RESUMEN
Nowadays, it is difficult to find a more complicated inflammatory disease of the abdominal organs in its pathogenesis than acute pancreatitis (AP). The application of antimediatory drugs and antimetabolites is the most promising direction in the correction of inflammatory pathological processes. The study of possible applications of a new group of drugs (monoclonal antibodies) that may trigger inflammation is also of great interest. The present study aimed to study the effect of infliximab on the lethality, volume, and nature of pancreatic lesions in severe necrotizing ductal pancreatic necrosis. The study was conducted on female Wistar rats (n=30) of similar age in the weight range of 200-250g. All manipulations were performed under general anesthesia by intraperitoneal injection of zoletil at a dose of 60 mg/kg, as well as chloral hydrate at a dose of 125 mg/kg. Model of severe acute necrotizing pancreatitis was performed through the injection of 0.5 ml of a buffer solution containing a bile acid salt-sodium taurocholate introductory. The animals were divided into the following groups: Group A (n=6): normal values; Group B (n=6): the mortality study was conducted in acute destructive pancreatitis in a period of 24 h; Group C (n=6): the simulation of acute severe necrotic pancreatitis was performed in this group along with the study of the volume of pancreatic lesions for a period of 6 h from the moment of modeling; Group D (n=6): in this group, the effect of infliximab (at a dose of 60 mkg/kg) was studied on mortality in severe destructive pancreatitis for a period of 24 h from the moment of modeling; Group E (n=6): in this group, the effect of infliximab (at a dose of 120 mkg/kg) was studied on the volume of pancreatic lesions in severe destructive pancreatitis for a period of 6 h from the moment of modeling. During the assessment of pancreatic damage, the mean±SD volume of pancreatic lesions was determined to be 34.8%±1.2% in a period of 6 h after modeling. Assessment of pancreatic damage in group E and the protective effect of infliximab at a dose of 60 mg/kg showed that the total volume of the necrotic pancreatic lesion was determined to be 21.3%±1.4% after a period of 6 h from the moment of AP modeling. In the course of this study, it was revealed that the application of infliximab at a dose of 60 mcg/kg led to a pronounced positive effect on the pancreatic lesion, manifested by up to 50% decrease in mortality for one day in group D. Infliximab had a definite protective effect in AP, decreasing the volume of the injury, as well as the mortality rate by half for 24 h. Therapy with anti-tumor necrosis factor with infliximab could significantly reduce the volume of pancreatic lesions in severe forms of pancreatic necrosis, which contributed to a pronounced decrease in mortality for 1 day from the moment of pathology reproduction.
Asunto(s)
Pancreatitis Aguda Necrotizante , Animales , Femenino , Ratas , Enfermedad Aguda , Infliximab/uso terapéutico , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Pancreatitis Aguda Necrotizante/patología , Ratas WistarRESUMEN
In the present study the analysis of dynamics of basic laboratory parameters of patients with acute cholecystitis (AC) in the four age groups subdivided according to the WHO classification into young, middle age, elderly and senile was carried out. The most pronounced changes were found in the senile age group in which the AC was accompanied by the decreased number of erythrocytes, low hemoglobin and total protein, leukocytosis, lower percentage of lymphocytes and the highest levels of ALT, AST, bilirubin and urea. Changes in the elderly and senile groups differed and in a number of cases were opposite. In the elderly and especially in the senile group the dynamics of the studied parameters related to surgery, was poorly expressed. These findings can be used in the preparation of the elderly and senile patients for AC surgery.
Asunto(s)
Colecistitis Aguda , Enfermedad Aguda , Adulto , Factores de Edad , Anciano , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Proteínas Sanguíneas/metabolismo , Colecistitis Aguda/sangre , Recuento de Eritrocitos , Humanos , Leucocitosis/etiología , Recuento de Linfocitos , Persona de Mediana Edad , Urea/sangreRESUMEN
It was analyzed the examination and treatment results of 100 patients who underwent resection of stomach by Billroth-I in case of peptic ulcer. Chronic disorders of duodenal patency were diagnosed in 86% of patients. The main role of chronic disorders of duodenal patency in postgastrectomy syndromes development was proved. There were a combination of reflux gastritis with dumping syndrome in 66.3% of patients, a combination of reflux gastritis with recurrent ulcer in 8.1% of patients. Correction of chronic disorders of duodenal patency is necessary stage in conservative and surgical treatment of postgastrectomy syndromes.
