Biomedical subjects

József Kaszaki

Publications and source records attributed to József Kaszaki.

17 recordsLinked to original sources

PubMed2006

In vitro and in vivo nuclear factor-kappaB inhibitory effects of the cell-penetrating penetratin peptide.

Penetratin is a cationic cell-penetrating peptide that has been frequently used for the intracellular delivery of polar bioactive compounds. Recent studies have just revealed the major role of polyanionic membrane proteoglycans and cholesterol-enriched lipid rafts in the uptake of the peptide. Both proteoglycans and lipid-rafts influence inflammatory processes by binding a wide array of proinflammatory mediators; thus, we decided to analyze the effect of penetratin on in vitro and in vivo inflammatory responses. Our in vitro luciferase gene assays demonstrated that penetratin decreased transcriptional activity of nuclear factor-kappaB (NF-kappaB) in tumor necrosis factor (TNF)-stimulated L929 fibroblasts and lipopolysaccharide-activated RAW 264.7 macrophages. Penetratin also inhibited TNF-induced intercellular adhesion molecule-1 expression in human endothelial HMEC-1 cells. Exogenous heparan sulfate abolished the in vitro NF-kappaB inhibitory effects of the peptide. Uptake experiments showed that penetratin was internalized by all of the above-mentioned cell lines in vitro and rapidly entered the cells of the lung and pancreas in vivo. In an in vivo rat model of acute pancreatitis, a disease induced by elevated activities of stress-responsive transcription factors like NF-kappaB, pretreatment with only 2 mg/kg penetratin attenuated the severity of pancreatic inflammation by interfering with IkappaB degradation and subsequent nuclear import of NF-kappaB, inhibiting the expression of proinflammatory genes and improving the monitored laboratory and histological parameters of pancreatitis and associated oxidative stress.

Amino Acid Sequence↗

PubMed2006

Beneficial effect of resveratrol on cholecystokinin-induced experimental pancreatitis.

Resveratrol is a phytoalexin with strong antioxidant and anti-inflammatory effects reaching high concentrations in red wine. The aim of our study was to test the effects of resveratrol pretreatment on cholecystokinin-octapeptide (CCK-8)-induced acute pancreatitis in rats. Animals were divided into a control group, a group treated with CCK-8 and a group receiving 10 mg/kg resveratrol prior to CCK-8 administration. Resveratrol ameliorated the CCK-8-induced changes in the laboratory parameters, and reduced the histological damage in the pancreas. The drug failed to improve the pancreatic antioxidant state, but increased the amount of hepatic reduced glutathione and prevented the reduction of hepatic catalase activity. Resveratrol-induced inhibition of nuclear factor kappa B (NF-kappaB) activation or reduction of the pancreatic tumor necrosis factor-alpha (TNF-alpha) concentration could not be demonstrated. In conclusion, the beneficial effects of resveratrol on acute pancreatitis seem to be mediated by the antioxidant effect of resveratrol or by an NF-kappaB-independent anti-inflammatory mechanism.

Acute Disease↗

PubMed2006

Intestinal nitric oxide synthase activity changes during experimental colon obstruction.

OBJECTIVE: The experiments in this study were designed to follow the time course of nitric oxide (NO) synthesis in the large bowel during acute mechanical ileus. MATERIAL AND METHODS: Occlusion of the mid-transverse colon was maintained for 420 min in anesthetized dogs. Strain-gauge transducers were used to analyze motility changes on the hepatic and lienal flexures, respectively. Constitutive NO synthase (cNOS) and inducible NOS (iNOS) activities were determined in tissue biopsies, and plasma nitrite/nitrate (NOx) level was measured in the portal blood. Following completion of the baseline studies, the animals were treated with either 7-nitroindazole (7-NI, selective neuronal NOS inhibitor), or N-nitro-L-arginine (NNA, non-selective NOS inhibitor). RESULTS: In the sham-operated group the cNOS activities differed significantly in the oral and aboral tissue samples (oral: 102.9; versus aboral: 62.1 fmol/mg protein/min). The obstruction elicited a significant increase in portal NOx and elevated tissue inducible NO synthase (iNOS) activity. NNA treatment decreased the motility index in both intestinal segments for 60 min, but 120 min later the motility index was significantly elevated (2.5-fold increase in the oral part, and 1.8-fold enhancement in the aboral segment, respectively). Treatment with 7-NI decreased the cNOS activity in the oral and aboral parts by approximately 40% and 70%, respectively, and suppressed the motility increase in the aboral colon segment. CONCLUSIONS: The motility of the colon was either significantly increased or decreased, depending on the type and selectivity of the NOS inhibitor compounds applied. NO of neuronal origin is a transmitter that stimulates peristaltic activity; but an increased iNOS/nNOS ratio significantly moderates the obstruction-induced motility increase.

