Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Choline Deficiency”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed2006

Angiotensin-II and vascular endothelial growth factor interaction plays an important role in rat liver fibrosis development.

Both angiotensin-II (AT-II) and vascular endothelial growth factor (VEGF) have been shown to play important roles in the progression of liver fibrosis. However, the interaction of AT-II with VEGF in the liver fibrosis has not been elucidated yet. The aim of the current study was to elucidate a possible association between these molecules, especially in conjunction with the hepatic stellate cells (HSC). The effect of AT-II type 1 receptor blocker (ARB) was assessed on several indices of choline-deficient l-amino acid-defined (CDAA)-induced liver fibrogenesis. This ARB significantly suppressed liver fibrosis development along with suppression of the VEGF expression and neovascularization in the liver. In the cultured activated HSC, AT-II induced VEGF in a dose- and time-dependent manner. ARB and LY333531, a protein kinase C (PKC) inhibitor, attenuated this augmentation. These results indicated that AT-II and VEGF interaction played an important role in liver fibrosis development, and that in the activated HSC, AT-II utilized type 1 receptor and PKC as an intracellular signaling pathway to induce VEGF.

Journal Article↗
PubMed2006

Exacerbation of dietary steatohepatitis and fibrosis in obese, diabetic KK-A(y) mice.

In this study, we investigated a dietary model of steatohepatitis caused by methionine- and choline-deficiency (MCD) in obese, diabetic KK-A(y) mice. Male KK-A(y) mice and C57Bl/6 mice were fed an MCD diet for up to 8 weeks, and liver pathology was evaluated. Hepatic steatosis and inflammatory infiltration were more prominent in KK-A(y) mice than in C57Bl/6 mice 4 weeks after feeding with MCD diet. MCD diet-induced increases in tumor necrosis factor (TNF)-alpha mRNA levels, as well as lipid peroxidation, in the liver were also potentiated significantly in KK-A(y) mice. Extended degree of hepatic fibrosis was observed in KK-A(y) mice as compared to C57Bl/6 mice 8 weeks after feeding with MCD diet. Indeed, alpha1(I)procollagen and transforming growth factor (TGF)-beta1 mRNA levels were significantly higher in KK-A(y) mice following dietary treatment. Serum adiponectin levels were elevated nearly two-fold when C57Bl/6 mice were given MCD diet for 4 weeks; however, serum adiponectin levels in KK-A(y) mice fed both the control- and MCD diet were the same, reaching the values almost 1/2 of those in C57Bl/6 mice. In conclusion, KK-A(y) mice exhibit increased susceptibility to MCD diet-induced steatohepatitis, where hypoadiponectinemia most likely plays a key role in exacerbation of both inflammatory and profibrogenic responses.

Journal Article↗
PubMed2004

Differentiation processes of oval cells into hepatocytes: proposals based on morphological and phenotypical traits in carcinogen-treated hamster liver.

Hepatic stem cells participate in the recovery process of liver with severe injury or impaired hepatocyte regeneration. Oval cells (an oval-shaped liver cell population newly emerging from the portal or periportal zones following severe hepatic cellular damage) are believed to be the progeny of liver stem cells and precursor cells of both hepatocytes and bile duct cells. An attempt was made to define the differentiation processes of hepatic oval cells into mature hepatocytes in hamsters fed a choline-deficient diet and treated with diethylnitrosamine and 2-acetyl aminofluorene, on the basis of histopathological, electron microscopical, histochemical and immunohistochemical characterization of hepatic cell components. Two putative differentiation pathways of oval cells toward mature hepatocytes are proposed, namely (1) the differentiation of ductular-like oval cells via ductular/acinar-type hepatocytes, and (2) the differentiation of individual oval cells via small hepatocytes. Those proposals were strongly supported by consistent immunoreactivity of the cells for OV-6, an oval cell marker, and differential expression patterns for CK19 and PAS-positive cytoplasmic glycogen granules.

