RESUMO
The aim of the present study was to determine the efficacy of LAB strains in reducing the intestinal toxicity of arsenite [As(III)] and its tissue accumulation. For this purpose, Balb/c mice were randomly separated in four groups. One group received no treatment (control), one group received only As(III) (30 mg/L) via drinking water and the remaining two groups received As(III) via water and a daily dose of two LAB strains (Lactobacillus intestinalis LE1 and Lacticaseibacillus paracasei BL23) by gavage during 2 months. The results show that both strains reduce the pro-inflammatory and pro-oxidant response observed at the colonic level, partially restore the expression of the intercellular junction proteins (CLDN3 and OCLN) responsible for the maintenance of epithelial integrity, and increase the synthesis of the major mucin of the colonic mucus layer (MUC2), compared to animals treated with As(III) alone. Microbial metabolism of short-chain fatty acids also undergoes a recovery and the levels of fatty acids in the lumen reach values similar to those of untreated animals. All these positive effects imply the restoration of mucosal permeability, and a reduction of the marker of endotoxemia LPS binding protein (LBP). Treatment with the bacteria also has a direct impact on intestinal absorption, reducing the accumulation of As in the internal organs. The data suggest that the protective effect may be due to a reduced internalization of As(III) in intestinal tissues and to a possible antioxidant and anti-inflammatory activity of the bacteria through activation of pathways such as Nrf2 and IL-10. In vitro tests show that the protection may be the result of the combined action of structural and metabolic components of the LAB strains.
Assuntos
Arsenitos , Água Potável , Camundongos , Animais , Mucosa Intestinal/metabolismo , Arsenitos/toxicidade , Lactobacillus , BactériasRESUMO
UNLABELLED: Mitochondria are the cell's powerhouse when organisms are grown in the presence of oxygen. They are also the source of reactive oxygen species that cause damage to the biochemical components of the cell and lead to cellular ageing and death. Under winemaking conditions, Saccharomyces yeasts exclusively have a fermentative metabolism due to the high sugar content of grape must. However, their production as an active dry yeast (ADY) form required aerobic propagation and a dehydration process. In these industrial steps, oxidative stress is particularly harmful for the cell. In this work, we analysed the impact of the mitochondrial genome on oxidative stress response, longevity and dehydration tolerance using the synthetic interspecific hybrids obtained between two S. cerevisiae and S. uvarum strains. The isogenic nature of nuclear DNA of such hybrids allowed us to analyse the impact of mitochondrial DNA for fermentative and oxidative stress conditions. Under grape must conditions, the inheritance of mitochondrial DNA poorly impacted the fermentative performance of interspecific hybrids, unlike the hybrids with S. cerevisiae mitochondrial inheritance, which displayed increased tolerance to oxidative stress and dehydration, and showed an extended chronological longevity when cells were grown with aeration. SIGNIFICANCE AND IMPACT OF THE STUDY: In modern oenology, yeast starters are employed to inoculate grape juice, usually in the form of active dry yeast (ADY). The dehydration process implies stressful conditions that lead to oxidative damage. Other yeast species and interspecific hybrids other than Saccharomyces cerevisiae may be used to confer novel properties to the final product. However, these yeasts are usually more sensitive to drying. Understanding the causes of oxidative stress tolerance is therefore necessary for developing the use of these organisms in industry. This study indicates the impact of mitochondrial DNA inheritance for oxidative stress resistance in an interspecific context using isogenic Saccharomyces cerevisiae × Saccharomyces uvarum hybrids.
