RESUMEN
Chronic hepatitis B virus (HBV) infection, which can lead to cirrhosis and hepatocellular carcinoma, is a major health threat worldwide. Classic patients with chronic hepatitis B are positive for hepatitis Be-antigen (HBeAg) and HBV-DNA. In the Mediterranean basin, 30-80% of patients with chronic hepatitis B (CHB) are HBeAg-negative, in contrast to Northern European countries and the US, where only 10-40% of CHB patients are lacking HbeAg. HBeAg-negative CHB usually runs a progressive course. The greatest problem with the treatment of HBeAg-negative CHB is the high relapse rate. Their end treatment response rates are similar to those of classic CHB patients, but after discontinuation of treatment most of them relapse. All the data available in the literature show that more than 80% of patients with HBeAg-negative CHB do not respond to the current approved therapies. A literature review and our experience with thymosin indicate that the combination of IFN alpha2b and T-alpha1 is better tolerated and more likely to induce a sustained response in HbeAg-negative chronic hepatitis B patients when compared to other currently available therapies. As thymosin-alpha1 treatment is relatively free from adverse effects, future controlled trials are needed, with a longer follow-up, in order to fully evaluate the role of the combination therapy of thymosin-alpha1 with other emerging therapeutic agents.
Asunto(s)
2-Aminopurina/análogos & derivados , Antígenos e de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Timosina/uso terapéutico , 2-Aminopurina/uso terapéutico , Antivirales/uso terapéutico , Quimioterapia Combinada , Famciclovir , Humanos , Interferones/uso terapéutico , Lamivudine/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéuticoRESUMEN
The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH) in 20% (v/v) ethanol on the first experimental day (day 0). One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70%) of 50 rats, moderate hemolysis in seven (14%), and no hemolysis in eight (16%). Thirty-three of 35 (94.2%) rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8%) had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.
Asunto(s)
Anemia Hemolítica/complicaciones , Hemólisis , Pancreatitis/etiología , Enfermedad Aguda , Amilasas/sangre , Animales , Modelos Animales de Enfermedad , Lipasa/sangre , Pancreatitis/sangre , Pancreatitis/patología , Factor de Activación Plaquetaria/análisis , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/análisisRESUMEN
The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20 percent. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH) in 20 percent (v/v) ethanol on the first experimental day (day 0). One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20 percent ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70 percent) of 50 rats, moderate hemolysis in seven (14 percent), and no hemolysis in eight (16 percent). Thirty-three of 35 (94.2 percent) rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8 percent) had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80 percent of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines
Asunto(s)
Animales , Ratas , Anemia Hemolítica , Hemólisis , Pancreatitis , Enfermedad Aguda , Amilasas , Modelos Animales de Enfermedad , Lipasa , Pancreatitis , Factor de Activación Plaquetaria , Ratas Wistar , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfaRESUMEN
The etiology of functional dyspepsia is not known. The objective of the present study was to determine the characteristics of functional dyspepsia in Western Turkey. We divided 900 patients with functional dyspepsia into three subgroups according to symptoms: ulcer-like (UL), 321 (35.6%), motility disorder-like (ML), 281 (31.2%), and the combination (C) of these symptoms, 298 (33.1%). All patients were submitted to endoscopic evaluation, with two biopsies taken from the cardia and corpus, and four from the antrum of the stomach. All biopsy samples were studied for Helicobacter pylori (Hp) density, chronic inflammation, activity, intestinal metaplasia, atrophy, and the presence of lymphoid aggregates by histological examination. One antral biopsy was used for the rapid urease test. Tissue cagA status was determined by PCR from an antral biopsy specimen by a random sampling method. We also determined the serum levels of tumor necrosis factor-alpha (TNF-alpha) and gastrin by the same method. Data were analyzed statistically by the Kolmogorov-Smirnov test and by analysis of variance. Hp and cagA positivity was significantly higher in the UL subgroup than in the others. The patients in the ML subgroup had the lowest Hp and cagA positivity and Hp density. The ML subgroup also showed the lowest level of Hp-induced inflammation among all subgroups. The serum levels of TNF-alpha and gastrin did not reveal any difference between groups. Our findings show a poor association of Hp with the ML subgroup of functional dyspepsia, but a stronger association with the UL and C subgroups.