Animals↗

PubMed2006

Chronic ethanol exposure impairs neuronal nitric oxide synthase in the rat intestine.

BACKGROUND: Nitric oxide (NO), synthesized by neuronal (nNOS), endothelial (eNOS), and inducible (iNOS) nitric oxide synthases, plays an essential role in the physiological functions of the gastrointestinal (GI) tract. Chronic ethanol intake has been shown to interfere with several of these physiological functions, leading to the pathological alterations observed in alcoholic individuals. Our aim therefore was to investigate the effects of chronic ethanol consumption on NOS isoforms in different GI segments. METHODS: Rats received either 20% aqueous ethanol solution or water for 8 weeks. Tissue samples of the duodenum, jejunum, ileum, and colon of the rats were used for measurement of the NOS activity, protein content, and nNOS immunohistochemistry. Anti-HuC/D immunohistochemistry was used to determine the total number of neurons. RESULTS: Measurement of the physiological constitutive NOS (cNOS) activity revealed a 20 times higher activity in the colon than in the small intestine and after chronic ethanol treatment demonstrated a significant decrease in the jejunum, ileum, and colon, while in the duodenum it remained unchanged compared with the control group. The physiological iNOS activity was higher in the ileum and colon than in the duodenum and jejunum, and these levels were not significantly affected by ethanol. Neuronal nitric oxide synthase immunohistochemistry revealed a significant decrease in the numbers of immunostained cells in all investigated intestinal segments, while the total number of myenteric neurons remained constant. The nNOS protein content measured by Western blotting indicated a significant decrease in the colon after ethanol consumption, while in other intestinal segments change was not detectable. CONCLUSIONS: This study has demonstrated for the first time that chronic ethanol consumption has a differential effect on NOS activity, NOS protein content, and the number of nitrergic neurons in different intestinal segments, suggesting that chronic ethanol administration affects the NO pathways in the enteric nervous system.

Animals↗

PubMed2005

The proteasome inhibitor MG132 protects against acute pancreatitis.

The cell-permeant MG132 tripeptide (Z-Leu-Leu-Leu-aldehyde) is a peptide aldehyde proteasome inhibitor that also inhibits other proteases, including calpains and cathepsins. By blocking the proteasome, this tripeptide has been shown to induce the expression of cell-protective heat shock proteins (HSPs) in vitro. Effects of MG132 were studied in an in vivo model of acute pancreatitis. Pancreatitis was induced in male Wistar rats by injecting 2 x 100 microug/kg cholecystokinin octapeptide intraperitoneally (ip) at an interval of 1 h. Pretreating the animals with 10 mg/kg MG132 ip before the induction of pancreatitis significantly inhibited IkappaB degradation and subsequent activation of nuclear factor-kappaB (NF-kappaB). MG132 also increased HSP72 expression. Induction of HSP72 and inhibition of NF-kappaB improved parameters of acute pancreatitis. Thus MG132 significantly decreased serum amylase, pancreatic weight/body weight ratio, pancreatic myeloperoxidase activity, proinflammatory cytokine concentrations, and the expression of pancreatitis-associated protein. Parameters of oxidative stress (GSH, MDA, SOD, etc.) were improved in both the serum and the pancreas. Histopathological examinations revealed that pancreatic specimens of animals pretreated with the peptide demonstrated milder edema, cellular damage, and inflammatory activity. Our findings show that simultaneous inhibition of calpains, cathepsins, and the proteasome with MG132 prevents the onset of acute pancreatitis.

