The impact of the association between Val16Ala-SOD2 SNP and SOD2 immunohistochemistry expression in the prognosis of patients with esophageal cancer.

INTRODUCTION: Esophageal cancer is an extensive public health issue worldwide, warranting the search for biomarkers related to its risk and progression. Previous studies have indicated an association between Val16AlaSOD2 single nucleotide polymorphism in the gene encoding the enzyme superoxide dismutase 2 and esophageal cancer. However, further investigations are needed to clarify its role in disease risk and progression. OBJECTIVE: To investigate the role of Val16AlaSOD2-SNP in esophageal cancer progression and in the survival of patients METHODS: Tumor samples were utilized for Val16Ala-SNP genotyping, while SOD2 expression levels in tissue were assessed using immunohistochemistry. A SOD2 Val16Ala-SNP database was used to obtain information on the genotype of healthy individuals. Risk and overall survival analyzes were performed. RESULTS: The Val16Ala SNP was associated with an increased risk of esophageal cancer (RR 2.18, 95%CI 1.23-3.86), regardless of age and gender, but did not have a significant effect on patient survival. In contrast, weak SOD2 expression demonstrated a significantly associated with poor overall survival after treatment, independent of other clinicopathological variables (HR, 0.41; 95% CI, 0.22-0.79 P = 0.007). CONCLUSIONS: Val16Ala SNP was positively associated with esophageal cancer, and the expression of SOD2 was an independent prognostic marker.

Review: Manipulation of follicle development to improve fertility of cattle in timed-artificial insemination programs.

The development of an ovulatory follicle is a fundamental premise for any reproductive management program that aims to optimize fertility in cattle. Controlling follicular development comprises the synchronized emergence of a new follicular wave, selection and growth of the dominant follicle, and synchronized ovulation of a high-quality oocyte. All these follicular events, primarily driven by gonadotropin secretion, occur under a very dynamic hormonal environment. In this sense, controlling follicular development demands essentially a precise manipulation of the hormonal environment to modulate gonadotropin secretion. Furthermore, the effectiveness of hormonal manipulation strategies in the management of follicular development depends on specific particularities of each situation, which can vary widely according to genetic groups (Bos taurus vs Bos indicus), nutritional, metabolic, and reproductive status. In this regard, the constant search for the refined synchrony between the hormonal treatments and reproductive events, considering these distinctions and particularities, have provided valuable information that contributed to the development of efficient reproductive programs. This manuscript discusses the physiological bases behind the development of fine-tuned timed-artificial insemination protocols for beef and dairy cattle that resulted in great improvements in reproductive efficiency of beef and dairy herds.

Mechanical properties of platelet-rich fibrin from patients on warfarin.

Platelet-rich fibrin (PRF) has been used increasingly in oral and maxillofacial surgery in recent years. The aim of this experimental study was to perform a mechanical evaluation of PRF from patients on warfarin. PRF samples were obtained from 21 patients on warfarin (mean INR 2.30 ± 0.89) and 21 non-anticoagulated patients (control; mean INR 1.08 ± 0.07). For the patients on warfarin, two experimental groups were formed based on the PRF centrifugation time: group A, 10 min (21 samples); group B, 18 min (20 samples). Control group samples (21 samples) were centrifuged for 10 min. Mechanical properties were evaluated by axial tensile test and suture retention test with an Instron 3345 universal testing machine. Mechanical parameters were compared between the groups using the Kruskal-Wallis test and Dunn's post-hoc test. Axial tensile values were similar in all groups. In the suture retention test, significantly lower values of deformation at maximum force were observed in the experimental group: group A (107.07 ± 25.05%) and group B (104.81 ± 16.79%) versus control (118.01 ± 17.61%) (P = 0.033). Moreover, maximum force was significantly lower in group A (0.17 ± 0.05 N) than in the control group (0.20 ± 0.06 N), while it was significantly higher in group B (0.22 ± 0.07 N) than in group A (P = 0.026). In conclusion, for patients on warfarin, the centrifugation time should be increased to 18 min in order to obtain PRF with superior performance.

Smoking behavior and secondhand smoke exposure among university students in northern Portugal: Relations with knowledge on tobacco use and attitudes toward smoking.