Assuntos
Mitocôndrias/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Vitis/microbiologia , Vinho/microbiologia , Dessecação , Fermentação , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Vitis/metabolismoRESUMO
Chronic exposure to inorganic arsenic [As(III) and As(V)] affects about 200 million people, and is linked to a greater incidence of certain types of cancer. Drinking water is the main route of exposure, so, in endemic areas, the intestinal mucosa is constantly exposed to the metalloid. However, studies on the intestinal toxicity of inorganic As are scarce. The objective of this study was to evaluate the toxicity of a chronic exposure to As(III) on the intestinal mucosa and its associated microbiota. For this purpose, BALB/c mice were exposed during 6 months through drinking water to As(III) (15 and 30 mg/L). Treatment with As(III) increased reactive oxygen species (43-64%) and lipid peroxidation (8-51%). A pro-inflammatory response was also observed, evidenced by an increase in fecal lactoferrin (23-29%) and mucosal neutrophil infiltration. As(III) also induced an increase in the colonic levels of pro-inflammatory cytokines (24-201%) and the activation of some pro-inflammatory signaling pathways. Reductions in the number of goblet cells and mucus production were also observed. Moreover, As(III) exposure resulted in changes in gut microbial alpha diversity but no differences in beta diversity. This suggested that the abundance of some taxa was significantly affected by As(III), although the composition of the population did not show significant alterations. Analysis of differential taxa agreed with this, 21 ASVs were affected in abundance or variability, especially ASVs from the family Muribaculaceae. Intestinal microbiota metabolism was also affected, as reductions in fecal concentration of short-chain fatty acids were observed. The effects observed on different components of the intestinal barrier may be responsible of the increased permeability in As(III) treated mice, evidenced by an increase in fecal albumin (48-66%). Moreover, serum levels of Lipopolysaccharide binding proteins and TNF-α were increased in animals treated with 30 mg/L of As(III), suggesting a low-level systemic inflammation.
Assuntos
Arsenitos , Água Potável , Camundongos , Animais , Arsenitos/metabolismo , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos BALB C , Homeostase , Camundongos Endogâmicos C57BLRESUMO
To ascertain the in vivo role of mycobacterial lipids phthiocerol dimycocerosates (PDIM) in experimental murine tuberculosis (Tb), airways infection was used to compare the parental virulent clinical isolate MT103 with its mutant fadD26, lacking PDIM. Lungs were assessed as the Tb-target organ and mediastinal lymph nodes as the corresponding lymphoid tissue, in order to quantify: the major T-cell subsets (CD4+/CD8+/gammadelta+) and their activation kinetics, bacillary burden, and in vivo cytotoxicity against inoculated target cells loaded with mycobacterial Ags. After 4 weeks, infection augmented total and activated CD4+ and CD8+ T cells in lungs and nodes mainly with MT103, while gammadelta+ T cells increased earlier in nodes. MT103 bacillary burden was bigger and appeared earlier than the mutant fadD26, especially in the lung than in mediastinal nodes. At day 14 of MT103 infection, there was no cytotoxicity in lungs and nodes; while with fadD26 there was some in the nodes. At day 21 of MT103 infection, important cytotoxicity was detected only in lungs; while with fadD26 both tissues showed important activity. Interestingly, unlike the infection with fadD26, cytotoxicity under MT103 fell considerably in the target organ (lung) from days 21 to 60, the advanced phase. Although upon airways infection both mycobacteria behaved similarly regarding T cell (CD4/CD8/gammadelta) stimulation kinetics; they differed in the magnitude of these responses, in the bacterial load within tissues, and to trigger in vivo cytotoxicity in lungs and regional lymph nodes. This highlights the relevance of certain mycobacterial lipids to modify crucial effector branches of immunity.
Assuntos
Citotoxicidade Imunológica , Lipídeos/fisiologia , Pulmão/imunologia , Linfonodos/imunologia , Linfócitos T/imunologia , Tuberculose/imunologia , Animais , Hipersensibilidade Tardia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tuberculose/microbiologiaRESUMO
Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity. RBT analogs 2-11 were synthesized and evaluated against M. avium 1581 and Mycobacterium tuberculosis susceptible and resistant strains in vitro. A selection of candidates were also assayed against non-replicating persistent (NRP) M. tuberculosis. Subsequent in vivo studies with the best preclinical candidate drugs 5 and 8, in a model of progressive pulmonary tuberculosis of Balb/C mice infected either with H(37)Rv drug-sensible strain or with multidrug resistant (MDR) clinical isolates, resistant to all primary antibiotics including rifampicin, were performed. The results disclosed here suggest that 5 and 8 have potential for clinical application.
