Minerais séricos, características morfométricas ósseas e deposição de minerais ósseos de frangos de corte alimentados com dieta com inclusão de bentonita / Serum minerals, bone morphometric characteristics and deposition of bone minerals from broilers fed diet containing bentonite

O objetivo deste trabalho foi avaliar a concentração sérica de cálcio, cloretos, ferro, fósforo e magnésio, as características morfométricas ósseas e a deposição de cálcio e fósforo nas tíbias de frangos de corte recebendo dieta com zero, 0,25 ou 0,50% de bentonita. Um ensaio foi conduzido com 288 frangos de corte de 14 a 21 dias de idade, submetidos a três dietas experimentais: sem inclusão (0,0); com inclusão de 0,25 e com inclusão de 0,50% do adsorvente bentonita. Não foram observadas diferenças (P>0,05) no desempenho das aves, nos níveis séricos de cálcio, cloretos, ferro e magnésio, no entanto os níveis de fósforo foram reduzidos (P<0,05) nas aves que ingeriram dieta com 0,50% de bentonita. Em relação às tíbias, observou-se redução (P<0,05) na matéria mineral (g e %) e no teor de cálcio com a inclusão de 0,50% de bentonita. Houve redução (P<0,05) nos níveis de fósforo das tíbias com a inclusão de 0,25 e 0,50% de bentonita. Conclui-se que a inclusão de até 0,50% do adsorvente de micotoxinas bentonita na dieta de frangos de corte não altera o desempenho zootécnico das aves. A inclusão de 0,25% de bentonita, na dieta de frangos de corte, não altera a concentração dos minerais séricos e a deposição de minerais nas tíbias, entretanto a inclusão de 0,5% reduz os níveis séricos de fósforo, o teor de matéria mineral e a concentração de cálcio e fósforo ósseos, sem afetar as características morfométricas ósseas.(AU)

The aim of this study was to evaluate performance, serum concentration of calcium, chloride, iron, magnesium, phosphorus, and bone characteristics, ash, calcium, and phosphorus in tibias of broilers receiving diet with zero, 0.25 or 0.50% of bentonite. No differences were found on performance of poultry, on serum mineral calcium, chloride, iron, magnesium, however phosphorus levels of broilers fed on diets containing 0.5% bentonite was reduced. With respect to tibia, reduction was observed on mineral matter (g and %) and calcium levels with inclusion of 0.50% bentonite, and reduction on phosphorus levels with inclusion of 0.25 or 0.50% of bentonite on diet. We conclude that the inclusion of up to 0.50% of mycotoxin adsorbent bentonite in diet of broiler does not change broiler performance. The inclusion of 0.25% of bentonite in diet of broiler does not change serum mineral concentration and mineral deposition; however, the inclusion of 0.5% decrease serum levels of phosphorus, the content of bone mineral matter, with not effects on bone morphometric characteristics.(AU)

Diseño de un programa de análisis de peligros y puntos críticos control (HACCP) para la producción de toxoide tetánico / Design of a program of hazard analysis and critical control point (HACCP) for production of Tetanus Toxoid

El toxoide tetánico es una neurotoxina modificada que induce la formación de una antitoxina protectora contra la enfermedad denominada tétanos. Este antígeno es obtenido a partir de procesos fermentativos con la bacteria anaerobia Clostridium tetani y es utilizado para la formulación de vacunas simples y combinadas inactivadas. Con el propósito de atender a las recomendaciones y regulaciones de la Organización Mundial de la Salud (OMS), el objetivo de este trabajo fue diseñar un Programa de Análisis de Peligros y Puntos Críticos de Control (HACCP) en la producción del antígeno Toxoide Tetánico, desde la recepción de la cepa certificada en el área de producción hasta el almacenamiento del toxoide tetánico purificado. Para ello, inicialmente se evaluó el cumplimiento de los prerequisitos (BPM, POES, BPL). Posteriormente, se procedió al diseño del plan HACCP mediante la ejecución de las 5 tareas preliminares y la aplicación de los 7 principios, conforme a la metodología descrita por la OMS. A partir del análisis de peligros en todas las etapas del proceso de producción del toxoide tetánico se identificaron 3 puntos críticos de control: detoxificación, filtración estéril final y almacenamiento de toxoide tetánico purificado. Se establecieron los límites críticos, los procedimientos de vigilancia, las acciones correctivas, los procedimientos de verificación y de documentación. La propuesta tiene como fin garantizar la calidad e inocuidad del producto elaborado, la protección del personal involucrado en el proceso y del medio ambiente con miras a la obtención de la certificación como laboratorio productor de vacunas