OBJECTIVES: To assess the prevalence of active smoking and secondhand smoke (SHS) exposure among college students in the north of Portugal, and analyze the relationship between knowledge about tobacco use and attitudes toward smoking. MATERIALS AND METHODS: This a cross-sectional study with a representative sample of college students (n=840) in one university in Portugal. A validated self-reported questionnaire was administered to a proportional stratified random sample during the academic year of 2018/2019. We evaluated associations between smoking status, SHS exposure, smokers peers, knowledge and attitudes toward smoking and sociodemographic variables. RESULTS: The results showed that 20.1% of the students surveyed were current smokers (7.3% occasional smokers, 2.9% regular smokers and 9.9% daily smokers). Most current smokers started smoking before the age of 17 (61.4%) and reported never having tried to quit smoking (59.7%). Only 34.4% of students reported (almost) not having been in enclosed spaces with smokers in the past 7 days. Exposure to SHS and having smoker friends contributes to the prevalence of tobacco use. In general, students showed favorable attitudes toward smoking, especially those who are smokers, have smoking friends and are more exposed to SHS. The level of knowledge about tobacco was moderate, with a higher number of correct responses by former smokers. CONCLUSIONS: These results suggests an urgent need for socio-educational programs for counseling on smoking cessation. In addition, is also strongly recommended that, throughout academic training, students develop personal and social skills for dealing with the tobacco epidemic.

Morphometry of bovine blastocysts produced in vitro in culture media with antioxidants cysteamine or oily extract of Lippia origanoides / [Morfometria de blastocistos bovinos produzidos in vitro em meio de cultura com antioxidantes cisteamina ou extrato oleoso de Lippia origanoides]

This study aimed to evaluate the ultrastructural morphometry of bovine embryos produced in vitro grown at different concentrations of antioxidants. After in vitro maturation and fertilization, the presumptive zygotes were assigned into five treatments. T1) without the addition of any antioxidants (negative control); T2) addition of 50µM/mL cysteamine; and T3, T4 and T5) adding 2.5µg/mL, 5.0µg/mL or 10.0µg/mL of the antioxidants derived from the oily extract from Lippia origanoides, respectively. On D7 of culture, the embryos in the blastocyst stage were fixed and prepared for electron transmission microscopy. These were evaluated for the proportion of cytoplasm-to-nucleus, cytoplasm-to-mitochondria, cytoplasm-to-vacuoles, cytoplasm-to-autophagic vacuoles and cytoplasm-to-lipid droplets. Blastocysts cultured in media containing oily extract of Lippia origanoides presented morphological characteristics such as high cell:mitochondria ratio and low cell:vacuoles and cell:autophagic vacuole ratio, possibly been morphological indicators of embryonic quality. Inner cell mass (ICM) from blastocysts cultured in media without any antioxidants had the highest cell:vacuole ratio. Similar results were found in the trophectoderm (TE) cells of blastocysts from treatment 2. Embryo culture media supplemented with antioxidants derived from Lippia origanoides oil produced embryos with a higher cytoplasmic proportion of organelles, such as mitochondria. Also, treatments without any antioxidants or with the addition of cysteamine presented cytoplasmic vacuolization, a characteristic related to production of poor-quality embryos.(AU)

Este estudo teve como objetivo avaliar a morfometria ultraestrutural de embriões bovinos produzidos in vitro e cultivados em diferentes concentrações de antioxidantes. Após a maturação e a fertilização in vitro, os possíveis zigotos foram divididos em cinco tratamentos: T1) sem adição de antioxidantes (controle negativo); T2) adição de 50µM/mL de cisteamina; e T3, T4 e T5) adição de 2,5µg/mL, 5,0µg/mL ou 10,0µg/mL dos antioxidantes derivados do extrato oleoso de Lippia origanoides, respectivamente. No D7 de cultivo, os embriões em estágio de blastocisto foram fixados e preparados para microscopia eletrônica de transmissão. Estes foram avaliados para a proporção entre citoplasma e núcleo, citoplasma e mitocôndria, citoplasma e vacúolos, citoplasma e vacúolos autofágicos e citoplasma e gotículas lipídicas. Blastocistos cultivados em meio contendo extrato oleoso de Lippia origanoides apresentaram características morfológicas como alta relação célula:mitocôndria e baixa relação célula:vacúolos e célula:vacúolo autofágico, possíveis indicadores morfológicos de qualidade embrionária. A massa celular interna (MCI) de blastocistos cultivados em meio sem quaisquer antioxidantes teve a maior razão célula:vacúolo. Resultados semelhantes foram encontrados nas células do trofectoderma (TE) de blastocistos do tratamento 2. Portanto, o meio de cultivo embrionário suplementado com antioxidantes derivados do óleo de Lippia origanoides produziu embriões com maior proporção citoplasmática de organelas, como mitocôndrias. Além disso, tratamentos sem antioxidantes ou com adição de cisteamina apresentaram vacuolização citoplasmática, característica relacionada à produção de embriões de baixa qualidade.(AU)