Assuntos
Mycobacterium avium/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Rifabutina/análogos & derivados , Tuberculose/tratamento farmacológico , Animais , Antituberculosos/química , Antituberculosos/farmacologia , Farmacorresistência Bacteriana , Camundongos , Camundongos Endogâmicos BALB C , Rifabutina/farmacologia , Relação Estrutura-AtividadeRESUMO
Oxytocin and vetrabutin chlorhydrate (VC) are used to reduce the duration of farrowing in swine. The objective of the present study was to evaluate the use of these products on intra-partum stillbirth (IPS) rate and asphyxia. At the onset of parturition, sows (n=180) were allocated to receive 2 mL of saline (control group), oxytocin (40 IU i.m.) or 100mg of VC per 60 kg of body weight, with all treatments given i.m. Oytocin-treated sows had a higher number of IPS than the VC and Control groups (means, 1.2, 0.8 and 0.6, respectively; P<0.001), and the highest percentage of ruptured umbilical cords (76.0, 9.4 and 37.5%; P<0.003). There were differences among groups for duration of farrowing (means, 163.0, 211.2 and 306.9 min in the oxytocin, VC and control groups; P<0.001), interval between piglets (13.9, 19.2 and 28.1 min; P<0.001), and in IPS, the incidence of ruptured umbilical cords was 76.0, 9.4 and 37.5% (P<0.003) and absence of a fetal heartbeat was 53.3, 16.9 and 12.5% (P<0.05). Although oxytocin decreased both duration of farrowing and interval between piglets by approximately 50% relative to control sows, it resulted in a significantly higher rate of IPS, in association with a much higher incidence of ruptured umbilical cord and absence of a fetal heartbeat. Treatment with VC reduced farrowing duration by approximately 1.5h, with an IPS rate that was not significantly different from controls but significantly lower than that of oxytocin-treated sows.
Assuntos
Asfixia/veterinária , Ocitocina/efeitos adversos , Natimorto/veterinária , Doenças dos Suínos/epidemiologia , Animais , Asfixia/epidemiologia , Asfixia/etiologia , Feminino , Parto , Gravidez , Ruptura Espontânea/veterinária , Suínos , Doenças dos Suínos/etiologia , Fatores de Tempo , Cordão Umbilical , Contração Uterina/efeitos dos fármacos , Contração Uterina/fisiologiaRESUMO
A 31-year-old patient with a clinical picture of obstructive jaundice had surgical treatment, and a primary carcinoid of the ampulla of Vater (VA) was found. The tumor was studied with light microscopy, immunohistochemistry, and electron microscopy. The neoplasm had histopathologic and cytopathologic features similar to those encountered in typical neuroendocrine neoplasms. It is interesting that immunohistochemical techniques disclosed the presence of vasointestinal polypeptide, cholecystokinin, and bombesin; however, unlike most neuroendocrine neoplasms arising in VA, no somatostatin-immunoreactive cells were found.
Assuntos
Ampola Hepatopancreática , Neoplasias do Ducto Colédoco/metabolismo , Doenças do Sistema Endócrino/metabolismo , Neoplasias do Sistema Nervoso/metabolismo , Adulto , Bombesina/metabolismo , Colecistocinina/metabolismo , Neoplasias do Ducto Colédoco/patologia , Doenças do Sistema Endócrino/patologia , Humanos , Masculino , Microscopia Eletrônica , Neoplasias do Sistema Nervoso/patologia , Somatostatina/metabolismo , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
The presence of an androgen-binding component in placenta was investigated in vitro using a tissue culture system of human placental explants. Explants of trophoblastic tissue from normal term placentas were kept in culture under appropriate conditions for at least 48 h in a serum-free medium. The existence of an androgen-binding protein was explored by binding assays, immunohistochemistry studies and Northern blot analyses of placental mRNA. Steady-state polyacrylamide gel electrophoresis and Scatchard plot analyses revealed the presence of a high affinity specific binding component for 5 alpha-dihydrotestosterone in cultured placenta. Immunohistochemical studies performed on intact placenta and on Percoll-gradient purified trophoblastic cells demonstrated the presence of specific immunoreactivity in the cytoplasm of syncytial cells. Northern blot analyses of placental mRNA showed a single hybridizable 32P-labeled human sex hormone-binding globulin (SHBG) cDNA band of approx. 1.6 kb which was identical in size to that obtained with liver mRNA. The results strongly suggest the placenta as an origin of SHBG and point out this tissue as an additional site of SHBG synthesis during pregnancy.
