Inflammatory Mediators Released in Pulmonary Tuberculosis Enhance Hyper-Coagulable States: A Crucial Role of Tissue Factor.

<b>Background and Objective:</b> Immune complexes and pro-inflammatory cytokines deduced from communicable diseases have been manifested to induce pro coagulopathy and tissue factor (TF) assertion in macrophages and the endothelial cells that remain at critical risk in tuberculosis (TB) patients. The current study was carried out among Sudanese patients with Pulmonary tuberculosis aimed to determine the long-term impacts of Tb infection on the coagulation cascade. <b>Materials and Methods:</b> A cross-sectional study was conducted among 30 patients who are already diagnosed with tuberculosis compared with the control group. Pulmonary Tuberculosis diagnosis of cases was emphasized in accordance with clinical examination, chest X-ray and positive Ziehl-Neelsen (ZN) smear. The questionnaire was used for the collection of demographic and baseline data. About 2.5 mL of venous blood was collected in trisodium citrate containers and 2.5 mL of blood was collected in EDTA container. SPSS version 21 statistical software was used for statistical analysis. <b>Results:</b> PLT count showed a significant difference (p = 0.03) with a mean (329.20×10³ and 287.60×10³ µL¹) among patients and control, respectively. APPT shows a significant difference (p = 0.00), Mean of PLT decreased as the disease progressed (336.20±36.02, 345.43±16.02, 511.04±42.02) showed a significant correlation between PLT count of test and duration of disease (p = 0.00). Additionally, a significant correlation between PLT count, MPV and APTT and the status of the patient's drug resistance was revealed (p<u><</u>0.02, 0.01 and 0.02). <b>Conclusion:</b> There is a significant alteration in coagulation parameters (PT, APTT and platelets count) among Sudanese pulmonary tuberculosis patients, which may indicate a feature of a hypercoagulable state.

Glutathione, Cysteine, and D-Penicillamine Role in Exchange of Silver Metal from the Albumin Metal Complex.

The purpose of this study is to investigate the exchange reaction taking place among the bovine serum albumin (BSA), 5,5'-dithiobis-(2-nitrobenzoic acid (ESSE), reduced glutathione, N-acetylcysteine, D-penicillamine (thiolates), and silver metal (AgI). For this purpose, stock solutions of BSA and Ellman's reagent were prepared by dissolving 264 mg of BSA in 5 ml of reaction buffer (0.1 M KH2PO4 at pH 7.8) and 23.8 mg of ESSE in 1.0 ml of reaction buffer which were mixed together. Mixture of BSA-AgI was prepared in a separate procedure by dissolving 0.17 mg of silver nitrate in 1 ml of reaction buffer and then dissolving BSA (200 mg) in the same solution of silver nitrate. Blocking of Cys-34 of BSA with AgI was confirmed by treating different dilutions of BSA-AgI (500 µM) solutions with the solutions of ESSE (85 µM) and ES- (85 µM) and recording the spectra (300-450) with a UV-visible spectrophotometer. The chromatographed AgI-modified BSA ((BSA-S)AgI)) samples (typically 500 µM) were subsequently mixed with thiolates (reduced glutathione, N-acetylcysteine, and D-penicillamine). AgI and modified BSA (typically 500 µM each) were treated with these low molecular weight thiolates and allowed to react overnight followed by chromatographic separation (Sephadex G25). The redox reactions of AgI-modified BSA with various low molecular weight thiols revealed a mechanically important phenomenon. In the case of reduced glutathione and N-acetylcysteine, we observed the rapid release of a commensurate amount of Ellman's anion, indicating that an exchange has taken place and low molecular weight thiols (RSH) substituted AgI species at the Cys-34 of BSA eventually forming disulfide (BSA-SSR) at Cys-34. It can be anticipated from the phase of study involving bovine serum albumin that low molecular weight thiolates (reduced glutathione and N-acetylcysteine) take off AgI which are attached to proteins elsewhere in the physiological system, making these toxic metals free for toxic action.

Statins-related peripheral neuropathy among diabetic patients.

BACKGROUND: Peripheral neuropathy (PN) is a complaint with often unidentified reasons. Some medicines, including statins therapy, are anticipated to be amongst the reasons for PN. AIMS: This study intended to assess the association of peripheral neuropathy with statins therapy amongst Type 2 diabetic patients. METHODS: At Penang General Hospital, 757 cases were categorized into two groups (564 with statins therapy and 193 without statins therapy). The diagnosis of PN was investigated retrospectively for a period of 10 years (2006-2016). Confounding risk factors as age, diabetes period, hypertension, glycemic control, other co-morbidity, and prescriptions were matched. RESULTS: About 129 (22.9%) cases from 564 statins users had PN. Only 30 (15.5%) subjects had PN from 193 statins non-users. Chi-square test showed a significant variance among statins treatment cohort and statin-free cohort in the occurrence of PN (P-value: 0.001). Spearman's investigation presented a positive correlation (r: 0.078, p-value: 0.031) among statins use and PN prevalence. Binary logistic regression was statistically significant for statins therapy as a predictor of peripheral neuropathy incidence (r2: 0.006, p-value: 0.027) amid diabetic patients. The relative risk of peripheral neuropathy connected with statins therapy is (RR: 1.47, 95% CI: 1.02-2.11). The excess relative risk is 47.1%. While the absolute risk (AR) is 7.3% and the number needed to harm (NNH) is 14. CONCLUSIONS: The study indicated a positive association between peripheral neuropathy and statins utilization. Peripheral neuropathy was higher amongst statins users than the statins-free group.

Thiol-disulfide exchange reactions occurring at modified bovine serum albumin detected using ellman's reagent (5, 5'-dithiobis (2-itrobenzoic acid).

Bovine serum albumin (BSA) is usually employed as a model protein because of being homologous with human serum albumin. Cysteine-34 of BSA has been oxidised with Ellman's reagent to produce BSA labelled with an Ellman's moiety (BSA-SE). The BSA-SE was then reacted with glutathione, N-acetylcysteine and D-penicillamine (D-pen). The two were able to release the Ellman's moiety bound at cysteine-34 while D-pen did not. Albumin labeled using Ellman's reagent was used to demonstrate the cleavage of a protein mixed disulphide. The kinetics of thiol disulfide interchange reactions involving formation of a chromophoric thiolate were determined by UV-visible spectroscopy. The reaction of thiolates with excess Ellman's reagent is used for quantitative estimation of thiol by measuring the absorption at λ, 412 nm. The disulfide exchange reactions occurring at Cys-34 of BSA was determined and the reduction of oxidized Cys-34 was studied in order to understand the reverse reaction. Spectroscopic evidence suggested that glutathione and N-acetylcysteine remove the label and produce BSA in a disulfide form. In contrast, D-pen reaction returned BSA to its thiolate form via mediation. It was observed that thio-disulfide exchange occurred at cysteine-34 labelled with Ellman's moiety. The implications to the redox status of plasma are discussed.

The statins effects on HbA1c control among diabetic patients: An umbrella review of systematic reviews and meta-analyses of observational studies and clinical trials.

Statins have impacts on the metabolism of glucose that might influence the progress of diabetes in non-diabetics or affect glycemic control in patients with existing diabetes. Experimental proof has been contradictory about whether some statins display beneficial properties while others indicate harmful impressions. Some systematic reviews of statins had stated conflicting findings on the concern of glucose metabolism. The current study investigates the published systematic reviews and meta-analyses to combine their results and give a clear situation regarding the influence of statins therapy on glycated hemoglobin (HbA1c). This study has valuable strength points; long follow-up period and big sample size.