Tetanus toxoid is a modified neurotoxin that induces the formation of protective antitoxin of the disease called tetanus. This antigen is obtained from fermentation processes with anaerobic bacteria Clostridium tetani and it is used to formulate simple and combined inactivated vaccines. In order to meet the recommendations and regulations of World Health Organization (WHO), the aim of this work was to design a Program of Hazard Analysis and Critical Control Points (HACCP) in the production of antigen Tetanus Toxoid, starting from the receipt of the certified strain in the production area through the storage of purified tetanus toxoid. For this, initially fulfilling the prerequisites (GMP, SSOP and GLP) was evaluated. Subsequently, we proceeded to design HACCP plan by running 5 preliminary tasks and application of the 7 principles, according to the methodology described by WHO. From the hazard analysis at all stages of the production process of tetanus toxoid three critical control points were identified: detoxification, final sterile filtration and storage of purified tetanus toxoid. Critical limits, monitoring procedures, corrective actions, verification and documentation procedures were established. The proposal aims to assure the quality and safety of the final product, the protection of personnel involved in the process and the environment, with a view to obtaining certification as a vaccine production laboratory

Evaluation of Potency on Diphtheria and Tetanus Toxoid for Adult Vaccines by In Vivo Toxin Neutralization Assay Using National Reference Standards

OBJECTIVES: Vaccinations against diphtheria and tetanus are essential in providing immunity against these bacterial infections. The potency of diphtheria and tetanus toxoid vaccines can be measured using the in vivo toxin neutralization assay. The limit of potency of this assay was determined only for children. Therefore, we assessed the potency of adult vaccines using this assay to identify the feasibility of limit for adult vaccines. METHODS: Fifteen lots of tetanus-reduced diphtheria and tetanus-diphtheria-acellular pertussis vaccines were used. In vivo toxin neutralization and lethal challenge assays were conducted on each vaccine to calculate the potencies of the toxoids. National reference standards for toxins and antitoxins were used for in vivo toxin neutralization assay. RESULTS: All 15 lots satisfied the limits of potency for lethal challenge assay. The potency of diphtheria and tetanus toxoids exceeded 1 and 8 units/mL, respectively, for in vivo toxin neutralization assay. CONCLUSION: Although additional studies are required for new assays and limits, the current level of potency for adult vaccines as determined by in vivo toxin neutralization assay, was demonstrated in this study. Such efforts to improve assays are expected to promote the development of diphtheria and tetanus vaccines for adults and to contribute to vaccine self-sufficiency.

Quality of horse F(ab)2 antitoxins and antirabies immunoglobulins: protein content and anticomplementary activity

Background Among other applications, immunotherapy is used for the post-exposure treatment and/or prophylaxis of important infectious diseases, such as botulism, diphtheria, tetanus and rabies. The effectiveness of serum therapy is widely proven, but improvements on the immunoglobulin purification process and on the quality control are necessary to reduce the amount of protein aggregates. These may trigger adverse reactions in patients by activating the complement system and inducing the generation of anaphylatoxins. Herein, we used immunochemical methods to predict the quality of horse F(ab)2 anti-botulinum AB, anti-diphtheric, antitetanic and anti-rabies immunoglobulins, in terms of amount of proteins and protein aggregates. Methods Samples were submitted to protein quantification, SDS-PAGE, Western blot analysis and molecular exclusion chromatography. The anticomplementary activity was determined in vitro by detecting the production of C5a/C5a desArg, the most potent anaphylatoxin. Data were analyzed by one-way ANOVA followed by Tukey's post-test, and differences were considered statistically significant when p 0.05. Results Horse F(ab)2 antitoxins and anti-rabies immunoglobulin preparations presented different amounts of protein. SDS-PAGE and Western blot analyses revealed the presence of protein aggregates, non-immunoglobulin contaminants and, unexpectedly, IgG whole molecules in the samples, indicating the non-complete digestion of immunoglobulins. The chromatographic profiles of antitoxins and anti-rabies immunoglobulins allowed to estimate the percentage of contaminants and aggregates in the samples. Although protein aggregates were present, the samples were not able to induce the generation of C5a/C5a desArg in vitro, indicating that they probably contain acceptable levels of aggregates...