Assuntos
Placenta/metabolismo , Globulina de Ligação a Hormônio Sexual/metabolismo , Western Blotting , Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Fígado/metabolismo , RNA Mensageiro/genéticaRESUMO
The case of a patient with idiopathic portal hypertension who was subjected to a selective shunt because of variceal bleeding is reported. Large pancreatic collaterals--the pancreatic siphon--were documented 2 years after the operation with loss of portal flow. At 14 years of follow-up, the pancreatic collaterals have disappeared gradually with normalization of portal venous flow in spite of patency of the shunt.
Assuntos
Hipertensão Portal/cirurgia , Pâncreas/irrigação sanguínea , Veia Porta/fisiopatologia , Derivação Portossistêmica Cirúrgica/efeitos adversos , Velocidade do Fluxo Sanguíneo , Circulação Colateral , Feminino , Seguimentos , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Splenocaval shunts have been used in this hospital since 1974 as an alternative to the distal splenorenal shunt. This report will detail the long-term results with this operation. METHODS: Thirty-three patients who were subjected to selective splenocaval shunts for treatment of hemorrhagic portal hypertension are reported. Mean age was 48.4 years. Twenty patients were women. Twenty-seven patients were in Child class A and six were in Child class B. RESULTS: There were five postoperative deaths. Two patients experienced rebleeding. One patient had shunt obstruction and one patient had severe clinical encephalopathy. Actuarial survival rate was 54.9% at 5 years and was 47.5% at 15 years. At the time of evaluation 12 patients were alive and well (shortest observation period, 2 months and longest observation period, 173 months). One of these patients has mild encephalopathy. CONCLUSIONS: Selective splenocaval shunts are a good alternative for treatment of hemorrhagic portal hypertension in patients with good liver function.
Assuntos
Hemorragia Gastrointestinal/cirurgia , Hipertensão Portal/cirurgia , Derivação Portocava Cirúrgica/métodos , Veia Esplênica/cirurgia , Análise Atuarial , Adolescente , Adulto , Idoso , Criança , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Hipertensão Portal/complicações , Masculino , Pessoa de Meia-Idade , Derivação Portocava Cirúrgica/efeitos adversos , Análise de SobrevidaRESUMO
Selective portosystemic shunts have been performed in our hospital since 1973 for the treatment of variceal bleeding secondary to portal hypertension. We report our experience in 139 selective operations performed in a 10-year period (1973 to 1983). One hundred thirty patients underwent elective nine underwent emergency surgery. Eighty-five patients were classified in the A functional group of Child, 42 in group B, and 12 in group C. The overall mortality rate in the emergency group was 44% and in the elective group, 13%. Ascitis and transitory hepatic failure were the most common postoperative complications. The long-term follow-up clinical encephalopathy rate was 16%. The survival rate according to the Kaplan-Meier survival analysis was 80% at 2 years, 68% at 5 years, and 67% at 10 years.
Assuntos
Hemorragia Gastrointestinal/etiologia , Hipertensão Portal/cirurgia , Derivação Portossistêmica Cirúrgica , Adolescente , Adulto , Idoso , Criança , Emergências , Feminino , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Derivação Esplenorrenal CirúrgicaRESUMO
HYPOTHESIS: Surgery for portal hypertension has evolved widely in the past decades. Selection criteria and the type of operations have evolved because of the appearance of other therapeutic alternatives, such as pharmacotherapy, endoscopic therapy, transjugular intrahepatic portosystemic shunt, and liver transplantation. We believe the surgical approach has a therapeutic role in a select patient population. DESIGN: Retrospective review of the medical records of patients operated on for bleeding portal hypertension in the past 50 years. SETTING: An academic tertiary care university hospital. PATIENTS AND METHODS: In a 50-year period, 1000 operations for the treatment of bleeding portal hypertension have been done, including shunts and devascularization procedures. In the past years, in low-risk (Child-Pugh classification A) selected patients, only portal blood flow-preserving operations have been done. RESULTS: Non-portal blood flow-preserving procedures had a wide spectrum of results, with a high encephalopathy rate and short long-term survival. The results with portal blood flow-preserving procedures in the past 10 years are as follows: operative mortality, 2.7%; postoperative encephalopathy, 6%; rebleeding, 6%; and shunt obstruction, 4%. CONCLUSIONS: Portal hypertension surgery has a role in elective operations and in low-risk selected patients, when portal blood flow-preserving procedures are done. The type of operation is selected according to the individual characteristics of each patient.
