ACE and ACE2 catalytic activity in the fecal content along the gut.

BACKGROUND: Angiotensin-converting enzyme (ACE) and ACE2 are two major enzymes of the renin-angiotensin-aldosterone system (RAAS), which control the formation/degradation of angiotensin (Ang) II and Ang1-7, regulating their opposite effects. We aimed at evaluating the catalytic activity of ACE and ACE2 in the intestinal content and corresponding intestinal tissue along the gut of Wistar Han rats. METHODS: Portions of the ileum, cecum, proximal colon, and distal colon, and the corresponding intestinal content were collected from Wistar Han rats. Enzyme activity was evaluated by fluorometric assays using different substrates: Hippuryl-His-Leu for ACE-C-domain, Z-Phe-His-Leu for ACE-N-domain, and Mca-APK(Dnp) for ACE2. ACE and ACE2 concentration was assessed by ELISA. Ratios concerning concentrations and activities were calculated to evaluate the balance of the RAAS. Statistical analysis was performed using Friedman test followed by Dunn's multiple comparisons test or Wilcoxon matched-pairs test whenever needed. KEY RESULTS: ACE and ACE2 are catalytically active in the intestinal content along the rat gut. The ACE N-domain shows higher activity than the C-domain both in the intestinal content and in the intestinal tissue. ACE and ACE2 are globally more active in the intestinal content than in the corresponding intestinal tissue. There was a distal-to-proximal prevalence of ACE2 over ACE in the intestinal tissue. CONCLUSIONS & INFERENCES: This work is the first to report the presence of catalytically active ACE and ACE2 in the rat intestinal content, supporting future research on the regulatory role of the intestinal RAAS on gut function and a putative link to the microbiome.

Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility.

Interaction between the Renin-Angiotensin System and Enteric Neurotransmission Contributes to Colonic Dysmotility in the TNBS-Induced Model of Colitis.

Angiotensin II (Ang II) regulates colon contraction, acting not only directly on smooth muscle but also indirectly, interfering with myenteric neuromodulation mediated by the activation of AT1 /AT2 receptors. In this article, we aimed to explore which mediators and cells were involved in Ang II-mediated colonic contraction in the TNBS-induced rat model of colitis. The contractile responses to Ang II were evaluated in distinct regions of the colon of control animals or animals with colitis in the absence and presence of different antagonists/inhibitors. Endogenous levels of Ang II in the colon were assessed by ELISA and the number of AT1/AT2 receptors by qPCR. Ang II caused AT1 receptor-mediated colonic contraction that was markedly decreased along the colons of TNBS-induced rats, consistent with reduced AT1 mRNA expression. However, the effect mediated by Ang II is much more intricate, involving (in addition to smooth muscle cells and nerve terminals) ICC and EGC, which communicate by releasing ACh and NO in a complex mechanism that changes colitis, unveiling new therapeutic targets.

2,4,6-trinitrobenzenesulfonic acid-induced colitis in Rattus norgevicus: a categorization proposal.

Reproducibility in animal research is crucial for its reliance and translational relevance. The 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced model of inflammatory bowel disease (IBD) is widely used but inconsistently and incompletely characterized throughout the literature. This hinders comparisons between studies and influences the low rate of translation of effective preclinical molecules. The purpose of this study was to categorize TNBS-induced colitis, based on macroscopic and microscopic scoring systems, and to identify basic routine parameters that could anticipate those categories. We retrospectively analysed male Wistar Rattus norvegicus (n=28 for the control group and n=87 for the TNBS group) and categorized TNBS-induced colitis in three phenotypes: Mild, Moderate and Severe colitis, as for human IBD. Also, we showed that the time course of food intake and fecal excretion (but not body weight, fluid intake or welfare scores) could foresee those categories. So, routine evaluation of food intake and fecal excretion may guide researchers in planning their experiments, selecting the animals with the severity of colitis that better matches their aims, or applying early humane endpoints to animals that will not be used in the experiments. In conclusion, categorizing TNBS-induced colitis enhances the reproducibility of data gathered with this experimental model and strengths its translational relevance.

Characterization of ethyl acetate and n-butanol extracts of Cymbopogon schoenanthus and Helianthemum lippii and their effect on the smooth muscle of the rat distal colon.