Animals↗
PubMed2005

The reduced tolerance of rat fatty liver to ischemia reperfusion is associated with mitochondrial oxidative injury.

BACKGROUND: Oxidative stress contributes to the pathogenesis of hepatic ischemia-reperfusion injury. This study aimed to determine whether fatty degeneration affects the oxidative damage during warm ischemia reperfusion and whether mitochondria, the major intracellular site of energy synthesis, represent a preferential target of this injury. MATERIALS AND METHODS: Fed rats with control or fatty liver induced by choline deficiency underwent 60' lobar ischemia and reperfusion. Oxidative damage was assessed by measuring in whole liver tissue and in isolated mitochondria the thiobarbituric acid-reactive substances (TBARs), protein carbonyls (PC), and total and oxidized glutathione (GSH and GSSG) concentrations. The mitochondrial F0-F1-ATPase content and the oxidative phosphorylation activity were also determined. Rat survival and ALT release were assessed as parameters of liver injury. RESULTS: In the whole liver tissue, with the exception of TBARs, no differences were observed for GSH, GSSG, and PC between the two groups throughout all of the experiment. In contrast, in isolated mitochondria, fatty infiltration was associated with a mild oxidative imbalance already under basal conditions. The preischemic differences in the mitochondrial TBARs, PC, and GSSG levels were significantly amplified by reperfusion in the presence of steatosis. The enhanced oxidative damage was associated to a reduced F0-F1-ATPase content and oxidative phosphorylation activity in fatty liver mitochondria. Finally, serum ALT levels were significantly greater and survival significantly lower in rats with steatotic liver. CONCLUSIONS: Fatty infiltration exacerbates mitochondrial oxidative injury during warm ischemia reperfusion. The increased oxidative stress can alter mitochondrial functions, including key processes for ATP synthesis, thus, contributing to the reduced tolerance to reperfusion injury.

Animals↗
PubMed2005

The nutritional status modulates preservation-reperfusion injury in rat fatty liver.

BACKGROUND: Microcirculation disturbances are essential factors of preservation injury in fatty liver. However, hepatocyte injury is also markedly excessive in fatty liver resulting, at least in part, from energy metabolism impairment and oxidative stress. Thus, this study aimed to determine whether nutritional status influences preservation injury in fatty liver and whether energetic substrate supplementation, alone or with a vasodilator, is protective. MATERIALS AND METHODS: Normal or fatty livers induced by a choline-deficient diet were isolated from fed and fasted rats, preserved in University of Wisconsin solution at 4 degrees C for 18 h, and then reperfused with Krebs-Henseleit solution at 37 degrees C for 120 min. Fasted rats with fatty liver were also treated as follows: (1) Glucose supplementation: rats had access to a glucose solution for 18 h prior procurement; (2) Prostaglandin (PG): alprostadil was continuously infused during reperfusion; (3) Combined treatment: Glucose supplementation + PG. RESULTS: Fasting-induced liver injury was significantly greater in fatty than normal liver. In fatty livers from fasted rats, all treatments reduced the alanine aminotransaminase release. Hepatic oxygen consumption improved in the glucose and glucose + PG groups, while PG infusion had no effect. Glucose supplementation did not affect portal pressure, which, in contrast, was reduced in livers receiving PG. Finally, all treatments lowered oxidative injury. CONCLUSIONS: Preservation injury in fatty liver is greatly related to nutritional status. Energetic substrate supplementation may represent a clinically feasible protective strategy and a multistep approach adding vasodilators could offer further benefit by acting on different pathogenetic mechanisms.

Alanine Transaminase↗
PubMed1988

Therapeutic regimens in acute experimental hemorrhagic pancreatitis. Effects of hydration, oxygenation, peritoneal lavage, and a potent protease inhibitor.

