Resposta tecidual a implantes de discos de poliuretana de mamona nas formas pré-moldada ou biomassa moldada

O trabalho teve por objetivo avaliar a resposta tecidual à implantação de discos de poliuretana derivada do óleo de mamona confeccionados de duas formas distintas, na forma pré-moldada fornecida pela indústria e em biomassa moldada no momento da aplicação, de forma a observar se haveria algum tipo de reação local tardia associada à possível continuidade do processo de endurecimento final do biomaterial. Foram utilizados 20 ratos, linhagem Wistar, fêmeas, com peso de 300-350g, nos quais foi inserido o disco pré-moldado no tecido subcutâneo do flanco direito e o de biomassa moldada no flanco esquerdo. Ambos os discos tinham 0,8cm de diâmetro por 0,5cm de espessura. Para o procedimento histológico, cinco ratos foram submetidos à eutanásia aos 3, 7, 15 e 30 dias de pós-cirúrgico. Os implantes e tecidos circundantes foram colhidos, processados e corados pela técnica de hematoxilina-eosina. Foi observada inicialmente uma reação inflamatória moderada, composta especialmente por células polimorfonucleares e macrófagos. Os linfócitos variaram de ausentes a discretos. A reação inflamatória diminui de intensidade à medida que se intensificou a formação de tecido conjuntivo fibroso ao redor dos implantes, porém sem modificação dos números de macrófagos. Sendo assim, conclui-se que ambos os discos de poliuretana induzem uma reação inflamatória similar, que varia de moderada a discreta na dependência do momento de avaliação.

Avaliação da função diastólica por meio de Doppler tecidual pulsado e colorido em gatos da raça Maine Coon geneticamente testados para a mutação no gene MyBPC-A31P

A cardiomiopatia hipertrófica (CMH) é a principal cardiopatia dos felinos e é caracterizada por hipertrofia miocárdica concêntrica, sem dilatação ventricular. Disfunções miocárdicas ocorrem em gatos com CMH, mas pouco se conhece a respeito destas alterações nos estágios iniciais da afecção. Em gatos da raça Maine Coon, a mutação no gene MyBPC-A31P está relacionada com a CMH de origem familial, porém, a correlação exata entre o genótipo e o fenótipo ainda é inconclusiva. A ecocardiografia tecidual é uma modalidade não invasiva que permite avaliação da função miocárdica e é mais sensível que a ecocardiografia convencional. Para avaliar as funções sistólica e diastólica, antes ou após a ocorrência de hipertrofia ventricular, gatos da raça Maine Coon (n=57), geneticamente testados para a mutação, foram avaliados por meio de ecocardiografias convencional e tecidual (nas modalidades Doppler tecidual pulsado e Doppler tecidual colorido). Posteriormente, foram fenotipicamente classificados em: normais (n=45), suspeitos (n=7) e acometidos pela CMH (n=5); e genotipicamente classificados em: negativos (n=28), heterozigotos (n=26) e homozigotos para a mutação (n=3). Valores de velocidades miocárdicas (Doppler tecidual pulsado e colorido) medidos na região basal e média do septo interventricular (SIV), da parede livre do ventrículo esquerdo (PVE), da parede anterior do ventrículo esquerdo (PAVE), da parede posterior do ventrículo esquerdo (PPVE) e do segmento radial da PVE, foram comparados nos diferentes grupos. Observou-se que as velocidades longitudinais Em (Doppler tecidual pulsado) na região média da PVE foram menores nos gatos com CMH quando comparados com suspeitos e normais. Os valores de Em/Am (Doppler tecidual colorido), na região basal do SIV, foram inferiores nos gatos com CMH quando comparados com suspeitos e normais. A relação E/Em (Doppler tecidual colorido), na região basal do SIV, foi maior nos gatos com CMH em relação aos suspeitos e normais, enquanto que os valores de Sm (Doppler tecidual colorido), em região basal da PVE, foram menores nos gatos heterozigotos quando comparados com os negativos, ambos sem hipertrofia ventricular. Observou-se correlação positiva entre a ocorrência de fusão das ondas Em e Am e a frequência cardíaca, assim como correlação positiva entre valores de Sm e Em e a frequência cardíaca (Doppler tecidual pulsado e colorido). A ecocardiografia tecidual é uma nova modalidade ecocardiográfica reprodutível em gatos que, isoladamente, não permite diferenciar gatos portadores da mutação antes do desenvolvimento de hipertrofia ventricular. Apresenta utilidade como auxílio no diagnóstico em fases iniciais, mas, apesar da expectativa para a identificação precoce de indivíduos portadores da CMH, ainda há necessidade de estudos mais extensos e com maior número de indivíduos.