Meningoencephalitis caused by Bovine alphaherpesvirus 5 in Pernambuco, Brazil / [Meningoencefalite causada pelo Bovine alphaherpesvirus 5 em Pernambuco, Brasil]

Objetivou-se descrever a ocorrência do Bovine alphaherpesvirus 5 (BoHV5) como causa de meningoencefalite não supurativa em bovinos do estado de Pernambuco, Brasil. Para tanto, 32 amostras de sistema nervoso embebidas em parafina foram obtidas de animais acometidos por doenças neurológicas atendidos na Clínica de Bovinos de Garanhuns da Universidade Federal Rural de Pernambuco (CBG-UFRPE), entre 2012 e 2016. As amostras foram analisadas quanto à presença do gene da glicoproteína C do BoHV5 por reação em cadeia da polimerase (PCR). Dois animais (6,25%) tiveram resultado positivo à PCR, e sua análise de sequenciamento indicou 100% de similaridade para o BoHV5. Os resultados histopatológicos desses dois animais revelaram lesões multifocais de meningoencefalite não supurativa associada à polioencefalomalácia, presença de corpúsculos de inclusão basofílicos, infiltração de células de Gitter e presença de manguitos perivasculares. A PCR se mostra uma importante ferramenta para diferenciação das infecções por BoHV5 de outras enfermidades neurológicas de bovinos, especialmente a raiva.(AU)

Tuberculosis infection in HIV vs. non-HIV patients.

OBJECTIVES: Tuberculosis (TB) is the most common opportunistic infection and cause of mortality among people living with HIV, and it is possible that it may also influence the evolution of the HIV infection. We assessed the differences between HIV-positive and -negative people infected with TB. METHODS: The present study is a cross-sectional retrospective study by electronic record revision. We included patients admitted to a tertiary hospital with a diagnosis of TB between 2011 and 2016, comparing those with HIV coinfection with non-HIV patients, according to demographic and clinical characteristics. RESULTS: This study included 591 patients, of whom 32% were HIV-coinfected. HIV-TB patients were younger, with a predominance of male gender. Considering TB risk factors, there was a higher prevalence of homelessness and intravenous drug use in the HIV group. In the non-HIV group, direct contact with other patients with TB and immunosuppression were more prevalent. Relative to TB characteristics, the HIV-coinfected group presents with a higher prevalence of disseminated disease and a higher occurrence of previous TB infection. Cancer was the most frequent cause of immunosuppression in the HIV group and the number testing positive for TB via microbiological culture was lower. Assessment of microbiological resistance and in-hospital mortality showed similar numbers in both groups. CONCLUSIONS: There are few papers comparing clinical course of TB between HIV-infected and non-infected patients. Our study differs from others in the literature as we focused on a country with middling incidence of TB and further characterized the differences between HIV-infected and non-infected patients which can contribute to the management of these patients.

Bases para um programa de controle da artrite encefalite caprina em rebanho leiteiro / [Bases for a program of control of caprine arthritis encephalite in dairy flock]

Objetivou-se avaliar um programa de controle da artrite encefalite caprina (AEC), por meio de testes diagnósticos sensíveis, separação de mãe e cria após o parto e medidas de manejo, com o intuito de formar rebanho livre do vírus. Utilizou-se um total de 47 cabritos da raça Saanen, mantidos isoladamente até o resultado dos primeiros testes de reação em cadeia de polimerase nested (PCR nested) e Western Blotting (WB), com base na coleta de sangue no momento do nascimento (M0). No PCR nested, quatro animais foram positivos, no M0, e foram eutanasiados. Posteriormente, os demais 43 cabritos foram submetidos à coleta de sangue aos 60 (M60) e 270 (M270) dias de vida para realização de novos testes de WB e PCR nested, que não detectaram animais positivos. Pode-se afirmar que a metodologia adotada neste estudo foi efetiva no controle da doença, nas fases de aleitamento e pós-aleitamento, e que a combinação do sistema de manejo, a fim de propiciar diminuição de risco de transmissão horizontal, com técnicas de diagnóstico mais apuradas, como o WB e a PCR nested, é relevante para elaboração de plano estratégico de controle da enfermidade.(AU)