In this study we evaluated the effects of hydration, oxygenation, peritoneal lavage, and the protease inhibitor gabexate mesilate in acute hemorrhagic pancreatitis induced by feeding mice a choline-deficient, ethionine-supplemented diet. Different groups of mice were kept at various concentrations of O2 (21%, 35%, and 45% O2), or were treated by either s.c. injections or i.p. injections of electrolyte solution at various doses (0, 4, 6, or 8 ml/day). Further groups were treated either with i.p. lavage, lavage with 1.5 mg/ml of gabexate, or i.p. injections of 100 mg/kg of gabexate without lavage. The potential benefits of the various regimens were assessed by measuring survival, various biochemical and histologic features, and alterations in hematocrit, pH, and blood gases. Increasing O2 concentrations reversed hypoxemia and acidosis, but had no effect on biochemical or morphologic alterations and did not improve survival. However, hydration by s.c. fluid markedly improved survival and normalized the hematocrit without having major effects on biochemical or morphologic alterations. Intraperitoneal fluid did not improve survival. Gabexate injections without lavage had a slight effect on survival and serum amylase concentration and very little effect on histology. Lavage without gabexate had a greater effect on survival, serum amylase, and histology. Addition of gabexate to the lavage fluid increased the beneficial effect of lavage. Increases in amylase and activated trypsin in ascites were markedly reduced by lavage and even more so by lavage with addition of gabexate. We conclude that sufficient hydration appears to be an important factor in supportive care for severe acute pancreatitis, whereas oxygenation without sufficient hydration has no major benefit. Peritoneal lavage with gabexate showed the greatest benefit of the various regimens for acute severe pancreatitis and is worthy of clinical trials.

Acute Disease↗
PubMed2003

Systemic nf-kappaB activation in a transgenic mouse model of acute pancreatitis.

BACKGROUND: Transcription factor NF-kappaB has been implicated in numerous human inflammatory diseases. Acute pancreatitis can result in remote tissue injury, but the involved mechanisms are unknown. This study evaluates the role of systemic NF-kappaB activation in the pathogenesis of lung inflammation in a transgenic pancreatitis model. MATERIALS AND METHODS: Using transgenic mice expressing photinus luciferase controlled by an NF-kappaB-dependent promoter, luciferase activity was measured in pancreas, liver, and lung tissues as a surrogate marker of NF-kappaB activity. Luciferase activity was measured by in vivo bioluminescence and correlated to an in vitro luciferase assay of organ homogenates. Following measurement of luciferase activity in uninjured animals, these animals were fed a choline-deficient, ethionine supplemented diet for 48 h to induce pancreatitis, and luciferase activity was then measured at 48, 60, 72, and 96 h. Lung inflammation was determined by total nucleated cell counts in bronchoalveolar lavage (BAL) fluid. RESULTS: Bioluminescence detected increased luciferase activity over the upper abdominal region at 48 and 60 h (P < 0.05), and over the thorax at 60 and 72 h (P < 0.05). Luciferase assays showed significantly increased luciferase activity in both liver and lung tissue at 48 (liver = P < 0.005, lung = P < 0.05) and 60 h (liver = P < 0.05, lung = P < 0.05) compared to activity in uninjured controls. Total nucleated cell counts in BAL fluid were significantly increased at 72 h (P < 0.05) compared with controls. CONCLUSION: In this model, NF-kappaB binding activity is increased in the liver and lung. These data suggest that the liver modulates pancreatitis-induced systemic inflammatory response syndrome (SIRS) and suggest strategies to reduce multisystem injury.

Acute Disease↗
PubMed1996

Timing of tumor necrosis factor antagonism is critical in determining outcome in murine lethal acute pancreatitis.

