SV-IV Peptide1–16 reduces coagulant power in normal Factor V and Factor V Leiden

Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Relationships between salt-sensitivity of blood pressure and sympathetic nervous system activity: a short review of evidence

Experimental and clinical studies provided evidence in favor of complex relationships between sympathetic nervous system activity and salt-sensitivity of blood pressure. Genetic and acquired metabolic alterations associated with a tendency to retain salt and water may generate salt-sensitivity of blood pressure and shift the pressure-natriuresis curve to the right, promoting an increase in blood pressure. Sympathetic activation is a factor contributing to this result. Chronic high dietary salt intake is followed by a derangement in mechanisms of central sympathetic inhibition and then by an enhanced peripheral sympathetic tone. This, in turn, may generate salt-sensitivity of blood pressure by affecting renal hemodynamics, tubular sodium and water handling. Insulin resistance and sodium and water retention are prompted by high-fat (as well as high carbohydrate) diets, and by an increase in body fat mass. Also, aging is a condition of impaired interactions of the above factors. A gain in weight due to reduced physical activity, not followed by a parallel decrease in calorie intake, brings to a fall in insulin sensitivity. In many cases, the natural age-related decline of renal function is associated with a reduced physical exercise, hyperinsulinemia and sodium retention; sympathetic nervous system activity is enhanced and causes an increase in blood pressure

Subinhibitory concentrations of metronidazole increase biofilm formation in Clostridium difficile strains

Resistance mechanism to metronidazole is still poorly understood, even if the number of reports on Clostridium difficile strains with reduced susceptibility to this antibiotic is increasing. In this study, we investigated the ability of the C. difficile strains 7032994, 7032985 and 7032989, showing different susceptibility profiles to metronidazole but all belonging to the PCR ribotype 010, to form biofilm in vitro in presence and absence of subinhibitory concentrations of metronidazole. The quantitative biofilm production assay performed in presence of metronidazole revealed a significant increase in biofilm formation in both the susceptible strain 7032994 and the strain 7032985 exhibiting a reduced susceptibility to this antibiotic, while antibiotic pressure did not affect the biofilm-forming ability of the stable-resistant strain 7032989. Moreover, confocal microscopy analysis showed an abundant biofilm matrix production by the strains 7032994 and 7032885, when grown in presence of metronidazole, but not in the stable-resistant one. These results seem to demonstrate that subinhibitory concentrations of metronidazole are able to enhance the in vitro biofilm production of the above-mentioned PCR ribotype 010 C. difficile strains, susceptible or with reduced susceptibility to this antibiotic, suggesting a possible role of biofilm formation in the multifactorial mechanism of metronidazole resistance developed by C. difficile