The molecular mechanism of Nystatin action is dependent on the membrane biophysical properties and lipid composition.

Nystatin (Nys) is a pore forming broad-spectrum and efficient antifungal drug with significant toxicity in mammalian organisms. In order to develop a non-toxic and more effective Nys formulation, its molecular mechanism of action at the cell membrane needs to be better understood. It is widely accepted that Nys activity and toxicity depend on the presence and type of membrane sterols. Taking advantage of multiple biophysical methodologies, we now show that the formation and stabilization of Nys aqueous pores, which are associated with Nys cytotoxicity, occur in the absence of membrane sterols. Our results suggest that the Nys mechanism of action is driven by the presence of highly ordered membrane domains capable of stabilizing the Nys oligomers. Moreover, Nys pore formation is accompanied by strong Nys-induced membrane reorganization that depends on membrane lipid composition and seems to underlie the Nys cytotoxic effect. Accordingly, in membranes enriched in a gel-phase forming phospholipid, Nys incorporates within the phospholipid-enriched gel domains, where it forms pores able to expand the gel domains. In contrast, in membranes enriched in gel domain forming sphingolipids, Nys-induced pore formation occurs through the destabilization of the gel phase. These results show that the Nys mechanism of action is complex and not only dependent on membrane sterols, and provide further insight into the molecular details governing Nys activity and toxicity.

Rhabdomyolysis as a clinical manifestation of association with ciprofibrate, sirolimus, cyclosporine, and pegylated interferon-α in liver-transplanted patients: a case report and literature review.

BACKGROUND: Rhabdomyolysis is a syndrome characterized by impaired metabolic integrity of myocytes, causing the release of intracellular constituents into the circulation, and can be a serious side effect of drug intake. CASE REPORT: This report describes a unique case of rabdomyolysis secondary in which ciprofibrate, sirolimus, cyclosporine, and pegylated interferon-α in a liver transplant patient was used. A 47-year-old male liver transplant recipient in 2009, who had hepatitis C and incidental hepatocellular carcinoma, underwent immunosuppressive therapy (cyclosporine and sirolimus). The patient is currently in treatment for viral recurrence with pegylated interferon-α and ribavirin; he had a history of hypertriglyceridemia treated with ciprofibrate. He had development of severe and generalized myalgia and fever after the eighth application of pegylated interferon-α and increasing doses of cyclosporine. Laboratorial tests showed acute renal failure and significant increase in creatine kinase. Rhabdomyolysis secondary to interaction of fibrate-cyclosporine-pegylated interferon-α was postulated. CONCLUSIONS: Medical professionals should be aware of possible drug interactions and should monitor patients receiving these drugs.

Pothomorphe umbellata: antifungal activity against strains of Trichophyton rubrum.

Trichophyton rubrum is a dermatophyte, which can cause infections in human skin, hair and nail. Pothomorphe umbellata (L.) Miq. (Piperaceae) is a native Brazilian plant, in which phytochemical studies have demonstrated the presence of steroids, 4-nerolidylcatechol, sesquiterpenes and essential oils. The objective of this study was to analyze the in vitro activity of extracts and fractions of P. umbellata on resistant strains of T. rubrum. The microdilution plate method was utilized to test Tr1, H6 and ΔTruMDR2 strains of T. rubrum; ΔTruMDR2 strain was obtained from H6 by TruMDR2 gene rupture, which is involved in multiple drugs resistance. The highest antifungal activity to all strains was observed for dichloromethane and hexane fractions of the 70% ethanolic extract which showed minimal inhibitory concentration (MIC) and minimal fungicide concentration (MFC) of 78.13 µg/mL. This antifungal activity was also obtained by 70% ethanolic extract, which presented MIC and MFC of 78.13 µg/mL to ΔTruMDR2, whereas the MIC values for Tr1 and H6 were 78.13 and 156.25 µg/mL, respectively. Our results suggest the potential for future development of new antifungal drugs from P. umbellata, especially to strains presenting multiple resistance.

Traumatic porencephalic cyst and cholesteatoma of the ear.

Porencephalic cyst expanding into the ear is a very rare complication of temporal bone fracture. We report a case of a 20-year-old male who developed a traumatic porencephalic cyst of the temporal lobe expanding into the ear through a tegmen fracture in association with a cholesteatoma. The clinical presentation was otitic meningitis. This occurrence was not encountered in any of the cases reviewed in the literature. The diagnosis, pathogenesis, treatment and prognosis of this condition are reviewed.

A longitudinal study of the prognostic significance of ventricular ectopic beats in the elderly.

The prognostic significance of ventricular ectopic beats occurring in healthy, elderly individuals has only been assessed previously in short-term, longitudinal studies. 30 healthy, elderly people underwent 24-hour ambulatory electrocardiographic monitoring and approximately 2.5 years later subsequent morbidity and mortality was assessed. 1 individual could not be traced and 4 had died. Details of the cardiovascular health status of the remaining 25 were assessed by a questionnaire. There was no correlation between the numbers of ventricular ectopic beats and subsequent cardiovascular morbidity. Similarly, the results show no differences between ventricular ectopic beat activity and mortality 2.5 years later. On the basis of this study it is concluded that routine 24-hour ambulatory ECG monitoring does not provide clinically relevant predictive information in regard to cardiovascular morbidity or mortality.