ETHNOPHARMACOLOGY RELEVANCE: Cymbopogon schoenanthus (C. schoenanthus) and Helianthemum lippii (H. lippii) are Saharan species found in the South West of Algeria, in the region of Bechar. Both plants are used in traditional medicine to treat gastrointestinal disorders. OBJECTIVE: The aim of our study was to characterize the composition of the ethyl acetate (EtOAc) and n-Butanol (n-BuOH) extracts of C. schoenanthus and H. lippii, and to elucidate and compare their effect on the reactivity of the rat distal colon. MAIN METHODS: The plants were macerated in a hydroalcoholic solution. After concentration, the aqueous solutions of the residues were submitted to liquid-liquid extractions to obtain EtOAc and n-BuOH extracts. The phenolic and flavonoid content of the extracts was determined by high performance liquid chromatography coupled with mass spectrometry with a time of flight analyzer (HPLC-TOF/MS). The effect of the extracts was tested on the rat distal colon, namely on the basal tone and on KCl- and Ach-induced precontracted preparations. RESULTS: HPLC-TOF/MS identified 32 phenols and flavonoids in the extracts. The four extracts relaxed the rat distal colon, the effect being noticed on the basal tone and on the KCl- and Ach-induced precontractions. The EtOAc and the n-BuOH extracts of H. lippii decreased the basal tone of the rat distal colon more markedly than the correspondent extracts of C. schoenanthus. Moreover, the n-BuOH extract of C. schoenanthus decreased the basal tone more markedly than the EtOAc extract of this plant but there was no difference between extracts of H. lippii. The EtOAc extracts of both C. schoenanthus and H. lippii totally reverted both the KCl- and the Ach-induced precontraction of the rat distal colon. However, the n-BuOH extracts of the two plants reverted the Ach-precontracted colon but not the colon that has been precontracted with KCl. CONCLUSION: Extracts of H. lippii contain a higher level of phenols compared to the extracts of C. schoenanthus. All extracts of C. schoenanthus and H. lippii caused marked relaxation of the isolated rat distal colon, either when applied directly or when tested over KCl- and Ach-induced precontraction. These results give support to the use of C. shoenanthus and H. lippii in traditional medicine, namely for gastrointestinal diseases.

Sinais de mudança em autismo: prisma, um instrumento de pesquisa / Signs of change in autism: prisma, an instrument of research / Señales de cambio en autismo: prisma, un instrumento de investigación / Signes de changement en autisme: prisma, un outil de recherche

Neste trabalho, apresentamos o Protocolo de Investigação Psicanalítica de Sinais de Mudança em Autismo, elaborado a partir de um projeto de pesquisa, subsidiado inicialmente pela Associação Psicanalítica Internacional, que busca mapear o desenvolvimento emocional de crianças com transtornos autísticos e sua evolução no tratamento psicanalítico, a fim de demonstrar à comunidade a efetividade do tratamento psicanalítico para promover mudanças psíquicas e favorecer o diálogo com outros profissionais de saúde.

In this paper, we introduce to the reader the Protocol of Psychoanalytic Investigation of Signs Mapping Change in Autism (Prisma). The protocol was developed from a research project, which was first funded by the International Psychoanalytical Association. The purpose is to assess the emotional development in children who suffer from autism spectrum disorders and to evaluate their progress in psychoanalytic treatment. The idea is to demonstrate to the community the effectiveness of psychoanalytic treatment in promoting psychic changes, and to encourage dialogue with other health professionals.

En este trabajo presentamos el Protocolo de Investigación Psicoanalítica de Señales de Cambio en Autismo (Prisma), elaborado a partir de un proyecto de investigación, inicialmente con subsidio de la Asociación Psicoanalítica Internacional, que busca mapear el desarrollo emocional de niños con trastornos autísticos y su evolución en el tratamiento psicoanalítico, con el objetivo de demostrar a la comunidad la eficacia del tratamiento psicoanalítico para promover cambios psíquicos y favorecer el diálogo con otros profesionales de la salud.

Dans ce travail, nous présentons le Protocole de Recherche Psychanalytique de Signes de Changement en Autisme (Prisma), élaboré à partir d'un projet de recherche, subventionné initialement par l'Association Psychanalytique Internationale, qui vise à dessiner le développement émotionnel des enfants atteints de troubles autistiques et leur évolution dans la cure psychanalytique, pour démontrer à la communauté l'efficacité des soins psychanalytiques dans la promotion de changements psychiques, et de favoriser le dialogue avec d'autres professionnels de santé.

