Influence of KIR gene diversity on the course of HSV-1 infection: resistance to the disease is associated with the absence of KIR2DL2 and KIR2DS2

Herpes simplex virus type 1 (HSV-1) causes lifelong latent infections in most humans. Periodical virus reactivations from latency in the neurons of sensitive ganglia lead to transport to mucocutaneous regions and productive replication, which results in recurrent inflammatory herpetic lesions or in asymptomatic virus shedding. The medical consequences of such lesions and the frequency of recurrences vary greatly in different subjects. Furthermore, many infected individuals never suffer manifestations of the disease, even when exposed to stimuli that trigger clinical recurrences in other humans. The origin of the variability in the clinical course of HSV-1 infection remains unexplained. Herpesviruses and other pathogens sabotage the expression of major histocompatibility complex class I molecules by infected cells, thus subverting T-cell-mediated immunity. Subversion of antigen presentation is counteracted by natural killer cells, which survey the human leukocyte antigen (HLA) expression by specific receptors. These include the killer cell immunoglobulin-like receptors (KIRs), which are encoded by a complex of extremely diverse and rapidly evolving genes. Here, we analyze the contribution of KIR gene diversity to the variable clinical course of HSV-1 infection by comparing the distribution of these genes in humans with clinical manifestations of the disease with that in asymptomatically infected donors. This study provides preliminary evidence that the receptors KIR2DL2 and KIR2DS2 predispose to symptomatic HSV-1 infection and favor the frequently recurring forms of the disease. Possible contribution of the 'HLA-C1' ligand to HSV-1 disease was not statistically supported. Because of an absolute genetic linkage between KIR2DL2 and KIR2DS2, we could not determine which receptor was primarily responsible for the observed association, but our results suggest that presence in the genome of KIR2DL2 and KIR2DS2 hinders an effective cellular response to HSV-1.     

Incidence and consequences of systemic arterial thrombotic events in COVID-19 patients

Journal of Thrombosis and Thrombolysis - A high incidence of thrombotic events, particularly deep vein thrombosis and pulmonary embolism, has been clearly documented in COVID-19 patients. In...     

Saccharomyces cerevisiae intervention for relieving flutamide-induced hepatotoxicity in male rats

The aim of this work was to investigate the protective role of baker's yeast Saccharomyces cerevisiae against the hepatotoxic effect of the drug flutamide that is widely used for treatment of metastatic prostate adenocarcinoma. Administration of flutamide to adult male rats in a dose of 100 mg/kg b.w. daily for 15 days resulted in serious hepatic injury. Highly significant increase in each of serum ALT, ALP, bilirubin, bile acids and cholesterol level, relative to the control group, was observed. Also, a highly significant increase in the serum glutathione-S-transferase isoforms: alpha-GST and pi-GST and each of TNF-alpha and NO levels was recorded. Moreover, highly significant decrease in hepatic glutathione peroxidase and superoxide dismutase activities was observed. In addition, the authors noticed a significant increase in serum testosterone levels with concomitant highly significant increase in serum acid phosphatase activity. Prophylactic treatment of male rats with baker's yeast in a dose of 4.8 mg/kg b.w. daily for 15 days, followed by a combination of flutamide (100 mg/kg b.w.) and yeast (4.8 mg/kg b.w.) daily for other 15 days resulted in marked improvement in rat's liver function, whereas the serum testosterone and acid phosphatase levels retained values parallel to those recorded for the flutamide-treated rats. Histological examination of liver tissues showed that flutamide caused hydropic degeneration, necrotic areas and marked increase in Kupffer cells. The central vein is congested with blood and signs of apoptosis appeared in the hepatocytes in the form of fragmentation of the nuclei and blebbing of the cytoplasm. On the other hand, in the rats treated with both yeast and flutamide, the hepatic cords were more regularly arranged, signs of degeneration or apoptosis were less pronounced and some hepatocytes appeared binucleated. The authors postulate that each one of the powerful antioxidative components in S. cerevisiae effectively participated in attenuation of the oxidative stress caused by flutamide metabolites, and in promoting regeneration of new hepatocytes and meanwhile could restore liver function beyond normal status.     

Rapunzel syndrome with a fatal outcome in a neglected child

The “Rapunzel” syndrome (a trichobezoar with a long tail extending from the stomach to the small bowel) is an uncommon disease. It is related to severe complications but rarely associates to a fatal outcome. We report a case of a 5-year-old girl admitted at the emergency department in cardiorespiratory arrest whose autopsy disclosed an ileal perforation that is caused by a long bezoar extending from the stomach to the small bowel. The authors discuss a possible link between Rapunzel syndrome and child neglect.     

Green tea constituents (-)-epigallocatechin-3-gallate (EGCG) and gallic acid induce topoisomerase I- and topoisomerase II-DNA complexes in cells mediated by pyrogallol-induced hydrogen peroxide

Green tea and its major active constituent, (-)-epigallocatechin-3-gallate (EGCG), are in clinical trials for the prevention and treatment of several diseases such as cancer. DNA topoisomerase (topo) poisons are commonly prescribed anticancer drugs that kill cancer cells by inducing topo-DNA complexes. Using purified topoisomerases, previous in vitro studies have shown that EGCG induces the formation of topo-DNA complexes. Because the activity of a drug on purified topoisomerases does not always represent the activity in a cell, we have used an immunofluorescence technique that allows the visualisation of topo I- and topo II-DNA complexes produced in individual cells to evaluate the activity of EGCG on both enzymes. High levels of topo I- and topo II-DNA complexes were observed in K562 leukaemia cells exposed to EGCG. Similar levels of topo I- and topo II-DNA complexes were visualised in cells treated with gallic acid (GA) (the acid part of the EGCG ester). Pyrogallol (PG) also induced topo-DNA complexes with both enzymes, therefore suggesting that the activity of EGCG and GA is mediated by their PG moieties. Catalase prevented both the cytotoxicity and the formation of topo I- and topo II-DNA complexes induced by EGCG, GA, PG and myricetin (a PG-containing flavonoid recently shown to induce topo I- and topo II-DNA complexes in cells), indicating that hydrogen peroxide mediates these activities. Hydrogen peroxide induced topo I- and topo II (α and β)-DNA complexes in a time- and dose-dependent manner. The formation of topo I- and topo II-DNA complexes in cells exposed to hydrogen peroxide correlated well with the induction of apoptosis, suggesting that the topo-DNA complexes induced at long exposure times by the compounds tested in our study may be apoptotic topo-DNA complexes. Finally, we report results suggesting that PG-containing drugs may selectively kill tumour cells by generating hydrogen peroxide.