We aimed to evaluate a program to control Caprine Arthritis Encephalitis (CAE), using diagnostic tests, separation of the mother and postpartum and other management measures, in order to form a free flock of the virus. We used a total of 47 Saanengoats in isolation until the results of the first nested Polymerase Chain Reaction (nested PCR) and Western Blotting (WB) tests, based on blood collection at the time of birth (M0). In the nested PCR, 4 animals were positive, at M0, and were eliminated. Later, the other 43goats were submitted to blood collection at 60 (M60) and 270 (M270) days of life to perform new tests of WB and nested PCR, which did not detect positive animals. We can affirm that the methodology adopted in this study was effective in the control of the disease, in the phase of breastfeeding and post-breastfeeding, and that the combination of the management system, which allows a reduction of risk of horizontal transmission, with more accurate diagnostic techniques, such as WB and nested PCR, is relevant for the elaboration of a strategic plan for the disease control.(AU)

Análise ultraestrutural do colágeno de feridas cutâneas de coelhos tratadas com plasma rico em plaquetas de equino / Ultrastructural analysis of the collagen of rabbit skin wounds treated with platelet-rich equine plasma

O colágeno é sintetizado e segregado no espaço extracelular e organizados em fibrilas estriadas de acordo com o tipo de tecido. Utilizaram-se 24 coelhos brancos da raça Nova Zelândia, com idade de 12 meses e com 3,0kg de peso corporal, para avaliar a porcentagem de colágeno das feridas cutâneas tratadas com plasma rico em plaquetas de equino e pomada contendo gentamicina, sulfanilamida, sulfadiazina, ureia e vitamina A. Os animais foram separados em quatro grupos de igual número e submetidos à remoção de pele na região das linhas médias dorsal torácica (feridas tratadas) e lombar (feridas controle). As feridas torácicas foram tratadas com plasma rico em plaqueta de equino e pomada contendo gentamicina, sulfanilamida, sulfadiazina, ureia e vitamina A, e as do grupo controle somente com a pomada. Dos animais do grupo I, foi coletado tecido cutâneo, para a avaliação histológica e a ultraestrutural, com três dias de pós-operatório; dos animais do grupo II, com sete dias; do grupo III, com 14 dias; e do grupo IV, com 21 dias. Decorrido o período de avaliação de cada grupo, foi coletado fragmento de pele para avaliação da porcentagem de colágeno, bem como do diâmetro e da densidade da fibrila de colágeno por microscopia eletrônica de transmissão. O tratamento com PRP de equino associado à aplicação tópica da pomada mostrou-se eficaz na maturação das fibrilas colágenas e na antecipação do processo cicatricial.(AU)

Collagen is synthesized and secreted into the extracellular space and organized into striated fibrils according to the tissue type. This study evaluated the concentration of collagen in rabbit skin wounds treated with equine platelet-rich plasma (PRP) and ointment containing gentamicin, sulfanilamide, sulfadiazine, urea, and vitamin A. Twenty-four New Zealand white rabbits aged 2 to 12 months and weighing 3.0kg were included. The animals were allocated equally into four groups and the skin was removed from the thoracic dorsal midline (treated wound) and lumbar (control wound) regions. The thoracic wounds were treated with equine PRP and ointment containing gentamicin, sulfanilamide, sulfadiazine, urea, and vitamin A, and the control group was treated with the ointment alone. For histological and ultrastructural assessment, cutaneous tissue was collected on postoperative days 3 (group I), 7 (group II), 14 (group III), and 21 (group IV). After the evaluation period, in each group, a skin fragment was collected for analysis of the collagen concentration, as well as the collagen fibril diameter and density by transmission electron microscopy. The results indicated that treatment with equine PRP combined with topical application of the ointment was effective in facilitating the maturation of collagen fibrils and the wound healing process.(AU)

Pretransplant Biopsy of Marginal Kidneys: Is It Necessary?

