RESUMO
BACKGROUND: Progesterone, estrogen and the hormonal complex of pregnancy have been responsible for some degree of colon hypomotility in human pregnancy. OBJECTIVE: To find out if estrogen, progesterone and the hormonal complex of pregnancy decrease colon myoelectric activity. METHODS: The study was performed in 37 healthy female rats in which electrodes were implanted on the serosa of the proximal ascendent, distal ascendent, transverse, and descendent colon. We analyzed the records of colon myoelectric activity in vivo in five groups: control, ovariectomized, ovariectomized and treated with estrogen, ovariectomized and treated with progesterone, and pregnant rats. RESULTS: We found a great variation in myoelectric activity in all groups studied. The mean of electric activity did not show statistical difference among the five groups, but pregnant rats had a statistically significant higher duration of maximum electric activity in all distances from the cecocolon junction. CONCLUSION: Pregnant rats had a statistically higher duration of maximum electric activity. If we could transpose these results to humans, this increase in duration of colon myoelectric activity could explain, in part, the slight constipation that some pregnant women have.
Assuntos
Colo/fisiologia , Estrogênios/fisiologia , Complexo Mioelétrico Migratório/fisiologia , Gravidez/fisiologia , Progesterona/fisiologia , Animais , Feminino , Modelos Animais , Ratos , Ratos WistarRESUMO
The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a complex process involving the uncoupling of mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase (COX). Rofecoxib, a selective inhibitor of COX-2, has shown less gastric damage, but the same beneficial effect is not clear in the case of the small bowel. Fifty-seven male Wistar rats (250-350 g) were divided into three groups (N=19 each) to evaluate the effect of this NSAID on the rat intestine. The groups received 2.5 mg/kg rofecoxib, 7.5 mg/kg indomethacin or water with 5% DMSO (control) given as a single dose by gavage 24 h before the beginning of the experiment. A macroscopic score was used to quantify intestinal lesions and intestinal permeability was measured using [51Cr]-ethylenediaminetetraacetic acid ([51Cr]-EDTA). The extent of intestinal lesion, indicated by a macroscopic score, was significantly lower when rofecoxib was administered compared to indomethacin (rofecoxib=0.0 vs indomethacin=63.6 +/- 25.9; P<0.05) and did not differ from control. The intestinal permeability to [51Cr]-EDTA was significantly increased after indomethacin (control=1.82 +/- 0.4 vs indomethacin=9.12 +/- 0.8%; P<0.0001), but not after rofecoxib, whose effect did not differ significantly from control (control=1.82 +/- 0.4 vs rofecoxib=2.17 +/- 0.4%; ns), but was significantly different from indomethacin (indomethacin=9.12 +/- 0.8 vs rofecoxib=2.17 +/- 0.4%; P<0.001). In conclusion, the present data show that rofecoxib is safer than indomethacin in rats because it does not induce macroscopic intestinal damage or increased intestinal permeability.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Indometacina/farmacologia , Intestino Delgado/efeitos dos fármacos , Isoenzimas/antagonistas & inibidores , Lactonas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/efeitos adversos , Indometacina/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Lactonas/efeitos adversos , Masculino , Permeabilidade/efeitos dos fármacos , Prostaglandina-Endoperóxido Sintases , Ratos , Ratos Wistar , SulfonasRESUMO
The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a complex process involving the uncoupling of mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase (COX). Rofecoxib, a selective inhibitor of COX-2, has shown less gastric damage, but the same beneficial effect is not clear in the case of the small bowel. Fifty-seven male Wistar rats (250-350 g) were divided into three groups (N = 19 each) to evaluate the effect of this NSAID on the rat intestine. The groups received 2.5 mg/kg rofecoxib, 7.5 mg/kg indomethacin or water with 5 percent DMSO (control) given as a single dose by gavage 24 h before the beginning of the experiment. A macroscopic score was used to quantify intestinal lesions and intestinal permeability was measured using [51Cr]-ethylenediaminetetraacetic acid ([51Cr]-EDTA). The extent of intestinal lesion, indicated by a macroscopic score, was significantly lower when rofecoxib was administered compared to indomethacin (rofecoxib = 0.0 vs indomethacin = 63.6 ± 25.9; P < 0.05) and did not differ from control. The intestinal permeability to [51Cr]-EDTA was significantly increased after indomethacin (control = 1.82 ± 0.4 vs indomethacin = 9.12 ± 0.8 percent; P < 0.0001), but not after rofecoxib, whose effect did not differ significantly from control (control = 1.82 ± 0.4 vs rofecoxib = 2.17 ± 0.4 percent; ns), but was significantly different from indomethacin (indomethacin = 9.12 ± 0.8 vs rofecoxib = 2.17 ± 0.4 percent; P < 0.001). In conclusion, the present data show that rofecoxib is safer than indomethacin in rats because it does not induce macroscopic intestinal damage or increased intestinal permeability.