Asunto(s)
Enfermedades Duodenales/etiología , Gastrectomía , Gastroenterostomía , Úlcera Péptica , Síndromes Posgastrectomía , Úlcera Gástrica , Adulto , Enfermedad Crónica , Enfermedades Duodenales/fisiopatología , Enfermedades Duodenales/prevención & control , Duodeno/fisiopatología , Duodeno/cirugía , Endoscopía Gastrointestinal/métodos , Femenino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Gastroenterostomía/efectos adversos , Gastroenterostomía/métodos , Motilidad Gastrointestinal , Humanos , Masculino , Persona de Mediana Edad , Úlcera Péptica/diagnóstico , Úlcera Péptica/fisiopatología , Úlcera Péptica/cirugía , Síndromes Posgastrectomía/diagnóstico , Síndromes Posgastrectomía/fisiopatología , Síndromes Posgastrectomía/prevención & control , Recurrencia , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/fisiopatología , Úlcera Gástrica/cirugía , Resultado del TratamientoRESUMEN
We assessed results of examination and treatment of 100 patients with ulcer disease who had undergone Bilroth-1 stomach resection. Chronic disorder of duodenal patency was revealed in 86% of the patients. This condition was shown to play the leading role in the development of post-gastric resection syndrome. Reflux-gastritis was associated with damping syndrome in 66.3% of the patients and with recurrent ulcer in 8.1%. It is concluded that conservative and surgical treatment of post-gastric resection syndrome should be aimed at correction of chronic disorders of duodenal patency.
Asunto(s)
Úlcera Duodenal/cirugía , Duodeno/fisiopatología , Gastrectomía/efectos adversos , Síndromes Posgastrectomía/etiología , Úlcera Gástrica/cirugía , Adulto , Enfermedad Crónica , Úlcera Duodenal/complicaciones , Duodeno/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndromes Posgastrectomía/diagnóstico , Síndromes Posgastrectomía/fisiopatología , Úlcera Gástrica/complicaciones , SíndromeRESUMEN
Treatment results of 763 patients with acute cholecystitis were analyzed. Destructive forms of the disease was diagnosed by the ultrasound examination in all cases. Choledocholithiasis was diagnosed in 35 (4.6%), choledocholithiasis with papilla Vatery stricture was in 9 (1.2%) patients and isolated papilla Vatery stricture was registered in 5 (0.7%) patients. All patients were attempted to treat laparoscopically with the use of original "Device for antegrade papillotomy" and "Method of antegrade bipolar papillosphincterotomy". Authors state, that a final decision about the possibility of endoscopic treatment of the acute cholecystitis can be made after detection of anatomical structures of the Calo triangle. By complicated forms of the disease a one-stage laparoscopic treatment should be preferred. Endoscopic papillosphincterotomy should be performed only by the enblocked concrement of the papilla Vatery.
Asunto(s)
Ampolla Hepatopancreática/cirugía , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colecistitis Aguda/diagnóstico , Colecistitis Aguda/cirugía , Esfinterotomía Endoscópica/instrumentación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Ampolla Hepatopancreática/fisiopatología , Procedimientos Quirúrgicos del Sistema Biliar/efectos adversos , Procedimientos Quirúrgicos del Sistema Biliar/métodos , Colecistitis Aguda/etiología , Colecistitis Aguda/fisiopatología , Coledocolitiasis/complicaciones , Coledocolitiasis/diagnóstico , Coledocolitiasis/fisiopatología , Endoscopios Gastrointestinales/normas , Diseño de Equipo , Femenino , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/normas , Esfinterotomía Endoscópica/efectos adversos , Resultado del TratamientoRESUMEN
The aryl-hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is a member of the bHLH-PAS family of proteins. The highest-affinity ligand of this receptor is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is a potent immunological, reproductive, and developmental toxicant. The mechanism of TCDD-induced toxicity and the gene modulations that result in toxicity have not been fully defined. The majority of work to date exploring AhR function has focused on agonist-activated AhR signaling. However, it is expected that a better understanding of AhR antagonism will lead to an improved understanding of TCDD toxicity and other AhR-mediated events. This study contributes to such investigations by utilizing the AhR antagonist 3'-methoxy-4'-nitroflavone (3'M4'NF) and a dioxin-responsive lacZ transgenic mouse model to characterize antagonism of the receptor system in vivo. The dose-response and time course of TCDD-induced transgene activation were evaluated in transgenic mice to provide information necessary to design 3'M4'NF in vivo studies. TCDD induction of the transgene was noted as early as 8 h after exposure in the lung. 3-miccrog/kg body weight TCDD was the lowest dose found to induce the reporter transgene. Finally, experiments were performed to evaluate the in vivo efficacy of 3'M4'NF. We found that 3'M4'NF inhibits TCDD-mediated reporter gene activation and CYP1A1 induction in vivo. Based on these findings, it is clear that DRE-lacZ animals and the antagonist 3'M4'NF represent important tools which will help in the identification of tissues where AhR is active, and to further characterize AhR-mediated signaling.
