Cytotoxic, genotoxic, and oxidative stress-inducing effect of an l-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cells.

Hepatocellular carcinoma incidence rates have increased worldwide, which encouraged the development of new chemotherapeutic drugs. l-Amino acid oxidases from snake venoms are cytotoxic towards human tumor cells in in vitro monoculture systems, which do not simulate the tumor microenvironment. We examined the antitumor potential of BjussuLAAO-II, an l-amino acid oxidase from Bothrops jararacussu venom, in hepatocarcinoma cells (HepG2) in monoculture and co-culture with human umbilical vein endothelial cells (HUVEC) in vitro. All the concentrations tested (0.25-5.00 µg/mL) were cytotoxic (MTT and clonogenic survival assays) towards HepG2 and HUVEC cells in monoculture, and increased oxidative stress by 2',7'-dichlorofluorescin diacetate fluorescence assay. Only 1.00 and 5.00 µg/mL exerted these effects in HepG2 cells co-cultured with HUVEC cells, and were genotoxic (comet assay) to HUVEC cells in monoculture. BjussuLAAO-II at 5.00 µg/mL induced DNA, but not chromosomal damage (micronucleus assay) in HepG2 cells in mono- and co-culture. The cytotoxicity and genotoxicity was more pronounced in monoculture, indicating that the tumor microenvironment influences the cellular response. BjussuLAAO-II caused cell death and DNA damage in HepG2 cells in vitro by inducing oxidative stress. Therefore, BjussuLAAO-II is a promising molecule for the development of new antitumor drugs.

Immunomodulation of allergic response in children and adolescents: What we can learn from lymphatic filarial infection.

BACKGROUND: Although it is well known that allergic diseases involve a strong Th2 immune response, with production of high levels of specific IgE allergen, knowledge on the association between filarial infection and allergies, among paediatric patients is scarce. OBJECTIVE: To evaluate the allergic response patterns in cases of filarial infection by comparing peripheral eosinophils, total IgE levels, immediate hypersensitivity and cytokine levels in children and adolescents in Brazil. METHODS: This was an exploratory study with three groups: (I) with filarial infection and without allergic diseases; (II) without filarial infection and with allergic diseases; and (III) without filarial infection and without allergic diseases. The prick test and specific IgE tests for aeroallergens were performed using five antigens. Peripheral eosinophils and total IgE were also evaluated. IL-4 and IL-5 were determined using whole-blood culture stimulated by three antigens. RESULTS: Eosinophilia and elevated levels of total IgE (≥400IU/dl) were observed in all groups. The prick test was positive in 56.6% of the cases. Group I presented hypersensitive responses similar to the allergic disease groups. In the whole-blood culture stimulated by Dermatophagoides pteronyssinus, average IL-4 production did not differ significantly among the groups, but IL5 production resulting from stimulation was greater in the allergic disease groups (p<0.05). CONCLUSIONS: The allergic response pattern in group with filarial infection was similar to that of the groups with and without allergic diseases, but the response to IL-5 in the culture stimulated by D. pteronyssinus was an exclusive characteristic of the allergic group.

Prevalence and factors associated with erectile dysfunction in patients with chronic kidney disease on conservative treatment.

Population with chronic kidney disease (CKD) has had many problems, and some of these have arisen from sexual disorders. The present study intends to determine the prevalence and the associated factors with erectile dysfunction (ED) among patients with CKD on conservative treatment (CKDCT). This transversal study was conducted from May 2013 to December 2015. The tools used were: medical records and the International Index of Erectile Function. Data were analyzed by univariate and multivariate logistic regression analysis. Among 245 patients that have participated of this study, ED was present in 71.02% and it was severe in 36.73%. Age greater than 50 years, body mass index lower than 25, diabetes mellitus, stages IV/V of CKD, cardiac conduction disturbances, benign prostatic hyperplasia, smoking, alcohol use, albumin <3.5 g per 100 ml and creatinine clearance between 15 and 29 ml min-1 per 1.73 m2 were associated with ED. Time of CKD was the only variable associated with ED independent of the presence of other factors. ED prevalence in patients with CKDCT is high and it is severe in more than half of them. Several factors are associated with ED in this population but the principal one is the time of CKD.

Conjunctival flora, Schirmer's tear test, intraocular pressure, and conjunctival cytology in neotropical primates from Salvador, Brazil.

BACKGROUND: This study aimed to establish reference values for selected ophthalmic diagnostic tests in healthy neotropical primates from Salvador, Brazil. METHODS: A total of 73 intact adults, including Callithrix jacchus (n = 31), Callithrix penicillata (n = 8), Cebus sp. (n = 22), and Cebus xanthosternos (n = 9) were used to evaluate the normal conjunctival bacterial flora. Cebus xanthosternos (n = 12) were used to evaluate tear production with Schirmer's tear test (STT), intraocular pressure (IOP), and conjunctival cytology. RESULTS: For all animals evaluated, Gram-positive bacteria were predominant. Results of the diagnostic tests in Cebus xanthosternos were as follows: STT: 14.92 ± 5.46 mm/minutes, IOP: 19.62 ± 4.57 mmHg, and conjunctival cytology revealed intermediate squamous epithelial cells in great quantities. CONCLUSIONS: These ophthalmic reference values will be particularly useful to diagnose discrete or unusual pathological changes in the neotropical primates eye.

