Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.

Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice.

Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/- -challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.

Experimental anisakid infections in mice.

Anisakidosis is a human parasitic disease caused by infections with members of the Anisakidae family. Accidental infection after fish intake affects the gastrointestinal tract as a consequence of mechanical damage caused by migrating larvae. Infections can also trigger allergies, hives, severe asthma or anaphylaxis with angioedema. Although mouse models of intraperitoneal antigenic stimulation exist, enabling immunological studies, few models using gastric introduction of live larvae are available for the study of immunological and gastrointestinal damage in mice. This study was designed to characterize serum reactivity against Anisakis spp. and Contracaecum spp. in Balb/c mice following orogastric inoculation and to assess gastrointestinal damage. These anisakid species were classified at the Universidade Federal Fluminense (UFF) School of Veterinary Medicine and materials for live larval inoculation were developed at the UFF Immunobiology laboratory. Live larvae were inoculated following injection with a NaCl solution. Blood samples were collected and sera screened for immunoglobulin (Ig)E and IgG anti-larva responses to both nematodes, specific for somatic and excretory/secretory antigens, by enzyme-linked immunosorbent assay (ELISA). The means of the optical densities were analysed using analysis of variance (ANOVA) with Tukey's post-hoc test and the general linear model. This analysis identified the presence of anti-IgG seroreactivity to both somatic and excretory/secretory Anisakis antigens in inoculated animals compared with controls (P< 0.001), and no gastric or intestinal damage was observed. These experiments demonstrated that introduction of live Contracaecum spp. into the gastrointestinal tract did not elicit serum sensitization in animals.

Correlation between total nitrite/nitrate concentrations and monoamine oxidase (types A and B) and semicarbazide-sensitive amine oxidase enzymatic activities in human mesenteric arteries from non-diabetic and type 2 diabetic patients

The aim of this study was to determine the correlation between total nitrite/nitrate concentrations (NOx) and the kinetic parameters of monoamine oxidase enzymes (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) in human mesenteric arteries. Arteries were from non-diabetic and type 2 diabetic patients with sigmoid or rectum carcinoma for whom surgery was the first option and who were not exposed to neo-adjuvant therapy. Segments of human inferior mesenteric arteries from non-diabetic (61.1 ± 8.9 years old, 7 males and 5 females, N = 12) and type 2 diabetic patients (65.8 ± 6.2 years old, 8 males and 4 females, N = 12) were used to determine NOx concentrations and the kinetic parameters of MAO-A, MAO-B and SSAO by the Griess reaction and by radiochemical assay, respectively. The NOx concentrations in arteries from diabetic patients did not differ significantly from those of the non-diabetic group (10.28 ± 4.61 vs 10.71 ± 4.32 nmol/mg protein, respectively). In the non-diabetic group, there was a positive correlation between NOx concentrations and MAO-B parameters: Km (r = 0.612, P = 0.034) and Vmax (r = 0.593, P = 0.042), and a negative correlation with the SSAO parameters: Km (r = -0.625, P = 0.029) and Vmax (r = -0.754, P = 0.005). However, in the diabetic group no correlation was found between NOx concentrations and the three kinetic parameters of the enzymes. These results suggest an important function of sympathetic nerves and vascular NOx concentrations in arteries of non-diabetic patients. Thus, these results confirm the importance of a balance between oxidants and antioxidants in the maintenance of vascular homeostasis to prevent oxidative stress.

Correlation between total nitrite/nitrate concentrations and monoamine oxidase (types A and B) and semicarbazide-sensitive amine oxidase enzymatic activities in human mesenteric arteries from non-diabetic and type 2 diabetic patients.