Asunto(s)
Dispepsia/microbiología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Adulto , Análisis de Varianza , Antígenos Bacterianos/análisis , Proteínas Bacterianas/análisis , Dispepsia/patología , Femenino , Gastrinas/análisis , Infecciones por Helicobacter/patología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estadísticas no Paramétricas , Factor de Necrosis Tumoral alfa/análisis , TurquíaRESUMEN
BACKGROUND/AIMS: The relationship between insulin resistance and the occurrence of fatty acid has been documented. Recently DHEA (dehydroepiandrosterone) was shown to have a protective effect against development of fatty liver in rats. We aimed to investigate the association of nonalcoholic fatty liver and serum levels of DHEA, obesity, fat distribution and insulin resistance and to evaluate the effect of DHEA on fatty liver, obesity and insulin resistance. METHODOLOGY: Thirteen postmenopausal women with nonalcoholic fatty liver and 14 postmenopausal women with normal liver histology were included into the study. Body mass index, waist-hip ratio, serum DHEA, DHEAS, triglyceride, cholesterol levels and insulin resistance were determined. Fatty liver was determined by ultrasound and established by liver biopsy and histology. Hyperinsulinemic euglycemic clamp studies were performed. RESULTS: The subjects in both groups were age matched (p > 0.05). Body mass index showed obesity in patients with fatty liver but not in control group (p = 0.01). Central obesity was present in women with fatty liver (p = 0.039). As expected, insulin resistance was significantly present in patients with fatty liver (p = 0.001). DHEA and DHEAS levels of women with fatty liver were greater than those of control group (p1 = 0.001 and p2 = 0.0001, respectively). DHEA and DHEAS were positively correlated with both body mass index and waist-hip ratio. However, glucose disposal rate was inversely and significantly correlated with DHEA and DHEAS levels. CONCLUSIONS: These data do not support the hypothesis that DHEA or DHEAS protect post-menopausal women against fatty liver, diabetes and obesity. Indeed, DHEA and DHEAS may be the cause of fatty liver, obesity (especially abdominal obesity) and diabetes in estrogen-deficient women.
Asunto(s)
Constitución Corporal , Climaterio/fisiología , Deshidroepiandrosterona/sangre , Hígado Graso/fisiopatología , Hiperinsulinismo/fisiopatología , Resistencia a la Insulina/fisiología , Obesidad/fisiopatología , Glucemia/metabolismo , Composición Corporal/fisiología , Índice de Masa Corporal , Colesterol/sangre , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Humanos , Hígado/fisiopatología , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
The etiology of functional dyspepsia is not known. The objective of the present study was to determine the characteristics of functional dyspepsia in Western Turkey. We divided 900 patients with functional dyspepsia into three subgroups according to symptoms: ulcer-like (UL), 321 (35.6 percent), motility disorder-like (ML), 281 (31.2 percent), and the combination (C) of these symptoms, 298 (33.1 percent). All patients were submitted to endoscopic evaluation, with two biopsies taken from the cardia and corpus, and four from the antrum of the stomach. All biopsy samples were studied for Helicobacter pylori (Hp) density, chronic inflammation, activity, intestinal metaplasia, atrophy, and the presence of lymphoid aggregates by histological examination. One antral biopsy was used for the rapid urease test. Tissue cagA status was determined by PCR from an antral biopsy specimen by a random sampling method. We also determined the serum levels of tumor necrosis factor-alpha (TNF-alpha) and gastrin by the same method. Data were analyzed statistically by the Kolmogorov-Smirnov test and by analysis of variance. Hp and cagA positivity was significantly higher in the UL subgroup than in the others. The patients in the ML subgroup had the lowest Hp and cagA positivity and Hp density. The ML subgroup also showed the lowest level of Hp-induced inflammation among all subgroups. The serum levels of TNF-alpha and gastrin did not reveal any difference between groups. Our findings show a poor association of Hp with the ML subgroup of functional dyspepsia, but a stronger association with the UL and C subgroups
