Biomedical subjects

A Dembiński

Publications and source records attributed to A Dembiński.

At least 19 recordsLinked to original sources

PubMed2006

Effect of ischemic preconditioning on pancreatic regeneration and pancreatic expression of vascular endothelial growth factor and platelet-derived growth factor-A in ischemia/reperfusion-induced pancreatitis.

UNLABELLED: Ischemic preconditioning has been shown to protect several organs from ischemia/reperfusion-induced injury. In the pancreas, protective effect of ischemic preconditioning has been shown against pancreatitis evoked by ischemia/reperfusion, as well as by caerulein. However, the effect of ischemic preconditioning on the course of acute pancreatic is unclear. The aim of our study was to evaluate the influence of ischemic preconditioning on pancreatic regeneration and pancreatic presence of platelet-derived growth factor-A (PDGF-A) and vascular endothelial growth factor (VEGF) in the course of ischemia/reperfusion-induced pancreatitis. METHODS: In male Wistar rats, ischemic preconditioning of the pancreas was performed by short-term clamping of celiac artery (twice for 5 min with 5 min interval). Acute pancreatitis was induced by clamping of inferior splenic artery for 30 min followed by reperfusion. Rats were sacrificed 1, 5, 12 h or 1, 2, 3, 5, 7, 9 and 21 days after the start of reperfusion. Severity of acute pancreatitis and pancreatic regeneration were determined by biochemical and morphological examination, expression of growth factors was determined by immunohistochemical analysis. RESULTS: In ischemia/reperfusion-induced pancreatitis, the pancreatic damage reached the maximal range between the first and second day of reperfusion, and was followed by subsequent pancreatic regeneration. Ischemic preconditioning alone caused mild passing pancreatic damage and an increase in plasma concentration of pro-inflammatory interleukin-1 and anti-inflammatory interleukin-10. Ischemic preconditioning applied before ischemia/reperfusion-induced pancreatitis reduced morphological and biochemical signs of the pancreatitis-evoked pancreatic damage and accelerated pancreatic regeneration. This effect was associated with improvement of pancreatic blood flow. Ischemic preconditioning, ischemia/reperfusion-induced pancreatitis and their combination increased the presence of VEGF in acinar and islet cells, and immunostaining for PDGF-A in blood vessels. This effect was maximally pronounced after combination of ischemic preconditioning plus pancreatitis and occurred earlier than after pancreatitis alone. CONCLUSIONS: Ischemic preconditioning reduces pancreatic damage and accelerates pancreatic healing in the course of ischemia/reperfusion-induced pancreatitis. This effect is associated with the increase in plasma concentration of anti-inflammatory interleukin-10, improvement of pancreatic blood flow and alteration of pancreatic immunohistochemical expression of PDGF-A and VEGF.

Animals↗

PubMed2006

Influence of ghrelin on gastric and duodenal growth and expression of digestive enzymes in young mature rats.

UNLABELLED: Ghrelin, a nature ligand for the growth hormone secretagogue receptor (GHS-R), stimulates a release of growth hormone, prolactin and adrenocorticotropic hormone. Also, ghrelin increases food intake in adult rats and humans and exhibits gastroprotective effect against experimental ulcers induced by ethanol or stress. The aim of present study was to examine the influence of ghrelin administration on gastric and duodenal growth and expression of pepsin and enterokinase in young mature rats with intact or removed pituitary. METHODS: Two week after sham operation or hypophysectomy, eight week old Wistar male rats were treated with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose) i.p. twice a day for 4 days. Expression of pepsin in the stomach and enterokinase in the duodenum was evaluated by real-time PCR. RESULTS: In animals with intact pituitary, treatment with ghrelin increased food intake, body weight gain and serum level of growth hormone and insulin-like growth factor-1 (IGF-1). These effects were accompanied with stimulation of gastric and duodenal growth. It was recognized as the significant increase in gastric and duodenal weight and mucosal DNA synthesis. In both organs, ghrelin administered at the dose of 8 nmol/kg caused maximal growth-promoting effect. In contrast to these growth-promoting effects, administration of ghrelin reduced expression of mRNA for pepsin in the stomach and was without effect on expression of mRNA for enterokinase in the duodenum. Hypophysectomy alone lowered serum concentration of growth hormone under the detection limit and reduced serum level of IGF-1 by 90%. These effects were associated with reduction in daily food intake, body weight gain and gastroduodenal growth. In hypophysectomized rats, administration of ghrelin was without significant effect on food intake, body weight gain or growth of gastroduodenal mucosa. Also, serum concentration of growth hormone or IGF-1 was not affected by ghrelin administration in rats with removed pituitary. CONCLUSION: Administration of ghrelin stimulates gastric and duodenal growth in young mature rats with intact pituitary, but inhibits expression of mRNA for pepsin in the stomach. Growth hormone and insulin-like growth factor-1 play an essential role in growth-promoting effects of ghrelin in the stomach and duodenum.