Assuntos
Hemorragia Gastrointestinal/cirurgia , Hipertensão Portal/cirurgia , Humanos , Derivação Portossistêmica Cirúrgica , Estudos Retrospectivos , Fatores de TempoRESUMO
Although people older than 65 years represent less than 5% of Mexico's registered population, medical care for elderly patients requires a multidisciplinary approach. In our academic university hospital, they are managed by a team of specialists. As an example of this approach, we evaluated the surgical treatment of bleeding portal hypertension in a highly selected elderly population. A retrospective study was done reviewing the files of 25 patients older than 65 years. All had good liver function (Child-Pugh class A and B) and had undergone elective surgery. Sixteen of them were women. The mean age was 68.8 years (age range, 65-76 years), and most had a diagnosis of cirrhosis. All patients were treated with portal blood flow-preserving procedures (selective shunts or Sugiura-Futagawa procedures). The operative mortality was 8%. Eight later deaths were recorded, with a mean follow-up of 25 months (range, 2-110 months). Survival (Kaplan-Meier) was 87% at 12 months, 54% at 60 months, and 45% at 110 months. Two rebleeding incidents were recorded as well as 3 cases of postoperative encephalopathy. We concluded that well-selected elderly patients, undergoing elective surgery with portal blood flow-preserving procedures, have a good postoperative outcome.
Assuntos
Hipertensão Portal/cirurgia , Fatores Etários , Idoso , Feminino , Humanos , Masculino , MéxicoRESUMO
A technique for intrahepatic reconstruction of the biliary tree after complex high injuries is described. The fundament of the procedure is the removal of a wedge of segment IV at the level of the hilar plate. When the hilar plate is reached and no adequate exposure of the ducts can be obtained, removing a 1 x 1-in wedge of segment IV between the gallbladder bed and the round ligament exposes the left and right ducts. An anteroposterior view of the plate is obtained instead of a caudocephalic dissection, exposing healthy, nonscarred ducts for reconstruction. We have used this approach in 22 patients, and adequate exposure of the ducts has been obtained, with a high success rate of patency of the anastomosis at a mean follow-up of 3 years. Twenty patients have a patent anastomosis, with a good quality of life and no restenosis.
Assuntos
Ductos Biliares/lesões , Ductos Biliares/cirurgia , Complicações Intraoperatórias/cirurgia , Adulto , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate whether splenectomy as a part of devascularization procedures is necessary. DESIGN: Prospective, controlled, randomized trial. SETTING: University hospital, referral center. PATIENTS: A total of 55 patients (Child-Pugh class A and B) with a history of bleeding portal hypertension were treated by means of a modified Sugiura-Futagawa procedure. Twenty-three patients underwent splenectomy and 22 did not. METHODS: Postoperative outcome was recorded and comparison of the 2 groups was done with the Fisher exact test. Kaplan-Meier survival curves were constructed. Main outcome and postoperative differences between the patients who underwent splenectomy and those who did not were investigated. RESULTS: Both groups were comparable in the postoperative period. Significant differences were observed in transfusion requirements and postoperative portal vein thrombosis, both favoring the group without splenectomy. No differences in rebleeding, encephalopathy rate, operative time, or postoperative complications were observed. CONCLUSION: Splenectomy is not routinely necessary in devascularization procedures for bleeding portal hypertension.
