Ebselen: A Promising Repurposing Drug to Treat Infections Caused by Multidrug-Resistant Microorganisms.

Bacterial multiresistance to drugs is a rapidly growing global phenomenon. New resistance mechanisms have been described in different bacterial pathogens, threatening the effective treatment of even common infectious diseases. The problem worsens in infections associated with biofilms because, in addition to the pathogen's multiresistance, the biofilm provides a barrier that prevents antimicrobial access. Several "non-antibiotic" drugs have antimicrobial activity, even though it is not their primary therapeutic purpose. However, due to the urgent need to develop effective antimicrobials to treat diseases caused by multidrug-resistant pathogens, there has been an increase in research into "non-antibiotic" drugs to offer an alternative therapy through the so-called drug repositioning or repurposing. The prospect of new uses for existing drugs has the advantage of reducing the time and effort required to develop new compounds. Moreover, many drugs are already well characterized regarding toxicity and pharmacokinetic/pharmacodynamic properties. Ebselen has shown promise for use as a repurposing drug for antimicrobial purposes. It is a synthetic organoselenium with anti-inflammatory, antioxidant, and cytoprotective activity. A very attractive factor for using ebselen is that, in addition to potent antimicrobial activity, its minimum inhibitory concentration is very low for microbial pathogens.

Nutrient intake is a predictor of lung function in obese asthmatic adolescents undergoing interdisciplinary therapy.

Asthma-obesity is a multifactorial disease with specific asthma phenotypes that aggravate due to overweight and an unbalanced diet. Furthermore, obese asthmatic patients are corticotherapy-resistant. Therefore, the aims of the present study were to evaluate the effects of an interdisciplinary intervention on food consumption, body composition, lung function and adipokines in asthmatic and non-asthmatic obese adolescents and to investigate the influence of nutrients on lung function. Obese non-asthmatic (n 42) and obese asthmatic (n 21) adolescents of both sexes were enrolled in the present study. Food intake, adipokine levels, body composition, asthma symptoms and lung function were assessed across the study. After the intervention of 1 year, there was a reduction (P ≤ 0·01) in BMI, body fat percentage, visceral and subcutaneous fat and an increase (P ≤ 0·01) in lean mass and all lung function variables in both groups, except the relation between forced expiratory volume in 1 s and forced vital capacity (FEV1:FVC) in non-asthmatic patients. Moreover, both groups decreased lipid and cholesterol consumption (P ≤ 0·01). The highest energy consumption (ß = -0·021) was associated with lower values of FVC. Similarly, carbohydrate consumption (ß = -0·06) and cholesterol were negative predictors (ß = -0·05) in FEV1:FVC. However, the consumption of Ca (ß = 0·01), fibres (ß = 1·34) and vitamin A (ß = 0·01) were positive predictors of FEV1:FVC. Asthma-obesity interdisciplinary treatment promoted an improvement on food consumption and lung function in adolescents and demonstrated that the consumption of nutrients influenced an increase in lung function.

Sub-Inhibitory Concentrations of Rifampicin Strongly Stimulated Biofilm Production in S. aureus.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus is an important pathogen and a frequent cause of infections associated with biofilm production in implantable medical devices. Biofilm production can be induced by sub-inhibitory concentrations (sub-MICs) of certain antibiotics, but few studies have researched this occurrence in S. aureus. In this study, we investigated the effect of sub-MICs of rifampicin and minocycline on biofilm production by five clinical and five non-clinical S. aureus isolates. METHODS: Microtiter Plate assay and Congo Red Agar Test were used to analyze the biofilm production. The biofilm composition was evaluated by the detachment assay with sodium metaperiodate and proteinase K. RESULTS: Rifampicin sub-MICs induced very high biofilm formation in seven isolates that were non-producers in Tryptic Soy Broth. In one producer isolate, the biofilm formation level was not affected by sub-MICs of this drug. Sub-MICs of minocycline did not induce biofilm production in all isolates tested and in two producer isolates, instead, MIC/2 and MIC/4 inhibited biofilm production. The results of the drugs in combination were similar to those with rifampicin alone. The biofilm matrix was identified as polysaccharide, except for one producer isolate, classified as proteinaceous. Polysaccharide biofilm producer isolates, when grown on Congo Red Agar without sucrose, but with sub-MICs of rifampicin, showed results in agreement with those obtained in Microtiter Plate Test. CONCLUSION: The high biofilm production induced by sub-MICs of rifampicin has potential clinical relevance, because this is one of the drugs commonly used in the impregnation of catheters. In addition, it is used adjunctively to treat certain S. aureus infections.