INTRODUCTION: Pretransplant kidney biopsy from marginal donors is used to guide the decision of whether to accept or discard organs for transplantation; however, there is controversy about this procedure, and the need for a pretransplant biopsy is still a debate. We sought to determine if histologic evaluation before implantation of marginal kidneys would influence the outcome. METHODS: A retrospective observational cohort study of marginal donor transplants at Centro Hospitalar e Universitário de Coimbra was done. From 2009 to 2016, 650 marginal kidney transplants were analyzed. We evaluated long-term graft survival in a cohort of patients who received marginal kidneys. The recipients were divided into 2 groups based on whether a pretransplant donor biopsy was performed. Continuous variables were summarized by mean and standard deviation or median and range, as applicable. Categorical variables were summarized by relative and absolute frequencies. The survival analysis was obtained and plotted using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The median age of recipients and donors were statistically different between both groups (P < .001), with the donors and the recipients being younger in the group without a pretransplant biopsy. The median cold ischemia time was higher in the biopsy group (P = .01). The survival analysis showed that graft survival didn't differ between the groups (P = .2). CONCLUSIONS: Selection of kidneys based on histological findings may not influence the graft survival and implies a higher cold ischemia time. More data are necessary to provide insight into which clinical, histologic, and biochemical parameters are necessary for decision making on kidney acceptance.

A Rare Manifestation of Tuberculosis in a Renal Transplant Patient: A Case Report.

Cutaneous lesions in the presence of fever in patients undergoing immunosuppressive therapy are a diagnostic challenge and may represent manifestations of multiple diseases, such as fungal infections, nocardiosis, lymphoproliferative diseases, zoonosis, and tuberculosis. The authors report a case of a 66-year-old white man with chronic kidney disease since 2014 (chronic pyelonephritis) who had a renal transplant in the previous 6 months. Induction therapy was performed with thymoglobulin, and his current immunosuppression scheme included tacrolimus, mycophenolate mofetil, and prednisolone. The patient had no history of pulmonary tuberculosis. The patient presented with 2 cutaneous lesions, localized on the back and abdomen, that appeared to be firm, painful, subcutaneous, erythematous nodules with an approximately 5 cm diameter overlying an infected focus and purulent material inside. The patient also had a fever and fatigue. Blood analysis showed pancytopenia with an elevation of inflammatory markers and graft dysfunction. Tissue cultures and skin biopsy with histological analysis were performed. Histopathology of the lesion showed a nonspecific inflammatory infiltrate without granulomas, and acid-fast bacillus staining was negative. Nevertheless, serum QuantiFERON testing was positive. But polymerase chain reaction finally confirmed the presence of Mycobacterium tuberculosis, which confirmed the diagnosis of cutaneous tuberculosis. A chest computed tomography scan showed a lung pattern of miliary tuberculosis. The patient was treated with multidrug tuberculosis therapy, resulting in lesion clearance after 3 weeks. Tuberculosis is a serious infection, especially in high-risk patients, such as those in an immunocompromised state. The incidence of cutaneous tuberculosis is rare, but it should be considered in patients presenting with atypical skin lesions suggestive of an underlying infectious etiology.

Efeito de diferentes tempos de exposição ao calor e de linhagens sobre o rendimento de carcaça e a composição química de peito de frangos de corte / Effect of different timing of exposure to heat and strains on the carcass yield and breast chemical composition of broiler

Investigaram-se os efeitos de diferentes tempos de exposição ao calor sobre o rendimento de carcaça, cortes e vísceras comestíveis e a composição química da carne de peito de frangos de corte de duas linhagens. Foram alojados 560 pintos de corte da linhagem Cobb 500 Slow® e 560 da Hubbard Flex® em 32 boxes. A partir do 14º dia, eles foram divididos nos ambientes térmicos: controle, uma hora, duas horas ou três horas diárias de estresse por calor. O rendimento de carcaça, peito sem osso, coxa e sobrecoxa com osso, asas, pés, fígado, moela e coração foi avaliado em seis aves de cada linhagem em cada ambiente térmico. Amostras foram obtidas para analisar matéria seca, extrato etéreo, proteína bruta e matéria mineral. O estresse cíclico por calor por até três horas diárias não influenciou o rendimento de carcaça, de peito sem osso, de coxa e sobrecoxa, de asa, de coração, de moela, de fígado e a composição química do peito. A linhagem Cobb 500 Slow® apresentou maior rendimento de peito. A Hubbard Flex® apresentou peito com maior percentual de matéria mineral e proteína. A linhagem Cobb é mais indicada à produção de peito, e a linhagem Hubbard à produção de frango inteiro.(AU)