Perfil de segurança dos soros heterólogos produzidos pelo Instituto Butantan, São Paulo-SP, no período de 2012 a 2015 / Safety profile of heterologous serum produced by the Butantan Institute, in São Paulo-SP, Brazil, from 2012 to 2015 / Perfil de seguridad de los sueros heterólogos producidos por el Instituto Butantan, São Paulo-SP, Brasil, en el período de 2012 al 2015

Resumo OBJETIVO: descrever o perfil de segurança dos soros heterólogos produzidos pelo Instituto Butantan (IB) de São Paulo-SP, Brasil. MÉTODOS: estudo descritivo dos relatos de eventos adversos (EA) pós-exposição aos soros produzidos pelo IB, codificados pela terminologia do Dicionário Médico para Atividades Regulatórias (MedDRA), notificados espontaneamente ao IB entre 2012 e 2015. RESULTADOS: foram notificados 52 usuários com algum evento adverso relacionado, principalmente, aos soros antibotrópico (n=11), antidiftérico (n=9) e antiofídico não especificado (n=9); observaram-se, em média, 3,2 EA por indivíduo; dos 173 EA notificados, 63,0% eram esperados por serem eventos descritos em bula; os EA mais notificados foram categorizados como afecções dos tecidos cutâneos e subcutâneos (30,6%); houve seis óbitos temporalmente relacionados ao uso de soros, porém essa associação foi descartada. CONCLUSÃO: no período estudado, os soros produzidos pelo IB não apresentaram alteração em seu perfil de segurança, já que os EA relatados eram esperados conforme informação descrita em bula.

Abstract OBJECTIVE: to describe the safety profile of the heterologous serum produced by the Butantan Institute (BI) of São Paulo-SP, Brazil. METHODS: a descriptive study of adverse events (AEs) post-exposure to serum produced by the BI, encoded in the medical terminology of the Medical Dictionary for Regulatory Activities (MedDRA), and spontaneously reported to BI from 2012 to 2015. RESULTS: 52 individuals reported AEs, mainly related to Bothrops antivenom (n=11), diphtheria antitoxin (n=9) and unspecified snakebite serum (n=9); a mean of 3.2 AEs per individual was observed; among the total of 173 AEs, 63.0% were expected considering that they were described in the package insert; most of them were classified as skin and subcutaneous tissue disorders (30.6%); there were six deaths temporally related to the use of serum, but this association was discarded. CONCLUSION: in the studied period, the serum produced by the BI had no changes in their safety profiles, considering that the AEs were expected, according to the information previously described in the package insert.

Resumen OBJETIVO: describir el perfil de seguridad de los sueros heterólogos producidos por el Instituto Butantan (IB) de São Paulo-SP, Brasil. MÉTODOS: estudio descriptivo de los informes de eventos adversos (EAs) post-exposición a los sueros del IB y codificados según el Diccionario Médico para Actividades Regulatorias (MedDRA). RESULTADOS: 52 usuarios presentaron EAs relacionados con los sueros antibotrópico (n=11), antidiftérico (n=9) y antiofídico no especificado (n=9); se observó, en los EAs, 3,2 de media por persona; de los 173 EAs reportados, 63,0% fueron "esperados", ya que figuran descritos en la bula farmacológica; los EAs más reportados fueron los trastornos de piel y tejido subcutáneo (30,6%); hubo seis muertes, pero se descartó la asociación con el uso de suero. CONCLUSIÓN: durante el período de estudio, los sueros del IB no mostraron ningún cambio en su perfil de seguridad, ya que los EAs reportados eran esperados conforme información descrita en la bula.