Heavy metal tolerance (Cr, Ag and Hg) in bacteria isolated from sewage

Samples of sewage from a university hospital and a chemistry technical school were analysed for the percentage of bacterial tolerance to chromium (Cr), silver (Ag) and mercury (Hg). Additionally, we investigated the effect of these metals on pigmentation and on some enzymatic activities of the metal tolerant strains isolated, as well as antimicrobial resistance in some metal tolerant Enterobacteriaceae strains. Tolerance to Cr was observed mainly in Gram positive bacteria while in the case of Ag and Hg the tolerant bacteria were predominately Gram negative. Hg was the metal for which the percentage of tolerance was significantly higher, especially in samples from the hospital sewage (4.1%). Mercury also had the most discernible effect on color of the colonies. Considering the effect of metals on the respiratory enzymes, one strain of Ag-tolerantBacillus sp. and one of Hg-tolerant P. aeruginosa were unable to produce oxidase in the presence of Ag and Hg, respectively, while the expression of gelatinase was largely inhibited in various Gram negative strains (66% by Cr). Drug resistance in Hg-tolerant Enterobacteriaceae strains isolated from the university hospital sewage was greater than 80%, with prevalence of multiple resistance, while the Ag-tolerant strains from the same source showed about 34% of resistance, with the predominance of mono-resistance. Our results showed that, despite the ability of metal tolerant strains to survive and grow in the presence of these elements, the interactions with these metals may result in metabolic or phisiological changes in this group of bacteria.

The impact of pregnancy on the HIV-1-specific T cell function in infected pregnant women.

Evidences indicate that pregnancy can alter the Ag-specific T-cell responses. This work aims to evaluate the impact of pregnancy on the in vitro HIV-1-specific immune response. As compared with non-pregnant patients, lower T-cell proliferation and higher IL-10 production were observed in T-cell cultures from pregnant patients following addition of either mitogens or HIV-1 antigens. In our system, the main T lymphocyte subset involved in producing IL-10 was CD4(+)FoxP3(-). Depletion of CD4(+) cells elevated TNF-α and IFN-γ production. Interestingly, the in vitro HIV-1 replication was lower in cell cultures from pregnant patients, and it was inversely related to IL-10 production. In these cultures, the neutralization of IL-10 by anti-IL-10 mAb elevated TNF-α release and HIV-1 replication. In conclusion, our results reveal that pregnancy-related events should favor the expansion of HIV-1-specific IL-10-secreting CD4(+) T-cells in HIV-1-infected women, which should, in the scenario of pregnancy, help to reduce the risk of vertical HIV-1 transmission.

Heavy metal tolerance (Cr, Ag AND Hg) in bacteria isolated from sewage.