Analysis of Variance↗

PubMed2006

Cannabinoids in acute gastric damage and pancreatitis.

UNLABELLED: Recent studies have shown that stimulation of cannabinoid 1 (CB1) receptor reduces the area of ischemic myocardial necrosis and affects activity of the digestive tract. The aim of the present study was to check whether the administration of CB1 receptor agonist or antagonist affects the stress-induced gastric ulceration and development of edematous pancreatitis. METHODS: Experiments were performed on rats. Gastric lesions were induced by water immersion and restrain stress (WRS). Acute pancreatitis was induced by cerulein. Prior to WRS or before and during cerulein administration, a natural endogenous ligand for CB1 receptor, anandamide was administered intraperitoneally at the dose of 0.8, 1.5 or 3.0 micromol/kg. A synthetic CB1 receptor antagonist, AM 251 (ALEXIS(R) Biochemicals) was administrated at the dose of 4 micromol/kg i.p. alone or in combination with anandamide at the dose of 1.5 micromol/kg. RESULTS: Administration of anandamide reduced gastric lesions and this effect was associated with am increase in gastric mucosal blood flow and mucosal DNA synthesis; whereas serum level of pro-inflammatory interleukin-1 beta was reduced. Treatment with AM 251 aggravated gastric damage and reversed protective effect of anandamide administration. Opposite effect was observed in the pancreas. Administration of anandamide increased dose-dependently the severity of pancreatitis. In histological examination, we observed an increase in pancreatic edema and inflammatory infiltration. Also, treatment with anandamide augmented the pancreatitis-induced increase in serum level of lipase, amylase, poly-C ribonuclease, and pro-inflammatory interleukin-1 beta; whereas pancreatic DNA synthesis was reduced. Treatment with AM 251 reduced histological and biochemical signs of pancreatic damage and reversed deleterious effect of anandamide in cerulein-induced acute pancreatitis. CONCLUSIONS: Activation of CB1 receptors evokes opposite effects in the stomach and pancreas: in the stomach, exhibits protective effect against stress-induced gastric mucosal lesions; whereas in the pancreas, increases the severity of cerulein-induced pancreatitis.

Acute Disease↗

PubMed2005

Role of afferent nerves and sensory peptides in the mediation of hepatic artery buffer response.

Intrahepatic arteries are richly innervated by both adrenergic and sensory vanilloid-sensitive (capsaicin-sensitive) fibers. Stimulation of capsaicin sensitive fibers has been shown to dilate the intrahepatic vessels by both releasing sensory neuropeptides and by modulating the adrenergic tone. However the participation of capsaicin-sensitive fibers in the mediation of the hepatic artery buffer response (HABR) has not been investigated yet. To explore the involvement of sensory innervation and sensory neuropeptides in the HABR, the experiments were performed on capsaicin-denervated Wistar rats. In addition, we used selective CGRP and tachykinin receptor antagonists to test the participation of CGRP, substance P and NK-A in HABR in the rat. In anesthetized rats the hepatic artery blood flow (HABF), microcirculatory hepatic blood flow (HBF) and portal blood flow (PBF) were determined. The HABR was induced by partial occlusion of the portal vein and maintaining the PBF at 10% of its control preocclusive value. In the control HABR the hepatic artery blood flow increased by 89% (p< 0.005) whilst the HBF at the same time decreased by 32% (p< 0.005) in comparison to preocclusive HABF and HBF values. In sensory-denervated rats the resting HBF and PBF were increased by 23% (p< 0.05) and 34% (p< 0.05), respectively in comparison to the control HBF and PBF values. In this group the induction of the HABR increased the hepatic artery blood flow by only 55% (p< 0.05), whilst the HBF was reduced by 45% (p< 0.05). Pretreatment with CGRP 8-37 (CGRP receptor antagonist) and NK-1 but not NK-2 nor NK-3 receptor antagonists significantly reduced the HABF by 43% (p< 0.05) and 25% (p< 0.05) as compared to the HABF value in the control HABR group. These findings support the hypothesis that the hepatic artery buffer response induced by reduction of the portal inflow to the liver by 90% is partially mediated by activation of capsaicin-sensitive sensory fibers in the liver, probably due to local tissue ischemia and hypoxia. The observed vasodilation in the vascular bed of the hepatic artery is due to stimulation of CGRP and NK-1 receptors.