Antiendotoxin effect of Jinhuaqingre capsules / 浙江大学学报·医学版

To investigate the anti-pyretic and anti-endotoxin effect of Chinese herb medicine Jinhuaqingre capsules.Thirty healthy male New Zealand rabbits with lipopolysaccharide-induced fever were divided into 5 groups (6 rabbits in each): animals in model group were given normal saline by gavage, animals in positive control group were given aspirin (0.2 g/kg), and animals in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0 or 1.5 g/kg, respectively. The changes in body temperature of rabbits were observed. Fifty healthy Kunming mice were divided into 5 groups (10 mice in each): mice in model group were given normal saline by gavage, mice in positive control group were given aspirin (0.2 g/kg), and those in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0, 1.5 g/kg, respectively. Matrix coloration method was used to detect the degradation rate of endotoxin in mice.The body temperature in rabbits of high and medium dose Jinhuaqingre capsule groups declined significantly 60 min after drug administration, and the temperature of high-dose group returned to the baseline after 300 min; while the body temperature of low-dose group started to decline at 180 min after drug administration. The endotoxin degradation rates in mice of high, medium and low dose groups was (56.73±3.12)%, (47.23±1.77)% and (21.08±2.30)% at 30 min after drug administration; those were (82.76±1.00)%, (64.75±1.77)% and (38.21±1.57)% at 60 min after drug administration, respectively.Chinese herb medicine Jinhuanigre capsules have anti-pyretic and anti-endotoxin effects, which may provide a new option for the treatment of heat-toxin syndrome.

The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii

Although analysis of toxin-antitoxin (TA) systems can be instructive, to date, there is no information on the prevalence and identity of TA systems based on a large panel of Acinetobacter baumannii clinical isolates. The aim of the current study was to screen for functional TA systems among clinical isolates of A. baumannii and to identify the systems’ locations. For this purpose, we screened 85 A. baumannii isolates collected from different clinical sources for the presence of the mazEF, relBE and higBA TA genes. The results revealed that the genes coding for the mazEF TA system were commonly present in all clinical isolates of A. baumannii. Reverse transcriptase-polymerase chain reaction analysis showed that transcripts were produced in the clinical isolates. Our findings showed that TA genes are prevalent, harboured by chromosomes and transcribed within A. baumannii. Hence, activation of the toxin proteins in the mazEF TA system should be investigated further as an effective antibacterial strategy against this bacterium.

Kinetics of epsilon antitoxin antibodies in different strategies for active immunization of lambs against enterotoxaemia / Cinética dos anticorpos antitoxina epsilon em diferentes estratégias de imunização ativa em cordeiros contra a enterotoxemia

Enterotoxaemia, a common disease that affects domestic small ruminants, is mainly caused by the epsilon toxin of Clostridium perfringens type D. The present study tested four distinct immunization protocols to evaluate humoral response in lambs, a progeny of non-vaccinated sheep during gestation. Twenty-four lambs were randomly allocated into four groups according to age (7, 15, 30 and 45 days), receiving the first dose of epsilon toxoid commercial vaccine against clostridiosis with booster after 30 days post vaccination. Indirect ELISA was performed after the first vaccine dose and booster to evaluate the immune response of the lambs. Results showed that for the four protocols tested all lambs presented serum title considered protective (≥0.2UI/ml epsilon antitoxin antibodies) and also showed that the anticipation of primovaccination of lambs against enterotoxaemia conferred serum title considered protective allowing the optimization of mass vaccination of lambs.