Acute Disease↗

PubMed2005

[Dual effects of nitric oxide in acute colon obstruction].

UNLABELLED: Nitric oxide (NO) plays central role in the pathophysiology of large bowel diseases. In the gastrointestinal tract the predominant form of nitric oxide synthase (NOS) isoenzymes is neuronal NOS (nNOS). The aims were to investigate the role of NO and the activation of NOS isoforms during acute colonic obstruction. Haemodynamic changes, large bowel motility and plasma levels of nitrate-nitrite (NOx) were observed for 7 hrs in anaesthetized dogs. Group 1 (n=6) served as sham-operated control. In groups 2 (n=8), 3 (n=6), and 4 (n=6) colon obstruction was initiated. Groups 3 and 4 were treated with non-selective NOS inhibitor N-nitro-L-arginine (NNA, 4 mg/kg) or with the selective nNOS inhibitor 7-nitroindazol (7-NI, 5 mg/kg) 3 hr after the obstruction. At the end of the experiments, tissue biopsies were taken from the oral and aboral parts of the colon to determine the constitutive and inducible NOS (cNOS and iNOS, respectively) activities. RESULTS: The cNOS activity of the colon was significantly higher orally then aborally in each group. After obstruction the characteristic features of hyperdynamic sepsis were observed. The obstruction caused significant increase in iNOS activity, which was significantly reduced by the NOS inhibitors. The obstruction increased the motility on both parts of the colon. The administration of NNA transiently inhibited, but later significantly increased the motility of the colon segments. Inhibition of nNOS by 7-NI treatment did not influence the hemodynamic parameters but decreased the motility. CONCLUSION: Neuronal NO increases colon motility at the early stage of large bowel obstruction, however, during a concomitant sepsis the excess of inducible NO will moderate this effect.

Acute Disease↗

PubMed2005

[Effects of phosphatidylcholine pretreatment during acute experimental biliary reflux].

UNLABELLED: Biliary regurgitation plays important role in gastro-esophageal reflux disease and postoperative complications. Our major aims were to find out the consequences of short-term exposure with luminal bile on mucosal microcirculation and nitric oxide synthesis, and to determine the effects of systemic phosphatidylcholine pretreatment in this condition. The experiments were performed on inbred mongrel dogs. Group 1 (n=5) served as a saline-treated control, while in group 2 (n=5) the esophagus was exposed to bile for 3 h. In group 3 (n=5) the animals were pre-treated with 7-nitroindazole (7-NI), to inhibit the neuronal isoform of nitric oxide synthase. In group 4 (n=5) phosphatidylcholine (PC) solution (50 mg/kg) was administered iv before the biliary challenge. The microcirculation of the mucosa was observed by intravital videomicroscopy; myeloperoxidase and nitric oxide synthase activities, the degree of mast cell degranulation and tissue damage were evaluated via tissue biopsies. Exposure to bile evoked significant mast cell degranulation and leukocyte accumulation, and the red blood cell velocity (VRBC) and the diameter of the postcapillary venules (VD) increased significantly. The tissue ATP content and constitutive nitric oxide synthase activity decreased, while the inducible nitric oxide synthase activity increased significantly as compared with the control values. 7-NI treatment significantly exacerbated the mucosal mast cell degranulation and tissue damage. In contrast, PC pretreatment reversed the bile-induced ATP depletion, the inducible nitric oxide synthase and myeloperoxidase activity increases, and the mast cell degranulation. CONCLUSIONS: The neuronal nitric oxide synthase--mast cell axis plays an important role in the esophageal mucosal defense system. Systemic PC pretreatment affords effective protection through ameliorating the bile-induced ATP depletion and secondary inflammatory reaction.

