Paracoccidioides brasiliensis pancreatic destruction in Calomys callosus experimentally infected

<p>Abstract</p> <p>Background</p> <p>The wild rodent <it>Calomys callosus </it>is notably resistant to <it>Trypanosoma cruzi </it>infection. In order to better characterize this animal model for experimental infections, we inoculated <it>C</it>. <it>callosus </it>intraperitoneally with <it>Paracoccidioides brasiliensis</it>, a thermally dimorphic fungus that causes a chronic disease with severe granuloma formation in the mouse and humans. The dissemination of <it>P. brasiliensis </it>cells through the lungs, liver, pancreas, and spleen was assessed by histological analysis.</p> <p>Results</p> <p>The animals were susceptible to infection and showed a granulomatous reaction. <it>C. callosus </it>presented peritonitis characterized by the presence of exudates containing a large number of yeast cells. Extensive accumulation of yeast cells with intense destruction of the parenchyma was observed in the pancreas, which reduced the glucose levels of infected animals. These lesions were regressive in the liver, spleen, and lungs until complete recovery. The role of estrogen during <it>C. callosus </it>infection with <it>P. brasiliensis </it>was addressed by infecting ovariectomized animals. It was observed a reduced inflammatory response as well as reduced extension of tissue damage. Removal of ovaries reestablished the normal glucose levels during infection.</p> <p>Conclusion</p> <p>Taken together, the results presented here reveal the pancreas as being an important organ for the persistence of <it>P. brasiliensis </it>during infection of <it>C. callosus </it>and that estrogen plays an important role in the susceptibility of the animals to this pathogen.</p

In Vitro Antimicrobial Susceptibility of Mycobacterium massiliense Recovered from Wound Samples of Patients Submitted to Arthroscopic and Laparoscopic Surgeries

Testing of rapidly growing species of mycobacteria (RGM) against antibacterial agents has been shown to have some clinical utility. This work establishes the MICs of seven antimicrobial agents following the guidelines set forth by the Clinical and Laboratory Standards Institute (CLSI) against eighteen isolates of Mycobacterium massiliense recovered from wound samples of patients submitted to minimally invasive surgery such as arthroscopy and laparoscopy. The isolates showed susceptibility to amikacin (MIC90 = 4 μg/mL) and clarithromycin (MIC90 < 1 μg/mL) but resistance to ciprofloxacin (MIC90 > 16 μg/mL), doxycycline (MIC90 > 32 μg/mL), sulfamethoxazole (MIC90 > 128 μg/mL), and tobramycin (MIC90 = 32 μg/mL), and intermediate profile to cefoxitin (MIC90 = 64 μg/mL). Therefore, we suggest that the antimicrobial susceptibilities of any clinically significant RGM isolate should be performed

The activity of a Hexameric M17 Metallo-Aminopeptidase is associated with survival of Mycobacterium tuberculosis

Mycobacterium tuberculosis is one of the most prevalent human pathogens causing millions of deaths in the last years. Moreover, tuberculosis (TB) treatment has become increasingly challenging owing to the emergence of multidrug resistant M. tuberculosis strains. Thus, there is an immediate need for the development of new anti-TB drugs. Proteases appear to be a promising approach and may lead to shortened and effective treatments for drug-resistant TB. Although the M. tuberculosis genome predicts more than 100 genes encoding proteases, only a few of them have been studied. Aminopeptidases constitute a set of proteases that selectively remove amino acids from the N-terminus of proteins and peptides and may act as virulence factors, essential for survival and maintenance of many microbial pathogens. Here, we characterized a leucine aminopeptidase of M. tuberculosis (MtLAP) as a cytosolic oligomeric metalloaminopeptidase. Molecular and enzymatic properties lead us to classify MtLAP as a typical member of the peptidase family M17. Furthermore, the aminopeptidase inhibitor bestatin strongly inhibited MtLAP activity, in vitro M. tuberculosis growth and macrophage infection. In murine model of TB, bestatin treatment reduced bacterial burden and lesion in the lungs of infected mice. Thus, our data suggest that MtLAP participates in important metabolic pathways of M. tuberculosis necessary for its survival and virulence and consequently may be a promising target for new anti-TB drugs

Determinação da imunogenicidade de proteínas de amostra de Mycobacterium bovis isolada de bovinos no estado de Goiás, Brasil

