Hemostasis and microvascular function in type 1 diabetes : effects of treatment with statin and aspirin

Background: Patients with type 1 diabetes often develop microvascular complications and are at increased risk of premature cardiovascular disease. Women with type 1 diabetes lack the normal female protection against cardiovascular disease and may even be at higher risk compared with men with type 1 diabetes. Development of vascular complications may in part be explained by changes in hemostatic function in type 1 diabetes. Formation of a fibrin clot is the last step of the coagulation cascade and the structure of the formed clot reflects the environment in which it is formed. Tighter and less permeable fibrin clots are more resistant against degradation and are associated with cardiovascular risk factors and disease. Aims: The aims of this work were to investigate in vitro fibrin clot properties in adult patients with type 1 diabetes in relation to sex and microvascular complications (Paper I); treatment effects of high-dose atorvastatin on fibrin clot properties (Paper II) and skin microvascular reactivity (Paper III); and effects of aspirin on fibrin clot properties (Paper IV). Methods: The results are based on three studies: Paper I, a descriptive study involving 236 patients (107 females) with type 1 diabetes; Papers II and III, a randomized double- blind cross-over study in which 20 patients (10 females) with type 1 diabetes and dyslipidemia were treated daily with atorvastatin 80mg/day or placebo for two months; and Paper IV, a randomized cross-over study in which 24 patients (12 women) with good glycemic control and 24 patients (12 women) with poor glycemic control were treated with low (75 mg) and high (320 mg) doses of aspirin. Fibrin clot properties were assessed by determination of the permeability coefficient (Ks) and by turbidimetric clotting and lysis assays. Thrombin generation was investigated by assessment of plasma levels of prothrombin fragment 1+2 and tissue factor-induced thrombin formation in vitro. Plasma fibrinogen concentrations were measured by means of the Clauss method. Circulating levels of platelet and endothelial microparticles were investigated by flow cytometry. In Paper III, the effect of atorvastatin treatment on forearm skin microcirculation was investigated by way of laser Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity. Various biochemical markers of endothelial function were also analyzed in this study. Results: Paper I. Fibrin clot properties in vitro did not differ between men and women with type 1 diabetes. Women had worse glycemic control and higher thrombin generation. In women, fibrinogen concentration was the only determinant of fibrin clot permeability, while age and glycemic control also influenced clot permeability in men. Females younger than 30 years had less permeable fibrin clots and prolonged lysis time compared with age-matched men. Tighter and less permeable fibrin clots were also found in patients with poor glycemic control and in patients with microvascular complications. Associations between fibrin clot properties and microvascular complications were independent of glycemic control. Paper II. Treatment with high-dose atorvastatin (80 mg daily) was associated with increased fibrin clot permeability and reduced thrombin generation potential. In addition, reduced platelet microparticle concentrations and expression of prothrombotic antigens of platelet microparticles were found during atorvastatin therapy, indicating reduced platelet activation. These effects were independent of the lipid-lowering effects of atorvastatin. Paper III. Impaired endothelial-dependent skin microvascular reactivity and glycemic control was observed during atorvastatin treatment, concomitantly with a tendency towards increased levels of circulating endothelial microparticles. Paper IV. Treatment with aspirin at 75 mg daily had no effect on fibrin clot permeability, clot density or lysis time, while treatment with aspirin at 320 mg daily increased fibrin clot permeability and lag time in the turbidimetric clotting analyses. The beneficial effects of aspirin at 320 mg daily were more pronounced in patients with poor glycemic control. Conclusions: Men and women with type 1 diabetes and no history of macrovascular disease have similar fibrin clot properties in vitro. Microvascular complications in type 1 diabetes are associated with formation of more prothrombotic fibrin clots. High-dose (80 mg/day) atorvastatin treatment in patients with type 1 diabetes and dyslipidemia induces positive effects on hemostatic function, while the endothelial-dependent skin microvascular function and glycemic control were impaired. Treatment with high-dose (320 mg/day) aspirin affects fibrin polymerization and increases fibrin clot permeability, whereas treatment with low-dose (75 mg/day) aspirin has no effect on fibrin clot characteristics in patients with type 1 diabetes

Outcome of Accidental Exposure Prone to Blood Borne Viral Infections in an Educational Hospital