Adenosine Triphosphate↗

PubMed2004

Flow motion in the intestinal villi during hemorrhagic shock: a new method to characterize the microcirculatory changes.

Conventional parameters are often inadequate to describe the dynamic flow changes in microcirculation. We used a novel approach to characterize oscillatory flow conditions in a canine model of hemorrhagic shock. Microcirculation in the ileal mucosal villi was visualized using intravital microscopy with the orthogonal polarization spectral imaging technique. The distribution of red blood cell velocity (RBCV) was estimated from the relative time periods of observed RBCV, and the average RBCV (A-RBCV) and its SD were then computed from the first and second moments of the RBCV distribution, respectively. Hemorrhagic shock (for 60 min) was followed by resuscitation with saline, hypertonic saline-Dextran solution (HSD, 7.2% NaCl-10% Dextran, 4 mL/kg), or HSD supplemented with the selective endothelin-A receptor antagonist ETR-p1/fl peptide (100 nmol/kg), respectively. The macrohemodynamic derangement (70% decrease in cardiac index and ileal blood flow) during shock was associated with the appearance of flow motion in the villi and an enhanced endothelin-1 release. The calculated A-RBCV was decreased by 40%. At resuscitation onset, continuous flow periods were transiently seen in 33%, 40%, and 50% of the experiments after saline, HSD, and HSD + ETR p1/fl treatment, respectively. HSD with or without endothelin-A antagonist treatment resulted in an increased relative duration of high-flow periods (by 20%) and a significant, 20% to 40% rise in A-RBCV. These results demonstrate that time-wise variability of RBCV should be used for the analysis of oscillatory flow conditions. The probabilistic estimation of A-RBCV provides a quantitative basis for comparison of the effectiveness of different resuscitation or vasoactive strategies.

Animals↗

PubMed2003

The anti-inflammatory effect of methylprednisolone occurs down-stream of nuclear factor-kappaB DNA binding in acute pancreatitis.

Glucocorticoids are potent anti-inflammatory drugs. The molecular mechanisms underlying these effects have not yet been fully revealed. The aim of the present study was to establish whether methylprednisolone pretreatment is beneficial and if it can block the pancreatic DNA binding of the transcription factor nuclear factor-kappaB (NF-kappaB) and proinflammatory cytokine synthesis during cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. Additionally, we set out to investigate the potential effects of methylprednisolone and CCK on pancreatic heat shock protein (HSP) synthesis. The dose-response (5-40 mg/kg) and time-course (6-72 h) curves of methylprednisolone on pancreatic HSP60 and HSP72 synthesis were evaluated following methylprednisolone treatment. We demonstrated that methylprednisolone specifically and dose-dependently induced HSP72 in the pancreas of rats, while it did not have a significant effect on HSP60 expression. The pancreatitis was induced near the peak level of HSP72 synthesis (2 x 30 mg/kg body weight [b.w.] methylprednisolone i.m. at an interval of 12 h, followed by a 12-h recovery period after the second injection of methylprednisolone) by administering 2 x 100 microg/kg CCK subcutaneously at an interval of 1 h. The injections of CCK in the vehicle-pretreated group significantly elevated the levels of pancreatic HSP60 and HSP72 2-4 h after the second CCK injection. Methylprednisolone pretreatment ameliorated many of the examined laboratory (the pancreatic weight/body weight [p.w./b.w.] ratio, the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic levels of tumor necrosis factor-alpha and interleukin-6, the degree of lipid peroxidation, protein oxidation, nonprotein sulfhydryl group content and the pancreatic myeloperoxidase activity) and morphological parameters of the disease. Methylprednisolone pretreatment did not influence pancreatic NF-kappaB DNA binding, but decreased proinflammatory cytokine synthesis in this acute pancreatitis model. The findings suggest that the anti-inflammatory effect of large doses of methylprednisolone in secretagogue-induced pancreatitis occurs downstream of NF-kappaB DNA binding, and that increased pancreatic HSP72 synthesis may play a role in the protective effect of the drug.

Acute Disease↗

PubMed2003

NF-kappaB activation is detrimental in arginine-induced acute pancreatitis.