Samples of sewage from a university hospital and a chemistry technical school were analysed for the percentage of bacterial tolerance to chromium (Cr), silver (Ag) and mercury (Hg). Additionally, we investigated the effect of these metals on pigmentation and on some enzymatic activities of the metal tolerant strains isolated, as well as antimicrobial resistance in some metal tolerant Enterobacteriaceae strains. Tolerance to Cr was observed mainly in Gram positive bacteria while in the case of Ag and Hg the tolerant bacteria were predominately Gram negative. Hg was the metal for which the percentage of tolerance was significantly higher, especially in samples from the hospital sewage (4.1%). Mercury also had the most discernible effect on color of the colonies. Considering the effect of metals on the respiratory enzymes, one strain of Ag-tolerant Bacillus sp. and one of Hg-tolerant P. aeruginosa were unable to produce oxidase in the presence of Ag and Hg, respectively, while the expression of gelatinase was largely inhibited in various Gram negative strains (66% by Cr). Drug resistance in Hg-tolerant Enterobacteriaceae strains isolated from the university hospital sewage was greater than 80%, with prevalence of multiple resistance, while the Ag-tolerant strains from the same source showed about 34% of resistance, with the predominance of mono-resistance. Our results showed that, despite the ability of metal tolerant strains to survive and grow in the presence of these elements, the interactions with these metals may result in metabolic or phisiological changes in this group of bacteria.

Enhanced Th17 phenotype in uninfected neonates born from viremic HIV-1-infected pregnant women.

Our objective was to evaluate the in vitro functional profile of T cells from uninfected neonates born from HIV-1-infected pregnant women who controlled (G1) or not (G2) the virus replication. We demonstrated that the lymphoproliferation of T cell to polyclonal activators was higher in the G2 as compared with G1. Nevertheless, no detectable proliferative response was observed in response to HIV-1 antigens in both neonate groups. Cytokine dosage in the supernatants of these polyclonally activated T cell cultures demonstrated that, while IL-10 was the dominant cytokine produced in G1, Th17-related cytokines were significantly higher in G2 neonates. The higher Th17 phenotype tendency in G2 was related to high production of IL-23 by lipopolysaccharide-activated monocyte-derived dendritic cells from these neonates. Our results demonstrated immunological disorders in uninfected neonates born from viremic HIV-1-infected mothers that can help to explain why some of these children have elevated risk of clinical morbidity and mortality due to pathological hypersensitivity.

IL-10-secreting T cells from HIV-infected pregnant women downregulate HIV-1 replication: effect enhanced by antiretroviral treatment.

OBJECTIVE: This study aimed to evaluate the impact of pregnancy-related immune events on the HIV-1 replication and to analyze their relationship with the risk of vertical transmission. METHODS: The peripheral blood from HIV-1-infected pregnant women who controlled (G1) or not controlled (G2) their plasma viral load was drawn, and the plasma and the T cells were obtained. The T-cell cultures were activated in vitro with anti-CD3 and anti-CD28, and the proliferation and cytokine production profile were evaluated after 3 days of incubation. The in-vitro HIV-1 replication was measured in culture supernatants in the seventh day following stimulation. The cytokines were also analyzed in the plasma. RESULTS: Our results demonstrated a lower T-cell proliferation and a lower interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma production in polyclonally activated T-cell cultures from G1 patients, when compared with G2. Furthermore, high levels of interleukin-10 were produced both systemically and by activated T-cell cultures from G1 patients. Interestingly, the neutralization of endogenous interleukin-10 by anti-interleukin-10 monoclonal antibody elevated both the inflammatory cytokines' release and the HIV-1 replication in the polyclonally activated T-cell cultures from G1 patients. Additionally, the maternal antiretroviral treatment significantly enhanced the systemic interleukin-10 production. Finally, the higher systemic interleukin-10 levels were inversely correlated with vertical virus transmission risk. CONCLUSION: These results indicate that a high tendency of pregnant women to produce interleukin-10 can help them control the HIV-1 replication, and this can reduce the risk of vertical transmission. Furthermore, our data suggest a role for maternal antiretroviral treatment in enhancing this phenomenon.

Altered immunological reactivity in HIV-1-exposed uninfected neonates.

