Primary cutaneous histoplasmosis difficult to treat in immunocompetent patient: case report and literature review.

Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum. The disease is endemic in several regions of tropical and temperate climate. The fungus presents opportunistic behavior, causing widespread infection in immunocompromised patients, resulting from complication of primary pulmonary infection, due to exogenous reinfection or reactivation of a quiescent source. In immunocompetent individuals, approximately 95% of pulmonary infections are asymptomatic. However, prolonged exposure to high amount spores may lead to acute or chronic lung infection. Due to the low amount of inoculum, primary cutaneous histoplasmosis caused by traumatic implantation is extremely rare and effectively treated with triazoles. Thus, the present study aims to report a case of primary cutaneous histoplasmosis that is difficult to treat in an immunocompetent patient, and to review the literature on the incidence of drug-resistant Histoplasma capsulatum strains in clinical practice.

Primary cutaneous histoplasmosis difficult to treat in immunocompetent patient: case report and literature review / Histoplasmose cutânea primária de difícil tratamento em paciente imunocompetente: relato de caso e revisão da literatura

ABSTRACT Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum. The disease is endemic in several regions of tropical and temperate climate. The fungus presents opportunistic behavior, causing widespread infection in immunocompromised patients, resulting from complication of primary pulmonary infection, due to exogenous reinfection or reactivation of a quiescent source. In immunocompetent individuals, approximately 95% of pulmonary infections are asymptomatic. However, prolonged exposure to high amount spores may lead to acute or chronic lung infection. Due to the low amount of inoculum, primary cutaneous histoplasmosis caused by traumatic implantation is extremely rare and effectively treated with triazoles. Thus, the present study aims to report a case of primary cutaneous histoplasmosis that is difficult to treat in an immunocompetent patient, and to review the literature on the incidence of drug-resistant Histoplasma capsulatum strains in clinical practice.

RESUMO A histoplasmose é uma infecção causada pelo fungo dimórfico Histoplasma capsulatum. A doença é endêmica em diversas regiões de clima tropical e temperado. O fungo apresenta comportamento oportunístico, causando infecção disseminada em pacientes imunocomprometidos, resultante da complicação da infecção pulmonar primária, por reinfecção exógena ou reativação de um foco quiescente. Em indivíduos imunocompetentes, cerca de 95% das infecções pulmonares são assintomáticas. No entanto, a exposição prolongada à quantidade elevada de esporos pode levar à infecção pulmonar aguda ou crônica. Devido à baixa quantidade de inóculo, a histoplasmose cutânea primária causada por implantação traumática é extremamente rara e efetivamente tratada com triazóis. Assim, o presente estudo tem como objetivos relatar um caso de histoplasmose cutânea primária de difícil tratamento em paciente imunocompetente, e revisar a literatura a respeito da incidência de cepas de Histoplasma capsulatum resistentes aos fármacos utilizados na prática clínica.

Thiosemicarbazone of lapachol acts on cell membrane in Paracoccidioides brasiliensis.

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin American countries. Amphotericin B, sulfonamides, and azoles may be used in the treatment of PCM. However, the high toxicity, prolonged course of treatment, and significant frequency of disease relapse compromise their use. Therefore, there is a need to seek new therapeutic options. We conducted tests with thiosemicarbazone of lapachol (TSC-lap) to determine the antifungal activity and phenotypic effects against several isolates of Paracoccidioides spp. In addition, we evaluated the toxicity against murine macrophages and the ability to enhance phagocytosis. Further, we verified that TSC-lap was active against yeasts but did not show any interaction with the drugs tested. The TSC-lap showed no toxicity at the concentration of 40 µg/ml in macrophages, and at 15.6 µg/ml it could increase the phagocytic index. We observed that this compound induced in vitro ultrastructural changes manifested as withered and broken cells beyond a disorganized cytoplasm with accumulation of granules. We did not observe indications of activity in the cell wall, although membrane damages were noted. We observed alterations in the membrane permeability, culminating in a significant increase in K+ efflux and a gradual loss of the cellular content with increase in the concentration of TSC-lap. In addition, we showed a significant reduction of ergosterol amount in the Pb18 membrane. These data reinforce the possible mechanism of action of this compound to be closely associated with ergosterol biosynthesis and reaffirms the antifungal potential of TSC-lap against Paracoccidioides spp.

Assessment of oral anticoagulation control at two pharmacist-managed clinics in Brazil.

Background Warfarin remains widely used by patients with cardiovascular diseases. When using warfarin, the quality of oral anticoagulation control is a critical determinant to minimize the risk of bleeding and thromboembolic events. Pharmacist engagement in patient care is relevant towards improving the quality of warfarin therapy. Objective To assess the quality of oral anticoagulation control measured by time in therapeutic range (TTR) at two pharmacist-managed anticoagulation clinics (AC). Method This study included adults with indication of continuous warfarin use. Patients were recruited at two AC of public hospitals in Brazil (2014-2015). Anticoagulation control was assessed by TTR using the Rosendaal method. Laboratory INR values were collected for the maximum period of follow-up (2009-2015). Results A total of 554 patients were studied. The median age was 63.7 [Quartile 1 (Q1) 54.3; Quartile 3 (Q3) 73.6] years, 57.4% female. The median TTR was 64.3% [Q1 54.0%; Q3 74.0%], and 344 (61.6%) patients had TTR ≥ 60%. Conclusion Pharmacist-managed AC have achieved an adequate TTR in Brazilian patients with low socioeconomic status. Interventions include face-to-face appointments for individual patient education, warfarin-dosing adjustments and monitoring of drug interactions. Pharmacists are important to improve adherence and the quality of warfarin therapy in low- and middle income countries.

Effect of radiation treatment on newly established human breast cancer cell lines MACL-1 and MGSO-3.

The characterization of new cell lines is an important tool to understand the biological processes involved in cancer treatments. In the present study, we used two newly established epithelial human breast cancer cell lines from primary sites MACL-1 and MGSO-3 and compared their susceptibility to the treatment with ionizing radiation (IR) with the commercial cell line MDA-MB-231. In the doses used (10 or 20 Gy), IR induced a reduction in cell viability and cell death, measured as DNA fragmentation, at 48 and 72 h after treatment. In addition, 48 h after treatment with IR, we observed an enhancement in the percentage of apoptotic cells. The broad-range caspases inhibitor zVAD-FMK inhibited cytotoxicity induced by IR. After 24 h, treatment with IR activated caspase-9 in MACL-1 and MDA-MB-231 but not in MGSO-3 cells. Thirty hours after treatment with IR (20 Gy), we observed an activation of caspases 8 and 3. These results suggest the involvement of caspases in the cell death induced by IR in two newly established cell lines. These cells may be useful in studies of breast cancer in defining basic mechanisms in molecular and cellular radiobiology and may contribute to the rational design of future models of cancer therapies.