Assuntos
Animais , Masculino , Ratos , Anti-Inflamatórios não Esteroides , Inibidores de Ciclo-Oxigenase , Indometacina , Intestino Delgado , Mucosa Intestinal , Intestino Delgado , Permeabilidade , Ratos WistarRESUMO
The effect of the reduction of intra-abdominal pressure on the lower esophageal sphincter pressure (LESP) and the 24-hour pH monitoring were studied in 16 patients with ascites before and after paracentesis. LESP did not change (P > 0.05) with the reduction of intra-abdominal pressure (before paracentesis: 17.48 mmHg and postparacentesis: 18.67 mmHg). The results were divided into two groups according to the achieved reduction in intra-abdominal pressure group A were those in who the reduction was greater than 70% and B consisted of those a reduction of less than 70%. LESP did not change even when results for each group were considered separately (P > 0.05): group A (before: 15.60 mmHg; after: 18.09 mmHg); group B (before: 23.09 mmHg; after: 20.40 mmHg). However the 24-h pH monitoring showed pathological reflux in patients with ascites that was reduced with the paracentesis (P < 0.05; total number of reflux episodes before paracentesis was 520.26, and after, 136.26). All pH-monitoring parameters were statistically different (P < 0.05) before and after the reduction of intra-abdominal pressure for group A but not for group B. LESP does not change significantly (P > 0.05) when the intra-abdominal pressure is significantly reduced (P < 0.05). Patients with ascites showed gastroesophageal reflux. Intra-abdominal pressure reduction greater than 70% lead to a significant reduction in gastroesophageal reflux.
Assuntos
Abdome/fisiologia , Ascite/fisiopatologia , Junção Esofagogástrica/fisiologia , Refluxo Gastroesofágico/prevenção & controle , Estudos de Casos e Controles , Humanos , Concentração de Íons de Hidrogênio , Hepatopatias/fisiopatologia , Monitorização Fisiológica , Paracentese , Pressão , Estudos ProspectivosRESUMO
The hypothesis of the role of iron overload associated with HFE gene mutations in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been raised in recent years. In the present study, biochemical and histopathological evidence of iron overload and HFE mutations was investigated in NASH patients. Thirty-two NASH patients, 19 females (59%), average 49.2 years, 72% Caucasians, 12% Mulattoes and 12% Asians, were submitted to serum aminotransferase and iron profile determinations. Liver biopsies were analyzed for necroinflammatory activity, architectural damage and iron deposition. In 31 of the patients, C282Y and H63D mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased in 30 patients, 2.42 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 31.3 g/dl, 33.1 12.7% and 219.8 163.8 g/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1% of the patients. Hepatic siderosis was observed in three patients and was not associated with architectural damage (P = 0.53) or with necroinflammatory activity (P = 0.27). The allelic frequencies (N = 31) found were 1.6 and 14.1% for C282Y and H63D, respectively, which were compatible with those described for the local population. In conclusion, no evidence of an association of hepatic iron overload and HFE mutations with NASH was found. Brazilian NASH patients comprise a heterogeneous group with many associated conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs, but not hepatic iron overload, and their disease susceptibility could be related to genetic and environmental features other than HFE mutations.
