Prevalence and lethality among patients with histoplasmosis and AIDS in the Midwest Region of Brazil.

Histoplasmosis is a systemic mycosis that is considered an important public health problem. In this work, we performed a descriptive, observational, cross-sectional and retrospective study with a secondary data analysis of medical records from 2000 to 2012 at a tertiary hospital. The study sample consisted of 275 patients with laboratory-confirmed Disseminated Histoplasmosis (DH)/AIDS. The results showed that the prevalence of DH associated with AIDS was 4.4%. The majority of patients were young adult men with fever in 84.2%, cough in 63.4%, weight loss in 63.1%, diarrhoea in 44.8% and skin manifestations in 27.6% of patients. In the overall cohort, the CD4 counts were low, but not significantly different in survivors and non-survivors. Higher levels of urea and lower levels of haemoglobin and platelets were observed in non-survivor patients (<.05). The global lethality was 71.3% (196/275). The results with high prevalence and lethality highlight the need to adopt measures to facilitate early diagnosis, proper treatment and improved prognosis.

Search for antifungal compounds from the wood of durable tropical trees.

Research on antifungal compounds from the durable wood from French Guiana Amazonian forest trees highlights the correlation between the activity of their extracts against wood-rotting fungi and human pathogens. The fractionation of an ethyl acetate extract of Sextonia rubra wood led to the isolation of rubrenolide (1) and rubrynolide (2). The potential of compounds 1 and 2 is described through the evaluation of their activity against 16 pathogenic fungi and their cytotoxicity toward NIH-3T3 mammalian fibroblast cells.

Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity.

Voriconazole (VCZ), a triazole with a large spectrum of action is one of the most recommended antifungal agents as the first line therapy against several clinically important systemic fungal infections, including those by Candida albicans. This antifungal has moderate water solubility and exhibits a nonlinear pharmacokinetic (PK) profile. By entrapping VCZ into liposomes, it is possible to circumvent certain downsides of the currently available product such as a reduction in the rate of its metabolization into an inactive form, avoidance of the toxicity of the sulfobutyl ether-beta-cyclodextrin (SBECD), vehicle used to increase its solubility. PKs and biodistribution of VCZ modified by encapsulation into liposomes resulted in improved antifungal activity, due to increased specificity and tissue penetration. In this work, liposomal VCZ resulted in AUC0-24/MIC ratio of 53.51 ± 11.12, whereas VFEND® resulted in a 2.5-fold lower AUC0-24/MIC ratio (21.51 ± 2.88), indicating favorable antimicrobial systemic activity. VCZ accumulation in the liver and kidneys was significantly higher when the liposomal form was used. Protection of the drug from biological degradation and reduced rate of metabolism leads to a 30% reduction of AUC of the inactive metabolite voriconazole-N-oxide (VNO) when the liposomal drug was administered. Liposomal VCZ presents an alternative therapeutic platform, leading to a safe and effective treatment against systemic fungal infections.

t(4;12)(q11;p13): a rare chromosomal translocation in acute myeloid leukemia.

We present a case of acute myeloid leukemia with t(4;12). This translocation is rare and has been observed in acute leukemias with different but immature phenotypes. To the best of our knowledge, there are around 15 descriptions of t(4;12) in AML, and most interesting, presenting morphological aspects of a pseudo-lymphoid cell with dysplasia of other series.

Vascular adventitia is a suitable compartment to transplant transduced vascular smooth muscle cells for ex vivo gene expression.

Vascular smooth muscle cells (VSMC) are ideal for systemic gene therapy because of their proximity to blood vessels and they have demonstrated long-term exogenous gene expression in vivo. However, the procedure generally followed to seed the transduced VSMC onto arteries denuded of endothelial cells usually induces stenosis and thrombosis, with a consequent high risk for use in humans. We demonstrate here that the vascular adventitia is a suitable place to introduce transduced VSMC and to secrete therapeutic proteins into the blood stream by a simple procedure, avoiding postoperative vascular complications. Transduced VSMC, with the retroviral vectors carrying the human growth hormone gene (hGH), were seeded into the adventitia of the rat abdominal aorta by single injection of a cell suspension. Based on the hGH and anti-hGH production in serum and on histological analysis of the removed aortas, we demonstrated hGH production over the 2-month experimental period. None of the animals used in the experiment showed stenosis, thrombosis, or other vascular or visible physiological abnormalities.

Secondary metabolites from Spirotropis longifolia (DC) Baill and their antifungal activity against human pathogenic fungi.

