Plasma concentrations of soluble CD40 ligand in smokers with acute myocardial infarction: a pilot study

Coronary artery disease (CAD) is believed to be the single leading cause of death in both men and women in the world. Smoking is the most important risk factor for CAD. Smoking increases platelet aggregation and thrombus formation. CD40 ligand (CD40L) is a transmembrane glycoprotein derived from activated platelets. It participates in thrombus formation during the acute phase of acute myocardial infarction (MI). Elevation of CD40L identifies the patients who are at highest risk for cardiac events and who are likely to benefit from treatment with the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonists. The purpose of this study was to evaluate levels of CD40L in smokers with acute MI. Fifty-seven patients with acute MI were enrolled in this study. Thirty-one smokers were compared with 26 non-smokers. Soluble CD40L level in the plasma was determined by a standard enzyme-linked immunosorbent assay. Circulating levels of CD40L were higher in the smokers’ group. Smokers with acute MI may have increased risk for thrombotic complications during acute MI, and optimal antiaggregant therapy should be administered

Effects of magnesium sulphate on liver ischemia/reperfusion injury in a rat model

Aim: To investigate the protective efficacy of magnesium sulphate in a model of rat liver ischemia-reperfusion (I/R) injury. Method: 32 adult female Wistar-Albino rats (250 to 350 g) were used in this experimental study. Rats were divided into 4 groups according to liver ischemia and magnesium sulfate application methods. Group 1 (C); control, group 2 (M); magnesium sulphate, group 3 (I/R); liver I/R, group 4 (I/R+M); I/R + magnesium sulphate treated. The blood samples were centrifuged for the study of aspartate aminotransferase (AST), alanine aminotransferase, prothrombin time (PT), international normalized ratio (INR) troponin I, total antioxidant status (TAS), total oxidant status (TOS) assays. The livers of the animals were removed at the end of the study and samples were taken for histopathological examination. Results: AST and INR values were significantly decreased in I/R+M group compared to I/R group. There was no significant difference in ALT values of the groups. Although not statistically significant, the TAS values were increased in I/R + M group compared to I/R group rats. In addition, the value of TOS was found to be lower in I/R + M group rats. In the histopathological examination, the mean values of apoptosis and necrosis were lower in the IR+M group compared to the IR group. Conclusion: The main finding of the present study suggested that magnesium sulphate pretreatment moderately decreased the liver damage through its anti-inflammatory and anti-oxidant effects in a rat model of liver I/R

Phenyl Bis-Sulfonamide Keap1-Nrf2 Protein–Protein Interaction Inhibitors with an Alternative Binding Mode

Inhibitors of Kelch-like ECH-associated protein 1 (Keap1) increase the activity of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) by stalling its ubiquitination and degradation. This enhances the expression of genes encoding proteins involved in drug detoxification, redox homeostasis, and mitochondrial function. Nrf2 activation offers a potential therapeutic approach for conditions including Alzheimer’s and Parkinson’s diseases, vascular inflammation, and chronic obstructive airway disease. Non-electrophilic Keap1-Nrf2 protein–protein interaction (PPI) inhibitors may have improved toxicity profiles and different pharmacological properties to cysteine-reactive electrophilic inhibitors. Here, we describe and characterize a series of phenyl bis-sulfonamide PPI inhibitors that bind to Keap1 at submicromolar concentrations. Structural studies reveal that the compounds bind to Keap1 in a distinct “peptidomimetic” conformation that resembles the Keap1-Nrf2 ETGE peptide complex. This is different to other small molecule Keap1-Nrf2 PPI inhibitors, including bicyclic aryl bis-sulfonamides, offering a starting point for new design approaches to Keap1 inhibitors

Phenyl Bis-Sulfonamide Keap1-Nrf2 Protein-Protein Interaction Inhibitors with an Alternative Binding Mode

