an immunofluorescence assay for synaptic quantification. Electrophysiological amplitude of field excitatory postsynaptic potentials (fEPSPs) in the input–output and LTP curves of mossy fiber were recorded. The cresyl violet staining of hippocampus sections was performed for the groups. Our results demonstrated that the omega-agatoxin-Aa2a treatment could recover the learning, and memory impairment caused by NMDA-induced excitotoxicity in rat hippocampus.

BackgroundSeveral clinical trials and meta-analyses have shown the advantageous effects of statins in populations with different levels of cardiovascular disease (CVD) risk. Considering the increasing cardiovascular risk among the Iranian population, the cost-effectiveness of the use of simvastatin 10 mg, as an Over-The-Counter (OTC) drug, for the primary prevention of myocardial infarction (MI) was evaluated in this modeling study, from the payer's perspective. The target population is a hypothetical cohort of 45-year CVD healthy men with an average (15 %) 10-year CVD risk.MethodsA semi-Markov model with a life-long time horizon was developed to evaluate the Cost-Utility-Analysis (CUA) and Cost-Effectiveness-Analysis (CEA) of the use of OTC simvastatin 10 mg compared to no-drug therapy. Two measures of benefits were used in the model; Quality-Adjusted-Life-Years (QALYs) for the CUA and Life-Years-Gained (LYG) for the CEA. To examine the robustness of the results, one-way sensitivity analysis and probabilistic sensitivity analysis were applied to the model.ResultsFor the base-case scenario with a discount rate of 0 % the estimated ICERs were 1113 USD/QALY and 935USD/LYG per patient (using governmental tariffs).No threshold has been determined in Iran for the cost-effectiveness of health-related interventions. However, according to the recommendation of WHO, this intervention can be considered highly cost-effective as its ICER is far less than the reported GDP per capita for Iran by World bank in 2013 ($4763).ConclusionsThis modeling study showed that the use of an OTC low dose statin (simvastatin 10 mg) for the primary prevention of myocardial infarction (MI) in 45-year men with a 10-year CVD risk of 15 % could be considered highly cost-effective in Iran, as it meets the WHO threshold of the annual GDP per capita ($4763).

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Aspirin is one of the certified medicines commonly used for the secondary prevention of myocardial infarction (MI). Aspirin side effects and gastrointestinal bleeding, in particular, have arisen debates on its use for the primary prevention of MI. The present research evaluates the cost-effectiveness of the use of aspirin in the primary prevention of MI among Iranian men with average cardiovascular disease (CVD) risk, using Markov modeling technique. The incremental cost-effectiveness ratios (ICERs) estimated to be 864 USA dollars (USD) per quality-adjusted life years (QALY) gained and 782 USD per life years gained (LYG) for each patient in the base-case scenario (public tariffs and no discounting). This research proves cost-effectiveness of the use of aspirin in the primary prevention of MI in targeted population, since the assessed ICERs are quite under the recommended threshold by WHO which is one gross domestic product (GDP) per capita ($5315.1 for Iran in 2015).

Background: Around 80% of the all non-melanoma skin cancer cases suffer from basal cell carcinoma (BCC). Mohs surgery is one of the common method used for treatment in recent years. There are several treatment methods for primary BCC. One of these methods is Mohs micrographic surgery (Mohs surgery), which has become popular in recent years. Objectives: The aim of this study was to investigate 4-year recurrence and factors affecting the recurrence of BCC patients after Mohs surgery. Methods: This is a retrospective cohort study. The study population included all BCCs, who underwent Mohs surgery in Alzarha Hospital in Isfahan between 2007 and 2014, and were monitored for recurrence for 4 years. Cox regression analysis was used to determine factors affecting time recurrence. Results: The most and least frequent locations of this disease are nose (30.3%) and body (0.5%). The most common locations for recurrence are scalp (50%), nose (15%), and around the eyes (15%). The 4-year recurrence frequency of BCC after Mohs surgery was 0.9%. Cox regression analysis relationship between determining factors affecting time recurrence was not significance. Conclusions: The causes of recurrence can include the less use of protective equipment in front of sunlight or low precision of doctors in the lesion surgery in locations of the body, arms, feet, head, neck, hands, legs or genital organs, and other parts of the body.

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