Assuntos
Fígado Gorduroso/etiologia , Antígenos de Histocompatibilidade Classe I/genética , Sobrecarga de Ferro/complicações , Proteínas de Membrana/genética , Mutação , Adulto , Idoso , Alanina Transaminase/análise , Biópsia , Estudos de Coortes , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Feminino , Ferritinas/análise , Proteína da Hemocromatose , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Transferrina/análiseRESUMO
The hypothesis of the role of iron overload associated with HFE gene mutations in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been raised in recent years. In the present study, biochemical and histopathological evidence of iron overload and HFE mutations was investigated in NASH patients. Thirty-two NASH patients, 19 females (59 percent), average 49.2 years, 72 percent Caucasians, 12 percent Mulattoes and 12 percent Asians, were submitted to serum aminotransferase and iron profile determinations. Liver biopsies were analyzed for necroinflammatory activity, architectural damage and iron deposition. In 31 of the patients, C282Y and H63D mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased in 30 patients, 2.42 + or - 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 + or - 31.3 g/dl, 33.1 + or - 12.7 percent and 219.8 + or - 163.8 æg/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1 percent of the patients. Hepatic siderosis was observed in three patients and was not associated with architectural damage (P = 0.53) or with necroinflammatory activity (P = 0.27). The allelic frequencies (N = 31) found were 1.6 and 14.1 percent for C282Y and H63D, respectively, which were compatible with those described for the local population. In conclusion, no evidence of an association of hepatic iron overload and HFE mutations with NASH was found. Brazilian NASH patients comprise a heterogeneous group with many associated conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs, but not hepatic iron overload, and their disease susceptibility could be related to genetic and environmental features other than HFE mutations
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fígado Gorduroso , Sobrecarga de Ferro , Mutação , Alanina Transaminase , Biópsia , Estudos de Coortes , Fígado Gorduroso , Ferritinas , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , TransferrinaRESUMO
BACKGROUND/AIM: The pathogenesis of Nonalcoholic Fatty Liver Disease remains largely unknown, but oxidative stress seems to be involved. The aim of this study was to evaluate the role of oxidative stress in experimental hepatic steatosis induced by a choline-deficient diet. METHODS: Fatty liver disease was induced in Wistar rats by a choline-deficient diet. The animals were randomized into three groups: I (G1) and II (G2), n=6 each--fed with a choline-deficient diet for four and twelve weeks respectively; Group III (control-G3; n=6)--fed with a standard diet for twelve weeks. Samples of plasma and liver were submitted to biochemical, histological and oxidative stress analysis. Variables measured included serum levels of aminotransferases (AST, ALT), cholesterol and triglycerides. Oxidative stress was measured by lucigenin-enhanced luminescence and the concentration of hydroperoxides (CE-OOH-cholesteryl ester) in the liver tissue. RESULTS: We observed moderate macro- and microvesicular fatty change in periportal zones G1 and G2 as compared to controls (G3). In G2, fatty change was more severe. The inflammatory infiltrate was scanty and no fibrosis was seen in any group. There was a significant increase of AST and triglycerides in G1 and G2 as compared to control group G3. The lucigenin-amplified luminescence (cpm/mg/min x 10(3)) was significantly increased in G1 (1393-/+790) and G2 (7191-/+500) as compared to controls (513-/+170), p<0.05. The concentrations of CE-OOH were higher in G1 (5.7-/+0.9 nmol/mg protein) as compared to control (2.6-/+0.7 nmol/mg protein), p<0.05. CONCLUSION: 1) Oxidative stress was found to be increased in experimental liver steatosis; 2) The production of reactive oxygen species was accentuated when liver steatosis was more severe; 3) The alterations produced by oxidative stress could be an important step in the pathogenesis of nonalcoholic fatty liver disease.
Assuntos
Deficiência de Colina/fisiopatologia , Colina/administração & dosagem , Fígado Gorduroso/fisiopatologia , Estresse Oxidativo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Colesterol/sangue , Dieta , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Peróxidos Lipídicos/metabolismo , Fígado/química , Fígado/metabolismo , Fígado/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Triglicerídeos/sangueRESUMO
The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53%) were homozygous and one (7%) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil.