A phytochemical study of the ethyl acetate extract of the roots and adventitious roots of Spirotropis longifolia, a monodominant tree species of the Guianan rainforest, has allowed the isolation of three compounds: 2-hydroxy-8,9-methylenedioxy-2',2'-dimethylpyrano-[5',6':4,3]-6a-prenyl-[6aS,11aS]-pterocarpan (spirotropin A), 2-hydroxy-8,9-methylenedioxy-2',2'-dimethyl-3',4'-dihydropyrano-[5',6':4,3]-6a-prenyl-[6aS,11aS]-pterocarpan (spirotropin B), and 5,7-dihydroxy-6,8-diprenyl-2'''',2''''-dimethylpyrano[5'''',6'''': 3',4']-isoflavone (spirotropone). In addition, 10 known compounds, trans-oxyresveratrol, trans-resveratrol, piceatannol, daidzein, genistein, isoprunetin, lupeol, latifolol, gnetin D and gnetin E, were also isolated. These compounds were evaluated for their antifungal activity and their cytotoxicity, and their structures were established by 1D and 2D NMR, HRMS, CD and optical rotation measurements.

Functional characterization of a synthetic hydrophilic antifungal peptide derived from the marine snail Cenchritis muricatus.

Antimicrobial peptides have been found in mollusks and other sea animals. In this report, a crude extract of the marine snail Cenchritis muricatus was evaluated against human pathogens responsible for multiple deleterious effects and diseases. A peptide of 1485.26 Da was purified by reversed-phase HPLC and functionally characterized. This trypsinized peptide was sequenced by MS/MS technology, and a sequence (SRSELIVHQR), named Cm-p1 was recovered, chemically synthesized and functionally characterized. This peptide demonstrated the capacity to prevent the development of yeasts and filamentous fungi. Otherwise, Cm-p1 displayed no toxic effects against mammalian cells. Molecular modeling analyses showed that this peptide possible forms a single hydrophilic α-helix and the probable cationic residue involved in antifungal activity action is proposed. The data reported here demonstrate the importance of sea animals peptide discovery for biotechnological tools development that could be useful in solving human health and agribusiness problems.

Structural and functional characterization of a multifunctional alanine-rich peptide analogue from Pleuronectes americanus.

Recently, defense peptides that are able to act against several targets have been characterized. The present work focuses on structural and functional evaluation of the peptide analogue Pa-MAP, previously isolated as an antifreeze peptide from Pleuronectes americanus. Pa-MAP showed activities against different targets such as tumoral cells in culture (CACO-2, MCF-7 and HCT-116), bacteria (Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 25923), viruses (HSV-1 and HSV-2) and fungi (Candida parapsilosis ATCC 22019, Trichophyton mentagrophytes (28d&E) and T. rubrum (327)). This peptide did not show toxicity against mammalian cells such as erythrocytes, Vero and RAW 264.7 cells. Molecular mechanism of action was related to hydrophobic residues, since only the terminal amino group is charged at pH 7 as confirmed by potentiometric titration. In order to shed some light on its structure-function relations, in vitro and in silico assays were carried out using circular dichroism and molecular dynamics. Furthermore, Pa-MAP showed partial unfolding of the peptide changes in a wide pH (3 to 11) and temperature (25 to 95°C) ranges, although it might not reach complete unfolding at 95°C, suggesting a high conformational stability. This peptide also showed a conformational transition with a partial α-helical fold in water and a full α-helical core in SDS and TFE environments. These results were corroborated by spectral data measured at 222 nm and by 50 ns dynamic simulation. In conclusion, data reported here show that Pa-MAP is a potential candidate for drug design against pathogenic microorganisms due to its structural stability and wide activity against a range of targets.

Improving the outcomes of elderly patients with acute myeloid leukemia in a Brazilian University Hospital.

OBJECTIVE: To evaluate the outcomes of acute myeloid leukemia patients who were older than 60 years of age at the time of diagnosis following the implementation of a treatment algorithm based on age, performance status, and cytogenetic results. METHODS: We retrospectively compared the results of 31 elderly acute myeloid leukemia patients (median age of 74 years) who were treated according to the new algorithm. RESULTS: Fifteen patients with a good performance status and no unfavorable karyotypes were treated with either intensive cytotoxic chemotherapy (<70 years, nine cases) or adapted etoposide, 6-thioguanine and idarubicine (>70 years, six cases); 16 cases with a poor performance status or unfavorable cytogenetics received supportive care only. Six patients achieved a complete remission and two achieved a partial remission after chemotherapy. There were three toxic deaths during induction, two in the adapted etoposide, 6-thioguanine and idarubicine group and one in the intensive cytotoxic chemotherapy group. The overall median survival time was 2.96 months, 1.3 months in the supportive care group, and 4.6 months in the treatment group. CONCLUSIONS: Our results illustrate the importance of treatment guidelines adapted to local resources in an attempt to improve the survival of elderly acute myeloid leukemia patients in developing countries.