[Image: see text] Inhibitors of Kelch-like ECH-associated protein 1 (Keap1) increase the activity of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) by stalling its ubiquitination and degradation. This enhances the expression of genes encoding proteins involved in drug detoxification, redox homeostasis, and mitochondrial function. Nrf2 activation offers a potential therapeutic approach for conditions including Alzheimer’s and Parkinson’s diseases, vascular inflammation, and chronic obstructive airway disease. Non-electrophilic Keap1-Nrf2 protein–protein interaction (PPI) inhibitors may have improved toxicity profiles and different pharmacological properties to cysteine-reactive electrophilic inhibitors. Here, we describe and characterize a series of phenyl bis-sulfonamide PPI inhibitors that bind to Keap1 at submicromolar concentrations. Structural studies reveal that the compounds bind to Keap1 in a distinct “peptidomimetic” conformation that resembles the Keap1-Nrf2 ETGE peptide complex. This is different to other small molecule Keap1-Nrf2 PPI inhibitors, including bicyclic aryl bis-sulfonamides, offering a starting point for new design approaches to Keap1 inhibitors

The effects of structured peer consultation program on school counselor in Turkey

The purpose of this study was to investigate the effect of Structured Peer Consultation Program on school counselor burnout in Gaziantep city, Turkey. A pre-test and post-test control group design was used to investigate the effect of the program. Maslach Burnout Inventory was administered for the pre-test and the post-test. The structured peer consultation program was applied to the experimental group for 5 weeks. ANCOVA was used to test the significant treatment effect of the Program on counselor burnout. The results of ANCOVA indicated that ANCOVA’s examining the treatment effects was significant on the dimensions of emotional exhaustion, depersonalization and personal accomplishment

Güneydoğu Anadolu Bölgesinde Görev Yapan Psikolojik Danışmanların Tükenmişlik Düzeyleri ve Bazı Demografik Değişkenlerle Tükenmişlik Arasındaki İlişkinin İncelenmesi

In this study, the level of three dimensions of burnout of counselors who work in region of Southeast Anatolia as a counselor wax investigated. Thus, the relation between three dimensions of burnout and salary, job expectations, workload, job satisfaction, age, years of experience as a counselor and number of counselors who work together and significant difference between dimensions of burnout and gender, department of graduation, and marital status were investigated. For this purpose, Personal Information Form and Maslach Burnout Inventory were administered to 227 volunteer counselors who work in region of Southeast Anatolia. The results of the analysis showed that the counselors who work in region of Southeast Anatolia had burnout in dimensions of emotional exhaustion and lack of personal accomplishment. It was found that there was a significant relationship between burnout and job satisfaction, salary, expectations, and workload. Thus, there was no significant difference between dimensions of burnout and gender, marital status, and department of graduation.Bu çalışmada, Güneydoğu Anadolu Bölgesinde görev yapan psikolojik danışmanların tükenmişliğin üç alt boyutundaki düzeyleri incelenmiş ve psikolojik danışmanın maaşa ilişkin algısı, işten beklentisi, iş yükü, işten aldığı doyum, yaş, görev yılı ve beraber çalıştığı psikolojik danışman sayısı ile tükenmişlik alt boyutları arasındaki ilişki ve cinsiyet, medeni durum, mezun olunan bölüm gibi değişkenler ile tükenmişlik boyutlarından alınan puanlarda fark olup olmadığı araştırılmıştır. Bu çalışmaya Güneydoğu Anadolu bölgesinde görev yapan 227 psikolojik danışman gönüllü olarak katılmıştır. Çalışmaya katılanlara Kişisel Bilgi Formu ve Maslach Tükenmişlik Ölçeği uygulanmış ve veriler SPSS ile analiz edilmiştir. Güneydoğu Anadolu bölgesinde görev yapan psikolojik danışmanların tükenmişliğin duygusal tükenme ve kişisel başarı alt boyutlarında tükenmişlik yaşadıkları ve tükenmişlik ile maaşa ilişkin algıları, işlerinden aldıkları doyum, işten beklentileri ve iş yükü ile ilgili algıları, arasında anlamlı ilişki olduğu bulunmuştur. Bu bulgulara ek olarak, cinsiyet, medeni durum ve mezun olunan bölüm değişkenlerine, göre tükenmişliğin alt boyutlarından alınan puan ortalamalarında anlamlı bir fark olmadığı bulunmuştur