Bovine tuberculosis, persists in several countries as a threat to health of the herds despite the efforts given to the control and eradication of the disease. In order to detect immunogenic proteins with a potential to be used in a bovine tuberculosis diagnosis test, serum samples obtained from reactors and no reactors to intradermal tuberculin test, were evaluated for reactivity to Mycobacterium bovis antigens from a bacilli originated in Goiás – Brazil. The proteins immunogenicity from M. bovis was obtained by Western blot according to the molecular weight profile. The majority of the PPD positive bovine (67.92%) recognized a protein with 26kDa, suggesting the use of this protein in a serological test for bovine tuberculosis.A tuberculose bovina persiste em vários países como ameaça à saúde dos rebanhos apesar dos esforços dispensados ao controle e erradicação da doença. O objetivo deste trabalho foi elucidar quais seriam as proteínas mais imunogênicas e, portanto, com potencial de serem utilizadas em novos testes de diagnóstico bovino da tuberculose. Amostras de soro obtidas de animais reatores e não reatores ao teste de tuberculinização intradérmica foram avaliados quanto ao reconhecimento de antígenos proteicos de Mycobacterium bovis, isolado de bovino no Estado de Goiás. A imunogenicidade das proteínas de M. bovis foi obtida por meio da técnica de Western blot. A maioria dos bovinos PPD positivos (67,92%) reconheceu o antígeno de 26kDa, sugerindo o seu uso potencial no desenvolvimento de um ensaio sorológico para a tuberculose bovina

Non-disulfide-Bridge peptide 5.5 from the Scorpion Hadrurus gertschi Inhibits the growth of mycobacterium abscessus subsp. massiliense

Multi-drug resistant microorganisms have been a growing concern during the last decades due to their contribution in mortality rates worldwide. Antimicrobial peptides (AMPs) are broad spectrum antimicrobial agents that display potent microbicidal activity against a wide range of microorganisms. AMPs generally have a rapid mode of action that reduces the risk of resistance developing among pathogens. In this study, an AMP derived from scorpion venom, NDBP-5.5, was evaluated against Mycobacterium abscessus subsp. massiliense, a rapidly growing and emerging pathogen associated with healthcare infections. The minimal bactericidal concentration of NDBP-5.5, AMP quantity necessary to stop bacteria visible growth, against M. abscessus subsp. massiliense was 200 μM, a concentration that did not induce hemolysis of human red blood cells. The therapeutic index was 3.05 indicating a drug with low toxicity and therefore good clinical potential. Treatment of infected macrophages with NDBP-5.5 or clarithromycin presented similar results, reducing the bacterial load. M. abscessus subsp. massiliense-infected animals showed a decrease in the bacterial load of up to 70% when treated with NDBP-5.5. These results revealed the effective microbicidal activity of NDBP-5.5 against Mycobacterium, indicating its potential as an antimycobacterial agent

Positive Effects of Extra-Virgin Olive Oil Supplementation and DietBra on Inflammation and Glycemic Profiles in Adults With Type 2 Diabetes and Class II/III Obesity: A Randomized Clinical Trial

Background: Evidence on the effects of dietary interventions on inflammatory markers in individuals with obesity and type 2 diabetes mellitus (T2DM) is scarce. Our study evaluated the effects of extra-virgin olive oil alone and in combination with a traditional Brazilian diet on inflammatory markers and glycemic profiles in adults with both T2DM and class II/III obesity. Methods: Adults aged 18-64 years with T2DM and class II/III obesity were randomized into two intervention groups: 1) extra-virgin olive oil only and 2) extra-virgin olive oil + a traditional Brazilian diet (OliveOil+DietBra). Data on sociodemographic characteristics, lifestyle, anthropometry, biochemical markers and inflammatory markers were collected. The primary outcomes were glycemic parameters and inflammatory markers. The body mass index (BMI) and weight were the secondary outcomes. Results: Forty individuals with T2DM and class II/III obesity were enrolled, and 34 (85%) completed the intervention course. The intake of olive oil was 37.88 ± 12.50 mL/day in the olive oil group and 37.71 ± 12.23 mL/day in the OliveOil+DietBra group, with no significant difference between groups (p = 0.484). Compared to the olive oil only group, the OliveOil+DietBra group had significantly lower levels of fasting insulin (p = 0.047) at the end of the intervention, whereas the other glycemic parameters were not altered. In the OliveOil+DietBra group, serum levels of inflammatory cytokines, IL-1α (p = 0.006) and adiponectin (p = 0.049) were lower and those of TNFα were higher (p = 0.037). There was a significant reduction in BMI and weight compared to the baseline values in the OliveOil+DietBra group (p = 0.015). Conclusions: The intervention with OliveOil+DietBra effectively decreased the levels of fasting insulin, IL-1α and adiponectin, suggesting its beneficial role in improving the inflammatory profiles and fasting insulin levels in adults with class II/III obesity and T2DM. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT02463435

Procena in vitro aktivacije proizvodnje azot oksida kao odgovor bovinih epitelnih ćelija endometrijuma i vagine i mononuklearnih krvnih ćelija na Mycoplasma bovis, Mycoplasma bovigenitalium i Ureaplasma diversum