The aim of this study was to determine the correlation between total nitrite/nitrate concentrations (NOx) and the kinetic parameters of monoamine oxidase enzymes (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) in human mesenteric arteries. Arteries were from non-diabetic and type 2 diabetic patients with sigmoid or rectum carcinoma for whom surgery was the first option and who were not exposed to neo-adjuvant therapy. Segments of human inferior mesenteric arteries from non-diabetic (61.1 ± 8.9 years old, 7 males and 5 females, N = 12) and type 2 diabetic patients (65.8 ± 6.2 years old, 8 males and 4 females, N = 12) were used to determine NOx concentrations and the kinetic parameters of MAO-A, MAO-B and SSAO by the Griess reaction and by radiochemical assay, respectively. The NOx concentrations in arteries from diabetic patients did not differ significantly from those of the non-diabetic group (10.28 ± 4.61 vs 10.71 ± 4.32 nmol/mg protein, respectively). In the non-diabetic group, there was a positive correlation between NOx concentrations and MAO-B parameters: Km (r = 0.612, P = 0.034) and Vmax (r = 0.593, P = 0.042), and a negative correlation with the SSAO parameters: Km (r = -0.625, P = 0.029) and Vmax (r = -0.754, P = 0.005). However, in the diabetic group no correlation was found between NOx concentrations and the three kinetic parameters of the enzymes. These results suggest an important function of sympathetic nerves and vascular NOx concentrations in arteries of non-diabetic patients. Thus, these results confirm the importance of a balance between oxidants and antioxidants in the maintenance of vascular homeostasis to prevent oxidative stress.

Ganhos funcionais e sua relação com os componentes de função em trabalhadores com lesão de mão / Functional gains and their relationship with functional components among workers with hand injuries

OBJETIVO: Este estudo teve como objetivos documentar os resultados da intervenção da Terapia Ocupacional em pacientes com lesões de mão por acidente de trabalho e examinar a relação entre os escores da avaliação funcional Canadian Occupational Performance Measure (COPM) com as variáveis força de preensão e diagnóstico, em três momentos (admissão, alta e follow-up). METODOLOGIA: Foi realizado um estudo observacional do tipo longitudinal. A amostra foi constituída de 42 indivíduos encaminhados ao Setor de Terapia Ocupacional de um Hospital da rede pública de Belo Horizonte. A instrumentação utilizada consistiu de dinamômetro Jamar para a mensuração da força de preensão, goniômetro de punho e dedos para a amplitude de movimento, monofilamentos de Semmes-Weinstein para a sensibilidade e a avaliação funcional COPM. RESULTADOS: Os parâmetros clínicos (força de preensão, amplitude de movimento, sensibilidade e desempenho funcional) mostraram ganhos importantes após a intervenção. Os escores do COPM inicial dobraram após a Terapia Ocupacional, fornecendo evidência de que os clientes melhoraram e ficaram satisfeitos com seu desempenho funcional. A força de preensão apresentou uma associação de baixa magnitude com as medidas avaliadas pelo COPM. Outros fatores podem estar associados ao uso funcional da mão, sendo que a força pode não ser suficiente para predizer a função da mão. Não foi detectada diferença entre os diagnósticos encontrados na amostra e os escores do COPM. CONCLUSÃO: As relações documentadas neste estudo indicam variáveis relevantes associadas aos ganhos após intervenção da Terapia Ocupacional e podem contribuir para uma atuação mais direcionada dos profissionais, no que concerne às expectativas do cliente.

OBJECTIVE: To document the outcomes from occupational therapy intervention among patients with hand injury resulting from work-related accidents, and to examine the relationships between the scores from the Canadian Occupational Performance Measure (COPM) functional assessment and variables such as grip strength and diagnosis, at three times (admission, discharge and follow-up). METHOD: An observational longitudinal study was conducted. The sample consisted of 42 individuals who were referred for occupational therapy services at a public hospital in Belo Horizonte. The instruments used included a Jamar dynamometer to measure grip strength, hand goniometer for wrist and finger range of motion, Semmes-Weinstein monofilaments for sensitivity and the COPM functional test. RESULTS: The clinical parameters (grip strength, range of motion, sensitivity and functional performance) showed significant gains after the intervention. The initial COPM scores doubled after occupational therapy, thus providing evidence that the patients improved and were satisfied with their functional performance. There was a slight association between grip strength and the measurements evaluated by COPM. Other factors may be associated with functional use of the hand, since strength may be insufficient for predicting hand function. No differences were found between the diagnoses found in the sample and the COPM scores. CONCLUSION: The relationships documented in this study indicate the variables that are relevant to gains following occupational therapy interventions. This may contribute towards achieving interventions that are better focused, in terms of patients' expectations.