Animals↗

PubMed2005

Variable effect of ghrelin administration on pancreatic development in young rats. Role of insulin-like growth factor-1.

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been primarily isolated from the human and rat stomach. Ghrelin has been shown to stimulate appetite and fat deposition in adult rats and humans. The aim of this study was to investigate the effect of ghrelin administration on pancreatic growth in suckling, weaned and peripubertal seven week old rats. Rats were treated with saline or ghrelin (4, 8 or 16 nmol/kg/dose) intraperitoneally twice a day: suckling rats were treated for 7 or 14 days starting from the first postnatal day, three week old weaned rats and seven weeks old rats were treated for 5 days. Treatment with ghrelin did not affect animal weight in suckling or weaned rats, whereas in young seven week old rats, ghrelin caused a significant increase in body weight. Ghrelin decreased food intake in weaned rats; whereas in seven week old rats, food intake was enhanced. In suckling rats, ghrelin decreased the pancreatic weight, pancreatic amylase content, DNA synthesis and DNA content. In contrast, ghrelin increased pancreatic weight, DNA synthesis, DNA content and amylase content in weaned or young seven week old rats. Pancreatic blood flow was not affected by ghrelin in any group of rats tested. Ghrelin increased serum level of growth hormone in all rats. This effect was weak in suckling rats, higher in weaned and the highest in seven week old animals. Ghrelin did not affect serum level of insulin-like growth factor-1 (IGF-1) in suckling rats. In weaned and in seven week old rats, treatment with ghrelin caused increase in serum level of IGF-1. We conclude that ghrelin reduces pancreatic growth in suckling rats; whereas in weaned and young seven week old animals, treatment with ghrelin increases pancreatic growth. This biphasic effect of ghrelin in young animals on pancreatic growth seems to be related to age-dependent changes of the release of anabolic IGF-1.

Amylases↗

PubMed2004

Influence of central and peripheral administration of pancreatic polypeptide on gastric mucosa growth.

UNLABELLED: Previous studies have shown that pancreatic polypeptide (PP) inhibits exocrine pancreatic secretion. The aim of present study was to determine the influence of PP administration on gastric growth and blood flow. METHODS: Study was performed on regularly fed, fasted or fasted and subsequently refed rats. Rats were treated with saline (intraperitoneally - i.p.), caerulein (0.24 nmol/kg/dose, i.p.), pentagastrin (0.38 micromol/kg/dose, i.p.) or PP (5 nmol/kg/dose, i.p. or 10 pmol/dose intracerebroventricularly - i.c.v.). Saline, caerulein, pentagastrin and PP were administered alone or in combination, 3 times daily during last 48 h of experiment. RESULTS: Treatment with pentagastrin increased gastric mucosa weight, mucosal DNA synthesis and gastric blood flow in all group tested. Intraperitoneal and i.c.v administration of PP alone reduced mucosal DNA synthesis in regularly fed and refed animals, and decreased gastric blood flow in refed animals. Combination of PP i.p. or i.c.v plus pentagastrin significantly reduced the pentagastrin-evoked increase in gastric mucosa weight, gastric DNA synthesis and gastric blood flow in fasted animals, as well as regularly fed animals. In refed animals, influence of PP administration on the pentagastrin-evoked increase in gastric mucosa weight was weak and statistically insignificant, but still i.p or i.c.v administration of PP significantly reduced gastric blood flow and mucosal DNA synthesis in this group of animals. Administration of caerulein caused weak, but significant increase in gastric DNA synthesis, gastric mucosa weight and gastric blood flow in fasted rats. In regularly fed animals, caerulein significantly increased only gastric DNA synthesis and gastric blood flow. In fasted animals with subsequent refeeding, caerulein was without effect on parameters tested in the stomach. Neither i.p. nor i.c.v administration of PP affected the caerulein-evoked effects in the stomach. CONCLUSIONS: Peripheral and central administration of PP inhibits food- and pentagastrin-stimulated growth of gastric mucosa. Similar effects of low central doses of PP as the high peripheral doses of PP suggests a crucial role of the central nervous system in the inhibitory effect of PP on gastric mucosa growth.

Animals↗

PubMed2004

Modulation of pancreatic enzyme secretion by melatonin and its precursor; L-tryptophan. Role of CCK and afferent nerves.

