Substantial Diversity in Cocirculating Omicron Lineages in Hospital Setting, Porto Alegre, Brazil.

We describe substantial variant diversity among 23 detected SARS-CoV-2 Omicron lineage viruses cocirculating among healthcare workers and inpatients (272 sequenced samples) from Porto Alegre, Brazil, during November 2022-January 2023. BQ.1 and related lineages (61.4%) were most common, followed by BE.9 (19.1%), first described in November 2022 in the Amazon region.

Efficacy and tolerability of lodenafil carbonate for oral therapy of erectile dysfunction: a phase III clinical trial.

INTRODUCTION: This is a phase III, prospective, randomized, double-blind, placebo-controlled clinical trial on lodenafil carbonate (LC), a novel phosphodiesterase 5 inhibitor developed in Brazil. AIM: Expanding information on LC efficacy and safety. MAIN OUTCOME MEASURES: International Index of Erectile Function (IIEF) erectile domain, positive answers to the sexual encounter profile (SEP)-2 and SEP-3 questions and incidence of adverse events (AEs). METHODS: A total of 350 men with erectile dysfunction (ED) of all degrees were randomized to placebo, LC 40 mg or LC 80 mg and followed for 4 weeks. They completed the IIEF and answered the SEP questions 2 and 3 after each intercourse without and with the use of LC. RESULTS: IIEF Erectile Domain scores without and with the use of medication were the following (mean [M] +/- standard deviation [SD]): placebo = 13.9 +/- 5.2 and 14.8 +/- 7.8; LC 40 mg = 13.6 +/- 5.3 and 18.6 +/- 8.0; LC 80 mg = 13.4 +/- 4.9 and 20.6 +/- 7.7 (analysis of variance [ANOVA] P < 0.01). Positive answers to SEP-2 without and with the use of medication were the following (M +/- SD): placebo = 55.3 +/- 43.2% and 52.1 +/- 41.4%; LC 40 mg = 46.4 +/- 44.3% and 63.5 +/- 42.0%; LC 80 mg = 50.2 +/- 40.9% and 80.8 +/- 32.3% (ANOVA P < 0.01). Positive answers to SEP-3 were the following: placebo = 20.2 +/- 32.3% and 29.7 +/- 38.1%; LC 40 mg = 19.6 +/- 34.3% and 50.8 +/- 44.4%; LC 80 mg = 20.8 +/- 33.2% and 66.0 +/- 39.3% (ANOVA P < 0.01). The patients with at least one AE were placebo = 28.7%, LC 40 mg = 40.9%, and LC 80 mg = 49.5%. AEs whose incidence was significantly higher with LC than with placebo included rhinitis, headache, flushing, visual disorder, and dizziness. CONCLUSIONS: LC showed a satisfactory efficacy-safety profile for oral therapy of ED.

Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi: a minireview.

Melanin pigments are substances produced by a broad variety of pathogenic microorganisms, including bacteria, fungi, and helminths. Microbes predominantly produce melanin pigment via tyrosinases, laccases, catecholases, and the polyketide synthase pathway. In fungi, melanin is deposited in the cell wall and cytoplasm, and melanin particles ("ghosts") can be isolated from these fungi that have the same size and shape of the original cells. Melanin has been reported in several human pathogenic dimorphic fungi including Paracoccidioides brasiliensis, Sporothrix schenckii, Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides posadasii. Melanization appears to contribute to virulence by reducing the susceptibility of melanized fungi to host defense mechanisms and antifungal drugs.

Additive effect of P10 immunization and chemotherapy in anergic mice challenged intratracheally with virulent yeasts of Paracoccidioides brasiliensis.

Paracoccidioidomycosis is a systemic granulomatous disease manifested in the acute/subacute or chronic forms. The anergic cases of the acute/subacute form are most severe, leading to death threatening conditions. Drug treatment is required to control the disease but the response in anergic patients is generally poor. A 15-mer peptide from the major diagnostic antigen gp43, named P10, induces a T-CD4+ helper-1 immune response in mice of different haplotypes and protects against intratracheal challenge with virulent P. brasiliensis. Presently, P10 immunization and chemotherapy were associated in an attempt to improve antifungal treatment in Balb/c mice made anergic by adding dexamethasone to the drinking water. The combined drug/peptide treatment significantly reduced the lung CFUs in infected anergic mice, largely preserved lung alveolar structure and prevented fungal dissemination to liver and spleen. Results recommend that a P10-based vaccine should be associated to chemotherapy for improved treatment of paracoccidioidomycosis aiming especially at anergic cases.

Melanin in the dimorphic fungal pathogen Paracoccidioides brasiliensis: effects on phagocytosis, intracellular resistance and drug susceptibility.

The fungal pathogen Paracoccidioides brasiliensis produces a melanin-like pigment in the presence of l-DOPA in vitro. We investigated whether melanization affected yeast uptake by alveolar and peritoneal macrophages, the intracellular resistance of fungal cells and their susceptibility to antifungal drugs. The interactions of melanized and nonmelanized P. brasiliensis with murine primary macrophages and J774.16 and MH-S macrophage-like cell lines were investigated. Melanized yeast cells were poorly phagocytosed by the cells even in the presence of complement. Melanization caused significant interference with the binding of cell wall components to lectin receptors on macrophages. Melanized cells were also more resistant than nonmelanized cells to the antifungal activity of murine macrophages. No difference in the susceptibilities of melanized and nonmelanized P. brasiliensis to antifungal drugs was observed using the minimum inhibitory concentration (MIC) method. However killing assays showed that melanization significantly reduced fungal susceptibility to amphotericin B and also protected against ketoconazole, fluconazole, itraconazole and sulfamethoxazole. The present results indicate that fungal melanin protects P. brasiliensis from phagocytosis and increases its resistance to antifungal drugs.