BACKGROUND: Tumor necrosis factor (TNF) is produced in large amounts within the pancreas, lungs, and liver during severe acute pancreatitis and is believed to mediate many of the detrimental consequences typical of this disease. Investigations into the benefit of TNF antagonism have suggested that TNF may also mediate processes that are protective to the host. METHODS: With the hypothesis that timing plays a role in these dissenting views, TNF was antagonized either prophylactically or therapeutically with a recombinant form of the soluble type I TNF receptor (TNFbp) during a lethal model of necrotizing pancreatitis induced by feeding a choline-deficient diet. Mortality was determined for 10 days in 390 female mice divided into three groups: control, TNFbp early (time, 0 to 5 days), and TNFbp late (time, 1.5 to 5 days). Pancreatitis severity and cytokine production were assessed daily. RESULTS: Animals in the control group had a 75% mortality rate that was significantly decreased by prophylactic TNF blockade (64%, p < 0.05). Delaying TNF antagonism until serum cytokines were elevated and pancreatitis was manifest decreased mortality to 42% (p < 0.001 versus control, p < 0.01 versus early). Early and late TNF blockade decreased pancreatic edema and serum amylase, lipase, interleukin-1, and interleukin-6 (all p < 0.05) but not TNF. Late antagonism typically resulted in the greatest attenuation of all these parameters. CONCLUSIONS: Blockade of TNF by the administration of a soluble TNF receptor attenuates the severity of pancreatitis, decreases the production of associated inflammatory cytokines, and significantly improves survival. Delaying antagonism until pancreatitis is manifest and circulating cytokines are elevated but not yet maximal appears to be more protective than simple prophylactic TNF antagonism.

Acute Disease↗
PubMed1996

Interleukin-10 prevents death in lethal necrotizing pancreatitis in mice.

BACKGROUND: Cytokines derived from macrophages may play an integral role in the evolution of acute pancreatitis. Interleukin-10 (IL-10), a potent antiinflammatory cytokine, prevents the activation of macrophages and their release of inflammatory cytokines. The aim of this study was to determine whether treatment with IL-10 decreased the severity of experimental acute pancreatitis. METHODS: Thirty female Swiss Webster mice were divided into three groups. Acute pancreatitis was induced by using a choline-deficient, 0.5% ethionine supplemented (CDE) diet. Group A (controls) received CDE diet alone. Group B was pretreated with 10,000 units of intraperitoneal IL-10 at the onset of feeding and every 8 hours thereafter. Group C received IL-10 33 hours after beginning the CDE diet and every 8 hours thereafter. One half of the animals in each group was killed at 54 hours; the remaining living animals were killed at 80 hours. Serum amylase levels (units per liter) were determined at 54 and 80 hours. Pancreata were harvested and fixed in formalin. Histologic characteristics were graded on a scale from 0 to 4 (normal to most abnormal) in a blinded fashion by two investigators. RESULTS: Serum amylase level and histologic score (edema, inflammation, hemorrhage, and necrosis) were significantly reduced when IL-10 was administered either prophylactically or therapeutically (p < 0.01). At 54 hours all animals were alive. Mortality was reduced at 80 hours in both groups treated with IL-10 compared with those fed the CDE diet alone (p < 0.001). CONCLUSIONS: These results suggested that macrophages play an integral role in determining the severity of acute pancreatitis in this animal model. The finding that IL-10 decreased inflammation and prevented death, even when given after acute pancreatitis was established, suggests that it may have potential for clinical use.

Amylases↗
PubMed2003

Oxidative stress, KLF6 and transforming growth factor-beta up-regulation differentiate non-alcoholic steatohepatitis progressing to fibrosis from uncomplicated steatosis in rats.