The transcription factor nuclear factor kappaB (NF-kappaB) has been shown to have a critical role in the pathogenesis of sodium taurocholate- and cerulein-induced acute pancreatitis by regulating the expression of many proinflammatory genes in the pancreas. Heat shock proteins (HSPs), on the other hand, protect the pancreas against cellular damage. The aims of the present study were: (i) to investigate pancreatic NF-kappaB activation, proinflammatory cytokine synthesis, and cytoprotective HSP induction during L-arginine- (Arg-) induced acute pancreatitis in rats, and (ii) to establish whether pretreatment with pyrrolidine dithiocarbamate (PDTC) or methylprednisolone (MP) can block the activation of pancreatic NF-kappaB and determine their effects on the severity of Arg-induced acute pancreatitis. The dose-response (3 or 4 g/kg) and time-effect (0.5-96 h) curves relating to the action of Arg on pancreatic NF-kappaB activation and IL-1beta, TNF-alpha, HSP60, and HSP72 synthesis were evaluated. Various doses of PDTC or MP were administered 1 h before the induction of pancreatitis. We demonstrated that Arg specifically and dose-dependently induces pancreatitis, activates NF-kappaB (only the 3 g/kg dose) and proinflammatory cytokine synthesis, and increases the expressions of HSP60 and HSP72 in the pancreas of rats. The lower dose of Arg induced a less severe pancreatitis, but larger increases in the levels of HSPs. The present work supports and extends earlier observations that NF-kappaB activation is a common mechanism in acute pancreatitis, although it is dose dependent and occurs at a later stage in Arg-induced pancreatitis as compared with other models. PDTC and MP pretreatment dose-dependently blocked NF-kappaB activation and proinflammatory cytokine expression and ameliorated many of the examined laboratory (the pancreatic weight/body weight ratio, the pancreatic myeloperoxidase activity, the pancreatic contents of protein, amylase and trypsinogen, the degrees of lipid peroxidation and protein oxidation, and the nonprotein sulfhydryl group content) and morphological parameters of the disease. These findings suggest that pretreatment with PDTC or MP has an anti-inflammatory effect during Arg-induced pancreatitis, which is at least partly mediated by the inhibition of NF-kappaB activation and proinflammatory cytokine synthesis. The increased levels of HSPs most probably act to limit the severity of the disease.

Acute Disease↗

PubMed2003

Thoracic epidural anesthesia improves the gastric microcirculation during experimental gastric tube formation.

BACKGROUND: Gastric tube formation is a surgical technique to reestablish the continuity of the gastrointestinal tract after esophagectomy. Our aims were to study the microcirculatory consequences of experimental gastric tube formation and characterize the effects of thoracic epidural anesthesia (TEA) during this condition. METHODS: The experiments were performed on mongrel dogs anesthetized with pentobarbital. The stomach was prepared for replacement according to the method of Akiyama, and TEA was induced with bupivacaine (1 mg/kg). Macrohemodynamics, intramucosal pH, and gastric motility changes were monitored, and intravital video-microscopy with orthogonal polarization spectral imaging technique was used to observe the gastric microcirculation. RESULTS: The gastric pull-up induced a significant decrease in intramucosal pH. The functional capillary density of the mucosa or subserosa did not change; the red blood cell velocity in the capillaries of the upper part of the gastric tube was decreased in the mucosa, as well as on the serosal side. After epidural anesthesia the red blood cell velocity returned to the baseline, and the gastric and intestinal motility index was significantly increased. CONCLUSIONS: TEA significantly improves the microcirculation of the distal portion of the gastric tube and increases the intestinal and gastric motility after gastric pull-up. The procedure is favorable and should be recommended during reconstructive esophageal surgery.

Anesthesia, Epidural↗

PubMed2003

[Thoracic epidural anesthesia improves the gastric microcirculation during experimental gastric tube formation].