This work aimed to evaluate immune events in HIV-1-exposed uninfected neonates born from mothers who control (G1) or not (G2) the plasma viral load, using unexposed neonates as controls. Cord blood from each neonate was collected, plasma and mononuclear cells were separated and the lymphoproliferation and cytokine pattern were evaluated. The results demonstrated that the in vitro lymphoproliferation induced by polyclonal activators was higher in the G2 neonates. Nevertheless, no cell culture responded to poll synthetic HIV-1 envelope peptides. The cytokine dosage in the plasma and supernatants of polyclonally-activated cultures demonstrated that, while IL-4 and IL-10 were the dominant cytokines produced in G1 and control groups, IFN-gamma and TNF-alpha were significantly higher in G2 neonates. Systemic levels of IL-10 observed among the G1 neonates were higher in those born from anti-retroviral treated mothers. In summary, our results indicate an altered immune responsiveness in neonates exposed in utero to HIV and support the role of maternal anti-retroviral treatment to attenuate it.

Interleucina 10 produzida por gestantes infectadas pelo HIV-1 diminui a replicaþÒo viral: efeito amplificado pela terapia anti-retroviral / Interleukin 10 produced by HIV-1 infected pregnant women reduces viral replication: effect enhanced by anti-retroviral therapy

Desde o inicio da epidemia da infecþÒo pelo HIV, o número de mulheres adultas jovens infectadas vem aumentando consideravelmente, fato esse que tem grande impacto na transmissÒo vertical do virus. Nesse sentido poucos trabalhos tÞm avaliado o impacto das citoninas maternas sobre a dinOmica da replicaþao viral durante a gestaþÒao. Estudos recentes desenvolvidos pelo nosso grupo demostraram uma relþÒó inversa entre a carga viral plasmática e a capacidade de gestantes infectadas pelo HIV-1 em produzir IL-10. Adicionalmente , a neutralizaþÒo desta citocina aumentou a capacidade replicativa do virus em culturas de células contendo linfocitos T ativados. O estudo aqui reportado teve como objetivo investigar os eventos moleculares relacionados O aþÒo anti-HIV-1 da IL-10 e o impscto da terapia antiretroviral sobre este fen¶meno. Nossos resultados demonstram que a capacidade da IL-10 em reduzir a secreþÒo de IL-1 e TNF-a, ambas envolvidas em favorecer a replicaþÒo do virus in vitro. Interessantemente, o tratamento anti-retroviral das gestantes elevou a produþÒo sistÞmica da IL-10. Esses resultados sugerem que a IL-10 produzida por gestantes infectadas pelo HIV-1 reduz a replicaþÒo do virus, e que esse efeito parece ser potencializado pelo tratamento anti-retroviral materno.(AU)

Interleucina 10 produzida por gestantes infectadas pelo HIV-1 diminui a replicação viral: efeito amplificado pela terapia anti-retroviral / Interleukin 10 produced by HIV-1 infected pregnant women reduces viral replication: effect enhanced by anti-retroviral therapy

Desde o inicio da epidemia da infecção pelo HIV, o número de mulheres adultas jovens infectadas vem aumentando consideravelmente, fato esse que tem grande impacto na transmissão vertical do virus. Nesse sentido poucos trabalhos tèm avaliado o impacto das citoninas maternas sobre a dinàmica da replicaçao viral durante a gestaçãao. Estudos recentes desenvolvidos pelo nosso grupo demostraram uma relçãó inversa entre a carga viral plasmática e a capacidade de gestantes infectadas pelo HIV-1 em produzir IL-10. Adicionalmente , a neutralização desta citocina aumentou a capacidade replicativa do virus em culturas de células contendo linfocitos T ativados. O estudo aqui reportado teve como objetivo investigar os eventos moleculares relacionados à ação anti-HIV-1 da IL-10 e o impscto da terapia antiretroviral sobre este fenômeno. Nossos resultados demonstram que a capacidade da IL-10 em reduzir a secreção de IL-1 e TNF-a, ambas envolvidas em favorecer a replicação do virus in vitro. Interessantemente, o tratamento anti-retroviral das gestantes elevou a produção sistèmica da IL-10. Esses resultados sugerem que a IL-10 produzida por gestantes infectadas pelo HIV-1 reduz a replicação do virus, e que esse efeito parece ser potencializado pelo tratamento anti-retroviral materno.