BACKGROUND/AIMS: Pathogenesis of non-alcoholic steatohepatitis (NASH) remains poorly understood. Cytochrome P450 2E1 (CYP 2E1), cytokines, oxidative stress and activation of hepatic stellate cells seem to play a role in this process. The aim was to determine the potential implication of these factors in the progression from uncomplicated steatosis to steatohepatitis with progressive fibrosis. METHODS: Animals were fed a standard diet, a 5% orotic acid-diet (OA) developing hepatic steatosis, or the methionine-choline deficient (MCD) diet inducing steatohepatitis for 2 and 6 weeks. Lipid peroxidation, CYP 2E1 expression and activity, expression of UCP-2, interleukin (IL)-6, transforming growth factor (TGF)beta1, KLF6 mRNAs, and activation of hepatic stellate cells were examined by gas chromatography, high-performance liquid chromatography, Western blotting, quantitative polymerase chain reaction and immunohistochemistry. RESULTS: Lipid peroxidation increased in the MCD model whereas only minor changes occurred in the OA model. KLF6 and TGFbeta1 mRNAs were selectively up-regulated in MCD animals. Stellate cell activation, inflammation and collagen deposition only occurred in the MCD group. CYP 2E1 expression and activity increased in the OA group while both decreased in MCD animals. UCP-2 and IL-6 mRNA increased in both groups. CONCLUSIONS: In the context of steatosis, lipid peroxidation is associated with inflammation and stellate cell activation with concomitant increase in TGFbeta1 production, possibly through up-regulation of KLF6.

Actins↗
PubMed1998

Hepatic OV-6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man.

BACKGROUND/AIMS/METHODS: Since in rat experiments, activation of progenitor cells is seen in conditions associated with hepatocyte injury or inhibited replication, we compared the activation and fate of human putative progenitor cells in regenerating liver versus chronic cholestatic disease, using immunohistochemistry, rat oval cell marker OV6 and a panel of bile ductular cell markers. We compared the results with different rat models: the choline-deficient acetylaminofluorene (CDAAF)- and alpha-naphthylisothiocyanate (ANIT)-model, using immunohistochemistry and electron microscopy. RESULTS: In very early stages of human liver regeneration, putative progenitor cells in the vicinity of portal tracts were immunoreactive for OV6, CK7, CK19 and chrom-A. In later stages of regeneration and in chronic cholestasis, reactive bile ductules (immunoreactive for OV6, CK7, CK19, chrom-A, NCAM) and intermediate hepatocyte-like cells (immunoreactive for OV6, CK7, chrom-A), became apparent, suggesting bidirectional differentiation of the putative progenitor cells. In regenerating human liver, intermediate hepatocyte-like cells became more numerous with time and extended far into the lobule. In advanced cholestasis, intermediate hepatocyte-like cells were less numerous and formed periportal rosettes and small clusters. In the CDAAF rat model (associated with inhibited hepatocyte replication), but not in the ANIT model, gradual differentiation of oval cells into hepatocytes was seen after stopping the diet. CONCLUSIONS: Our results in human liver suggest that reactive ductules and intermediate hepatocyte-like cells originate at least partly from activation and differentiation of "progenitor cells". In regeneration after submassive necrosis, in analogy with what is seen in rat models, differentiation towards hepatocytes is more pronounced than in chronic cholestasis.

Animals↗
PubMed1999

Carcinogenicity of heterocyclic amines for the pancreatic duct epithelium in hamsters.

Effects of eight heterocyclic amines (HCAs) on pancreatic duct carcinogenesis were investigated in a rapid production model in hamsters. N-Nitrosobis(2-oxopropyl)amine (BOP) was given to effect initiation, followed by augmentation pressure consisting of four daily i.p. injections of 500 mg/kg DL-ethionine, a choline-deficient (CD) diet, a single i.p. injection of 800 mg/kg L-methionine and a s.c. injection of 20 mg/kg BOP. After two cycles of augmentation pressure, the HCAs 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-9H-pyrido[2,3-b]indole (AalphaC), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) or 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [4,8-DiMeIQx) were administered in the diet for 50 or 70 days. The numbers of pancreatic ductal hyperplasias (H) and a total lesions including, atypical hyperplasia (AH), carcinomas in situ (CIS) and invasive carcinomas, were increased in hamsters given the diet containing 0.02% Trp-P-1 for 50 days. This result was confirmed and extended by the finding of increased numbers of invasive carcinomas in hamsters given 0.02% Trp-P-1 for 70 days. The number and incidence of invasive carcinomas were also elevated in hamsters given the diet containing 0.06% 4,8-DiMeIQx for 50 days. These results suggest a possible involvement of Trp-P-1 and 4,8-DiMeIQx in pancreatic duct carcinogenesis.