Melatonin, a pineal hormone, is also produced in the gastrointestinal tract. Melatonin receptors have been detected in the stomach, intestine and pancreas. This indole inhibits insulin secretion but its role in the physiological modulation of exocrine pancreatic function is yet unknown. The aim of this study was to evaluate the pancreatic secretory effect of melatonin and its precursor; L-tryptophan given intraduodenally (i.d.) to the conscious rats with intact or capsaicin deactivated sensory nerves. CCK(1) receptor antagonist; tarazepide, was used in the part of the study to determine the involvement of CCK in the secretory effects of melatonin. The secretory studies were performed on awaken rats surgically equipped with silicone catheters, one of them was inserted into pancreato-biliary duct, the other one--into duodenum. Melatonin (1, 5 or 25 mg/kg) or L-tryptophan (10, 50 or 250 mg/kg) were administered i.d. Samples of pancreatic juice were collected in 15 minutes aliquots. Tarazepide (2,5 mg/kg i.p.) was given to the rats 15 min prior to the administration of melatonin or L-tryptophan. Neurotoxic dose of capsaicin (100 mg/kg s.c.) was used to deactivate afferent nerves and thus to assess the role of these nerves in the melatonin-induced pancreatic enzyme secretion. Administration of melatonin (1, 5 or 25 mg/kg i.d.) or L-tryptophan (10, 50 or 250 mg/kg i.d.) significantly increased pancreatic amylase outputs. Deactivation of sensory nerves by capsaicin or administration of CCK(1) - receptor antagonist; tarazepide, reversed the stimulatory effects of melatonin or L-tryptophan on pancreatic secretory function. Administration of melatonin or its amino-acid precursor to the rats resulted in the significant and dose-dependent rises of melatonin and CCK plasma levels. We conclude that melatonin or its precursor; L-tryptophan stimulates pancreatic enzyme secretion via stimulation of CCK release and activation of duodeno-pancreatic reflexes.

Amylases↗

PubMed2004

Immunohistochemical expression of FGF-2, PDGF-A, VEGF and TGF beta RII in the pancreas in the course of ischemia/reperfusion-induced acute pancreatitis.

UNLABELLED: Acute pancreatitis leads to pancreatic damage followed by subsequent regeneration. The aim of our study was to evaluate the presence of growth factors in the course of spontaneous pancreatic regeneration after ischemia/reperfusion (I/R)-induced pancreatitis. METHODS: In rats, I/R was evoked by clamping of splenic artery for 30 min followed by reperfusion. Rats were sacrificed 1, 5, 12 h or 1, 2, 3, 5, 7, 9 or 21 days after removal of vascular clips. Pancreatic blood flow (PBF), plasma lipase, interleukin-1beta (IL-1beta), interleukin-10, pancreatic cells proliferation and morphological signs of pancreatitis were determined. Pancreatic presence of fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta type II receptor (TGFbeta RII) was detected by immunohistochemisty. RESULTS: Exposure to I/R led to the development of acute necrotizing pancreatitis followed by regeneration. Morphological features showed maximal pancreatic damage between the 1(st) and 2(nd) day of reperfusion. It was correlated with a maximal increase in plasma lipase, and pro-inflammatory IL-1beta concentration, as well as, a reduction in PBF and pancreatic DNA synthesis. I/R increased FGF-2 content in pancreatic acinar cells between the 12(th) and 24(th) h, and between 5(th) and 9(th) day of reperfusion. At the 2(nd) day the presence of FGF-2 in pancreatic acinar cells was reduced. After I/R PDGF-A appeared in pancreatic vessels from the 12(th) h to 5 (th) day of reperfusion. PDGF-A was not observed in pancreatic acinar cells in the control or in I/R group. In pancreatic ducts, the presence of PDGF-A was reduced between the 1(st) and 3(rd), and between 7(th) and 9(th) day of reperfusion. In acinar cells, VEGF content was increased after I/R at the time between the 1(st) and 24(th) h, and between 3(rd) and 7(th) day of reperfusion. At the 2(nd) day of reperfusion, VEGF was not detected in the pancreatic acinar cells. Moreover, VEGF was found in the inflammatory infiltration, in the tubular complexes between the 2(nd) and 5(th) day, and in granulation tissue at the 9(th) day of reperfusion. In pancreatic acinar cells, I/R caused an increase in TGFbeta RII presence between the 5(th) and 24(th) h, and between 7(th) and 9(th) day of reperfusion. Between the 2(nd) and 5(th) day of reperfusion the acinar presence of TGFbeta RII was reduced. In the pancreatic ducts, the presence of TGFbeta RII was increased after I/R from the 1(st) h to 9(th) day of observation. Four weeks after induction of acute pancreatitis, the pancreatic regeneration was completed and the presence of growth factors tested returned to control value. CONCLUSIONS: The presence of FGF, VEGF, PDGF-A and TGFbeta RII is modified in the course of I/R-induced acute pancreatitis. Maximal content of FGF, VEGF and TGFbeta RII has been observed in early stage of pancreatic regeneration suggesting the involvement these factors in pancreatic recovery.