Cardiovascular autonomic response to food ingestion in patients with gastritis: a comparison between Helicobacter pylori-positive and -negative patients.

BACKGROUND: Feeding evokes a cardiovascular response associated to an increased sympathetic drive. The role of the parasympathetic component in this regard is less clear. Improvement of postprandial vasovagal complaints after Helicobacter pylori eradication in three cases led us to assess autonomic response to feeding in H. pylori-positive patients in search for an exacerbated parasympathetic response. MATERIAL AND METHODS: Patients with mild or moderate chronic histologic gastritis were studied. Subjects with the same diagnosis but testing negative for H. pylori were used as controls. Noninvasive cardiovascular tests were applied before and after feeding. RESULTS: On sympathetic tests, standing postprandial blood pressure was lower than preprandially in 5/12 H. pylori-positive patients and in 0/9 controls, p = .045. Resting postprandial BP on handgrip test was significantly lower than preprandially only in H. pylori-positive patients (71 +/- 8 versus 76 +/- 6 mmHg, p = .0068). Regarding parasympathetic tests, the 4-s unloaded exercise revealed greater initial heart rate response to unloaded cycling after feeding than preprandially again only in H. pylori-positive patients (1.40 +/- 0.20 versus 1.33 +/- 0.17, p = .0195). On tests influenced by both branches of the autonomic system, a difference was seen in the chronotropic response to handgrip. Postprandial heart rate on effort of H. pylori-positive patients was not higher than preprandially in contrast to controls [intervals between 2 consecutive R waves on electrocardiogram (R-R intervals) of 666 +/- 39 versus 685 +/- 62 ms, p = .0195], suggesting blunted sympathetic activation in the former. CONCLUSION: Supporting the observations that motivate the study, our findings indicate blunted sympathetic reactivity and exacerbated vagal response to feeding in H. pylori-positive patients.

Primary columellar angiosarcoma: a case report.

Angiosarcoma of the head and neck, a rare malignancy, is associated with a high degree of invasiveness and poor survival. A high level of suspicion followed by histopathologic and immunohistochemical studies is warranted in order to arrive at a well-timed and accurate diagnosis. We report the case of a 56-year-old man who developed an unusually small neoplasm in the nasal columella. Rapid diagnosis allowed for simple treatment with surgical excision, a rare circumstance because most of these tumors require extensive surgery. Close long-term follow-up of patients with angiosarcoma of the head and neck is vitally important.

Interação de metais pesados com bactérias isoladas de águas de esgoto / Heavy brass interaction with isolated bacterias of waters sewer

Amostras de águas de esgoto foram estudadas quanto à freqüência de u.f.c./mL, em meios de cultura acrescidos de diferentes concentrações de sais de metais pesados, e quanto a alguns aspectos referentes à interação bactérias-metais. Não foram observadas diferenças significativas na tolerância ao cobre, à prta e ao cromo entre as amostragens de esgoto de um hospital universitário (HU) e de uma escola técnica de química (ETQ). Porém, freqüências significativamente mais elevadas foram expressas para o mercúrio pela amostragem bacteriana do HU, bem como para o cromo pela amostragem de esgoto do tanque de tratamento aeróbio de uma indústria química (IQ). A resistência a antimicrobianos em enterobactérias do esgoto da EQ tolerantes a metais foi discreta, enquanto nas estirpes Hg e Cu-tolerantes do esgoto hospitalar os percentuais foram elevados (82,1 por cento e 61,0 por cento, respectivamente), com o predomínio de multirresistência (60,7 por cento) nas primeiras, sugerindo ocorrência de associação não fortuita entre os fenômenos de Hg-tolerância e antibiótico-resistência. Os tratamento de choque pelo frio em amostras de esgoto não protegeram a microbiota contra os efeitos tóxicos de Ag, Cr e Hg, enquanto a exposição da 20 ug/mL de CuSO4, ao contrário, elevou o percentual médio de u.f.c/mL, em relação aos controles. Algumas atividades enzimáticas (oxidase, gelatinase e redução do nitrato) mostraram-se passíveis de serem afetadas em cultivos na presença de metais, embora sem prejuízo da viabilidade bacteriana. Os íons dos metais Cr, Hg e Ag mostraram-se também capazes de afetar a pigmentação de algumas cepas.A maioria das amostras Hg-tolerantes testadas mostrou-se capaz de utilizar fenol e benzoato como única fonte de carbono, enquanto nas amostras Cr-tolerantes esse comportamento foi mais discreto. Na presença de 5 ug/mL, algumas amostras degradaram feno (24h) e benzoato (48h). Entre as amostras Cr-tolerantes, destaca-se uma cepa de B. cepacia (JT50) que degradou fenol na presença de até 200 ug/mL de K2Cr2O7. Análises de filtraedos do cultivo dessa amostra em Meio Mínimo com fenos e K2Cr2O7 indicaram ausência de processos de bioacumulação/biossorção, bem como conversão de Cr/179+ a Cr6+.