Animals↗
PubMed2002

Cellular origin of hepatocellular carcinomas.

There are four levels of cells in the hepatic lineage which may respond to different carcinogenic regimens: (1) the mature hepatocyte, which responds to diethylnitrosamine (DEN) hepatocarcinogenesis. (2) The bile duct progenitor cells, which give rise to cholangiocellular carcinomas when the furan model is used or when hamsters infected with liver flukes (Clornorchis sinensis) are exposed to dimethylnitrosamine. (3) The ductular 'bipolar' progenitor cell which gives rise to hepatocellular carcinomas (HCC) in several N-2-acetylaminofluorene (N-2-AAF) based regimens, and (4) the periductular stem cell, which is the cell of origin of HCC induced by the choline deficiency models of hepatocarcinogenesis. Extrahepatic (bone marrow) origin of the periductular stem cells is supported by recent data showing that hepatocytes may express genetic markers of donor hematopoietic cells after bone marrow transplantation.

Animals↗
PubMedDate not supplied

Hepatic Kupffer cell blockade reduces mortality of acute hemorrhagic pancreatitis in mice.

Inflammatory cytoklines derived from the liver may cause distant organ failure and death in severe pancreatitis. To minimize liver cytokine release, we studied the effects of Kupffer cell blockade on the mortality rate and severity of inflammation in a model of that disease. Thirty mice were divided into three groups. Group I received gadolinium chloride (l mg/100 g intravenously), which blocks Kupffer cell activity, and regular food. Groups 2 and 3 were fed a choline-deficient, ethionine-supplemented diet and developed severe pancreatitis. Group 2 (control) received intravenous saline solution, and group 3 received gadolinium chloride. Animals were killed at 72 hours. Serum levels of tumor necrosis factor-alpha and interleukin-1Beta, interleukin-6, and interleukin-10 were determined by enzyme-linked immunosorbent assay. Lung neutrophil infiltration was assessed by myeloperoxidase assay. Pancreatic inflammation was scored in a blinded manner. In a separate experiment, mortality rates were determined in saline- and gadolinium-treated animals (n=100). Gadolinium reduced the levels of all the cytoklines and lung myeloperoxidase (P<0.05). Gadolinium also reduced the mortality rate (52% vs. 86%; P <0.001). However, the degree of pancreatic inflammation was unchanged by gadolinium treatment. These data support the hypothesis that mortality in severe pancreatitis may in part be related to the secondary release of hepatic cytokines.

Acute Disease↗
PubMed1998

Dietary cystine and liver triacylglycerols in rats: effects of dietary lysine and threonine.

Addition of excess cystine to a wheat gluten diet did not alter rat liver triacylglycerols or serum cholesterol. However, if the cystine-enriched diet was supplemented with lysine and threonine, rats accumulate triacylglycerols and show increased serum cholesterol. Increases in hepatic triacylglycerols can be prevented by the further addition of methionine. This diet further increases serum cholesterol. We conclude that accumulation of triacylglycerols in the liver might be due to an increased methionine requirement, induced by the addition of excess cystine, and therefore to choline deficiency.

Amino Acids↗
PubMed2000

Loss of inhibitory growth regulation by TGF-beta1 in preneoplastic lesions in rat liver.

Injection of pig serum into rats twice a week for eight weeks induced transforming growth factor-beta1 (TGF-beta1) mRNA expression and protein production resulting in liver fibrosis without parenchymal cell injury. Eight-week treatment with pig serum reduced bromodeoxyuridine (BrdU) -positive hepatocytes 24 hr after 70% partial hepatectomy compared to that in the livers of rats treated with saline for eight weeks. Administration of a choline-deficient L-amino acid-defined (CDAA) diet for six weeks with pig serum coadministration, after pretreatment with pig serum for eight weeks, led to the development of preneoplastic lesions that were positive for the placental form of glutathione S-transferase (GSTP). Eight-week pretreatment with pig serum induced more GSTP-positive lesions and TGF-beta1 mRNA expression and protein concentration in the livers of rats subsequently fed a CDAA diet for six weeks than in rats fed the CDAA diet with saline treatment. These results indicate that TGF-beta1 induced by pig serum treatment inhibited hepatocyte proliferation but failed to prevent the development of preneoplastic lesions in a CDAA diet model.