The effects of different exposure periods under heat on the carcass yield, cuts and edible organs and breast chemical composition of broilers from two strains were investigated. Five hundred and sixty Cobb 500 Slow® and 560 Hubbard Flex® broiler chicks were housed in 32 pens and from the 14th day on, they were divided in thermal environments: control, 1 hour, 2 hours or 3 hours a day under heat stress. Carcass yield, boneless breast, thigh and drumstick with bone, wings, feet, liver, gizzard and heart were evaluated in six birds of each strain in each thermal environment. Samples were obtained to assess dry matter, ether extract, crude protein and mineral matter. The cyclic heat stress for up to three hours a day did not influence 33 the carcass yield, boneless breast, thigh and drumstick, wing, heart, gizzard, liver, and the breast chemical composition. Cobb 500 Slow® strain had higher breast yield. Hubbard Flex® had breast with higher percentage of mineral matter and protein. Cobb strain is best designed to breast production, and Hubbard is best for whole chicken production.(AU)

Technetium-99m-labeled lapachol as an imaging probe for breast tumor identification. / Lapachol marcado con tecnecio 99m como sonda de imágenes para la identificación de tumores de mama.

OBJECTIVE: Breast cancer is a health problem worldwide with high incidence and mortality rates. It is well known that the development of more sensitive and specific diagnostic methods is of great importance since an early diagnosis is essential to successfully treat tumors. Lapachol is a natural compound, belonging to the naphthoquinone group that has been widely used in traditional medicine to treat various illnesses, including cancer. The aim of this study was to evaluate technetium-99m (99mTc) labeled lapachol as an imaging probe for breast cancer identification. METHODS: To achieve this purpose, lapachol was labeled with 99mTc, radiochemical purity and in vitro stability were determined. Blood clearance, in healthy mice, and biodistribution, in 4T1 tumor-bearing mice, were also evaluated. RESULTS: Lapachol was successfully labeled with 99mTc, with high values of radiochemical yield (95.9±3.4%). In vitro stability showed that the radiolabeled complex remained stable for up to 24h, with values above 90% for both saline and plasma (95.6±3.6% and 96.4±1.7%, respectively). The radiolabeled complex decays in a biphasic manner, with a half-life of distribution and elimination equal to 3.3 and 50.0min, respectively. Biodistribution and scintigraphic images showed high uptake in organs of excretion (kidneys, liver, and intestine). It could be also noted that tumor uptake was higher than the muscle at all time points. Tumor-to-muscle ratio reaches ∼4.5 at 24h after administration. CONCLUSION: These findings suggest that 99mTc-lapachol can be a potential diagnostic agent for breast tumors.

Non-invasive imaging techniques and assessment of carotid vasa vasorum neovascularization: Promises and pitfalls.

Carotid adventitia vasa vasorum neovascularization (VVn) is associated with the initial stages of arteriosclerosis and with the formation of unstable plaque. However, techniques to accurately quantify that neovascularization in a standard, fast, non-invasive, and efficient way are still lacking. The development of such techniques holds the promise of enabling wide, inexpensive, and safe screening programs that could stratify patients and help in personalized preventive cardiovascular medicine. In this paper, we review the recent scientific literature pertaining to imaging techniques that could set the stage for the development of standard methods for quantitative assessment of atherosclerotic plaque and carotid VVn. We present and discuss the alternative imaging techniques being used in clinical practice and we review the computational developments that are contributing to speed up image analysis and interpretation. We conclude that one of the greatest upcoming challenges will be the use of machine learning techniques to develop automated methods that assist in the interpretation of images to stratify patients according to their risk.

Anti-ophidian activity of Bredemeyera floribunda Willd. (Polygalaceae) root extract on the local effects induced by Bothrops jararacussu venom

Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 µg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 µg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3′,4′-OH flavonoids are known inhibitors of phospholipases A2.

Staphylococcus Infection-Associated Glomerulonephritis in a Kidney Transplant Patient: Case Report.