Assuntos
Hemorragia Gastrointestinal/cirurgia , Hipertensão Portal/cirurgia , Esplenectomia , Adolescente , Adulto , Idoso , Feminino , Hemorragia Gastrointestinal/mortalidade , Humanos , Hipertensão Portal/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To compare 2 techniques of esophageal transection in our modification of the Sugiura-Futagawa procedure for the treatment of bleeding portal hypertension in low-risk patients who cannot undergo surgery to have shunts placed. DESIGN: A prospective controlled trial comparing 2 variants of transection (classic, complete section of the anterior muscularis externa and whole mucosa; modified, placement of a circumferential running suture without opening the mucosa). SETTING: Academic university hospital. PATIENTS: Eighty-three low-risk patients (Child-Pugh score A and B) with a history of bleeding portal hypertension were operated on (35 classic, 48 modified transections) between 1989 and 1996. Both groups were comparable. MAIN OUTCOME MEASURES: Postoperative dehiscence of the transection was evaluated as well as fistulization, postoperative stenosis, rebleeding, postoperative endoscopic findings, survival, and mortality. RESULTS: Fistulization was observed in 1 (2%) of the patients in the modified group, and dehiscence in 1 patient (2%). In the classic group, 3 (8%) of the patients had dehiscence (relative risk, 2.6) and 1 (2%) of the patients, fistulization. No differences were observed regarding rebleeding (6 patients [6%] vs 5 patients [7%]), postoperative stenosis (4 patients [8%] vs 5 patients [10%]), postoperative endoscopic findings, survival, and mortality (early and late). CONCLUSION: The modified variant of the transection has a lower frequency of postoperative dehiscence, with the same long-term results.
Assuntos
Varizes Esofágicas e Gástricas/cirurgia , Esôfago/cirurgia , Hemorragia Gastrointestinal/cirurgia , Hipertensão Portal/complicações , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/mortalidade , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Humanos , Hipertensão Portal/mortalidade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Procedimentos Cirúrgicos Operatórios/métodos , Taxa de SobrevidaRESUMO
In Balb/c mice with pulmonary tuberculosis, there is a switch from a protective Th1-dominated cytokine profile to a non-protective profile with a Th2 component. This switch occurs while the adrenals are undergoing marked hyperplasia. Treatment with the anti-glucocorticoid hormones dehydroepiandrosterone or 3 beta, 17 beta-androstenediol, during the period of adrenal hyperplasia, maintains Th1 dominance and is protective. We investigated the effects of these hormones as therapeutic agents by administering them from day 60, when the switch to the non-protective cytokine profile was already well established. Given at this time (day 60), doses that were protective when given early (from day 0) were rapidly fatal. A physiological dose of the glucocorticoid corticosterone was also rapidly fatal. However when the corticosterone and the anti-glucocorticoid (AED or DHEA) were co-administered, there was protection, with restoration of a Th1-dominated cytokine profile, enhanced DTH responses, and enhanced expression of IL-1 alpha and TNF alpha. Therefore this combination of steroids has an emergent property that is quite unlike that of either type of steroid given alone. It may be possible to exploit the ant-inflammatory properties of glucocorticoids while preserving a Th1 bias, by combining glucocorticoids with DHEA or suitable metabolites.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Androstenodióis/administração & dosagem , Desidroepiandrosterona/administração & dosagem , Tuberculose Pulmonar/tratamento farmacológico , Androstenodióis/imunologia , Animais , Corticosterona/sangue , Desidroepiandrosterona/imunologia , Combinação de Medicamentos , Hipersensibilidade/imunologia , Imuno-Histoquímica , Hibridização In Situ , Interleucina-1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Análise de Sobrevida , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
When mice were infected with virulent Mycobacterium tuberculosis H37Rv by the intra-tracheal route, there was an early phase of adrenal hyperplasia, histologically resembling the adrenocorticotropic (ACTH)-driven changes seen in Cushing's disease. This was followed at 3 weeks by progressive atrophy until the weight of the adrenals was approximately 50% of that seen in control uninfected mice, in spite of the fact that the adrenals were not infected. All layers of the adrenal cortex were affected, but the medulla was normal. Electron microscope studies revealed apoptosis. The switch from adrenal hyperplasia to adrenal atrophy corresponded to onset of an IgG1 response recognising a wide range of mycobacterial components in Western blots. Delayed type hypersensitivity (DTH) responses were seen throughout, but differed in their sensitivity to TNF alpha. Thus if TNF alpha was injected at 24 h into DTH sites elicited during the phase of adrenal hyperplasia, there was no increment in swelling at 48 h. However similar injections of TNF alpha resulted in a doubling of the swelling in DTH sites elicited during the phase of adrenal atrophy. This may be relevant to the pathogenesis of cytokine-mediated tissue damage in the human disease. If 2 months before mice received the intratracheal infection, they were pre-immunised with 1 x 1097) autoclaved Mycobacterium vaccae, a stimulus previously shown to induce a Th1 pattern of response, the early increase in adrenal weight was attenuated and delayed, and the subsequent atrophy did not occur. In sharp contrast, pre-immunisation with 1 x 10(9) autoclaved M. vaccae, known to prime a mixed pattern of cytokine release (IFN gamma and IL-4), resulted in adrenal atrophy that began within 4 days of infection, and was complete by day 14. These results suggested that the pattern of cytokine release provoked by the infection, modulated the adrenal changes, perhaps in synergy with products derived from the organisms themselves. Since we have already shown that profound adrenal changes also occur in human tuberculosis, we now propose that a change somewhere in the cytokine-hypothalamo-pituitary-adrenal axis may underlie the T cell dysfunction and immunologically-mediated tissue damage in this disease.