Asunto(s)
Flavonoides/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Operón Lac/efectos de los fármacos , Dibenzodioxinas Policloradas/toxicidad , Receptores de Hidrocarburo de Aril/genética , Animales , Western Blotting , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Flavonoides/sangre , Regulación de la Expresión Génica/genética , Genes Reporteros/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Factores de Tiempo , Activación Transcripcional , beta-GalactosidasaRESUMEN
beta-galactosidase (beta-gal), the product of the E. coli LacZ gene, has been used extensively as a reporter in numerous systems. Until recently, the most commonly used method of detecting beta-gal reporter enzymatic activity was a colormetric assay based on the cleavage of the beta-gal substrate 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside (X-gal) to form a blue precipitate. However, when increased sensitivity is needed, many investigators now turn to alternate substrates that produce fluorescent or luminescent products upon cleavage by beta-gal. These products are much more easily quantified than X-gal. The luminescent and fluorometric assays work very well in cultured cells but are often less sensitive in whole tissue lysates. In this study, we have evaluated the sensitivity of a fluorescent and a luminescent substrate in whole tissue lysates cleared of red blood cells or washed with PBS only. We have found that both assays show increased low-end sensitivity in tissues with reduced levels of hemoglobin (Hb). Hb is apparently able to quench luminescent and, to a lesser degree, fluorescent reporter light emission. Therefore, steps should be taken to reduce Hb levels either by lysis, perfusion, or both to enhance the sensitivity of these assays.
Asunto(s)
Eritrocitos/metabolismo , Genes Reporteros , Hemoglobinas/metabolismo , beta-Galactosidasa/genética , Animales , Activación Enzimática , Operón Lac , Mediciones Luminiscentes , Biología Molecular/métodos , Sensibilidad y Especificidad , beta-Galactosidasa/metabolismoRESUMEN
This laboratory has previously reported data suggesting that aryl hydrocarbon receptor (AhR) signaling may have a net potentiating effect on the DNA damaging potential of cigarette smoke. The experiments described in this report extend these studies by testing whether the potent AhR antagonist 3'-methoxy-4'-nitroflavone (3'M4'NF) can modify the in vivo genetic toxicity of benzo[a]pyrene (B[a]P) and the complex mixture of chemicals in cigarette smoke condensate (CSC). Initial experiments were designed to determine 3'M4'NF doses which can antagonize AhR in vivo but which have little effect on constitutive cytochrome P4501A (CYP1A) activity. These experiments took three forms: (i) zoxazolamine paralysis tests, a functional assay of cytochrome P450 CYP1A activity in 3'M4'NF-treated C57Bl/6J mice; (ii) co-treatment of AHR: null allele mice with 150 mg/kg B[a]P plus a range of 3'M4'NF concentrations in order to evaluate the potential of the flavone to interact with non-AhR targets which may affect B[a]P toxicity; (iii) an evaluation of the in vivo AhR antagonist activity of 3'M4'NF using transgenic mice which carry a dioxin-responsive element-regulated lacZ reporter. Once an appropriate dose range was determined, C57Bl/6J mice were challenged with B[a]P or CSC with and without 3'M4'NF co-treatment. Chromosome damage was measured by scoring the frequency of micronuclei in peripheral blood reticulocytes. Data presented herein suggest that 3'M4'NF can protect mice from B[a]P-induced bone marrow cytotoxicity and genotoxicity. Furthermore, CSC-associated genotoxicity was abolished by the flavonoid. These data add support to our hypothesis that AhR signaling has a net potentiating effect on the genetic toxicity and, presumably, carcinogenicity of cigarette smoke.