Antimicrobial and mercury chloride resistance in vibrio isolates from marine fish of the southeastern brazilian region

Foram analisadas 199 amostras de víbrios isolados de trato intestinal de peixes marinhos, representados pela tainha (Mugil sp.) e corvina (Micropogon sp.) capturados em águas de baía e da orla litorânea da cidade do Rio de Janeiro, compreendendo V. anguillarum (52), V.haveyi (41), V. proteolyticus (39), V. campbelli (13) V. alginlyticus (10), V. splendidus (8), V. marinus (2), V.logei (1), V. parahaemolyticus (1) e Vibrio sp. - halofílico (32). O antibiograma, para oito drogas e o resistograma ao cloreto de mercúrio apontaram a taxa de 96,4 por cento para a presença de marcadores, congregando os percentuais de 77,0 por cento para a resistência antimicrobiana e de 21,8 por cento, para aquela associada ao Hg. A multirresistência (>ou = 3 marcos) foi significativa (p<0,05) na ordem de 71,0 por cento, bem como a incidência de fenótipo Hgr nas cepas multirresistentes (64,2 por cento), englobando apenas aquelas advindas do pescado corvina. Os marcos Su e Ap, além de Sm mostraram-se em destaque no cômputo gera e tambem no conjunto de amostras resistentes ao Hg. Indistintamente de espécie, a totalidade das culturas revelou a presença de pelo menos um marcador, excetuando V.parahaemolyticus. A conjugaçäo de 28 amostras de víbrios com cepas de Escherichia coli K12 revelou a transferência de marcadores em 71,4 por cento dos experimentos. Transconjugantes para Su, Sm, Km e Ap foram observados a partir das culturas doadoras de V.anguillarum e V.harveyi. Näo foram isoladas colônias transconjugantes para o marco Hg. Os resultados indicam a associaçäo entre esses dois marcadores nas amostras de víbrios, possivelmente, em consequência do processo de evoluçäo dos marcadores de resistência no bioma marinho

Hiperplasia linforreticular reativa e benigna do estômago, tipo nodular: apresentaçäo de dois casos / Reactive and benign lymphoreticular hyperplasia of the stomach, nodular type: presentation of 2 cases

Relatam-se dois casos de hiperplasia linforreticular reativa e benigna do estômago, tipo nodular, e enfatizam-se os principais aspectos clínicos, radiológicos, endoscópicos e histopatológicos. Acentua-se que a correlaçäo endoscópica e histopatológica é fundamental para o diagnóstico dessa entidade

Metástases cutâneas de adenocarcinoma de duodeno: relato de um caso / Cutaneous metastasis of duodenal adenocarcinoma: report of a case

Apresenta-se um caso de metástases cutâneas de adenocarcinoma duodenal, com ampla documentaçäo, enfatizando-se a raridade dessas lesöes nesse tipo de tumor