Enterotoxemia, uma das mais comuns enfermidades que acomete os pequenos ruminantes domésticos, é causada principalmente pela toxina épsilon de Clostridium perfringens tipo D. O presente estudo avaliou a resposta humoral conferida por quatro protocolos distintos de primovacinação na progênie de ovelhas não vacinadas durante a gestação. Vinte e quatro cordeiros foram aleatoriamente divididos em quatro grupos de acordo com a idade (dias) que receberam a primeira dose da vacina comercial contra clostridiose contendo toxóide epsilon na sua formulação. Todos os cordeiros foram vacinados aos 7, 15, 30 ou 45 dias de idade e receberam um reforço da dose 30 dias após a vacinação. A avaliação sorológica dos cordeiros pelo teste de ELISA indireto foi realizada por ocasião da administração da primeira dose da vacina. Os resultados elucidaram não haver comprometimento da resposta imune de cordeiros vacinados tanto aos 7, 15, 30 ou 45 dias de idade associada ao reforço da dose 30 dias após, demonstrando assim que a antecipação da primeira vacinação conferiu proteção aos cordeiros contra a enterotoxemia, permitindo otimizar o planejamento da vacinação em massa dos cordeiros.

Antitoxin treatment for liver abscess caused by Clostridium perfringens

No abstract available.

Effect of biotherapeutics on antitoxin IgG in experimentally induced Clostridium difficile infection.

Purpose: Recurrent diarrhoea after successful treatment of primary Clostridium difficile associated disease (CDAD) occurs due to bowel flora alterations and failure to mount an effective antibody response. Apart from antibiotics, risk factors include immunosuppressive and acid-suppressive drug administration. Biotherapeutics such as probiotic and epidermal growth factor (EGF) may offer potential effective therapy for CDAD. Materials and Methods: The effect of biotherapeutics in mounting an antibody response against C. difficile toxins was studied in BALB/c mice challenged with C. difficile after pre-treatment with ampicillin, lansoprazole or cyclosporin. Sera from sacrificed animals were estimated for antitoxin IgG by enzyme linked immunosorbent assay. Results: Antitoxin IgG was significantly higher (P<0.05) in C. difficile challenged groups compared to unchallenged controls, but insignificant (P>0.05) in animals in which C. difficile was given after pre-treatment with cyclosporin compared to those without any pre-treatment, or pre-treatment with antibiotic or lansoprazole. In inter-subgroup comparisons also significant anomaly in production of antitoxin IgG was found. The antitoxin IgG levels were raised in animals administered C. difficile after pre-treatment with ampicillin, but lower in animals administered cyclosporin. High levels of antitoxin IgG were also found in the serum samples of animals receiving lansoprazole and C. difficile. Conclusions: Probiotics showed their beneficial effect by boosting the immune response as seen by production of antitoxin IgG. Oral administration of EGF did not affect the immune response to C. difficile toxins as significant increase was not observed in the serum antitoxin IgG levels in any of the groups investigated.

Surto familiar de botulismo no estado do Ceará: relato de caso / Familiar outbreak of botulism at Ceará state, Brazil: case report

Relato de surto familiar de botulismo por intoxicação alimentar, envolvendo um óbito, onde foram encontradas lacunas no preenchimento do prontuário. O objetivo foi descrever a patologia chamando a atenção dos profissionais de saúde para o fornecimento adequado de informações relevantes para a investigação epidemiológica de doenças de notificação compulsória.

Report of a family outbreak of botulism food poisoning involving a death, where gaps in the completion of medical records were identified. The study aimed to describe the pathology and emphasize to health professionals the need to provide adequate information relevant to epidemiological investigation of compulsory notification diseases.

Sophoridine inhibits NF-kappaB signaling pathway activation in kidney tissue of endotoxemia mice / 药学学报

This study is to investigate the effects of sophoridine on NF-kappaB signaling pathway in kidney tissue of endotoxemia mice and the mechanism involved. BALB/c mice were challenged with lipopolysaccharide (LPS) caudal vein injection, then sophoridine was administered by intraperitoneal injection. Totally 50 mice were divided into 5 groups: control group, LPS model group, sophoridine treatment 12 mg x kg(-1) group, 6 mg x kg(-1) group and 3 mg x kg(-1) group. All animals were sacrificed at 6 hours after treatment. Kidney and blood samples were harvested. IKKbeta mRNA and TNF-alpha mRNA expression of renal tissue was measured by the reverse transcription polymerase chain reaction (RT-PCR), and phosphorylation IKKbeta protein (pIKKbeta) was detected by immunohistochemistry. NF-kappaB P65 protein expression and distribution of renal tissue were observed by Western blotting and immunofluorescence laser confocal microscopy. Serum TNF-alpha level was detected by radioimmunoassay. The results showed that the sophoridine significantly reduced the expression of IKKbeta mRNA and pIKKbeta protein, and inhibited the expression of NF-kappaB P65 protein and decreased the entry nuclear rate of NF-kappaB P65 in the renal tissue of endotoxemia mice. Thereby the renal TNF-alpha mRNA expression and serum TNF-alpha level were significantly reduced. These results suggest that sophoridine could inhibit inflammatory reaction induced by LPS through inhibiting activation of NF-kappaB signaling pathway.