Virucidal evaluation of sodium dichloroisocyanurate formulation against nucleopolyhedroviruses of silkworm / Avaliação antiviral do formulado de sódio dicloroisocianurato contra o nucleopoliedrovírus do bicho-da-seda

This study evaluated the effectiveness of a disinfectant with low corrosive action and which is not toxic to the environment, the sodium dichloroisocyanurate formulation, on the Bombyx mori nucleopolyhedrovirus (BmNPV). For this, 5th-instar B. mori silkworm larvae were divided into four experimental groups of 4 replicates with 15 larvae each, totalling 60 larvae per group. The groups were fed with mulberry (Morus sp.) leaf discs containing: BmNPV treated with the disinfectant, untreated BmNPV, only the disinfectant, and water (control). The results showed that the disinfectant does not inactivate the BmNPV and also exerts a negative effect on the insect"s resistance.

O estudo avaliou a eficiência de um desinfetante que apresenta baixa ação corrosiva e que não é tóxico ao meio ambiente, o formulado de sódio dicloroisocianurato, sobre o nucleopoliedrovírus Bombyx mori (BmNPV). Para tanto, lagartas do bicho-da-seda, B. mori, de 5º instar foram divididas em quatro grupos experimentais, 4 repetições com 15 lagartas cada, totalizando 60 lagartas por grupo. Os grupos foram alimentados com discos foliares de amoreira (Morus sp.) contendo: o BmNPV tratado com o desinfetante (solução 1); o BmNPV não tratado (solução 2); apenas o desinfetante (solução 3); e água (solução 4, controle). Os resultados mostraram que o desinfetante não inativa o BmNPV e também exerce efeito negativo na resistência do inseto.

Neutralization of pharmacological and toxic activities of Bothrops jararacussu snake venom and isolated myotoxins by Serjania erecta methanolic extract and its fractions

Most of the snakebites recorded in Brazil are caused by the Bothrops genus. Given that the local tissue damage caused by this genus cannot be treated by antivenom therapy, numerous studies are focusing on supplementary alternatives, such as the use of medicinal plants. Serjania erecta has already demonstrated anti-inflammatory, antiseptic and healing properties. In the current study, the aerial parts of S. erecta were extracted with methanol, then submitted to chromatographic fractionation on a Sephadex LH20 column and eluted with methanol, which resulted in four main fractions. The crude extract and fractions neutralized the toxic activities of Bothrops jararacussu snake venom and isolated myotoxins (BthTX-I and II). Results showed that phospholipase A2, fibrinogenolytic, myotoxic and hemorrhagic activities were inhibited by the extract. Moreover, the myotoxic and edematous activities induced by BthTX-I, and phospholipase A2 activity induced by BthTX-II, were inhibited by the extract of S. erecta and its fraction. The clotting time on bovine plasma was significantly prolonged by the inhibitory action of fractions SF3 and SF4. This extract is a promising source of natural inhibitors, such as flavonoids and tannins, which act by forming complexes with metal ions and proteins, inhibiting the action of serineproteases, metalloproteases and phospholipases A2.

Antiophidian properties of plant extracts against Lachesis muta venom

Snakebites comprise a serious health problem in several countries due to their global incidence, which exceeds 2.5 million per year, and the elevated number of victim fatalities. To counteract envenomations, antivenoms have been used regularly for more than a century. Apart from side effects including anaphylactic reactions, antivenoms are not able to efficiently neutralize local tissue damage, which contributes to increasing the severity and morbidity observed in patients. This fact, in turn, may be responsible for economic hardship, particularly in rural populations of developing countries. In the present work, we evaluated the antiophidian properties of 12 Brazilian plant extracts against the hemolytic, coagulant, hemorrhagic and proteolytic effects of Lachesis muta venom. Taken together, our data revealed that most of these aqueous products were capable of inhibiting those activities at different levels, except for Sapindus saponaria extract. In contrast, Stryphnodendron barbatiman extract completely neutralized all the analyzed biological activities. Thus, we may conclude that Brazilian flora may also be useful against L. muta accidents.

Antifungal activity of volatile constituents of Eugenia dysenterica leaf oil.

The essential oil from the hydrodistillation of Eugenia dysenterica leaves consisted mainly of beta-caryophyllene and alpha-humulene as the major sesquiterpene, while limonene and alpha-thujene were the major monoterpene hydrocarbons. The main oxygenated mono and sesquiterpene constituents were alpha-terpineol and beta-caryophyllene oxide, respectively. The oil was investigated against eight strains of Candida albicans, 35 strains of Cryptococcus neoformans var. neoformans, and two C. neoformans var. gattii isolated from HIV-infected individuals with candidosis or cryptococcal meningitis using the agar dilution method. Based on the minimal inhibitory concentration (MIC) values, the most significant results were obtained against Cryptococcus strains. It was observed that 22 strains were inhibited at a concentration of 250 microg/ml, whereas four exhibited potent inhibition with MIC values below 125 microg/ml against 10(6) UFC/ml organisms. We found MICs > or = 3.12 microg/ml for 91.6, 50 and 30% of all Cryptococcus strains in relation of amphotericin B, fluconazole and itraconazole, respectively.