The effect of methotrexate and azathioprine on the serum levels of IgA-a1-antitrypsin complex in juvenile chronic arthritis

In the present study we investigated the influence of methotrexate (MTX) and azathioprine (AZA) on the serum levels of the IgA-a1-antitrypsin (IgA-AT) complex in patients with the systemic form of juvenile chronic arthritis (JCA). Fifty-six JCA patients (22 treated with MTX, 18 treated with AZA, and 16 not treated with any immunosuppressive agent) were enrolled in the study. MTX dosage ranged from 0.3 to 0.5 mg kg-1 week-1, while AZA was given daily at an average dose of 1 mg/kg. MTX was given for 13 months (SD = 7 months) whereas AZA for 11 months (SD = 6 months). The average value of the complex was higher in JCA patients than in both control groups (0.74 ± 0.73 U vs 0.37 ± 0.13 U (control children), P<0.001 and vs 0.23 ± 0.12 U (control adults), P<0.001). Values exceeding the normal range were found in twenty-two JCA patients (39.4%). Serum IgA-AT level was lowest in the MTX group compared to AZA and non-treated patients (0.56 ± 0.24 U, 0.76 ± 0.43 U, 0.95 ± 0.52 U, respectively, P<0.05). IgA values exceeding normal levels for age were found in 14% of the patients. A correlation between the levels of the IgA-AT complex and C-reactive protein (r = 0.43, P<0.01), a1-acid-glycoprotein (r = 0.45, P<0.01), a1-antichymotrypsin (r = 0.52, P<0.01), a1-antitrypsin (r = 0.40, P<0.01) and IgA (r = 0.56, P<0.01) was established

Urinary secretory IgA after nutritional rehabilitation

We studied the secretory IgA (sIgA) response of the mucosal urinary tract of malnourished children before and after nutritional rehabilitation. sIgA concentration (mg/l) was determined by ELISA in 187 children aged 3 months to 5 years. The children, who frequented a day care center, were divided into four groups, according to nutritional status: 57 were eutrophic, 49 were undergrown, 57 were moderately malnourished and 24 were severely malnourished. In addition, dip slide (Urotube, Roche) and dip-stick (Combur 9-Boehringer) tests showed that children had no bacteriuria or any other urinary abnormalities. Plasma albumin concentration (g/dl) was significantly lower (P<0.005) in the severely malnourished group (mean 3.0 ± 0.3 SD) than in the eutrophic group (mean 4.0 ± 0.5 SD). When each nutritional state was analyzed, no significant differences in the sIgA were found between the 0 |-| 1 and 1 -| 5 year age range. In the moderately and severely malnourished groups, sIgA (0.36 and 0.45, respectively) was significantly lower than in the eutrophic (0.69) and undergrown (0.75) groups. Ninety-five children were included in the 8-month follow-up study; 30 children were excluded from the follow-up because 4 had bacteriuria, 11 had leukocyturia, 8 had proteinuria and 7 had hematuria. Among the malnourished children, 40% showed nutritional improvement (P<0.05) and significantly increased sIgA as compared to reference values for the eutrophic and undergrown groups. These data suggest that malnourished children have a significantly lower urinary sIgA than eutrophic children. After nutritional rehabilitation, they develop local immunity with a significant increase in sIgA.

IgA response in serum and gut secretion in sensitized mice fed with the dust mite Dermatophagoides pteronyssinus extract

Induced oral tolerance to mucosal-exposed antigens in immunized animals is of particular interest for the development of immunotherapeutic approaches to human allergic diseases. This is a unique feature of mucosal surfaces which represent the main contact interface with the external environment. However, the influence of oral tolerance on specific and natural polyreactive IgA antibodies, the major defense mechanism of the mucosa, is unknown. We have shown that oral administration of an extract of the dust mite Dermatophagoides pteronyssinus (Dp) to primed mice caused down-regulation of IgE responses and an increase in tumor growth factor-ß secretion. In the present study, we observed that primed inbred female A/Sn mice (8 to 10 weeks old) fed by gavage a total weight of 1.0-mg Dp extract on the 6th, 7th and 8th days post-immunization presented normal secretion of IL-4 and IL-10 in gut-associated lymphoid tissue and a decreased production of interferon gamma induced by Dp in the draining lymph nodes (13,340 ± 3,519 vs 29,280 ± 2,971 pg/ml). Mice fed the Dp extract also showed higher levels of serum anti-Dp IgA antibodies and an increase of IgA-secreting cells in mesenteric lymph nodes (N = 10), reflecting an increase in total fecal IgA antibodies (N = 10). The levels of secretory anti-Dp IgA antibodies increased after re-immunization regardless of Dp extract feeding. Oral tolerance did not interfere with serum or secretory IgA antibody reactivity related to self and non-self antigens. These results suggest that induction of oral tolerance to a Dp extract in sensitized mice triggered different regulatory mechanisms which inhibited the IgE response and stimulated systemic and secretory IgA responses, preserving the natural polyreactive IgA antibody production.