Animals↗

PubMed2002

The influence of epidermal growth factor on the course of ischemia-reperfusion induced pancreatitis in rats.

UNLABELLED: Acute pancreatitis is accompanied by the enhanced expression of EGF in the pancreas and the administration of EGF was found to exhibit the beneficial effect on edematous cerulein-induced pancreatitis. Therefore, we decided to determine the influence of EGF on necro-hemorrhagic pancreatitis induced by ischemia and reperfusion (I/R). Acute pancreatitis was induced in rats by restricting the pancreatic blood flow (PBF) in the inferior splenic artery for 30 min using microvascular clips. EGF was administered three times daily (10 microg/kg per dose s.c.) starting immediately after the clips removal. Rats were sacrificed on day 1, 3, 5, 10 and 21 following ischemia. PBF was measured using a laser Doppler flowmeter. Morphological signs of pancreatitis, as well as the levels of plasma amylase, lipase, interleukin-1beta and interleukin-10 concentration and pancreatic cell proliferation were examined. RESULTS: Ischemia with reperfusion caused acute necro-hemorrhagic pancreatitis with a histological and biochemical manifestation of pancreatic damage, followed by a spontaneous regeneration. The administration of EGF caused the reduction in the histological signs of pancreatic damage, such as necrosis, edema and leukocyte infiltration, and accelerated the pancreatic repair. Also, EGF treatment significantly attenuated the reduction in pancreatic blood flow and DNA synthesis. The activity of plasma amylase and lipase, as well as plasma interleukin-1beta and interleukin-10 concentrations were decreased in EGF treated animals. CONCLUSIONS: EGF exerts beneficial influence on the course of I/R induced pancreatitis and this effect seems to be related to the reduction in the activation of pro-inflammatory interleukin cascade, the improvement of PBF, and the increase in pancreatic cell growth.

Amylases↗

PubMed2002

Influence of leptin administration on the course of acute ischemic pancreatitis.

Leptin is involved in the regulation of food intake and previous studies have shown that leptin affects the inflammatory response in various tissues. The objective of this study was to examine the influence of leptin administration on the development and the course of acute ischemic pancreatitis. Acute pancreatitis was induced by limitation of pancreatic blood flow by clamping of inferior splenic artery for 30 min, followed by reperfusion. Leptin was administered three times daily at the dose 10 or 50 microg/kg. Animals were sacrificed 1, 3, 5, 10 and 21 days after removal of vascular clips. Administration of leptin reduced development of pancreatic damage and accelerated pancreatic regeneration what was manifested by the improvement of pancreatic histology, the decrease in serum lipase and amylase activity, and the reduction in serum interleukin-1beta concentration. Also, treatment with leptin caused the increase in the pancreatic blood flow and pancreatic DNA synthesis. Leptin administration was without effect on serum interleukin-10 concentration. Leptin at the dose 50 microg/kg was more effective than 10 microg/kg. We conclude that leptin reduces the pancreatic damage in the course of ischemic pancreatitis and accelerates the pancreatic tissue repair. The beneficial effects of leptin appear to be dependent on the improvement of pancreatic blood flow, the increase in pancreatic cell growth, and the limitation of pro-inflammatory interleukin-1beta release.

Amylases↗

PubMed2001

Hepatocyte growth factor attenuates pancreatic damage in caerulein-induced pancreatitis in rats.

Hepatocyte growth factor (HGF) overexpression was reported in experimental and clinical acute pancreatitis. These observations prompted us to determine the effect of HGF administration on the development of caerulein-induced pancreatitis in rats. Acute pancreatitis was induced by s.c. infusion of caerulein (10 microg/kg/h) for 5 h. HGF was administrated twice (30 min before caerulein or saline infusion and 3 h later) at the doses: 0.4, 2, 10 or 50 microg/kg s.c. Immediately after cessation of caerulein or saline infusion, the pancreatic blood flow, plasma amylase and lipase activity, plasma cytokines concentration, cell proliferation, and morphological signs of pancreatitis were examined. Caerulein administration induced acute edematous pancreatitis manifested by 41% decrease in DNA synthesis, 53% inhibition of pancreatic blood flow, a significant increase in plasma amylase and lipase activity, plasma interleukin-1beta and interleukin-6 concentration, as well as, the development of the histological signs of pancreatic damage (edema, leukocyte infiltration, and vacuolization). Administration of HGF without induction of pancreatitis increased plasma interleukin-10. Treatment with HGF, during induction of pancreatitis, increased plasma interleukin-10 and attenuated the pancreatic damage, what was manifested by histological improvement of pancreatic integrity, the partial reversion of the drop in DNA synthesis and pancreatic blood flow, and the reduction in pancreatitis evoked increase in plasma amylase, lipase, and interleukin-1beta and interleukin-6 levels. HGF administrated at the dose 2 microg/kg exhibited a similar beneficial effect as administration of HGF at the doses 10 or 50 microg/kg. Treatment with HGF at the dose 0.4 microg/kg was less effective. We conclude that: (1) administration of HGF attenuates pancreatic damage in caerulein-induced pancreatitis; (2) this effect seems to be related to the increase in production of interleukin-10, the reduction in release of interleukin-1beta and interleukin-6, and the improvement of pancreatic blood flow.

