The complete tautomeric mixture consisting of nine prototropic tautomers has been studied in the gas phase at the DFT(B3LYP)/6-311?G(d,p) level for neutral, oxidized, and reduced cytosine. Rotational isomerism of the exo -OH group and geometrical isomerism of the exo =NH group have also been considered. Tautomeric conversions possible for cytosine have been compared with those for its structural models, 4-amino-and 2-hydroxypyrimidine. Effects of intramolecular interactions between neighboring groups for cytosine are analogous to those observed for model compounds. Although they are not very strong, they are sufficient to influence tautomeric equilibria and relative stabilities of individual tautomers. One-electron oxidation and one-electron reduction change tautomeric preferences. Tautomers that are rare forms for neutral cytosine become favored ones for oxidized and reduced cytosine. Aromaticity is not the main factor that dictates the tautomeric preferences. Stability of functional groups seems to be more important than full electron delocalization.
The development of metabolic derangements as a result of HIV treatment has been an important area of research since the introduction of zidovudine in the 1980’s. Antiretroviral therapy has intensely evolved in the last three decades, with new drugs gradually incorporated into everyday clinical practice. With the life expectancy of people living with HIV rapidly approaching that of their HIV-negative counterparts, the influence of these antiretrovirals on the development of the components of the metabolic syndrome remains of major interest to clinicians and their patients. In this review, we aimed to discuss the impact of cART on components of the metabolic syndrome, i.e., weight, plasma lipid levels, plasma glucose levels, and blood pressure, describing the influence of cART classes and of individual antiretrovirals. We also aimed to outline the limitations of the research conducted to date and the remaining knowledge gaps in this area.
Objectives Ascites and spontaneous bacterial peritonitis (SBP) are among the most important complications of decompensated liver cirrhosis. In clinical practice, new inflammation biomarkers are needed for the early diagnosis of SBP, as well-known biomarkers, such as C-reactive protein (CRP), procalcitonin (PCT), or peripheral blood white blood cell (WBC) count, lack the required specificity and sensitivity. The aim of the study was to evaluate the significance of heparin-binding protein (HBP) in comparison to CRP, PCT, WBC, and D-dimers in the diagnosis of SBP. Design Cross-sectional descriptive single-center study. Setting Department of Infectious and Tropical Diseases and Hepatology, Medical University of Warsaw, Poland. Patients All patients admitted to the aforementioned department with decompensated liver cirrhosis and ascites between February 1, 2016, and June 30, 2017. Intervention Several markers (HBP, CRP, PCT, WBC, and D-dimers) were analysed in blood serum in regard to their potential use in the diagnosis of SBP in patients with decompensated liver cirrhosis and ascites. We correlated the levels of the aforementioned markers with an ascitic fluid polymorphonuclear count using simple linear regression and multiple linear regression. Sensitivities, specificities, and positive and negative predictive values for SBP were calculated for the aforementioned makers of inflammation. Measurements and Main Results A total of 63 patients with decompensated liver cirrhosis and ascites participated in the study. The etiology of liver cirrhosis was varied (HCV: n = 40, HBV: n = 13, HCV/HBV: n = 4, AIH: n = 3, PBC: n = 2, and haemochromatosis: n = 1). After the peritoneal tap, 31 patients were determined to have SBP (defined as an ascitic fluid polymorphonuclear count > 250 cells/μL) and 32 patients had no evidence of SBP on peritoneal tap. A very weak, but statistically significant, correlation of HBP, WBC, and D-dimer levels with the peritoneal fluid polymorphonuclear (PMN) count was observed in the simple regression model, but multivariable analysis using the multiple regression model showed that only D-dimers correlated with peritoneal fluid PMNs independently from other inflammation biomarkers. A D-dimer cutoff value of 1500 ng/mL was determined optimal for ruling out SBP due to high sensitivity (96.8%) and a high negative predictive value (92.9%), although predictably, this marker was not useful for confirming SBP due to low specificity (40.6%) and a low positive predictive value (61.2%). The usefulness of D-dimers was limited by the fact that only 22.2% of the studied patients had D-dimer levels below 1500 ng/mL. HBP and WBC showed little to no predictive value in this study. Conclusions D-dimers < 1500 ng/mL make the diagnosis of SBP unlikely, although the peritoneal tap is still the reference method in such situations. In the studied group, the determination of HBP was of no diagnostic benefit in the diagnosis of SBP.