BACKGROUND: Staphylococcus infection-associated glomerulonephritis is a rare cause of graft dysfunction in kidney transplant. Suspicion should be high in the setting of elevation of serum creatinine, active urinary sediment, with or without hypocomplementemia, and simultaneous Staphylococcus aureus infection. A kidney biopsy is usually diagnostic. CASE REPORT: A 56-year-old man, who received a kidney transplant in 1998, with basal serum creatinine of 1.2 mg/dL and normal urinary sediment, was admitted to our kidney transplantation unit with graft dysfunction and a urinary tract infection caused by S aureus with septicemia, treated with antibiotics, in the context of recently intensified immunosuppression for a primary immune thrombocytopenia diagnosed 3 weeks earlier. After antibiotic treatment, the patient persisted with graft dysfunction, edema, and hypertension, with a S aureus isolation in the urine culture, active urinary sediment, and low C3. A kidney biopsy was performed, showing diffuse proliferative endocapillary and mesangial glomerulonephritis, with IgA(++) and C3(++) mesangial and endocapillary deposits in immunofluorescence. The patient was treated symptomatically and maintained his regular immunosuppression. At the last follow-up, his serum creatinine value was stable at 2.5 mg/dL. CONCLUSIONS: The onset of a nephritic syndrome with a simultaneous S aureus infection should lead to suspicion of this uncommon entity, confirmed histologically. Despite its association with poor graft survival, our patient's graft survival remained stable.

Intestinal intussusception secondary to enteritis caused by Pythium insidiosum in a bitch: case report / Intussuscepção intestinal secundária à enterite causada por Pythium insidiosum em uma cadela: relato de caso

We report a case of intestinal intussusception secondary to enteritis caused by Pythium insidiosum infection in a 1-year-old mixed breed bitch that died after a 30-day history of bloody diarrhea, anorexia, weight loss, listlessness, dehydration, and pale mucous membranes. Necropsy revealed two areas of intussusception, one jejunum-jejunal and one ileum-cecum-colic. The first intussusception showed slight congestion of the intestinal loop, which was resolved by manual traction, while the second intussusception exhibited thickening, irregular yellow spots, and transmural congestion. Histologically, the jejunum-jejunal segment had ischemic lesions secondary and ileum-cecum-colic intussusception there was also necrotizing, pyogranulomatous enteritis associated with negative images of intralesional fungal hyphae that were well visualized by silver impregnation. Immunohistochemistry identified the hyphae as Pythium insidiosum. The diagnosis was made based on the histological changes and confirmed by immunohistochemistry. We can conclude that enteritis by P. insidiosum in dogs can occasionally cause intestinal intussusception and result in acute death.(AU)

Relata-se um caso de intussuscepção intestinal secundária à enterite causada por Pythium insidiosusm em uma cadela, sem raça definida, com um ano de idade, que morreu após apresentar 30 dias de diarreia sanguinolenta, anorexia, perda de peso, apatia, desidratação e mucosas pálidas. Na necropsia verificaram-se duas áreas de intussuscepções, sendo uma jejuno-jejunal e outra íleo-ceco-cólica. Na primeira havia discreta congestão, que foi desfeita pela tração manual, e na segunda observou-se espessamento segmentar, focos amarelados irregulares e congestão transmural do intestino. Microscopicamente, no segmento jejuno-jejunal observaram-se moderadas lesões isquêmicas secundárias à intussuscepção, e no segmento íleo-ceco-cólica verificou-se enterite piogranulomatosa e necrosante, segmentar, associada a imagens negativas de hifas intralesionais, impregnadas pela prata. Pela imuno-histoquímica, as hifas foram imunomarcadas para Pythium insidiosum. O diagnóstico foi realizado com base nas características microscópicas das lesões e morfotintoriais das hifas e foi confirmado pela imuno-histoquímica. De acordo com esses dados, é possível concluir que a infecção intestinal por P. insidiosum em cães pode causar intussuscepção e morte.(AU)

Fibrogenesis in Kidney Transplant: Dysfunction Progress Biomarkers.

INTRODUCTION: Fibrogenesis markers, such as alpha-actin (AA), CD163 (macrophages), and E-cadherin, have been studied as chronic kidney allograft injury (CAI) predictors, a major cause of allograft failure. OBJECTIVE: Investigate the value of these markers in predicting CAI and initiation of dialysis. MATERIALS AND METHODS: Retrospective analysis of 26 kidney allograft biopsies (from 22 patients with CAI) during 2 years, evaluating intensity and percentage of marked cells on glomeruli and tubulointerstitial compartment. At the time of the biopsy, patients were 45.5 ± 15.8 years and 4.2 years after transplant, and they had a mean glomerular filtration rate (GFR) of 25.8 ± 9.9 mL/min. From an average of 8.5 glomeruli per biopsy, there was ≤25% sclerosis in 17 cases, 26% to 50% in 5, and >50% in 4. Interstitial fibrosis or tubular atrophy affected ≤25% of cortical area in 14 cases, 26% to 50% in 8, and >50% in 2. Twelve patients started dialysis 5.8 ± 4.7 years after transplant, with an average GFR 20.9 mL/min at the time of the biopsy. RESULTS: There was a higher intensity and percentage of CD163-marked cells in the tubulointerstitial compartment in advanced interstitial fibrosis. We found an association between intensity of AA in the tubulointerstitial compartment and initiation of dialysis (P = .003) and a negative correlation between intensity of E-cadherin loss and GFR (r = -0.56, P = .012). CONCLUSIONS: In our study, intensity of tubulointerstitial AA was shown to be a predictor of initiation of dialysis, and E-cadherin loss intensity was associated to CAI progression. However, prospective and larger studies are needed to evaluate the predictive value of these markers.

Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic Correlates in a 10-year Retrospective Study.

INTRODUCTION: There is a high incidence of nephrotic proteinuria in renal transplant recipients, which is an accurate predictor of graft loss. Despite this, its histologic correlates and prognostic implications are still not well characterized. We assessed the clinical and histological correlates of kidney transplantation patients with nephrotic range proteinuria. METHODS: We have retrospectively analyzed clinical and histological data from 50 kidney transplantation biopsy specimens from 44 renal transplant recipients with nephrotic range proteinuria between 2006 and 2015. The median follow-up time was 93 months (range, 14 months to 190 months). RESULTS: The mean age of the patients was 45.2 ± 13.7 years and our cohort included 86% recipients of deceased-donor grafts. The maintenance immunosuppressive regimen included calcineurin inhibitors in 68% and mammalian target of rapamycin inhibitors in 32% of patients. The average proteinuria was 6.9 ± 3.8 g/d and 52% of patients presented with nephrotic syndrome. The main histological findings were transplant glomerulopathy (22%), de novo glomerular disease (22%), and recurrence of primary disease (22%). Tubular atrophy and interstitial fibrosis was present in 78% of the biopsy specimens. Thirty-one patients (62%) lost the graft at follow-up. There was no statistically significant difference between the histologic diagnosis nor the proteinuria levels and the outcome of the graft. CONCLUSIONS: The main causes of nephrotic range proteinuria in patients undergoing biopsy were transplant glomerulopathy, recurrence of the underlying disease, and de novo glomerulonephritis. Nephrotic range proteinuria was related to a high rate of graft loss.

Polyomavirus Nephropathy: Ten-Year Experience.

BACKGROUND: Polyomavirus nephropathy (BKVN) is an important cause of chronic allograft dysfunction (CAD). Recipient determinants (male sex, white race, and older age), deceased donation, high-dose immunosuppression, diabetes, delayed graft function (DGF), cytomegalovirus infection, and acute rejection (AR) are risk factors. Reducing immunosuppression is the best strategy in BKVN. The objective of our study was to evaluate CAD progression after therapeutic strategies in BKVN and risk factors for graft loss (GL). METHODS: Retrospective analysis of 23 biopsies, from patients with CAD and histological evidence of BKVN, conducted over a period of 10 years. Glomerular filtration rate was <30 mL/min in 16 patients at the time of the BKVN diagnosis. RESULTS: BKVN was histologically diagnosed in 23 recipients (19 men, 4 women). All patients were white, with age of 51.2 ± 12.1 years (6 patients, age >60 years), and 22 had a deceased donor. Diabetes affected 4 patients, DGF occurred in 3, cytomegalovirus infection in 2, and AR in 15. All patients were medicated with calcineurin inhibitors (CNI) (95.7% tacrolimus) and corticoids, and 16 also received an antimetabolite. One year after antimetabolite reduction/discontinuation and/or CNI reduction/switching and/or antiviral agents, graft function was decreased in 11 patients, increased/stabilized in 10, and unknown in 2. GL occurred in 9 patients. Older age (hazard ratio, 1.76; 95% confidence interval, 0.94-3.28) and DGF (hazard ratio, 2.60; 95% confidence interval, 0.54-12.64) were the main risk factors for GL. The lower GFR at the time of the BKVN diagnosis was associated with an increased risk of initiation of dialysis. CONCLUSIONS: GL occurred in 39.1% of patients with BKVN and DGF; older age and lower GFR at the time of diagnosis were important risk factors. Early diagnosis of BKVN is essential to prevent GL.