Amylases↗

PubMed2001

Pancreatic damage and regeneration in the course of ischemia-reperfusion induced pancreatitis in rats.

The objective of this study was to assess the biochemical and histological signs of pancreatic damage development and pancreatic recovery in the course of ischemia-reperfusion induced pancreatitis. Acute pancreatitis was induced in rats by limitation of pancreatic blood flow (PBF) in inferior splenic artery for 30 min using microvascular clips, followed by reperfusion. Rats were sacrificed at the time: 1 h, 12 h, 24 h, and 2, 3, 5, 7, 10, 14, 21 and 28 days after ischemia. PBF was measured using laser Doppler flowmeter. Plasma amylase, interleukin 1beta (IL-1beta) and interleukin 10 (IL-10) concentration, pancreatic DNA synthesis, as well as, morphological features of pancreatic damage were examined. Ischemia with reperfusion caused acute necrotizing pancreatitis followed by pancreatic regeneration. After removal of microvascular clips, PBF was reduced and the maximal fall of PBF was observed 24 h after ischemia, then PBF grew reaching the control value at 28th day. Plasma amylase activity was increased between 12th h and 3rd day with maximum at 24 h after ischemia. Also plasma IL-1beta and IL-10 were elevated with maximal value at the first and second day after ischemia, respectively. DNA synthesis was maximally reduced at the first day (by 70%) and from second day the reversion of this tendency was observed with full restoration of pancreatic DNA synthesis within four weeks. Morphological features of pancreatic tissue showed necrosis, strongly pronounced edema and leukocyte infiltration. Maximal intensity of morphological signs of pancreatic damage was observed between first and second day of reperfusion. During pancreatic regeneration between second and tenth day after ischemia the temporary appearance of chronic pancreatitis-like features such as fibrosis, acinar cell loss, formation of tubular complexes and dilatation of ducts was observed. The regeneration was completed within four weeks after pancreatitis development. We conclude that partial and temporary pancreatic ischemia followed by reperfusion causes acute necrotizing pancreatitis with subsequent regeneration within four weeks. Pancreatic repair after necrotizing pancreatitis is connected with the increase in plasma IL-10 concentration and transitory formation of tubular complexes.

Animals↗

PubMed2001

Histamine in stress ulcer prophylaxis in rats.

BACKGROUND: Gastrin and its analogues increase the gastric acid secretion, but also enhance mucosal defense mechanisms. On the other hand, increased formation of histamine leading to an increase in gastric acid secretion is accompanied with gastroprotection and acceleration of gastric ulcer healing. AIM: Of this study was to examine the effect of histamine on stress induced gastric ulcers in rats. METHODS: Male Wistar rats were exposed to water immersion and restrain stress (WRS) for 3.5 h at 23 degrees C. Before WRS rats were pretreated with saline, histamine, ranitidine or omeprazole. RESULTS: WRS produces gastric lesions which were strongly reduced by ranitidine or omeprazole. Also treatment with histamine markedly reduced ulcer area evoked by WRS. Addition of histamine to ranitidine or omeprazole caused an additional reduction in ulcer area. Gastroprotective effect of histamine was accompanied with the increase in gastric blood flow (GBF). Administration of omeprazole or ranitidine alone was without significant effect on GBF. Histamine caused an slight decrease in gastric luminal pH, whereas ranitidine or omeprazole significantly increased gastric luminal pH. Plasma interleukin-1beta was significantly reduced after administration of omeprazole, ranitidine, or histamine, however, the effect of histamine was less pronounced. DNA synthesis was increased after administration of omeprazole, ranitidine or histamine when compared with WRS alone. Administration of histamine in combination with ranitidine or omeprazole caused an additional increase in DNA synthesis. CONCLUSIONS: Histamine exhibits protective effect and increases gastroprotective effect of ranitidine and omeprazole against stress-induced gastric lesions. This effect of histamine seems to be independent on gastric acid secretion but related to the increase in gastric blood flow and the reduction in activation of cytokine cascade.