O autismo e a clínica dos estados autísticos

O conceito psicanalítico de estados autísticos concedeu à compreensão do autismo uma condição com possibilidade de mudança. Ainda que o diagnóstico identifique essas crianças como autistas, cada uma delas tem um mundo interno com diferentes oportunidades de evolução. A autoestimulação sensorial está associada à dispersão de sentido no autismo. O uso estereotipado dos objetos e do próprio corpo, destituídos de suas funções, mantém a dispersão, impedindo o reconhecimento e o contato com o não-eu. A autora demonstra através de exemplos clínicos que diferentes níveis de funcionamento mental estão em ação ainda que não possam ser percebidos inicialmente.(AU)

The psychoanalytic concept of autistic states allowed the understanding of autism as a condition with the possibility of changing. Even if the diagnosis identifies children as autists each of them has an internal world with different opportunities of evolution. The sensorial auto stimulation is associated to the dispersion of the senses in autism. The stereotyped use of objects and of its body deprived of their own functions keeps the dispersion and prevents the acknowledgement of and the contact with the not-me. The author describes through some clinical examples that different levels of mental activity are still working even if they are do not recognized initially.(AU)

Resection of the epileptogenic lesion abolishes seizures and reduces inflammatory cytokines of patients with temporal lobe epilepsy.

Persistent neuroinflammation is implicated in the pathogenesis of seizures and neuronal degeneration of temporal lobe epilepsy (TLE). Circulating level of inflammatory cytokines was determined during inter-ictal period of 25 non-operated and 10 patients (OP) submitted to anterior temporal lobectomy. OP patients showed marked reduction of IL-1ß, TNFα, MIP-1α, but not IL-6 and TGF-ß1. Paired analysis done before and after lobectomy showed reduction of inflammatory cytokines but increased TGF-ß1 levels, and lack of seizures for more than 6 months. Maintenance of high TGF-ß1 and IL-6 cytokines in both groups suggests a role in down-regulation of neuroinflammation and promotion of brain tissue remodeling for neuronal reorganization.

Intestinal helminthes and/or Toxocara infection are unrelated to anti-HBs titers in seven-year-old children vaccinated at birth with recombinant hepatitis B vaccine.

The aim of this investigation was to evaluate the possible effect of nematode infection on anti-HBs antibody levels in the serum of seven-year-old schoolchildren vaccinated at birth with the recombinant hepatitis B vaccine. Anti-HBs and anti HBc antibodies were evaluated in the sera of 100 schoolchildren with at least one intestinal nematode and/or a positive serological reaction for anti-Toxocara antibodies and in 95 schoolchildren without intestinal helminthiasis or serum anti-Toxocara antibodies. Both groups were from public elementary schools located on the urban periphery of Vitória, ES, Brazil. Among these 195 children, the median anti-HBs antibody titer was 31.3 IU/ml and the frequency of titers less than 10 IU/ml was 33.8% (95% CI: 27.1-40.4%). There were no significant differences between the medians of anti-HBs titers or the frequency of titers less than 10 IU/ml between the groups with or without helminthes (29.5 and 32.9 IU/ml and 33 and 34.7%, respectively; p>0.05). Even when the children with intestinal nematodes and/or anti-Toxocara antibodies and with blood eosinophil counts over 600/mm(3) were compared with children without infection from intestinal nematodes and without anti-Toxocara antibodies, with blood eosinophil counts less than 400 eosinophils/mm(3), these differences were not significant. None of the children presented anti-HBc antibodies. In conclusion, infections with intestinal nematodes and/or the presence of anti-Toxocara antibodies did not interfere with the anti-HBs antibody titers in seven-year-old children vaccinated at birth with the recombinant hepatitis B vaccine.

Intestinal helminthes and/or Toxocara infection are unrelated to anti-HBs titers in seven-year-old children vaccinated at birth with recombinant hepatitis B vaccine

The aim of this investigation was to evaluate the possible effect of nematode infection on anti-HBs antibody levels in the serum of seven-year-old schoolchildren vaccinated at birth with the recombinant hepatitis B vaccine. Anti-HBs and anti HBc antibodies were evaluated in the sera of 100 schoolchildren with at least one intestinal nematode and/or a positive serological reaction for anti-Toxocara antibodies and in 95 schoolchildren without intestinal helminthiasis or serum anti-Toxocara antibodies. Both groups were from public elementary schools located on the urban periphery of Vitória, ES, Brazil. Among these 195 children, the median anti-HBs antibody titer was 31.3IU/ml and the frequency of titers less than 10IU/ml was 33.8 percent (95 percent CI: 27.1-40.4 percent). There were no significant differences between the medians of anti-HBs titers or the frequency of titers less than 10IU/ml between the groups with or without helminthes (29.5 and 32.9IU/ml and 33 and 34.7 percent, respectively; p>0.05). Even when the children with intestinal nematodes and/or anti-Toxocara antibodies and with blood eosinophil counts over 600/mm³ were compared with children without infection from intestinal nematodes and without anti-Toxocara antibodies, with blood eosinophil counts less than 400 eosinophils/mm³, these differences were not significant. None of the children presented anti-HBc antibodies. In conclusion, infections with intestinal nematodes and/or the presence of anti-Toxocara antibodies did not interfere with the anti-HBs antibody titers in seven-year-old children vaccinated at birth with the recombinant hepatitis B vaccine.