Anti-snake venom: use and adverse reaction in a snake bite study clinic in Bangladesh

Snakebites can present local or systemic envenomation, while neurotoxicity and respiratory paralysis are the main cause of death. The mainstay of management is anti-snake venom (ASV), which is highly effective, but liable to cause severe adverse reactions including anaphylaxis. The types of adverse reaction to polyvalent anti-snake venom have not been previously studied in Bangladesh. In this prospective observational study carried out between 1999 and 2001, in the Snake Bite Study Clinic of Chittagong Medical College Hospital, 35 neurotoxic-snake-bite patients who had received polyvalent anti-snake venom were included while the ones sensitized to different antitoxins and suffering from atopy were excluded. The common neurotoxic features were ptosis (100%), external ophthalmoplegia (94.2%), dysphagia (77.1%), dysphonia (68.5%) and broken neck sign (80%). The percentage of anti-snake venom reaction cases was 88.57%; pyrogenic reaction was 80.64%; and anaphylaxis was 64.51%. The common features of anaphylaxis were urticaria (80%); vomiting and wheezing (40%); and angioedema (10%). The anti-snake venom reaction was treated mainly with adrenaline for anaphylaxis and paracetamol suppository in pyrogenic reactions. The average recovery time was 4.5 hours. Due to the danger of reactions the anti-snake venom should not be withheld from a snakebite victim when indicated and appropriate guidelines should be followed for its administration.(AU)

Protective effects of vitamin E on ethane dimethane sulfonate-induced testicular toxicity in rats / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To evaluate the protective/ameliorative effects of vitamin E (vit E) on ethane dimethane sulfonate (EDS)-induced testicular toxicity in rats.</p><p><b>METHODS</b>The rats were assigned to eight groups, seven rats in each, and were injected intraperitoneally with vehicle, a single dose of ethane dimethane sulfonate (EDS) (75 mg/kg bodyweight), vit E (100 mg/kg bodyweight) or EDS + vit E for 3? days. Thereafter, the rats were weighed, anaesthetized with ether and killed by cervical dislocation. The left testis weights were recorded and the relative testis weights were calculated. The left testes were processed for routine paraffin embedding. Three right testes from each group were taken randomly and then processed for routine electron microscopy. Tissue sections were examined using light and electron microscopy, and were scored for histopathological changes.</p><p><b>RESULTS</b>Vit E coadministration did not prevent the bodyweight loss on days 3 and 7. However, vit E administration prevented the EDS-induced testicular-weight loss in rats that received vit E for 3 days but not 7 days. The relative testis weight was higher on day 3 (instead of on day 7) than other groups. Nevertheless, the testis histology was not markedly protected by vit E in the EDS-treated rats. Detailed microscopic assessment showed few Leydig cells and abundant fibroblast-like cells indicating only some protection.</p><p><b>CONCLUSION</b>Vit E cotreatment showed partial protective effects on the testicular weight and testicular histology in rats that received EDS.</p>

Mutagenicity of Pueraria mirifica Airy Shaw & Suvatabandhu and antimutagenicity of Thunbergia laurifolia Linn.