A profissionalização da fisioterapia em Minas Gerais / Professionalization of physical therapy in Minas Gerais

OBJETIVO: Com base em estudo qualitativo, utilizando a história oral e a análise de documentos, procurou-se identificar as raízes da fisioterapia em Minas Gerais, a fim de discutir o processo de profissionalização e o desenvolvimento da identidade do fisioterapeuta neste Estado. METODOLOGIA: O foco do estudo foi dirigido principalmente a Belo Horizonte, no período compreendido entre 1950 e 1980. O referencial teórico utilizado foi a sociologia das profissões, e teve como guia os cinco passos de profissionalização descritos por Wilensky¹ que são a necessidade da ocupação tornar-se de dedicação exclusiva, o estabelecimento de procedimentos de instrução e seleção, a formação de uma associação profissional, a regulamentação da profissão e a adoção do código de ética. Na pesquisa de campo, foram utilizadas entrevistas do tipo semi-estruturada para colher depoimentos de pessoas consideradas chave, mediante amostragem em série, e o método escolhido foi a análise de conteúdo. RESULTADOS: Avalia-se que o processo de profissionalização da fisioterapia em Minas Gerais é marcado pela hegemonia médica na saúde e que a indefinição das atribuições e competências foram os fatores que motivaram os conflitos internos e externos. CONCLUSÕES: Conclui-se que, para a afirmação efetiva da fisioterapia como profissão, torna-se necessária a delimitação das especificidades do seu saber e do seu fazer (teoria e prática), identificando o papel do fisioterapeuta na equipe multidisciplinar de saúde.

Knowledge about transplantation and attitudes toward organ donation: a survey among medical students in northeast Brazil.

During the registration for the second semester of 2002, 779 of the 1001 students from the Medical School, Federal University of Bahia, Brazil, answered an anonymous multiple-choice questionnaire including demographic variables, knowledge about transplantation issues, and willingness to donate organs. Mean age was 21.9 +/- 2.9 years (range: 17 to 51 years); 59.5% were men. Regarding the knowledge of which organs and tissues could be transplanted, 99.1% answered kidneys, 96.1% heart, 88.2% liver, 41.1% lung, 24.0% pancreas, 9% bowel, 98.3% corneas, 89.5% bone marrow, 38.1% heart valves, 47.7% skin, and 18.5% bone and tendons. Regarding the criteria of death, 82.4% answered that it is the lack of all brain activity, 8.2% cardiac arrest, 5.2% irreversible coma, and 4.2% did not know. As to the Brazilian transplantation law, 47.3% did not know, 51% had heard about it, and 1.7% answered that they knew the law in detail. As to the willingness to donate organs, 538 (69.2%) were donors. Of 239 nondonors, 51.1% answered the reason for not donating was the lack of confidence in the heath system, 14.3% had no knowledge of the matter, 17.7% were concerned about organ removal before brain death, and 1.7% for religious reasons. The percentage of those willing to donate organs was greater among spiritualists than among Catholics and Protestants. The results of this study support a greater emphasis on providing information regarding transplantation in medical schools to improve the knowledge of future heath care professionals about transplantation and organ donation issues.

Anti-inflammatory effect of the latex from Calotropis procera in three different experimental models: peritonitis, paw edema and hemorrhagic cystitis.

Latex from Calotropis procera is widely used in folk medicine as a rich source of biologically active compounds capable of promoting diverse benefits such as control of dermal fungal infections, antimicrobial activities and pain relief among other useful properties. The aim of this work was to characterize the anti-inflammatory effect of a non-dialysable protein fraction recovered from the rubber-free latex using three different experimental models when administrated intravenously. In vivo neutrophil migration induced by carrageenin (500 microg) was severely inhibited by doses of latex proteins reaching maximum inhibition (80%) at 100 mg/kg. Paw edema exacerbated by the effect of carrageenin was almost completely suppressed after 4 hours and was controlled within the first hour following latex protein administration. However, the same latex fraction was completely unable to control the paw edema invoked with dextran stimulation (400 microg), suggesting that the inhibitory effect of the latex is likely to be cell-mediated. Iphosphamide-induced vesical edema in mice was also largely prevented by the latex protein fraction. These results indicate that an effect similar to that of mesna, the classical drug used for this purpose, is operative. Our findings suggest that the sample tested seems to act over a wide spectrum as a novel anti-inflammatory agent. The results also suggest that the active molecules are of a proteinaceous nature despite the presence of numerous secondary metabolites naturally occurring in the C. procera latex.

[Cytomegalovirus infection in an infant with epidermolysis bullosa]. / Infecção citomegálica em lactente portador de epidermólise bolhosa.

The authors report and discuss the case of an infant bearer of Epidermolysis Bullosa who was affected by acquired Cytomegalovirus infection.