Animals↗
PubMed1997

Tissue-specific cytokine production during experimental acute pancreatitis. A probable mechanism for distant organ dysfunction.

Our purpose was to determine if cytokines are produced systemically during acute pancreatitis. Proinflammatory cytokines are elevated during acute pancreatitis and have been implicated in the progression of pancreatitis-associated multiple organ dysfunction. Whether these mediators are produced within all tissues or very few specific organs is not known. Edematous pancreatitis was induced in adult male mice by IP injection of cerulein. Necrotizing pancreatitis was induced in young female mice by feeding a choline-deficient, ethionine supplemented diet. Animals were sacrificed as pancreatitis worsened, with multiple organs prepared for tissue mRNA and protein analysis by RT-PCR and immunoblotting. Pancreatitis severity was established by histologic grading and serum amylase and lipase. There was no cytokine mRNA or protein detectable prior to the induction of pancreatitis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) mRNA and protein were detected within the pancreas early in the course of pancreatitis in both models, coinciding with the development of hyperamylasemia (both P < 0.001). Interleukin-6 was produced in the pancreas after pancreatitis was more fully developed (P < 0.001). IL-1 beta and TNF-alpha were subsequently produced in large amounts in lung, liver, and spleen but never within kidney, cardiac muscle, or skeletal muscle. A significant delay between pancreatic and distant organ cytokine production was always observed. It is concluded that proinflammatory cytokines are produced within the pancreas and within organs known to develop dysfunction during severe pancreatitis. Cytokine production is tissue specific, correlates with disease severity, and occurs within the pancreas first and subsequently within distant organs.

Actins↗
PubMed2002

Effect of ursodeoxycholic acid on hepatic steatosis in rats.

Ursodeoxycholic acid (UDCA) has been shown to have hepatoprotective effects in various liver diseases. This drug has also been found to be effective in patients with nonalcoholic steatohepatitis, improving hepatic steatosis (HS) significantly. The aim of this study was to evaluate whether UDCA has an effect on both preventing and regressing HS in rats. To induce fatty liver, a choline-deficient diet (CDD) was used. For the rats assigned to receive UDCA, a 1.5% UDCA solution was administered at a dose of 25 mg/kg/day using an oral feeding tube. Assessment of HS was based on the quantification of percentage of hepatocytes containing lipid vacuoles. Forty-three male Wistar rats were randomly divided into two protocols. In protocol I, 7 rats were fed a standard diet (SD) plus UDCA for 30 days (control group). In protocol II, 19 rats were fed CDD and 17 rats were fed CDD plus UDCA for 30 days. At the end of this period, after performing liver biopsies, either SD or SD plus UDCA was started in both CDD-fed rats and CDD plus UDCA-fed rats for 30 days in a random order without the knowledge of the degrees of steatosis developed. At the end of this period, liver biopsies were repeated in order to evaluate whether UDCA has an effect on the regression of HS. In protocol I, there were no specific findings on the histological examination of the livers at 30 days. In protocol II, the percentage of HS in CDD plus UDCA-fed rats was significantly lower than CDD-fed rats at the end of the same period (percentage of steatosis, mean +/- SD: 12.2 +/- 29.6 to 23.2 +/- 34.1 respectively, P = 0.0201); after starting either SD or SD plus UDCA, steatosis was almost completely regressed at 30 days in all rats that developed that steatogenic changes. UDCA seems to prevent HS in rats; addition of UDCA to SD does not cause a further contribution in regressing HS.

Animals↗