Thunbergia laurifolia Linn has been reputed to have antitoxic effects for all toxic substances. In this present study, we evaluated its effect against the mutagenicity induced by aqueous extracts from Pueraria mirifica Airy Shaw & Suvatabundhu in male rats. The formation of micronuclei in polychromatic erythrocytes was induced by oral administration of an aqueous extract of P. mirifica at the doses of 400, 600, and 800 mg/kg to the rats for 30 days. The results were that the extracts of P. mirifica at doses of 600 and 800 mg/kg acted as a mutagenic agent by inducing higher frequencies of micronuclei as compared to the controls. For the antimutagenic test, P. mirifica extract at a dose of 600 mg/kg (minimal effective dose) was mixed with fresh and dried extracts of T. laurifolia in proportions of 7:3 and 1:1, respectively. The results of 4-week-treatment indicated that aqueous extracts of T. laurifolia, prepared by both fresh and dry methods, could significantly inhibit the induction of micronuclei as induced by P. mirifica. It could be concluded from the results that, under certain circumstances, T. laurifolia exhibits a significant antimutagenic activity. The use of P. mirifica and T. laurifolia as fusion herbal medicines is suggested.

Integrins, cancer and snake toxins (mini-review)

Integrins encompass a family of transmembrane heterodimeric proteins of adhesion that maintain cells attached to other cells and to the extracellular matrix (ECM). Integrins work as bi-directional mechanotransducers, conveying mechanical signal from outside to inside the cell through a cascade of phosphorylation signals. On the other hand, the signal from inside to outside controls the strength and affinity of integrin adhesion. As proteins of focal contact, integrins are involved in diverse cell functions, such as cell activation, migration, growth, and survival. In the development of neoplastic disease and metastatic tumor, integrins can influence cancer invasiveness and progression, as well as mediate the formation of new blood vessels (angiogenesis). Diverse snake venom toxins have the ability to interact with multiple integrins, what results in inhibition of cell attachment, inhibition of angiogenesis, and induction of apoptotic death of tumor and vascular endothelial cells. The aim of this review is to present data about snake venom toxins that bind to integrins and evoke antiangiogenesis and antitumoral effects

Extracto de frutos enteros de Punica granatum L como agente protector del daño inducido por el peróxido de hidrógeno / Punica granatum L whole fruit extract as a protection against the hydrogen peroxide-induced damage

Punica granatum L (Punicaceae) es una planta medicinal cuyo fruto posee propiedades terapéuticas. El extracto obtenido a partir de frutos enteros se encuentra en fase de estudios preclínicos con el propósito de ser utilizado para el tratamiento de enfermedades virales. En los últimos años, algunas investigaciones experimentales han sido dirigidas al estudio de las propiedades antigenotóxicas de este extracto como una valiosa propiedad adicional. Algunos fitocomponentes del fruto de la granada muestran una actividad antioxidante potente y existen resultados experimentales que demuestran su capacidad como agentes antimutagénicos naturales. El presente trabajo expone los resultados obtenidos al valorar, en este extracto de granada, su capacidad de disminuir el daño inducido por el peróxido de hidrógeno en células de ovario de Hamster chino cultivadas in vitro. Se realizaron experimentos de carácter citogenético como es el intercambio de cromátidas hermanas y citofluorimétrico: la fluorimetría de la diclofluoreceína oxidada. En las condiciones experimentales de esta investigación, el extracto de frutos enteros de granada fue capaz de secuestrar especies reactivas del oxígeno producidas por el peróxido de hidrógeno, mecanismo mediante el cual ejerce su acción protectora del ADN frente a las lesiones causadas por este agente

Punica granatum L. (Punicaceae) is a medicinal plant whose fruit has therapeutical properties. The whole fruit extract is under preclinical study, with the objective of being used for viral disease treatment. In the last few years, some experimental research has been aimed at studying the antigenotoxic characteristics of this extract as an additional valuable property. Some phytocomponents of Punica granatum L. fruit show powerful antioxidative activity and certain experimental results prove their capacity as natural antimutagenic agents. The present paper set forth the results achieved in evaluating the capacity of this extract to reduce hydrogen peroxide-induced damage in in vitro cultured ovarian cells from Chinese Hamster. Cytogenetic experiments such as the exchange of sister chromatids and the cytofluometric test, i.e, oxidized diclofluorescein fluorimetry were performed. Under the experimental conditions of this research work, the Punica granatum whole fruit extract could sequestrate reactive oxygen species caused by hydrogen peroxide, a mechanism that allows it to protect the DNA against the lesions provoked by this agent.