O objetivo dessa investigação foi avaliar um possível efeito de infecções por nematóides sobre os níveis de anticorpos anti-HBs no soro de escolares de sete anos de idade, vacinados ao nascer com a vacina recombinante para hepatite B. Anticorpos anti-HBs e anti-HBc foram avaliados no soro de 100 escolares portadores de pelo menos um nematóide intestinal e/ou uma reação sorológica positiva para anticorpos anti-Toxocara e em 95 escolares sem helmintíases intestinais e sem anticorpos séricos anti-Toxocara, todos matriculados em escolas primárias públicas situadas na periferia urbana de Vitória, ES, Brasil. Nas 195 crianças, a mediana dos títulos dos anticorpos anti-HBs foi 31,3UI/ml, e a freqüência de títulos inferiores a 10UI/ml foi de 33,8 por cento (IC a 95 por cento:27,1- 40,4 por cento). Não houve diferença significativa entre as medianas dos títulos de anti-HBs ou da freqüência de títulos inferiores a 10 UI/ml entre as crianças com ou sem helmintos (29,5 e 32,9 UI/ml e 33 e 34,7 por cento, respectivamente; p >0.05). Mesmo quando comparadas crianças com nematóides intestinais e/ou anticorpos anti-Toxocara com eosinófilos circulantes acima de 600/mm³, com crianças sem infecção com nematóides intestinais e sem anticorpos anti-Toxocara, com menos de 400 eosinófilos/mm³, aquelas diferenças não foram significativas. Nenhuma das crianças apresentou anticorpos anti-HBc. Em conclusão, infecções com nematóides intestinais e/ou presença de anticorpos anti-Toxocara não interferem nos títulos de anticorpos anti-HBs em crianças de sete anos de idade, vacinadas ao nascer com a vacina recombinante para hepatite B.

[Synanthropic flies (Diptera: Cyclorrapha) and their microhymenoptera parasitoids (Insecta: Hymenoptera) at Monte Mor poultry production system, São Paulo, Brazil]. / Moscas sinantrópicas (Diptera: Cyclorrapha) e seus parasitóides microhimenópteros (Insecta: Hymenoptera) num plantel avícola de Monte Mor, São Paulo, Brasil.

A survey of synanthropic flies and their microhymenopteran parasitoids was conducted at the Capuavinha poultry farm, municipality of Monte Mor, State of São Paulo, Brazil, from 1991 to 1992. Bird manure samples were collected biweekly for examined and selected by the following methods: flotation in water, dissected pupae, and sentinel pupae. The species of flies more abundant were: Chrysomya putoria (Wiedeman) (41.2% - Calliphoridae), Muscidae: Muscina stabulans( Fallén) (27.3%), Musca domestica Linnaeus (23.9%), Fannia pusio (Stein) (5.3% - Fanniidae) e Sepsidae (2.3%). The pupal parasitoids were: Tachinaephagus zealandicus (Ashmead) (72.4% - Encyrtidae), Pteromalídeos: Spalangia gemina Boucek (9.2%), S. cameroni (Perkins) (7.3%), S. endius (Walker) (3.7%), Muscidifurax raptoroides (Kogan e Legner) (1.5%), Pachycrepoideus vindemiae (Rondani) (0.8%), Nasonia vitripennis Walker (0.06%). Trichopria sp. Nixon (Diapriídeo 5.5%) detected only in C. putoria pupae (t=-1,5269; P <0,1296). Some significant mean values were obtained for parasitoids in the collected hosts (t = 0.9540; Pr <0.0001), proportion of collected pupae and parasitoids with respect to the collecting site (F = 60.85; Pr <0.0001; F = 358.35; P <0.0001) and for the host species and parasitoid species (F = 2.58; Pr <0.0001; F = 9. 48; P <0.0001). The dissected host species was significant for proportion dissected pupae (F = 1.57; Pr <0.2053). These results concerning the insect fauna can be of help for an appropriate management of this poultry farm in terms of the control of synanthropic flies.

Curativo do grande queimado: oclusivo ou de exposiçäo? / Dressing of the severely burned one: occlusive or explosed?

As autoras discorrem sobre os dois tipos de curativos utilizados no tratamento do grande queimado, fazendo consideraçöes acerca de suas vantagens e desvantagens. Trata-se de um relato baseado em observaçöes efetuadas em dois serviços especializados.