Background: The risk for transmission of blood-borne viruses (BBVs) such as Human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) due to occupational exposure is a major concern in the health care setting.Materials and Methods: This study among 337 health care workers (HCWs) accidentally exposed to BBVs was carried out from January 2009 to March 2015. The data were reviewed in labbafinejhad hospital, Tehran, Iran.Results: 4 HCWs had exposure to HBS Ag positive, which HBS antibody titer of them was higher than 10 mlu/ml, 6 HCWs were exposed to HCV seropositive patients underwent laboratory investigations for  HCV-antibody on 4,12, 24 weeks that results were negative. 3 cases had exposure to HIV seropositive patients which received standard antiretroviral post exposure prophylaxis.Conclusion: Timely performance for PEP (Post Exposure Prophylaxis) reducing BBVs transmission among HCWs.prophylaxis. Conclusions: Timely performance for  PEP(Post Exposure Prophylaxis) reducing BBVs transmission among HCWs.Key words: Outcome; Accidental Exposure; Blood Borne Viral Infection

Design and Synthesis of Novel Tetrapeptide Analogues as New Cytotoxic Agents

New series of compounds based on a tetrapeptide scaffold containing methyl sulfonyl group at the para position of a phenyl ring were synthesized and their cytotoxic activities were examined against several human cancer cell lines including MCF-7 (breast cancer Cell Line), HepG2 (human liver cancer Cell Line), HT-29 (Human Colorectal Adenocarcinoma Cell Line) and A549 (adenocarcinomic human alveolar basal epithelial cells) using MTT assay. Based on the results, among the synthesized peptides, 5e, 5f, 1g, and 3g were the most potent cytotoxic compounds that were more toxic than the reference compound, Celecoxib, against the tested cell lines. These compounds could be candidate for finding cytotoxic agents with new peptide scaffolds which show COX-2 inhibitory activity as well. HIGHLIGHTS•A group of tetrapeptides was reported as COX-2 inhibitors with antiproliferative activity.•New tetrapeptides containing methyl sulfonyl group at the para position of a phenyl ring were synthesized.•Some of novel compounds exhibited more potent cytotoxic effect than Celecoxib as the reference

Evaluation of the Clinical, Laboratory and Imaging Findings of Patients with COVID-19 and Their Associations with Clinical Outcomes in an Iranian Hospital: A Cross-Sectional Study

Background: Coronavirus disease 2019 (COVID-19) is a concern in the medical community as the virus spreads around the world. It has a heavy global burden, particularly in low-income countries. This virus has its specific outcomes in each population. Hence, it is necessary to design studies to find the epidemiological behaviour of this virus. Materials and Methods: This cross-sectional study was conducted in the Labbafinezhad hospital, Tehran, Iran. Demographic features include age, sex, past medical history, drug history, habitual file, influenza vaccination history, recent exposure history, clinical symptoms or signs, and the recorded symptoms. The clinical examination and para-clinical assessment, including chest computed tomography (CT) and laboratory testing on admission, were recorded. Results: It was found that patients with a history of kidney transplantation, high level of LDH, high level of AST, and increased neutrophil to lymphocyte ratio are most at risk of death. Conclusion: Parameters mentioned could help practitioners predict patient outcomes, and necessary interventions could be considered in this regard

Effects of adding convalescent plasma therapy for treatment of COVID-19 patients with severe and critical symptoms: a descriptive study of 12 cases

Background: Severe symptoms of COVID-19 could be actually life-threatening and fatal. No effective treatmenthas been proposed yet. Plasma from COVID19 recovered patients may be effective according to past similarstudies of some other viral infections.Materials and Methods: This study was conducted at the infectious disease ward of Shahid Labbafi NejadHospital (Tehran, Iran) from 3rd of April 2020 up until 3rd of May 2020. Clinical information for the 12 patients,before and after receiving convalescent plasma transfusion was obtained from a review of the hospital computermedical system retrospectively and analyzed.Results: Out of 12 patients with Covid-19 who received convalescent plasma, 7 patients were male (58.3%)and 5 were female (41.7%). The mean age of the patients was 52 years. Among them, 50% (n=6), improvedand discharged and the rest of them died. Mean O2 saturation of patients with final outcome of death anddischarged before plasma therapy were 67 (33%) and 77 (83%), respectively, an improvement, defining partialresolution of lesions of chest CT scan or stop in progression of infiltrations was detected in all of 6 dischargedpatients.Conclusion: Convalescent plasma may have effective role in improving O2 saturation, lymphopenia and CT scanlesions and also decreasing inflammatory factors of cases with severe manifestations but could not changeprognosis for critically ill patients. Therefore, an early administration of convalescent plasma may be helpful

Comparison of the Efficacy of Sofosbuvir and Kaletra on the Outcome of COVID-19. Is Sofosbuvir A Potential Treatment For COVID-19?