Effects of eugenol on excitation-contraction coupling in skeletal muscle.

The effects of eugenol on the excitation-contraction coupling of the toad (Bufo paracnemis) sartorius were studied. Eugenol (0.1-2.5 mM) blocked the contracture induced by 80 mM K+. At 2.5 mM, it decreased the depolarization, induced by 80 mM K+, by 14 mV. This is not sufficient to explain the complete blockade of the potassium contracture. At higher concentrations (3-12 mM), eugenol induced contractures, without causing a depolarization of the membrane. Contractures were blocked by procaine and potentiated by caffeine and by cooling of the muscle. For concentrations of eugenol in the upper range of the dose-response curve (10 mM), the contracture was independent of the Ca++ concentration in the medium. At lower concentrations (5 mM), the contractures induced by eugenol were potentiated by divalent cations, in the order: Mg++ < Ba++ < Zn++ < Co++ < Ca++ < Mn++. We infer that the eugenol-induced contractures are caused, primarily, by a release of Ca++ from the sarcoplasmic reticulum and, secondarily, by a mechanism related to the presence of some divalent cations in the extracellular space.

Estudo radiologico comparativo da coluna lombar sintomatica e assintomatica. / Comparative radiological study of the symptomatic and asymptomatic lumbar spine

Baseados no exame de 439 pacientes de ambos os sexos, 183 sintomaticos e 256 assintomaticos, os autores, a semelhanca de outros trabalhos publicados sobre o assunto, chegam a conclusao de que a presenca de osteofitos e bastante alta (68,6%) em pacientes com idade acima de 40 anos e que isso nem sempre constitui por si so a causa de dor da coluna vertebral baixa.Os autores chamam a atencao para o tratamento dessa enfermidade que em 90% dos casos responde bem a formas de tratamento conservadoras, mais simples e menos dispendiosas. Eles tambem mencionam certas condutas que deveriam ser observadas como rotina quando exames radiologicos da area sao necessarios, particularmente para individuos jovens e para aqueles com sintomas agudos e subagudos

Sifilis congenita. Incidencia, morbidade e mortalidade no Hospital Universitario Antonio Pedro(HUAP). / Congenital syphilis. Incidence, morbidity and mortality in the Hospital Universitario Antonio Pedro (HUAP)

Os autores apresentam dados especificos que comprovam a alta incidencia da sifilis nas gestantes que frequentam a maternidade do Hospital Universitario Antonio Pedro (Niteroi - RJ), onde obtiveram cerca de 5% de reacoes sorologicas positivas (VDRL) num total de 17.639 amostras do sangue do cordao umbilical examinadas, concentrando-se a positividade, na grande maioria dos casos, nas diluicoes 1:16 e 1:32, enquanto que a mortalidade incluiu mais fortemente nas diluicoes mais elevadas (1:32 e 1:64).Baseados nos dados estatisticos obtidos, procuram tracar o "perfil da gestante sifilitica" como o de "uma mulher gravida,de baixa condicao social, geralmente de cor preta, solteira, com idade entre 15 e 20 anos, que nao frequentou o ambulatorio pre -natal". Finalmente, sugerem maior propaganda do exame pre-natal para combater a morbidade e a mortalidade da sifilis neonatal

Aleitamento materno nas classes sociais media e alta. / Breast feeding in middle and upper social classes

O autor faz uma analise sobre as dificuldades do aleitamento materno, tece comentarios sobre as suas vantagens e apresenta dados estatisticos referentes as classes medias e alta.Como decorrencia do trabalho, o autor sugere uma serie de medidas destinadas a estimular a alimentacao materna em nosso meio

Pseudocisto do pancreas. / Pancreatic pseudocyst

Os autores apresentam 34 casos de pseudocisto de pancreas documentados e operados num periodo de 30 anos no HSE. Houve predominancia do sexo masculino (76%) e dos casos provocados por pacreatite (73%), prevalecendo a pancreatite de origem alcoolica. Todos os pacientes foram submetidos a tratamento cirurgico, e a drenagem interna foi realizada na maioria dos casos (68%), dando-se preferencia a pseudocistogastrostomia. Quatro pacientes foram submetidos a exerese do pseudocisto. A mortalidade foi de 23,5%, ocorrendo com maior frequencia, bem como as complicacoes, nos casos em que foi realizada a drenagem externa