Background Coagulation disorders in patients with liver cirrhosis are a common clinical problem. Cirrhosis should be considered a state of impaired blood clotting or an imbalance of the whole coagulation system. Cirrhosis-induced coagulopathy encompasses disturbances in both the procoagulant and anticoagulant systems. This mechanism may promote the development of thrombosis with portal vein thrombosis (PVT), which is considered an obstacle to orthotopic liver transplantation (OLT). We assessed serum ADAMTS-13 levels in patients with decompensated liver cirrhosis, with and without PVT. Material and Methods Serum ADAMTS-13 levels, age, platelet count (PLT), and INR (international normalized ratio) were evaluated in (n = 64) patients with liver cirrhosis either with PVT (group 1, n = 31) or without PVT (group 2, n = 33). The results were compared with those from healthy volunteers (group 3, n = 37). Liver cirrhosis was based on Desmet's classification of chronic hepatitis in liver biopsy stage ≥ 3 or liver elastography F-score ≥ 3. Serum ADAMTS-13 levels were measured with Quantikine® ELISA Human ADAMTS13 Immunoassay, R&D Systems Inc. We used Welch's F-test, Games-Howell, one-way ANOVA, Bonferroni test, and logistic regression to determine whether ADAMTS-13 levels were a predictor that was independent of MELD and Child-Pugh scores. All results (P < 0.05) were considered statistically significant. Results The mean serum ADAMTS-13 level in patients with PVT was significantly lower than that in patients without PVT (P = 0.001) and controls (P = 0.001). The mean serum ADAMTS-13 level in patients without PVT was significantly lower than that in controls (P = 0.001). ADAMTS-13 levels were significantly associated with PVT accounting for the Child-Pugh or MELD score in the logistic regression model. Conclusions Low serum ADAMTS-13 levels can be a useful indicator of portal thrombosis in patients with decompensated liver cirrhosis irrespective of Child-Pugh or MELD scores. Further research is needed to determine whether ADAMTS-13 levels will find use in everyday clinical practice.
Background. Erysipelas and cellulitis are common, acute, bacterial infections of the skin and subcutaneous tissue. The incidence of these infections is growing, and the recurrence rate is high. Effective antibiotic prophylaxis is available, but insufficient data exist on the risks factors for recurrent infection. Purpose. To compare comorbidities and laboratory findings in patients with single-episode and recurrent erysipelas/cellulitis in order to identify risk factors for recurrent erysipelas/cellulitis. Methods. A cross-sectional study, which included patients hospitalized in the Department of Infectious and Tropical Diseases and Hepatology of the Medical University of Warsaw due to erysipelas and cellulitis during 3 consecutive years (July 2016–June 2019). Results. The study included 163 patients, of which 98 had a first episode of erysipelas/cellulitis and 65 had a recurrence. The recurrent infection was significantly associated with a history of lymphedema (12.3% in the recurrent group vs. 2.0% in the first-episode group, p=0.015), a higher BMI (35.4 vs. 31.2, respectively, p=0.002), chronic obstructive pulmonary disease (10.8% vs. 2.0%, p=0.030), and a shorter history of symptoms prior to hospitalization (6.0 days vs. 11.8 days, p=0.004). Patients with the first episode of infection were more likely to have had minor local trauma directly preceding the symptoms of infection (20.4% in the first-episode group vs. 1.5% in the recurrent group, p=0.001). Conclusions. Patients with lymphedema and obesity should be viewed at high risk of developing recurrence of erysipelas and thus should be considered as candidates for antibiotic prophylaxis and other prevention methods. Minor local trauma directly preceding the skin infection does not by itself confer a higher risk for erysipelas recurrence. More research is needed to assess the association of recurrent skin and soft-tissue infection to preceding minor local trauma, individual components of the metabolic syndrome, and COPD.
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