Background: The COVID-19 is a family of large enveloped non-segmented positive-sense RNA viruses which was first reported in December 2019 in Wuhan, China with a cluster of unexplained pneumonia. Although various medications have been tried to manage the COVID-19 pandemic, there is no exclusive medication or vaccine so far. In this study, we aimed to focus on the effectiveness of Hydroxychloroquine + Kaletra (lopinavir/ritonavir) versus Hydroxychloroquine + Sofosbuvir in patients hospitalized with COVID-19 to given the urgent need for an effective drug against SARS-CoV-2 in the current pandemic context. Materials and Methods: Fifty-four eligible patients with moderate to severe COVID-19 symptoms, according to the WHO criteria entered the study. Patients were randomized into two treatment groups. Thirty-two patients received Hydroxicholoroquine (400 mg stat) and Kaletra (400/100 mg q 12 h) as a control group (group A) and the trial group of 22 patients, received Hydroxicholoroquine (200 mg q 12 h) plus Sofosbuvir (400 mg daily) (group B) for a period of 7 to 14 days. Eventually, collected data included demographic characteristics, underlying diseases, clinical symptoms, laboratory data, and mortality were analyzed. Results: There was no significant difference in age, sex, and underlying diseases between the two groups. There was no significant statistical difference between the two groups on the seventh day of treatment in terms of cough relief, leukocyte count, and improvement of lymphopenia however in terms of the time of defervescence of fever, there was a significant difference between the two groups. Conclusion: Therefore, it can be said that our study is one of the first studies in the world to evaluate the effectiveness of sofosbuvir in the treatment of patients with COVID-19. According to our results, although Kaletra was assumed as an effective therapy, its superiority over Sofosbuvir was confined to the earlier effervescence of the 7-day fever and sofosbuvir can be used as an effective treatment, especially in patients with underlying heart disease who are at risk for arrhythmias with Kaletra

Dibromidobis(pyrazine-2-carboxamide-κN 4)zinc

The title complex, [ZnBr2(C5H5N3O)2], shows crystallographic mirror symmetry with the Zn atom and the two bromine ligands located on the mirror plane. The Zn atom is four-coordinated in a distorted tetra­hedral fashion by two N atoms from two pyrazine-2-carboxamide ligands and two Br atoms. Only one of the amino H atoms is involved in an N—H⋯O hydrogen bond. The crystal packing is further stabilized by weak N—H⋯N and C—H⋯O inter­actions

Dichloridobis(pyrazine-2-carboxamide-κN 4)zinc(II)

In the crystal of the title compound, [ZnCl2(C5H5N3O)2], the mol­ecule has m symmetry, with the ZnII cation and Cl− anions located on the mirror plane. The ZnII cation is coordinated by two Cl− anions and two pyrazine-2-carboxamide ligands in a distorted ZnCl2N2 tetra­hedral geometry. The two pyrazine rings are nearly perpendicular to each other [dihedral angle = 86.61 (10)°]. Inter­molecular N—H⋯O and N—H⋯N hydrogen bonds and weak C—H⋯O inter­actions stabilize the crystal packing

catena-Poly[[[aqua­(pyrazine-2-carboxamide-κ2 N 1,O)zinc]-μ-pyrazine-2-carboxamide-κ3 N 1,O:N 4] dinitrate]

In the crystal of the title compound, {[Zn(C5H5N3O)2(H2O)](NO3)2}n, the ZnII cation is N,O-chelated by two pyrazine-2-carboxamide (PCA) ligands and is further coordinated by one water mol­ecule and by one pyrazine-N atom from an adjacent PCA ligand in a distorted ZnN3O3 octa­hedral geometry. One of the two independent PCA ligands bridges two ZnII cations, forming a zigzag polymeric chain running along the c axis. In the crystal, the NO3 − anions link to the chain via O—H⋯O and N—H⋯O hydrogen bonding. Weak inter­molecular C—H⋯O inter­actions also occur