Comparative study of IgA nephropathy with and without crescents

Glomerular crescents were analyzed as a prognostic factor in retrospectively reviewed data from 144 patients with biopsy-proven IgA nephropathy. Crescents were found in 26 (18%) patients, and detected in 2 to 100% of glomeruli in each specimen. In 5% of the patients more than 50% of the glomeruli were affected. Thirty patients with IgA nephropathy without crescents were studied as a control group. Mean age was 30.3 ± 9.4 and 30.2 ± 12.0 years for the patients with and without crescents, respectively, and males prevailed in both groups. The length of follow-up was 23.2 ± 41.6 months for patients with crescents and 29.3 ± 35.3 months for patients without crescents. Eighty percent of the patients with crescents were hypertensive, compared to 27% of the non-crescent control group (P < 0.05). Mean serum creatinine at the time of diagnosis was 3.9 ± 2.9 and 1.9 ± 2.1 mg/dl for the patients with and without crescents, respectively. Initial urinary protein excretion was higher in patients with crescents (4.6 ± 3.5 vs 1.2 ± 0.9 g/day; P < 0.05). At the end of follow-up 17 patients (77.3%) from the crescent group and 3 (11.1%) from the non-crescent group had end-stage renal disease (P < 0.0001). The presence of crescents was associated with higher levels of initial serum creatinine and urinary protein excretion, and a higher frequency of hypertension and progression to end-stage renal disease.

Genetic potential for an acute inflammatory response in IgA glomerulonephritis in mice

Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 ± 0.4 vs 0.3 ± 0.1 mg/mL, P < 0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 ± 0.3 vs 1.1 ± 0.9 macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.

Effect of hyperoxia on the intestinal IgA secretory component in neonatal rats and on intestinal epithelial cells in vitro

Oxygen therapy is essential for the treatment of some neonatal critical care conditions but its extrapulmonary effects have not been adequately investigated. We therefore studied the effects of various oxygen concentrations on intestinal epithelial cell function. In order to assess the effects of hyperoxia on the intestinal immunological barrier, we studied two physiological changes in neonatal rats exposed to hyperoxia: the change in intestinal IgA secretory component (SC, an important component of SIgA) and changes in intestinal epithelial cells. Immunohistochemistry and Western blot were used to detect changes in the intestinal tissue SC of neonatal rats. To detect intestinal epithelial cell growth, cells were counted, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Giemsa staining were used to assess cell survival. Immunohistochemistry was used to determine SC expression. The expression of intestinal SC in neonatal rats under hyperoxic conditions was notably increased compared with rats inhaling room air (P < 0.01). In vitro, 40% O2 was beneficial for cell growth. However, 60% O2 and 90% O2 induced rapid cell death. Also, 40% O2 induced expression of SC by intestinal epithelial cells, whereas 60% O2did not; however, 90% O2 limited the ability of intestinal epithelial cells to express SC. In vivo and in vitro, moderate hyperoxia brought about increases in intestinal SC. This would be expected to bring about an increase in intestinal SIgA. High levels of SC and SIgA would serve to benefit hyperoxia-exposed individuals by helping to maintain optimal conditions in the intestinal tract.

Reduction of the amount of intestinal secretory IgA in fulminant hepatic failure

Intestinal barrier dysfunction plays an important role in spontaneous bacterial peritonitis. In the present study, changes in the intestinal barrier with regard to levels of secretory immunoglobulin A (SIgA) and its components were studied in fulminant hepatic failure (FHF). Immunohistochemistry and double immunofluorescent staining were used to detect intestinal IgA, the secretory component (SC) and SIgA in patients with FHF (20 patients) and in an animal model with FHF (120 mice). Real-time PCR was used to detect intestinal SC mRNA in the animal model with FHF. Intestinal SIgA, IgA, and SC staining in patients with FHF was significantly weaker than in the normal control group (30 patients). Intestinal IgA and SC staining was significantly weaker in the animal model with FHF than in the control groups (normal saline: 30 mice; lipopolysaccharide: 50 mice; D-galactosamine: 50 mice; FHF: 120 mice). SC mRNA of the animal model with FHF at 2, 6, and 9 h after injection was 0.4 ± 0.02, 0.3 ± 0.01, 0.09 ± 0.01, respectively. SC mRNA of the animal model with FHF was significantly decreased compared to the normal saline group (1.0 ± 0.02) and lipopolysaccharide group (0.89 ± 0.01). The decrease in intestinal SIgA and SC induced failure of the intestinal immunologic barrier and the attenuation of gut immunity in the presence of FHF.