Assuntos
Antígenos HLA/genética , Antígenos HLA-A/genética , Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I/genética , Proteínas de Membrana , Mutação/genética , Adulto , Idade de Início , Idoso , Substituição de Aminoácidos , Sequência de Bases , Brasil/epidemiologia , Testes Genéticos , Hemocromatose/epidemiologia , Proteína da Hemocromatose , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53 percent) were homozygous and one (7 percent) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil
Assuntos
Humanos , Animais , Masculino , Adulto , Pessoa de Meia-Idade , Hemocromatose , Antígenos HLA-A , Idade de Início , Substituição de Aminoácidos , Sequência de Bases , Brasil , Testes Genéticos , Hemocromatose , Heterozigoto , Homozigoto , Mutação , PrevalênciaRESUMO
The detection of anti-actin (AAA) by immunofluorescence is hindered by the presence of a serum factor. To better understand how it interferes with AAA detection, we tested sera from 20 patients with autoimmune hepatitis, and from 21 healthy adults, diluted 1:10 and prepared as follows: (A) diluted with PBS; (B) inactivated at 56 degrees C, and diluted with PBS; (C) diluted with 34 mM EDTA/PBS; (D) heated and diluted with EDTA/PBS. To reveal AAA, a fluorescein-labelled anti-human IgG was used in the process of indirect immunofluorescence. In a parallel assay, the substrate, acetone-fixed human fibroblasts, was preincubated with sera prepared as if it were to identify AAA, but instead, a rhodamine-phalloidin was used to identify F-actin, by direct immunofluorescence. All sera from patients were reactive to AAA when heat-inactivated and/or calcium-chelated, and 60% of them when diluted with unmodified sera (P=0.004). F-actin continued to be present after preincubation with heat-inactivated or calcium-chelated sera from patients and healthy controls, and in 41.5% of reactions with unmodified serum (P=0.0000001). The heat inactivation and the calcium chelation were both efficient procedures for maintaining the microfilament structure intact after serum incubation and, therefore, for identifying AAA.
Assuntos
Actinas/imunologia , Actinas/metabolismo , Autoanticorpos/sangue , Cálcio/fisiologia , Temperatura Alta , Proteínas dos Microfilamentos/fisiologia , Fatores de Despolimerização de Actina , Actinas/sangue , Adulto , Autoanticorpos/análise , Cálcio/sangue , Destrina , Imunofluorescência , Hepatite Autoimune/sangue , Hepatite Autoimune/imunologia , Humanos , Proteínas dos Microfilamentos/sangue , Polímeros/metabolismoAssuntos
Circulação Hepática/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Silimarina/farmacologia , Verapamil/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/ultraestrutura , Circulação Hepática/efeitos dos fármacos , Medições Luminescentes , Estresse Oxidativo/efeitos dos fármacos , Ratos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/ultraestrutura , Fatores de TempoRESUMO
BACKGROUND/AIMS: Susceptibility to autoimmune hepatitis (AIH) has been linked to different HLA-DR antigens. Recently, AIH type 1 was associated with polymorphisms in the tumor necrosis factor alpha gene promoter (TNFA) at position -308. In this respect, the frequency of the TNFA*2 allele, in linkage disequilibrium with HLA-DRB1*0301, was shown to be significantly increased in whites with AIH type 1. The aim of this study was to assess the role of TNFA alleles in conferring susceptibility to AIH, studying a population where the disease is not primarily associated with HLA-DRB1*03. METHODS: The determination of HLA-DRB1 and TNFA alleles was performed in 92 patients with AIH type 1, 29 subjects with AIH type 2 and 83 healthy controls by polymerase chain reaction-based techniques. RESULTS: The distribution of TNFA alleles was similar in patients with AIH types 1 and 2, when compared with controls. In addition, the TNFA*2 allele was identified in patients carrying HLA-DR antigens other than HLA-DRB1*03. Interestingly, higher gammaglobulin levels were observed in TNFA*2 positive patients. CONCLUSIONS: Our data indicate that susceptibility to AIH remains primarily linked to the HLA-DRB1 locus, and suggest that the association of AIH with TNFA*2 previously observed in whites might be secondary to a linkage disequilibrium with HLA-DRB1*0301.