Genital mycoplasmosis is a condition present in bovine production systems, and the most important agents involved are Mycoplasma bovis, Mycoplasma bovigenitalium and Ureaplasma diversum. Some aspects of their pathogenesis remain unclear. This study was designed in order to evaluate their ability to stimulate mononuclear cells from the endometrium, vagina and peripheral blood of cycling and healthy cows to produce nitric oxide (NO). Cellular cultures of endometrial, vaginal and peripheral blood cells from 33 healthy cows were cultivated with Mycoplasma bovis, Mycoplasma bovigenitalium and Ureaplasma diversum originated from the 4th passage in culture broth and the NO production was measured by the Greiss reaction. Confi rmation of the presence of mononuclear cells and of the agents during and after the NO assay was done by Giemsa stained smears and further cultivation and detection by PCR reaction. Mononuclear cells from all samples produced NO. Mycoplasma bovigenitalium stimulated higher NO production than the others (p<0.05). Endometrial cells produced less NO than vaginal or blood cultured cells. In conclusion, it seems that Mycoplasma bovis, Mycoplasma bovigenitalium, and Ureaplasma diversum are able to activate mononuclear cells and induce the production of NO, thus suggesting that this pathway is elicited in response to the primary infection by these agents. More studies are necessary to verify why these agents remain in the bovine reproductive tract for long periods and how they reassume deleterious effects.Genitalna mikoplazmoza je stanje koje može biti prisutno u reproduktivnom sistemu goveda, a najznačajniji agensi koji je izazivaju su Mycoplasma bovis, Mycoplasma bovigenitalium i Ureaplasma diversum. Neki od aspekata patogeneze nisu još uvek u potpunosti razjašnjeni. Ova studija je kreirana kako bi se procenila njihova sposobnost stimulisanja mononuklearnih ć elija iz endometrijuma, vagine i periferne krvi krava u ciklusu i zdravih krava da proizvode azotni oksid (NO). Ć elijske kulture ć elija endometrijuma, vagine i periferne krvi 33 zdrave krave uzgajane su sa Mycoplasma bovis, Mycoplasma bovigenitalium i Ureaplasma diversum proisteklim iz 4 pasaže u bujonu, a proizvodnja NO merena je Greiss reakcijom. Potvrda prisustva mononuklearnih ć elija, kao i infektivnih agenasa tokom i posle određivanja NO, urađena je Giemsa bojenjem na razmazima, kao i daljom kultivacijom i detekcijom PCR reakcijom. Mononuklearne ć elije iz svih uzoraka proizvodile su NO. Mycoplasma bovigenitalium stimulisala je već u proizvodnju NO od ostalih (

Resposta inflamatória e deposição de colágeno após implante intramuscular com polimetilmetacrilato em camundongos Balb/c

O preenchimento de tecidos com partículas tem sido largamente utilizado, entretanto, é necessário estudar suas possíveis reações adversas. Este estudo avaliou a resposta inflamatória e deposição de colágeno após implante intramuscular de polimetilmetacrilato (PMMA) em camundongos BALB/c. Implantou-se 100 ìl de PMMA na pata direita e, posteriormente, realizou-se a pesagem dos músculos e coletou-se tecido para análise histopatológica e imunohistoquímica. Na morfometria encontrou-se microesferas de 10,9 a 50 mm. Houve diferença na pesagem dos músculos

Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals

AbstractBiomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV−) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV− individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV+ individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC=0.96 for HIV− TB, 0.95 for HIV+ TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB

Soroepidemiologia de Neospora Caninum e Toxoplasma Gondii em bovinos da raça curraleiro curraleiro cattle breed health status for neosporosis and toxoplasmosis.

RESUMO: Este estudo comparou a soroprevalência de N. caninum e T. gondii em bovinos Curraleiros ao de outras raças bovinas (Nelore, Girolando, Guzerá e Caracu). Foram utilizadas 119 fêmeas bovinas adultas provenientes de quatro propriedades localizadas nos estados de Goiás e Tocantins e na divisa entre Goiás, Minas Gerais e Bahia. Animais soropositivos para N. caninum foram encontrados em todas as propriedades e o número de Curraleiros reagentes foi significativamente maior em relação aos bovinos Guzerá e Nelore. Também foram identificados anticorpos anti-T. gondii nos animais em todas as propriedades. A prevalência de soropositivos para T. gondii foi semelhante entre Curraleiros e bovinos das raças Nelore, Girolando e Guzerá; entretanto, foi significativamente maior em relação à raça Caracu. ABSTRACT: This study compared the health status of Curraleiro cattle and other breeds (Nellore, Girolando, Guzera, and Caracu) for toxoplasmosis and neosporosis screening against anti-Neospora caninum and anti-Toxoplasma gondii antibodies, respectively. We used 119 female bovines of Curraleiro, Guzera, Nellore, Caracu, and Girolando breeds from four farms in Goias and Tocantins states and in the border of Goias, Minas Gerais, and Bahia states. All the farms had seropositive bovines for N. caninum. The number of seropositive Curraleiro cattle was significantly higher than the number of Guzera and Nellore cattle. Also, antibodies against toxoplasmosis were found in animals from all properties. There was no significant difference between the number of seropositive Curraleiro cattle and the breeds Nellore, Girolando, and Guzerá; however, it was significantly higher than the number of seropositive animals of Caracu breed