Nefropatia por IgA: análise histológica e correlação clínico-morfológica em pacientes do Estado de Minas Gerais

INTRODUÇÃO: A Nefropatia por IgA (NIgA) é a glomerulopatia primária mais comum. OBJETIVO: Classificar a NIgA segundo a nova proposta de Classificação de Oxford. MÉTODOS: Foram analisadas biópsias do Serviço de Nefropatologia da UFTM, no período de 1996 a 2010, com diagnóstico de NIgA. Foram avaliados gênero, idade, presença de hematúria, padrões/intensidade das lesões, deposições de IgA, IgG, IgM, Kappa, Lambda, C3, C1q e fibrinogênio. Histologicamente, as biópsias foram caracterizadas conforme a Classificação de Oxford, e realizou-se a correlação clínico-morfológica. RESULTADOS: Das 164 biópsias avaliadas, houve predomínio do gênero masculino (53,7%) e adulto (93,3%). Caracterizando os pacientes conforme a classificação de Oxford, obtivemos predominância M0 (85,3%), S1 (53,1%), E0 (65,2%) e T0 (70,1%). À correção clínico-morfológica, observamos maior proteinúria M1 em relação a M0 (p < 0,008), menor taxa de filtração glomerular estimada (p < 0,001) e maior frequência de hipertensão (p < 0,001) comparando-se T0,T1 e T2. À imunofluorescência, predominância de IgA (100% dos casos), com codeposição de C3 (99,37% dos casos), Kappa (96,25%), Lambda (91,25%) e IgM (76,92%). Foi observada correlação entre a intensidade de deposição de IgA com C3, Kappa e Lambda. CONCLUSÃO: No presente estudo, a NIgA foi predominante em homens, mais comuns foram os padrões M0, S1, E0 e T0, com maior proteinúria e aumento da hipercelularidade mesangial, além de maior prevalência de hipertensão/pior função renal conforme a gravidade das repercussões túbulo-intersticiais.

Corticotherapy response in primary IgA nephropathy

INTRODUCTION: Some beneficial effects from long-term use of corticosteroids have been reported in patients with IgA nephropathy. OBJECTIVE: This retrospective study aimed to evaluate the outcome of proteinuria and renal function according to a protocol based on a 6-month course of steroid treatment. METHOD: Twelve patients were treated with 1 g/day intravenous methylprednisolone for 3 consecutive days at the beginning of months 1, 3, and 5 plus 0.5 mg/kg oral prednisone on alternate days for 6 months (treated group). The control group included 9 untreated patients. RESULTS: Proteinuria (median and 25th and 75th percentiles) at baseline in the treated group was 1861 mg/24h (1518; 2417 mg/24h) and was 703 mg/24h (245; 983) and 684 mg/24h (266; 1023) at the 6th (p < 0.05 vs. baseline) and 12th months (p < 0.05 vs. baseline), respectively. In the control group the proteinuria was 1900 mg/24h (1620; 3197) at baseline and was 2290 mg/24h (1500; 2975) and 1600 mg/24h (1180; 2395) at the 6th and 12th months, respectively (not significant vs. baseline). When compared with the control group, the treated group showed lower proteinuria (p < 0.05) during the follow-up and a higher number of patients in remission (p < 0.05) at the 6th and 12th months. Renal function did not change during the follow-up and the adverse effects were mild in most of the patients. CONCLUSION: The 6-month course of steroid treatment was effective in reducing proteinuria during the 12 months of the follow-up, and was well-tolerated by most of the patients.