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Dispepsia , Infecciones por Helicobacter , Helicobacter pylori , Análisis de Varianza , Dispepsia , Gastrinas , Infecciones por Helicobacter , Reacción en Cadena de la Polimerasa , Receptores de Colecistoquinina , Estadísticas no Paramétricas , Factor de Necrosis Tumoral alfa , TurquíaRESUMEN
If cytotoxin-associated gene A (CagA) status affects the response rates of therapy, then it may be possible to predict Helicobacter pylori eradication rates. We aimed to evaluate the response to eradication treatment of H. pylori infection in CagA-positive and CagA-negative patients. A total of 184 patients (93 males, 91 females, mean age 42.6 ± 12.8 years) with H. pylori-positive chronic gastritis were studied. Subjects underwent a gastroscopy and biopsy specimens were taken from the gastric antrum, body, and fundus. Before the eradication therapy was given all patients were tested for CagA, TNF-alpha and gastrin levels. They were then prescribed lansoprazole (30 mg bid), clarithromycin (500 mg bid), and amoxicillin (1.0 mg bid) for one week. On the 8th week a second endoscopy was performed and further biopsy specimens were obtained from the same sites as in the initial endoscopy. One hundred and twenty-seven patients (69.1 percent) were found to be CagA positive and 57 patients (30.9 percent) were CagA negative. The total eradication rate was 82.6 percent. In the CagA-positive group this rate was 87.4 percent, and in the CagA-negative group it was 71.9 percent (P = 0.019). TNF-alpha levels were higher in the CagA-positive than in the CagA-negative group (P = 0.001). However, gastrin levels were not different between groups (P = 0.421). Our findings revealed that CagA-negative status might be a risk factor for failure of H. pylori triple therapies. The CagA pathogenicity island gives a growth advantage to H. pylori strains and has been associated with an increase in the inflammatory response at the gastric mucosal level. These properties could make CagA-positive H. pylori strains more susceptible to antibiotics
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Antígenos Bacterianos/sangre , Helicobacter pylori , Infecciones por Helicobacter/sangre , Proteínas Bacterianas/sangre , Distribución de Chi-Cuadrado , Enfermedad Crónica , Infecciones por Helicobacter/tratamiento farmacológico , Factores de Riesgo , Factor de Necrosis Tumoral alfa , TurquíaRESUMEN
If cytotoxin-associated gene A (CagA) status affects the response rates of therapy, then it may be possible to predict Helicobacter pylori eradication rates. We aimed to evaluate the response to eradication treatment of H. pylori infection in CagA-positive and CagA-negative patients. A total of 184 patients (93 males, 91 females, mean age 42.6 +/- 12.8 years) with H. pylori-positive chronic gastritis were studied. Subjects underwent a gastroscopy and biopsy specimens were taken from the gastric antrum, body, and fundus. Before the eradication therapy was given all patients were tested for CagA, TNF-alpha and gastrin levels. They were then prescribed lansoprazole (30 mg bid), clarithromycin (500 mg bid), and amoxicillin (1.0 mg bid) for one week. On the 8th week a second endoscopy was performed and further biopsy specimens were obtained from the same sites as in the initial endoscopy. One hundred and twenty-seven patients (69.1%) were found to be CagA positive and 57 patients (30.9%) were CagA negative. The total eradication rate was 82.6%. In the CagA-positive group this rate was 87.4%, and in the CagA-negative group it was 71.9% (P = 0.019). TNF-alpha levels were higher in the CagA-positive than in the CagA-negative group (P = 0.001). However, gastrin levels were not different between groups (P = 0.421). Our findings revealed that CagA-negative status might be a risk factor for failure of H. pylori triple therapies. The CagA pathogenicity island gives a growth advantage to H. pylori strains and has been associated with an increase in the inflammatory response at the gastric mucosal level. These properties could make CagA-positive H. pylori strains more susceptible to antibiotics.