We studied the effects of gastric tube formation and thoracic epidural anaesthesia (TEA) on gastric microcirculation, hemodynamic and bowel motility changes. The experiments were performed on pentobarbital-anesthetized, mongrel dogs. Mean arterial pressure (MAP), gastric and mesenteric blood flow (Transonic Systems Inc.) and small bowel motility changes (strain gauge technique) were monitored. The stomach was prepared according to the method of Akiyama. TEA was induced by injecting Bupivacain 1 mg/kg. Orthogonal polarization spectral imaging (OPS) technique (Cytoscan A/R, Cytometrics, PA, USA) was used to observe in vivo microcirculatory changes. The gastric pull-up caused significant decrease in intramucosal pH and red cell velocity (RBCV) in terminal arterioles of the upper part of gastric tube both on the mucosal and serosal side. After TEA the RBCV returned to baseline level and the intestinal motility index significantly increased. Functional capillary density of the mucosa or subserosa did not change during the experiments. MAP was significantly reduced by 30%, while the arterial blood flow in gastric and mesenteric arteries was significantly increased. TEA significantly improves microcirculation of the distal portion of the gastric tube and increases intestinal motility. These results show that epidural anaesthesia is favourable and should be recommended during reconstructive oesophageal surgery.

Anesthesia, Epidural↗

PubMed2003

[Changes in microcirculation of esophageal mucosa during acute experimental reflux. Pathogenic role of the biliary component].

UNLABELLED: Our aims were to examine microcirculation during experimental reflux esophagitis in dogs. We compared the effects of microcirculation of the mucosa to 3-hr exposure with acid, mixed acid and bile, we measured the changes in constitutive and inducible nitric oxide synthase activity (cNOS and iNOS). METHODS: The microcirculation of the upper esophagus was investigated by intravital videomicroscopy. The functional capillary density (FCD), relative vessel area (RVA) and red blood cell velocity (RBCV) were measured. Mucosal barrier integrity was examined by vascular and epithelial permeability indices. Myeloperoxidase (MPO) enzyme activity, cNOS, iNOS activities and microscopic damage were examined in biopsies. RESULTS: The vascular permeability index, the RBCV and the RVA increased significantly in the treated groups, the FCD significantly decreased after acid exposure. The MPO and iNOS activities were significantly elevated in all treated groups. The cNOS activity did not change after exposure to acid + bile or acid, but significantly decreased after sole bile treatment. Severe mucosal damage was observed after bile exposure. CONCLUSION: Bile induced characteristic microcirculatory changes during experimental reflux esophagitis. Tissue damage and leukocyte infiltration could be exacerbated by bile-induced cNOS inhibition.

Animals↗

PubMed2003

[The role of glucocorticoid-dependent mechanisms in the progression of experimentally induced acute pancreatitis].

BACKGROUND: The effects of glucocorticoids on acute pancreatitis (AP) have remained contradictory. To investigate the time courses of the effects of the exogenous glucocorticoid agonists dexamethasone (DEX) and hydrocortisone (HYD) and a glucocorticoid antagonist (RU-38486), and to characterize the local and systemic responses in experimental AP. METHODS: The glucocorticoid agonists and antagonist were administered just before AP induction. Serum amylase activity determinations, IL-6 bioassays, pancreatic weight/body weight ratio measurements and survival analysis were performed. Liver and lung injuries were assessed via neutrophil leukocyte infiltration in myeloperoxidase (MPO) assays, tissue adenosine triphosphate (ATP) level determinations and histology. RESULTS: In the glucocorticoid agonist groups, the survival rate increased, while the serum amylase level, the IL-6 activity and the pancreatic weight/body weight ratio decreased significantly as compared with the control and RU-treated groups. AP resulted in significant decreases in tissue ATP levels in both the liver and the lung. In the DEX- or HYD-treated groups, the liver ATP levels were significantly elevated, while both the liver and the lung MPO levels were attenuated as compared with the AP and RU-treated groups. CONCLUSIONS: These results suggest that glucocorticoids may play important roles in mitigating the progression of the inflammatory reaction during the early phases of AP.