Improving the outcomes of elderly patients with acute myeloid leukemia in a Brazilian University Hospital

OBJECTIVE: To evaluate the outcomes of acute myeloid leukemia patients who were older than 60 years of age at the time of diagnosis following the implementation of a treatment algorithm based on age, performance status, and cytogenetic results. METHODS: We retrospectively compared the results of 31 elderly acute myeloid leukemia patients (median age of 74 years) who were treated according to the new algorithm. RESULTS: Fifteen patients with a good performance status and no unfavorable karyotypes were treated with either intensive cytotoxic chemotherapy (<70 years, nine cases) or adapted etoposide, 6-thioguanine and idarubicine (>70 years, six cases); 16 cases with a poor performance status or unfavorable cytogenetics received supportive care only. Six patients achieved a complete remission and two achieved a partial remission after chemotherapy. There were three toxic deaths during induction, two in the adapted etoposide, 6-thioguanine and idarubicine group and one in the intensive cytotoxic chemotherapy group. The overall median survival time was 2.96 months, 1.3 months in the supportive care group, and 4.6 months in the treatment group. CONCLUSIONS: Our results illustrate the importance of treatment guidelines adapted to local resources in an attempt to improve the survival of elderly acute myeloid leukemia patients in developing countries.

Myelodysplastic syndromes: histopathology as prognostic factor

Bone marrow biopsy allows evaluation of cellularity, abnormal localization of immature precursors and fibrosis in myelodysplastic syndrome. It has been considered important to make diagnosis and prognosis of this disorder. The object of this study evaluated the influence of histopathological parameters, such as cellularity, erythroid/myeloid ratio, abnormal localization of immature precursors and marrow fibrosis, on survival of myelodysplastic syndrome patients. Forty-six patients, admitted from April 1985 to June 1998, and diagnosed as being myelodysplastic syndrome according to French-American-British criteria, were selected. There were 20 males and 26 females, with median age of 61 years. Forty-six bone marrow smears and 36 trephine biopsies were reviewed. Mean survival of hypocellular cases was 64.8 months and of hyper and normocellular cases was 31.8 months. Patients with predominance of erythroid hyperplasia had mean survival of 50.8 months, greater than those with predominance of myeloid hyperplasia (20.3 months). There was no statistical difference in survival of patients with or without abnormal localization of immature precursors and with or without marrow fibrosis. Bone marrow biopsy is a useful tool for the identification of parameters that influence prognosis in myelodysplastic syndrome. Hypocellularity and erythroid hyperplasia were correlated with longer survival while myeloid hyperplasia with poorer survival

A biópsia de medula óssea propicia a avaliação da celularidade global, dos precursores imaturos de localização anormal e de fibrose nas sídromes mielodisplásicas. O método tem sido considerado importante também para o diagnóstico e prognóstico da síndrome. O objetivo deste estudo foi o de o observar a influência de parâmetros histológicos como a celularidade, a relação eritróide mielóide, a presença de precursores imaturos de localização anormal e fibrose medular na sobrevida de pacients com a síndrome. De abril de 1985 a junho de 1998, 46 pacientes diagnosticados segundo os critérios do grupo Franco, Americano, Britânico foram estudados. A casuística era composta de 20 pacientes do sexo masculino e de 26 do sexo feminino com idade média de 61 anos. Foram revisados 46 esfregaços de aspirado de medula óssea e 36 cortes histológicos de bioópsia de medula óssea. A sobrevida média dos casos de hipocelularidade foi de 64,8 meses e dos casos que eram hiper ou normocelulares foi de 31,8 meses. Pacientes com a predominância de hiperplasia tiveram sobrevida média de 50,8 meses, que foi superior aos que apresentavam hiperplasia mielóide (20,3 meses). Não houve diferença estatística na sobrevida dos pacientes que apresentaram ou não fibrose medular. A biópsia de medula óssea deve ser considerada útil na identificação de prâmetros que influenciam no prognóstico da síndrome mielodisplásica. A hipocelularidade e a hiperplasia eritrocitária está realcionada com a sobrevida maior, enquanto a hiperplasia mielóide com a sobrevida mais curta.

WR2721 (amifostina) e radioproteçäo da medula óssea / WR2721 (amifostina) and bone marrow radioprotection

A medula óssea é bastante radiosensível e dependendo da intensidade, suas alteraçöes podem causar a morte de indivíduos expostos, pela Síndrome Aguda da Radiaçäo.Constitui-se também num tecido crítico para a interaçäo de drogas e radiaçäo, durante o tratamento de doenças malignas, às vezes, limitando tais procedimentos. No presente artigo säo abordadas as características do radioprotetor amifostina e seu papel na proteçäo da medula óssea irradiada.