Asunto(s)
Antígenos Bacterianos/sangre , Proteínas Bacterianas/sangre , Gastritis/microbiología , Infecciones por Helicobacter/sangre , Helicobacter pylori , Adulto , Distribución de Chi-Cuadrado , Enfermedad Crónica , Femenino , Gastritis/sangre , Gastritis/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factor de Necrosis Tumoral alfa/análisis , TurquíaRESUMEN
We investigated the protective role of fish oil (FO-source of n-3 FA) enriched diet (in the first protocol) in 20 rats and FO administration intrarectally (in the second protocol) in 40 rats with trinitrobenzene (TNB) colitis. All colonic specimens were pathologically evaluated, myeloperoxidase enzyme activities were measured, leukotriene B4 (LTB4) and LTC4 levels were determined by radioimmunoassay. In the first protocol 10 rats (group A1) were fed with 8% sunflower and cotton oil enriched diet and (group A2) with 8% FO enriched diet for 6 weeks. At the end of this period, TNB (30 mg in 0.25 ml of 30% ethanol) were intrarectally administered. After 2 weeks, rats were sacrificed. MPO activities (2.47 versus 30.17), LTB4 (34.5 versus 903.3) and LTC4 (77.7 versus 456.0) levels were significantly reduced in group A2 compared with group A1 (P<0.005). There was also a significant difference in pathologic scores (1.55 versus 2.12, P<0.002) between two groups. In the first part of the second protocol, 20 male rats were randomized into two equal groups (B1 and B2) and TNB colitis was induced. After 1 day, 1 ml of saline (group B1) or n-3 FA enemas (group B2) were administered every day for 2 weeks. At the end of this period, rats were sacrificed and evaluated as done for previous groups. Although there was no significant difference between the two groups in comparison with MPO enzyme activities and pathologic scores, the LTB4 (130.1 versus 971.0) and LTC4 (126.0 versus 532.0) levels of FO group were significantly reduced (P<0.005). In the second part of the second protocol, 20 male rats were randomized into two groups. One millilitre of saline (group B3) or FO enemas (group B4) were administered to rats every day for 3 days. At the fourth day, TNB-colitis was induced and after 24 h rats were sacrificed. We could not find any significant difference in MPO activities, pathologic scores, LTB4 and LTC4 levels between groups B3 and B4. In conclusion, FO enriched diet decreased both pathologic damage and tissue LT levels. The second protocol of our study revealed that the long-term FO enemas decreased the LTB4 and LTC4 levels; however, did not have any beneficial effect on the tissue lesions. Short periods of FO enemas did not have a protective role in the occurrence of experimental colitis. The present study showed that FO enemas significantly decreased LT levels. The protective effect of FO (oral and enema) in TNB colitis may open a new insight into the treatment of inflammatory bowel disease.
Asunto(s)
Colitis/tratamiento farmacológico , Enema , Ácidos Grasos Omega-3/administración & dosificación , Animales , Colitis/inducido químicamente , Colon/química , Colon/enzimología , Colon/patología , Vías de Administración de Medicamentos , Ácidos Grasos Omega-3/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mucosa Intestinal , Leucotrienos/análisis , Masculino , Peroxidasa/análisis , Ratas , Ratas Wistar , TrinitrobencenosRESUMEN
BACKGROUND/AIMS: Increased susceptibility to infection in patients with obstructive jaundice is well recognized. Depression of reticuloendothlial system phagocytic function and suppression of cellular immunity suggested by in vivo studies have been postulated as the cause. It has been shown that increased serum soluble interleukin-2 receptor (sIL-2R) levels are the marker of immune system activation, especially T cell activation. The purpose of this study was to evaluate cellular immune system activation by measuring serum sIL-2R levels in 18 patients with obstructive jaundice (11 with choledocholithiasis, 7 with malignant obstructive jaundice), 10 patients with liver cirrhosis and 10 healthy subjects. MATERIAL AND METHODS: Serum sIL-2R levels were measured by using ELISA (Boehringer Manheim). Lymphocyte subgroups were determined by flowcytometry. Serum immungolubulins (IgG, IgA, IgM) and autoantibodies such as antinuclear antibody, rheumatoid factor, anti-thyroglobulin and anti-microsomal antibody were measured. RESULTS: The levels of serum sIL-2R were found to be 47.1-121.2 (mean 77.3, SD +/- 20.1) pmol/l in healthy subjects, 82.8-199.2 (mean 150.9 +/- 32.2) pmol/L in patients with liver cirrhosis and 32.6-172.5 (mean 121.7 +/- 40.6) pmol/L in patients with obstructive jaundice. Serum sIL-2R levels were significantly higher in patients with liver cirrhosis or obstructive jaundice than in healthy subjects (p < 0.01 and p < 0.05 respectively). There is a significant difference in levels between patients with choledocholithiasis and with malignant obstructive jaundice (p < 0.01). Serum sIL-2R levels were measured higher in patients with liver cirrhosis than those in patients with obstructive jaundice (p < 0.059). CONCLUSIONS: In patients with obstructive jaundice, and to a lesser extent in those with liver cirrhosis, in vivo activation of immune system may be considered possible.