Relato de Caso - Nefropatia de IgA associada ao ANCA com evolução favorável

ResumoIntrodução:Os anticorpos anticitoplasma de neutrófilos (ANCA) comumente estão relacionados a glomerulonefrites rapidamente progressivas (GnRP) com padrão pauci-imune. Apesar disso, a literatura mostra uma incidência além da esperada de ANCA nas GnRP por imunocomplexos. A nefropatia por imunoglobulina A (NIgA) crescêntica é uma das GnRP que pode se associar ao ANCA.Objetivo:Relatar caso de NigA com sinais clínicos de mau prognóstico associado ao ANCA com evolução favorável após imunossupressão.Método:Foi relatado caso de paciente com 38 anos com quadro de hipertensão arterial (HAS), insuficiência renal (CKD-EPI- 37 ml/min/1,73 m2), proteinúria subnefrótica e hematúria. Nos antecedentes pessoais, relatava epistaxes ocasionais, rinossinusite e episódio de artrite com remissão espontânea. Durante a investigação diagnóstica, foram detectados ANCA positivo 1/160 e anti-PR3, porém, com biópsia renal compatível com NIgA com 38% de crescentes na amostra. Foi realizado diagnóstico de NIgA associada ao ANCA, sendo indicado tratamento imunossupressor por seis meses com corticoterapia (pulsoterapia com metilprednisolona 1 g por 3 dias, seguido de prednisona 1 mg/kg/dia) e ciclofosfamida (500 mg com aumento crescente da dose até 750 mg/m2). Paciente evolui com recuperação da função renal, além da redução da proteinúria e da titulação de ANCA.Conclusão:A importância da identificação dessa sobreposição está no comportamento agressivo dessa doença caracterizada pela presença de crescentes, atrofia tubular e disfunção renal que podem regredir com início precoce da imunossupressão.

Patogênese e tratamento da glomerulonefrite - uma atualização

Resumo A presente revisão traz os conceitos mais atuais acerca dos fatores de risco genéticos, eventos etiológicos, respostas nefritogênicas e tratamento dos principais tipos de glomerulonefrite (GN) imunomediada. Tais patologias incluem GN pós-infecciosa, nefropatia por IgA, doença por anticorpo antimembrana basal glomerular (anti-MBG), vasculite associada a ANCA (VAA) e nefrite lúpica. Apesar da(s) etiologia(s) da maioria dos casos de GN permanecer indefinida, acredita-se que seu início se deva, em grande parte, a insultos ambientais, particularmente na forma de processos infecciosos que deflagram respostas de hospedeiro em indivíduos geneticamente suscetíveis, levando assim a quadros de GN. A concepção mecanicista em torno dessas patologias evoluiu a partir da visão mais antiga de que a maioria seria consequência do aprisionamento glomerular de complexos imunes pré-formados para a percepção atual de que as mesmas, em sua maioria, são doenças autoimunes por natureza mediadas por anticorpos e linfócitos T reativos a auto-antígenos. O tratamento da GN não tem acompanhado os progressos na compreensão de sua patogênese. Os papéis recentemente atribuídos a mediadores mais antigos como complemento e proteínas reguladoras do complemento lançam luz sobre novos alvos terapêuticos.

Prevalencia de enfermedad celiaca en Latinoamérica: revisión sistemática de la literatura y meta-análisis

Introducción: La enfermedad celiaca (EC) es una enfermedad autoinmune (EA) intestinal desencadenada por la ingesta de gluten. Por la falta de información de la presencia de EC en Latinoamérica (LA), nosotros investigamos la prevalencia de la enfermedad en esta región utilizando una revisión sistemática de la literatura y un meta-análisis. Métodos y resultados: Este trabajo fue realizado en dos fases: La primera, fue un estudio de corte transversal de 300 individuos Colombianos. La segunda, fue una revisión sistemática y una meta-regresión siguiendo las guías PRSIMA. Nuestros resultados ponen de manifiesto una falta de anti-transglutaminasa tisular (tTG) e IgA anti-endomisio (EMA) en la población Colombiana. En la revisión sistemática, 72 artículos cumplían con los criterios de selección, la prevalencia estimada de EC en LA fue de 0,46% a 0,64%, mientras que la prevalencia en familiares de primer grado fue de 5,5 a 5,6%, y en los pacientes con diabetes mellitus tipo 1 fue de 4,6% a 8,7% Conclusión: Nuestro estudio muestra que la prevalencia de EC en pacientes sanos de LA es similar a la notificada en la población europea.

La reforma educativa de Juan de Z????iga en la Universidad de Salamanca

En este art??culo se se??ala que la visita de Juan de Z????iga y la reforma de la universidad en 1594, supuso un cambio muy importante del r??gimen universitario salmantino. El autor afirma que esta reforma fue tan notable como la precedente de Covarrubias de 1561, y que los dos cuerpos jur??dicos, de Covarrubias y de Z????iga, fueron los m??s relevantes estatutos de la universidad, como as?? queda reflejado en la recopilaci??n de 1625, que tuvo vigencia hasta las transformaciones de la primera mitad del siglo XIX.