Animals↗

PubMed2001

Effect of sensory nerves and CGRP on the development of caerulein-induced pancreatitis and pancreatic recovery.

The function of primary sensory neurons is to receive and transmit information from external environment and these neurons are able to release neuromediators from the activated peripheral endings. The aim of this study was to determine the influence of sensory nerves and administration of their mediator--calcitonin gene related peptide (CGRP) on the course of acute pancreatitis (AP). Ablation of sensory nerves was performed by neurotoxic dose of capsaicin (100 mg/kg). Single or repeated episodes of AP were induced by caerulein infusion (10 microg/kg/h for 5 h). Five repeated AP were performed once a week. Capsaicin at the dose which stimulates sensory nerves (0.5 mg/kg/dose) or CGRP (10 microg/kg/dose) was administrated before and during or after single induction of AP, as well as, after each induction of repeated AP. Rats were killed at the time 0, 3 or 9 h after single induction of AP or two weeks after last induction of repeated AP. Ablation of sensory nerves aggravated pancreatic damage in caerulein-induced AP. Treatment with stimulatory doses of capsaicin or CGRP before and during single induction of AP attenuated the pancreatic damage in morphological examination. This effect was also manifested by partial reversion of AP evoked drop in DNA synthesis and pancreatic blood flow (PBF). Administration of CGRP after single AP induction aggravated histologically manifested pancreatic damage. The further decrease in PBF and DNA synthesis was also observed. Animals with five episodes of AP showed almost full pancreatic recovery two weeks after last induction of AP concerning all parameters tested. In stimulatory doses of capsaicin treated rats, we observed the decrease in pancreatic amylase and fecal chymotrypsin activity, as well as, the drop in DNA synthesis. Similar but less pronounced effects were observed after treatment with CGRP. We conclude that effect of sensory nerves and CGRP on AP is two-phase and time dependent. Stimulation of sensory nerves or the administration of CGRP during development of AP exhibits protective effects against pancreatic damage induced by caerulein overstimulation. After induction of AP, persistent activity of sensory nerves and presence of CGRP aggravate pancreatic damage and lead to functional insufficiency typical for chronic pancreatitis.

Acute Disease↗

PubMed2000

Epidermal growth factor accelerates pancreatic recovery after caerulein-induced pancreatitis.

We examined the influence of endogenous and exogenous epidermal growth factor (EGF) on pancreatic repair after acute pancreatitis. Caerulein-induced pancreatitis was evoked in rats with intact or removed salivary glands and EGF (10 microg/kg) was administered starting 24 h after cessation of caerulein infusion. The dose of EGF 10 microg/kg was chosen because it was the most effective in preliminary experiments when 1, 10 or 50 microg/kg of EGF was used. Caerulein administration caused acute edematous pancreatitis with biochemical and histological manifestation of pancreatic damage, followed by spontaneous regeneration. The effect of salivectomy on the course of acute pancreatitis was slight, resulting in additional reduction in pancreatic blood flow, DNA synthesis and in an increase in plasma interleukin 1beta level. Treatment with EGF accelerated the healing of pancreatic damage, causing an increase in pancreatic blood flow and DNA synthesis. EGF caused faster normalization of plasma amylase and lipase activity and plasma interleukin 1beta concentration, as well as, this peptide accelerated the restoration of pancreatic amylase activity. On histological examination, EGF caused reduction of pancreatic damage and acceleration of tissue repair. We conclude that EGF reduces the severity of pancreatic damage evoked by caerulein-induced pancreatitis-related pancreatic damage and accelerates tissue repair. The beneficial effects of EGF appear to depend, at least in part, on the improvement of pancreatic blood flow, as well as on an increase of pancreatic cell growth and limitation of the activation cytokine release.

Amylases↗

PubMed2000

Gastroprotective effect of histamine and acid secretion on ammonia-induced gastric lesions in rats.