Acute Disease↗

PubMed2002

Dynamic in vivo observation of villus microcirculation during small bowel autotransplantation: effects of endothelin-A receptor inhibition.

BACKGROUND: The aims of this study were to characterize the structural and microcirculatory changes in single intestinal villi during ischemia and reperfusion and determine the site of action of endothelin (ET)-A receptor inhibition during compromised mucosal perfusion. METHODS: Small bowel autotransplantation was performed in anesthetized dogs. One group was treated with the ET-A receptor antagonist ETR-p1/fl peptide. The epithelial thickness and villus microcirculatory parameters were observed by orthogonal polarization spectral imaging; the leukocyte-endothelial cell interactions were quantified with fluorescence videomicroscopy. RESULTS: Sixty-minute cold ischemia and 240-min reperfusion induced a decrease in villus functional capillary density and leukocyte-endothelial cell interactions. The epithelial layer was gradually removed, but denuded villi were not observed. ET-A receptor inhibition reduced the leukocyte adherence and attenuated epithelial exfoliation and the decrease in villus functional capillary density. CONCLUSIONS: ET-A receptor activation mediates microvascular dysfunction through precapillary blockades and leukocyte-endothelial cell interactions after cold ischemia and reperfusion in the canine small bowel.

Animals↗

PubMed2002

Induction of HSP72 by sodium arsenite fails to protect against cholecystokinin-octapeptide-induced acute pancreatitis in rats.

A number of investigators have demonstrated that the preinduction of heat-shock protein (HSP) expression (particularly HSP60 and HSP72) by hyper- or hypothermia may have a protective effect against cerulein-induced acute pancreatitis. The aim of the present study was to induce HSPs in the pancreas and lungs by thermal (hot-water immersion, HWI) and nonthermal methods (injection of sodium arsenite intraperitoneally) and to investigate the potential effects of HSP preinduction on cholecystokinin-octapeptide (CCK) induced acute pancreatitis and pancreatitis-associated lung injury in rats. The dose-response and time-effect curves observed following HWI and sodium arsenite treatments were evaluated. Animals were injected with 3 x 75 microg/kg CCK subcutaneously at intervals of 2 hr at the peak level of HSP synthesis, as determined by Western blot analysis. The rats were killed by exsanguination through the abdominal aorta 2 or 6 hr after the last CCK injection. HWI and the injection of sodium arsenite significantly elevated the expression of HSP72 in the pancreas and lungs, whereas they did not influence the levels of HSP60. Overall, HWI pretreatment had a protective effect against CCK-induced pancreatitis and pancreatitis-associated lung injury. In contrast, the nonthermal preinduction of HSP72 by sodium arsenite did not result in any beneficial effects on the measured parameters of the disease. The findings suggest that the preinduction of HSP72 is not sufficient to protect against CCK-induced acute pancreatitis and pancreatitis-associated lung injury or that the beneficial effect of hyperthermia may not be exclusively related to HSP72 expression.

Acute Disease↗

PubMed2002

Endothelin-1 induces mucosal mast cell degranulation and tissue injury via ETA receptors.

The effects of endothelin-1 (ET-1) on mucosal mast cells are of special interest, since they may be an important component of the tissue response that occurs during ischaemic preconditioning or ischaemia/re-oxygenation injuries. Increasing doses of ET-1 were administered intravenously to anaesthetized rats. In a second series of experiments, animals were pretreated with the ET(A) receptor antagonists BQ-610 or ETR-P1/fl peptide, or with the ET(B) receptor antagonist IRL-1038. Intestinal perfusion changes were recorded, and the proportion of degranulated mast cells and the degree of mucosal damage were determined in ileal biopsies. ET-1 induced dose-dependent alterations in the haemodynamic and morphological parameters, and caused significant mast cell degranulation. These changes were inhibited significantly by pretreatment with the ET(A) receptor antagonists, but not with the ET(B) receptor antagonist. We conclude that a cross-talk exists between endothelial cell-derived humoral mediators and the intestinal mast cell system.

Analysis of Variance↗