[Cryptococcus neoformans isolated from patients with AIDS]. / Cryptococcus neoformans isolados de pacientes com AIDS.

Cryptococcosis is considered the most frequent fungal systemic opportunist infection in patients with AIDS. C. neoformans var. neoformans infects the patients with AIDS more often than C. neoformans var. gattii which has been rarely isolated from patients with AIDS. Even in endemic regions of C. neoformans var. gattii, the variety of neoformans is still the most common agent diagnosed in cryptococcosis of patients with AIDS. Cerebrospinal fluid (CSF) from fifty patients with neurocryptococcosis associated with AIDS were studied. The fungi were isolated in agar Sabouraud medium, and were identified by microscopic and macroscopic examination by agar Sabouraud, agar niger and Christensen's urea medium. The variety was determined based on a color characteristic reaction on glycine-L-canavanina-bromothymol blue agar. From all of the fifty patients' cerebrospinal fluid (CSF) we were able to recover C. neoformans. The isolates were identified as C. neoformans var. neoformans in 47 patients and as C. neoformans var. gattii. in the 3 remaining patients. These findings suggest that both varieties, gattii and neoformans, are agents of neurocryptococcosis in patients with AIDS.

[The etiology and epidemiology of dermatophytoses in Goiânia, GO, Brazil]. / Etiologia e epidemiologia das dermatofitoses em Goiânia, GO, Brasil.

Dermatophytoses are superficial infections that may lead to lesions of keratinized tissues, like skin, hair and nails. A total of 6068 individuals from Goiânia, GO, with suspected dermatophytic lesions were examined over a period of five years (1993-1997) in order to determine the incidence and etiology of dermatophytosis. Material collected from different body parts was submitted to direct microscopic examination using KOH, cultured in Sabouraud agar and microscopically examined for colony morphology, with the identification of 1595 dermatophytes. Trichophyton rubrum (37.4%), T. mentagrophytes (36.4%) and Microsporum canis (16%) were the species most frequently isolated. Dermatophytes were more frequently found producing lesions in the feet (30.5%), inguinal and crural regions (17.8%) and glabrous body regions (15.5%). The distribution of the different infected body sites was determined in terms of the respective etiologic agents found. Better hygiene conditions and an early diagnosis are the most important tools to control and reduce the incidence of dermatophytosis in Goiânia, GO.

Primary malignant rhabdoid tumor of the cerebellum.

Malignant rhabdoid tumor (MRT) is a recently described variety of childhood renal neoplasm. MRT arising primarily in the central nervous system (CNS) is still a rather unfamiliar pathological entity and is frequently misdiagnosed as medulloblastoma or primitive neuroectodermal tumor (PNET). We describe a 7-month-old boy who harbored a CNS-MRT that originated within the IV ventricle and invaded the brain stem and the cerebellar hemispheres. After an initial documented good response to chemotherapy the tumor recurred locally 9 months after operation. We discuss clinical and histopathological features distinguishing between PNET/medulloblastoma and MRTs. Current literature on MRT of the CNS is briefly reviewed.

Hearing loss from combined exposures among petroleum refinery workers.

Workers from a refinery (n = 438) were interviewed, had their hearing tested and had their exposures to noise and solvents assessed. Measurements suggested that most exposures to noise and solvents were within exposure limits recommended by international agencies; however, the prevalence for hearing loss within the exposed groups ranged from 42 to 50%, significantly exceeding the 15-30% prevalence observed for unexposed groups. The adjusted odds ratio estimates for hearing loss were 2.4 times greater for groups from aromatics and paraffins (95% CI 1.0-5.7), 3 times greater for the maintenance group (95% CI 1.3-6.9) and 1.8 times greater for the group from shipping (95% CI 0.6-4.9), when compared to unexposed workers from the warehouse and health clinic. The results of acoustic reflex decay tests suggest a retrocochlear or central auditory pathway involvement in the losses observed in certain job categories. These findings indicate that factors in addition to noise ought to be considered when investigating and preventing occupational hearing loss.

The child with a mass on its head: diagnostic and surgical strategies.

A series of 65 pediatric patients with scalp or calvarial masses is reported on. The majority of children presented with a disfiguring or painful mass on the head. Clinical findings suggested the correct diagnosis in 39/65 cases, skull radiographs in 46/65, and CT in 49/65. Taking the combined results of clinical and radiological studies, 54/65 of the lesions were accurately diagnosed. Tumor excision was curative in 43 of 48 patients who were operated on. Most scalp and calvarial neoplasms were benign; only 5/65 children harboured a malignant lesion. There was no mortality related to surgery in the series. Surgical intervention seems to be indicated in most cases, both for diagnosis and for treatment.