Assuntos
Ligação Genética , Hepatite Autoimune/genética , Polimorfismo Genético/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença/genética , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The involvement of the gastrointestinal tract in the co-infection of HIV and Leishmania is rarely reported. We report the case of an HIV-infected adult man co-infected with a disseminated form of leishmaniasis involving the liver, lymph nodes, spleen and, as a feature reported for the first time in the English literature, the pancreas. Light microscopy showed amastigote forms of Leishmania in pancreatic macrophages and immunohistochemical staining revealed antigens for Leishmania and also for HIV p24. Microscopic and ultrastructural analysis revealed severe acinar atrophy, decreased zymogen granules in the acinar cytoplasm and also nuclear abnormalities such as pyknosis, hyperchromatism and thickened chromatin. These findings might correspond to the histologic pattern of protein-energy malnutrition in the pancreas as shown in our previous study in pancreas with AIDS and no Leishmania. In this particular case, the protein-energy malnutrition may be due to cirrhosis, or, Leishmania or HIV infection or all mixed. We believe that this case represents the morphologic substratum of the protein energy malnutrition in pancreas induced by the HIV infection. Further studies are needed to elucidate these issues.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções por HIV/complicações , Leishmaniose Visceral/complicações , Pancreatopatias/complicações , Desnutrição Proteico-Calórica/etiologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Adulto , Evolução Fatal , Infecções por HIV/patologia , Humanos , Leishmaniose Visceral/patologia , Masculino , Pancreatopatias/patologiaRESUMO
UNLABELLED: Triple therapy is accepted as the treatment of choice for H. pylori eradication. In industrialized countries, a proton pump inhibitor plus clarithromycin and amoxicillin or nitroimidazole have shown the best results. Our aims were: 1. To study the eradication rate of the association of a proton pump inhibitor plus tinidazole and clarithromycin on H. pylori infection in our population. 2. To determine if previous treatments, gender, age, tobacco, alcohol use, and non-steroidal anti-inflammatory drugs (NSAIDs) change the response to therapy. METHODS: Two hundred patients with peptic ulcer (upper endoscopy) and H. pylori infection (histology and rapid urease test - RUT) were included. A proton pump inhibitor (lanzoprazole 30 mg or omeprazole 20 mg), tinidazole 500 mg, and clarithromycin 250 mg were dispensed twice a day for a seven-day period. Eradication was assessed after 10 to 12 weeks of treatment through histology and RUT. RESULTS: The eradication rate of H. pylori per protocol was 65% (128/196 patients). This rate was 53% for previously treated patients, rising to 76% for not previously treated patients, with a statistical difference p<0.01. No significant difference was observed regarding sex, tobacco use, alcohol consumption, and NSAID use, but for elderly patients the difference was p = 0.05. Adherence to treatment was good, and side effects were mild. CONCLUSIONS: A proton pump inhibitor, tinidazole, and clarithromycin bid for seven days resulted in H. pylori eradication in 65% of the patients. Previous treatments were the main cause of treatment failure.
Assuntos
Antibacterianos/administração & dosagem , Claritromicina/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Omeprazol/análogos & derivados , Úlcera Péptica/tratamento farmacológico , Inibidores da Bomba de Prótons , Tinidazol/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Esquema de Medicação , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Feminino , Humanos , Lansoprazol , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Úlcera Péptica/microbiologia , Resultado do TratamentoRESUMO
The objective of the present study was to assess intestinal permeability in patients with infection caused by Strongyloides stercoralis. Twenty-six patients (16 women and 10 men), mean age 45.9, with a diagnosis of strongyloidiasis were evaluated. For comparison, 25 healthy volunteers (18 women and 7 men), mean age 44.9, without digestive disorders or intestinal parasites served as normal controls. Intestinal permeability was measured on the basis of urinary radioactivity levels during the 24 h following oral administration of chromium-labeled ethylenediaminetetraacetic acid ((51)Cr-EDTA) expressed as percentage of the ingested dose. The urinary excretion of (51)Cr-EDTA was significantly reduced in patients with strongyloidiasis compared to controls (1.60 +/- 0.74 and 3.10 +/- 1.40, respectively, P = 0.0001). Intestinal permeability is diminished in strongyloidiasis. Abnormalities in mucus secretion and intestinal motility and loss of macromolecules could explain the impaired intestinal permeability.