Assuntos
Glândulas Suprarrenais/patologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/etiologia , Tuberculose Pulmonar/patologia , Glândulas Suprarrenais/imunologia , Glândulas Suprarrenais/ultraestrutura , Animais , Anticorpos Antibacterianos/biossíntese , Atrofia , Hiperplasia , Hipersensibilidade Tardia/etiologia , Imunização , Intubação Intratraqueal , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium/imunologia , Tamanho do Órgão , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Although several effective therapeutic options are available for bleeding from portal hypertension, surgery has a well-defined role in the management of patients with good liver function who are electively operated. The aim of this investigation was to evaluate the operative mortality and morbidity of portal blood flow-preserving procedures in a highly select patient population. The records of 148 patients operated on between 1996 and 2000 using one of two techniques (selective shunts or a Sugiura-Futagawa operation [complete portoazygos disconnection]) were analyzed with particular attention to operative mortality, postoperative rebleeding, and encephalopathy. Survival was calculated according to the Kaplan-Meier method. Sixty-one patients had distal splenorenal shunts placed, and 87 patients had a devascularization procedure. Operative mortality for the group as a whole was 1.2%. In the group with selective shunts, the rebleeding rate was 4.9%, the encephalopathy rate was 9.8%, and the shunt obstruction rate was 1.6%. Survival at 24 months was 94% and at 48 months was 92%. In those undergoing devascularization, the encephalopathy rate was 5% and the rebleeding rate was 14%. Survival at 24 months was 90% and at 48 months was 86%. Portal blood flow-preserving procedures have very low morbidity and mortality rates at specialized centers. In addition, a low rebleeding rate is associated with a good quality of life. Low-risk patients with bleeding portal hypertension should be considered for surgical treatment.
Assuntos
Hipertensão Portal/cirurgia , Derivação Esplenorrenal Cirúrgica , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/cirurgia , Humanos , Morbidade , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/mortalidade , Derivação Esplenorrenal Cirúrgica/efeitos adversos , Derivação Esplenorrenal Cirúrgica/mortalidadeRESUMO
The use of small-diameter portosystemic shunts for the treatment of bleeding esophageal varices caused by portal hypertension has emerged as an outgrowth of the development of polytetrafluoroethylene vascular grafts, which allow the use of a narrow lumen. We report our experience with this type of graft over a 10-year period. Thirty-three patients with good liver function (Child-Pugh class A) were electively operated. The average age of these patients was 45 years (range 17 to 71 years). Twenty-nine patients had liver cirrhosis, one had portal fibrosis, and three had idiopathic portal hypertension. Operative mortality was 3%, and the rebleeding rate was 15%. Postoperative encephalopathy was observed in 14 patients (11%), three of whom had grade III to IV encephalopathy. The remaining 11 patients, had mild encephalopathy that was easily controlled. Postoperative angiography showed shunt patency in 81% of the patients, reduction in portal vein diameter in 33% of the patients, and portal vein thrombosis in 6%. Good postoperative quality of life was observed in 63% of the patients. Survival according to the Kaplan-Meier actuarial method was 81% at 12 months, 56% at 60 months, and 36% at 10 years. These shunts are a good alternative for patients being considered for surgery in whom other portal blood flow preserving procedures (i.e., elective shunts, devascularization with esophageal transection) are not feasible.