Standardization the PCR technique for the detection of delta toxin in Staphylococcus spp

Coagulase-negative staphylococci (CNS), components of the normal flora of neonates, have emerged as important opportunistic pathogens of nosocomial infections that occur in neonatal intensive care units. Some authors have reported the ability of some CNS strains, particularly Staphylococcus epidermidis, to produce a toxin similar to S. aureus delta toxin. This toxin is an exoprotein that has a detergent action on the membranes of various cell types resulting in rapid cell lysis. The objectives of the present study were to standardize the Polymerase Chain Reaction (PCR) technique for the detection of the gene responsible for the production of delta toxin (hld gene) in staphylococcal species isolated from catheters and blood cultures obtained from neonates, and to compare the results to those obtained with the phenotypic synergistic hemolysis method. Detection of delta toxin by the phenotypic and genotypic method yielded similar results for the S. aureus isolates. However, in S. epidermidis, a higher positivity was observed for PCR (97.4 por cento) compared to the synergistic hemolysis method (86.8 por cento). Among CNS, S. epidermidis was the most frequent islate and was a delta toxin producer. Staphylococcus simulans and S. warneri tested positive by the phenotypic method, but their positivity was not confirmed by PCR for the hld gene detection. These results indicate that different genes might be responsible for the production of this toxin in different CNS species, requiring highly specific primers for their detection. PCR was found to be rapid and reliable method for the detection of the hld gene in S. aureus and S. epidermidis

Interação das enterotoxinas estafilocócicas com o sistema imune do hospedeiro / Interaction of staphylococcal exterotoxins with the immmune system of the host

As enterotoxinas estafilocócicas estão entre as principais causas de intoxicação alimentar e, possivelmente, da síndrome do choque tóxico não menstrual. Essas enterotoxinas são também denominadas de superantígenos, pela capacidade de serem potentes ativadores de células T e macrófagos. Os superantígenos ligam-se diretamente às moléculas classe II do complexo de histocompatibilidade principal sobre as células apresentadoras de antígenos e estimulam células T que expressam os elementos VB do seu receptor. A produção excessiva de citocinas por essas células e pelos macrófagos é responsável pela patôgenese da intoxicação alimentar. Essas citocinas incluem o fator de necrose tumoral-a (TNF-a), o interferon-y (IFN-y), a interleucina-l (IL-1) e mediadores proinflamatórios com potentes efeitos no sistema imune, com o óxido nítrico (NO), que apresenta tanto efeito cintotóxico como regulador.

Rabbit antivenom efficacy against myotoxic and neurotoxic activities of Bothrops jararacussu venom and Bothropstoxin-I

Bothrops jararacussu venom and its major toxin bothropstoxin-I (BthTX-I) possess myotoxic and neurotoxic properties. The efficacy of a rabbit antivenom raised against B. jararacussu venom in the neutralization of physiological, biochemical, and morphological changes induced by the venom and its major toxin BthTX-I was studied in mouse isolated phrenic nerve-diaphragm (PND) and extensor digitorum longus (EDL) preparations. The times required for 50 per cent neuromuscular blockade in PND and EDL preparations for venom were 70ñ11.5 (S.E.M., n=5) min and 58ñ8 (n=16) (50 µ/mL), and for BthTX-I 31ñ6 (n=3) min and 30ñ3 (n=5) min (20 µg/mL), respectively. After 120 min incubation, creatine kinase (CK) concentrations in solution containing the EDL preparations were 3464ñ346 U/L after exposure to venom (50 µg/mL, n=5) and 3422ñ135 U/L to BthTX-I (20µg/mL, n=4), respectively. Rabbit antivenom dose-dependently neutralized venom and toxin-induced neuromuscular blockade in both preparations and effectively prevented venom and toxin-induced CK release from EDL. Histological analysis showed that rabbit antivenom neutralized morphological damage caused by B.jararacussu venom and BthTX-I in EDL preparations. these results indicate that rabbit antivenom effectively neutralized the biological activities of B.jararacussu venom and BthTX-I.