Asunto(s)
Benzo(a)pireno/toxicidad , Nicotiana , Plantas Tóxicas , Receptores de Hidrocarburo de Aril/fisiología , Transducción de Señal/fisiología , Humo/efectos adversos , Animales , Benzo(a)pireno/antagonistas & inhibidores , Cromosomas/efectos de los fármacos , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Inhibidores del Citocromo P-450 CYP1A2 , Daño del ADN , Flavonoides/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Receptores de Hidrocarburo de Aril/antagonistas & inhibidores , Receptores de Hidrocarburo de Aril/genética , Transducción de Señal/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/patologíaAsunto(s)
Linfocitos B/metabolismo , Dinoprostona/biosíntesis , Mediadores de Inflamación/fisiología , Isoenzimas/genética , Macrófagos/metabolismo , Prostaglandina-Endoperóxido Sintasas/genética , Transducción de Señal , Animales , Linfocitos B/enzimología , Células Cultivadas , Ciclooxigenasa 2 , Macrófagos/enzimología , Ratones , Fenotipo , Regulación hacia ArribaAsunto(s)
Subgrupos de Linfocitos B/metabolismo , Regulación Leucémica de la Expresión Génica , Isoenzimas/biosíntesis , Leucemia Linfocítica Crónica de Células B/metabolismo , Proteínas de Neoplasias/biosíntesis , Células Madre Neoplásicas/metabolismo , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Prostaglandinas/biosíntesis , Animales , Anticuerpos Antiidiotipos/farmacología , Subgrupos de Linfocitos B/enzimología , Subgrupos de Linfocitos B/patología , Ligando de CD40/inmunología , Diferenciación Celular , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Dinoprostona/biosíntesis , Dinoprostona/genética , Inducción Enzimática , Humanos , Inflamación/enzimología , Inflamación/metabolismo , Inflamación/patología , Interferón gamma/farmacología , Isoenzimas/genética , Leucemia Linfocítica Crónica de Células B/enzimología , Leucemia Linfocítica Crónica de Células B/patología , Lipopolisacáridos/farmacología , Activación de Linfocitos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/patología , Proteínas de la Membrana , Ratones , Proteínas de Neoplasias/genética , Células Madre Neoplásicas/enzimología , Prostaglandina-Endoperóxido Sintasas/genética , Prostaglandinas/genética , ARN Mensajero/biosíntesis , Células Th2/inmunología , Células Tumorales Cultivadas/metabolismoRESUMEN
B/macrophage cells are biphenotypic leukocytes of unknown function that simultaneously express B lymphocyte (IgM, IgD, B220, CD5) and macrophage (phagocytosis, F4/80, Mac-1) characteristics. B/macrophage cells can be generated from purified mouse B lymphocytes incubated in fibroblast-conditioned medium. A potential role for B/macrophage cells in inflammation was shown by their ability to express prostaglandin H synthase-1 (COX-1) and prostaglandin H synthase-2 (COX-2) and by their production of prostaglandin (PG) E(2). COX-1 and COX-2 mRNA expression is not observed in the precursor B lymphocytes and is not known to be a property of B lineage cells. In contrast, COX-2 and the prostanoids PGE(2), PGF(2alpha) and PGD(2) are highly inducible in B/ macrophage cells upon stimulation with lipopolysaccharide, CD40 ligand, or via engagement of surface IgM, supporting a role for these cells in inflammation. PGD(2) and its metabolites are of interest because they activate the nuclear receptor PPARgamma that regulates lipid metabolism. The B/macrophage represents the first instance of a normal B-lineage cell capable of expressing COX-2. Importantly, B/macrophage cells were identified in vivo, providing evidence that they may play a significant role in immune responses. Since PGE(2) blunts IL-12 production, its synthesis by B/macrophage cells may shift the balance of an immune response towards Th2 and humoral immunity.