Assuntos
Absorção Intestinal , Strongyloides stercoralis , Estrongiloidíase/fisiopatologia , Adulto , Idoso , Animais , Estudos de Casos e Controles , Radioisótopos de Cromo/urina , Ácido Edético/urina , Feminino , Humanos , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade , Permeabilidade , Estrongiloidíase/urinaRESUMO
The objective of the present study was to assess intestinal permeability in patients with infection caused by Strongyloides stercoralis. Twenty-six patients (16 women and 10 men), mean age 45.9, with a diagnosis of strongyloidiasis were evaluated. For comparison, 25 healthy volunteers (18 women and 7 men), mean age 44.9, without digestive disorders or intestinal parasites served as normal controls. Intestinal permeability was measured on the basis of urinary radioactivity levels during the 24 h following oral administration of chromium-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) expressed as percentage of the ingested dose. The urinary excretion of 51Cr-EDTA was significantly reduced in patients with strongyloidiasis compared to controls (1.60 + or - 0.74 and 3.10 + or - 1.40, respectively, P = 0.0001). Intestinal permeability is diminished in strongyloidiasis. Abnormalities in mucus secretion and intestinal motility and loss of macromolecules could explain the impaired intestinal permeability
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Radioisótopos de Cromo/farmacocinética , Ácido Edético/farmacocinética , Absorção Intestinal , Strongyloides stercoralis , Estrongiloidíase/parasitologia , Estudos de Casos e Controles , Radioisótopos de Cromo , Radioisótopos de Cromo/urina , Ácido Edético , Ácido Edético/urina , Mucosa Intestinal/metabolismo , Permeabilidade , Estrongiloidíase/diagnósticoRESUMO
BACKGROUND: The pathogenesis of non-steroidal anti-inflammatory drug (NSAID) enteropathy is complex. It involves uncoupling of mitochondrial oxidative phosphorylation which alters the intercellular junction and increases intestinal permeability with consequent intestinal damage. Metronidazole diminishes the inflammation induced by indomethacin but the mechanisms remain speculative. A direct effect on luminal bacteria has traditionally been thought to account for the protective effect of metronidazole. However, a protective effect of metronidazole on mitochondrial oxidative phosphorylation has never been tested. AIMS: To assess the protective effect of metronidazole on mitochondrial uncoupling induced by indomethacin and also on the increased intestinal permeability and macroscopic damage. MATERIAL AND METHODS: The protective effect of metronidazole was evaluated in rats given indomethacin; a macroscopic score was devised to quantify intestinal lesions, and intestinal permeability was measured by means of (51)Cr-ethylenediaminetetraacetic acid. The protective effect of metronidazole against mitochondrial uncoupling induced by indomethacin was assessed using isolated coupled rat liver mitochondria obtained from rats pretreated with metronidazole or saline. RESULTS: Metronidazole significantly reduced the macroscopic intestinal damage and increase in intestinal permeability induced by indomethacin; furthermore, at the mitochondrial level, it significantly reduced the increase in oxygen consumption in state 4 induced by indomethacin and caused less reduction of the respiratory control rate. CONCLUSION: Our study confirmed the beneficial effects of metronidazole on intestinal damage and intestinal permeability, and demonstrated, for the first time, a direct protective effect of metronidazole on uncoupling of mitochondrial oxidative phosphorylation caused by NSAIDs.
Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Indometacina/farmacologia , Metronidazol/farmacologia , Mitocôndrias/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , Animais , Interações Medicamentosas , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Consumo de Oxigênio/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Wistar , Análise de Regressão , Estatísticas não Paramétricas , Desacopladores/farmacologiaRESUMO
BACKGROUND: Pancreatic involvement in AIDS is rarely mentioned in medical literature. AIMS: To identify the main morphological patterns of the pancreas using optical and electron microscopy in AIDS patients. DESIGN: An open, prospective, and sequential study in a tertiary institutional hospital. METHODS: Consecutive post-mortems of 109 AIDS patients and 38 controls (1995). Baseline characteristics of AIDS patients and controls were evaluated. Morphological analysis consisted of: (i) semi-quantitative score of acinar and parenchymal elements; (ii) qualitative analysis of ducts, vascular components, nerves, and Langerhans' islets; (iii) specific stains and immunohistochemistry for opportunistic agents; (iv) ultrastructural data. RESULTS: The mean age of AIDS patients was 37 years; 80% were male; 60% were white; 21% were alcoholic. All patients with AIDS had normal blood amylase, blood glucose, and pancreatic ultrasound. Histological findings were: acinar atrophy (60%), few zymogen granula in acinar cytoplasm (52%), abnormalities in acinar nucleus (65%), pancreatic steatosis (66%), and focal necrosis (17%). Immunohistochemistry revealed: mycobacteriosis (22%), toxoplasmosis (13%), cytomegalovirus (9%), Pneumocystis carinii (9%), and HIV p24 antigen in macrophage cytoplasm (22%). Ultrastructural examination showed: decreased zymogen granula, enlargement and proliferation of the endoplasmic reticulum and mitochondria, nuclear abnormalities, and increased lipid droplets in acinar cytoplasm. CONCLUSION: Pancreatic involvement in AIDS is very frequent (90%) and is usually asymptomatic. Morphological changes showed three patterns of pancreatic alterations: 'nutritional-like', inflammatory and both of these together. The 'nutritional-like' pattern (atrophy, few zymogen granula and steatosis) may be due to many factors such as nutritional characteristics (Kwashiorkor-like) induced by the HIV infection or related to the HIV virus itself.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/patologia , Síndrome da Imunodeficiência Adquirida/patologia , Pâncreas/patologia , Pancreatopatias/etiologia , Pancreatopatias/patologia , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Adulto , Autopsia , Feminino , Humanos , Masculino , Microscopia Eletrônica , Estudos ProspectivosRESUMO
A low frequency of Helicobacter pylori in the gastric mucosa of patients with alkaline gastritis has been reported. At the same time, it can be noted that the growth of bacteria can be inhibited by bile acids. We studied 40 patients with chronic gastritis related to Helicobacter pylori in order to determine the effect of ursodeoxycholic acid on this infection. Diagnoses of the infection and the inflammatory process were obtained by histologic study of gastric biopsies collected during endoscopy. Two groups were studied: group I received ursodeoxycholic acid - 300 mg/day, and group II received the placebo, twice a day, both for 28 days. The colonization by Helicobacter pylori and the intensity of the mononuclear and polymorphonuclear inflammatory infiltrate were determined before (time 1) and after (time 2) treatment. Ursodeoxycholic acid had no effect on the Helicobacter pylori infection. A significant reduction in the intensity of the mononuclear inflammatory infiltrate of the gastric antrum mucosa was observed in patients from group I, when we compared not only times 1 and 2 but also groups I and II. However, this was not the case with the body mucosa. We concluded that ursodeoxycholic acid had no action on the colonization by Helicobacter pylori or on the polymorphonuclear inflammatory infiltrate, but it caused a significant reduction in the intensity of the mononuclear inflammatory infiltrate of the gastric antrum.
Assuntos
Colagogos e Coleréticos/farmacologia , Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Helicobacter pylori/efeitos dos fármacos , Ácido Ursodesoxicólico/farmacologia , Adulto , Colagogos e Coleréticos/uso terapêutico , Feminino , Mucosa Gástrica/efeitos dos fármacos , Gastrite/tratamento farmacológico , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Masculino , Antro Pilórico/efeitos dos fármacos , Antro Pilórico/microbiologia , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
Even though the seroprevalence of H. pylori may be high in the normal population, a minority develops peptic ulcer. Colonization of the gastric mucosa by more pathogenic vacA strains of H. pylori seems to be associated with enhanced gastric inflammation and duodenal ulcer. H. pylori genotyping from positive CLOtests was developed to determine the vacA genotypes and cagA status in 40 duodenal ulcer patients and for routine use. The pathogenic s1b/ m1/ cagA genotype was the most frequently occurring strain (17/42.5%); only two (5%) patients presented the s2/ m2 genotype, the less virulent strain. Multiple strains were also detected in 17 (42.5%) patients. Multiple strains of H. pylori colonizing the human stomach have been underestimated, because genotyping has been performed from cultures of H. pylori. We concluded that genotyping of H. pylori from a positive CLOtest had the advantages of reducing the number of biopsies taken during endoscopy, eliminating the step of culturing H. pylori, and assuring the presence of H. pylori in the specimen being processed.