BACKGROUND: Previous studies have shown that ammonia produced by Helicobacter pylori urease or administrated intragastrically exhibits a toxic effect on the gastric mucosa. In the present study we investigated the influence of histamine and gastric acid secretion on ammonia (NH4OH)-induced gastric lesions. METHODS: The gastric mucosa in rats was exposed to NH4OH (1.5 ml of 250 mM solution) under basal conditions, after administration of histamine (1 mg/kg), urea with urease, and ranitidine (40 mg/kg subcutaneously) given alone or in combination. We measured the area of gastric lesions, gastric blood flow (GBF), plasma gastrin concentration, DNA synthesis, gastric acid secretion and gastric luminal concentration of PGE2. RESULTS: Application of NH4OH resulted in the formation of acute gastric lesions. This effect was accompanied by a fall in GBF, a rise in gastric pH, and a reduction in mucosal DNA synthesis. Administration of histamine 30 min prior to NH4OH reduced the area of gastric lesions. This was accompanied by an increase in GBF, DNA synthesis, and prostaglandin E2 (PGE2) production. Ranitidine given prior to NH4OH enhanced gastric mucosa damage, and reduced GBF and DNA synthesis. This effect was accompanied by a reduction in gastric acid secretion. Ranitidine given prior to histamine abolished gastric acid secretion and the protective effect of histamine against NH4OH-induced damage; these effects were accompanied by a decrease in GBF, DNA synthesis, and concentration of PGE2. Pretreatment with 2% urea with urease given prior to NH4OH reduced NH4OH lesions. This effect was associated with an increase in gastric acid secretion, gastric generation of PGE2, GBF, and DNA synthesis. Ranitidine given prior to urea with urease inhibited gastric acid secretion and the gastroprotective effect of urea-urease gastroprotection. CONCLUSIONS: Histamine and gastric secretion exhibit a protective effect against ammonia-induced gastric lesions. This effect appears to depend upon the stimulation of gastric acid secretion and PGE2 production, and the improvement of gastric microcirculation.

Ammonia↗

PubMed2000

The influence of sensory nerves and CGRP on the pancreatic regeneration after repeated episodes of acute pancreatitis in rats.

Stimulation of capsaicin sensitive nerves or administration of calcitonin gene-related peptide (CGRP) before induction of acute pancreatitis (AP) attenuates pancreatic damage, whereas CGRP administration after development of AP aggravates lesion of pancreatic tissue. The aim of this study was to determine the effect of prolonged activity of sensory nerves or CGRP administration on the pancreatic repair after repeated episodes of AP. Five episodes of acute caerulein-induced pancreatitis (10 microg/kg/h for 5 h s.c.) were performed at weekly intervals in rats receiving either vehicle or capsaicin at the sensory nerve stimulatory dose (0.5 mg/kg, 3 times daily), or CGRP (10 microg/kg, 3 times daily). Two weeks after the last induction of AP morphological signs of pancreatic damage, pancreatic blood flow (PBF), serum and pancreatic amylase activity, fecal chymotrypsin activity, pancreatic weight, pancreatic RNA and DNA content, as well as, serum interleukin-1beta (Il-1beta ) were assessed. Pancreata of animals receiving vehicle alone showed almost full recovery within two weeks after last episode of pancreatitis induction. In capsaicin-treated group of rats, we observed the increase in PBF by 44% and in serum Il-1beta concentration by 91%. The pancreatic amylase activity, fecal activity of chymotrypsin, pancreatic nucleic acids content and DNA synthesis were decreased. In rats treated with CGRP the alterations in PBF, serum Il-1beta concentration, as well as, in pancreatic and fecal activity of enzymes were similar to capsaicin treated group but less pronounced. We conclude that prolonged activity of capsaicin-sensitive sensory nerves and the presence of their main mediator-CGRP during pancreatic regeneration after AP leads to pancreatic functional insufficiency typical for chronic pancreatitis.

Acute Disease↗

PubMed2000

Morphological changes and morphological-functional correlations in acute experimental ischemia/reperfusion pancreatitis in rats.

The etiology of acute pancreatitis, apart from alcohol abuse and cholelithiasis may also include a vascular component responsible for pancreatic ischemia. It is now acknowledged that chronic pancreatitis may be a consequence of the acute variant, but it remains unclear what factors influence this sequence of morphological changes. In order to clarify this issue we proposed a model of experimental acute pancreatitis in rats induced by a 30 min reduction of blood flow in inferior splenic artery followed by reperfusion. Rats were sacrificed at 1 h, 12 h, 24 h, and 2, 3, 5, 7, 14, 21, 28 days after cessation of ischemia. We performed histopathological examination of pancreatic tissue and measured pancreatic blood flow, plasma amylase activity and interleukin-1 beta concentration. The present findings indicate that transient pancreatic ischemia leads to the development of acute necro-haemorrhagic pancreatitis. The morphological features of acute inflammation are correlated positively with functional disorders. In some cases the features of chronic pancreatitis may appear transiently after the acute phase, whereas the repair of postinflammatory injury involves the regeneration of acinar cells.

Acute Disease↗