Biomedical subjects

P Ceranowicz

Publications and source records attributed to P Ceranowicz.

29 records · Page 2Linked to original sources

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↗

PubMed1999

Calcitonin gene-related peptide can attenuate or augment pancreatic damage in caerulein-induced pancreatitis in rats.

UNLABELLED: We have recently shown that treatment with calcitonin gene-related peptide (CGRP) before and during induction of acute pancreatitis exhibits a protective effect against pancreatic damage evoked by overdose of caerulein. Studies in the stomach have shown that administration of CGRP exhibits dual action on gastric mucosa, CGRP administration before induction of gastric lesions, protects gastric mucosa against damage, whereas treatment with this peptide after development of gastric ulcer exacerbates mucosal injury. These observations prompt us to determine the influence of CGRP administrated before and after induction of pancreatitis on development and evolution of pancreatic tissue damage. METHODS: Acute pancreatitis was induced by s.c. infusion of caerulein (10 microg/kg/h) for 5 h. CGRP was administrated (10 microg/kg s.c. per dose) 30 min prior to caerulein infusion and 3 h later during caerulein infusion or at the time 1 h, 4 h and 7 h after the end of caerulein infusion. Rats were sacrificed at the time 0 h, 3 h or 9 h after cessation of caerulein administration. The pancreatic blood flow (PBF), plasma activity of amylase, plasma interleukin-1beta concentration, cell proliferation, biochemical and morphological signs of pancreatitis were examined. RESULTS: Caerulein-induced pancreatitis (CIP) led to 42% decrease in DNA synthesis, 30% inhibition of PBF, as well as, a significant increase in pancreatic weight, plasma amylase activity, plasma interleukin-1beta concentration, and development of the histological signs of pancreatic damage (edema, leukocyte infiltration and vacuolization). Treatment with CGRP prior and during induction of CIP attenuated the pancreatic damage what was manifested by partial reversion of the drop in DNA synthesis (40.9+1.7 v. 34.2+2.0 dpm/microg DNA) and PBF (83+3% v. 70+3%). Increases in pancreatic weight and plasma interleukin-1beta were reduced. Morphology showed improvement of pancreatic integrity. Administration of CGRP after induction of CIP aggravated pancreatic damage what was manifested by additional decrease in PBF and DNA synthesis. Also pancreatic weight as well as histological signs of pancreatic damage were increased. CONCLUSIONS: (1) Administration of CGRP before and during induction of pancreatitis protects pancreas against pancreatic damage. (2) Treatment with CGRP after development of CIP aggravates pancreatic damage.

Animals↗

PubMed1998

Comparison of epidermal growth factor and transforming growth factor-beta1 expression in hormone-induced acute pancreatitis in rats.

Overexpression of transforming growth factors (TGF) in acute pancreatitis (AP) suggested that these substances play an important role in pancreatic repair and remodeling but the contribution of epidermal growth factor (EGF), that is well known to promote cell growth and regeneration, has not been investigated. The aim of this study was to compare the gene and immunohistochemical expression of EGF and TGF-beta1, cell proliferation, and biochemical parameters in AP induced by infusion of a supramaximal dose of caerulein in rats. The rats were sacrificed at 0, 12, 24, 48, 72 h, 5 and 10 days after the termination of caerulein infusion. Pancreatic tissue DNA synthesis, cell proliferation, histological and immunohistochemical assessments and plasma amylase were estimated following induction of AP. The mRNA expression for EGF and TGF-beta1 was evaluated by reverse transcription-polymerase chain reaction. During 10 days of the study after induction of AP a gradual normalization of biochemical and histological parameters was observed. DNA synthesis and cell proliferation which were significantly decreased at 0 and 24 h, increased significantly at 48 and 72 h, and then gradually decreased reaching at day 10 the values similar to those of vehicle-treated control rats. In these control rats the EGF mRNA or immunohistochemical expression was not detected, while the TGF-beta1 expression was weak. After induction of AP, the mRNA and immunohistochemical expression of EGF showed an increase during the initial 5 days, while those of TGF-beta1 showed a marked increase between 0 and 48 h and then again at day 10. We confirm that: (1) the expression of TGF-beta1 during AP is biphasic with an initial increase probably related to pancreatic damage and inhibition of cell proliferation and with the later phase of increase accompanied by the stimulation of the synthesis of extracellular matrix components and (2) AP is accompanied by an induction of synthesis of EGF that occurs in the initial phase of AP, probably limiting the extent of AP, and enhancing the stimulation of the pancreatic repair and regeneration.

Acute Disease↗

PubMed1997

Role of sensory nerves in pancreatic secretion and caerulein-induced pancreatitis.

Sensory nerves are implicated in gastroprotection and regulation of visceral circulation but their role in exocrine secretion and pancreatic circulation in intact pancreas and in acute pancreatitis has not been established. We investigated the role of sensory fibers in pancreatic secretion in vivo and amylase release from pancreatic slices (containing nerve fibers) or isolated pancreatic acini, and in caerulein-induced pancreatitis. In conscious rats, the stimulation of sensory nerves by low dose of capsaicin given intraduodenally (0.25-0.5 mg/kg) reduced basal pancreatic secretion, whereas dose of 1 mg/kg increased this secretion. Deactivation of sensory nerves by neurotoxic dose of capsaicin (100 mg/kg over 3 days s.c.) 10 days before tests failed to affect basal secretion but diminished the secretion induced by feeding or the diversion of pancreatic juice. In pancreatic slices, capsaicin (10(-10)-10(-6) M) increased enzyme secretion and this response was abolished by atropine (10(-6) M) or previous deactivation of sensory nerves. In pancreatic acini, capsaicin failed to affect basal and stimulated amylase secretion in response to caerulein or urecholine. In intact rats, stimulatory dose of capsaicin (0.5 mg/kg i.g.) caused about 32% increase of pancreatic blood flow and it was without any effect on the pancreatic DNA synthesis, weight, RNA, DNA and protein content. In contrast, neurotoxic dose of capsaicin caused a reduction (by 27%) in pancreatic blood flow followed by a significant decrease in RNA content and DNA synthesis in pancreatic tissue. Infusion of caerulein (10 g/kg-h) for 5 h produced acute edematous pancreatitis accompanied by over 60% decrease in DNA synthesis, nearly 50% inhibition of pancreatic blood flow, and a significant increase in pancreatic weight, protein content and plasma amylase concentration. Stimulatory dose of capsaicin attenuated the pancreatic tissue damage in caerulein induced pancreatitis, as manifested by a significant reversal of pancreatic blood flow and DNA synthesis decrease. Capsaicin induced inactivation of sensory nerves prior to pancreatitis caused an increase of all parameters of pancreatic damage; pancreatic blood flow dropped by 68%, DNA synthesis decreased by 70%; pancreatic weight, protein content and plasma amylase were also significantly enhanced. We conclude that sensory neurons are involved in the regulation of pancreatic secretion by an indirect mechanism and exhibit a beneficial effect on the pancreatic integrity, mainly due to improving the pancreatic blood flow.

Amylases↗

PubMed1997

Expression of transforming growth factor-beta 1 and epidermal growth factor in caerulein-induced pancreatitis in rat.

Growth factors such as TGF-beta 1 and EGF are known to modulate the deposition of extracellular matrix components and tissue repair and to affect the cellular growth but their expression in the course of pancreatitis has not been studied. In this study we investigated the gene expression of TGF-beta 1 mRNA and EGF mRNA and other parameters of the pancreas including DNA synthesis, blood flow (PBF), tissue protein content and plasma amylase during the induction of acute pancreatitis. Supramaximal dose of cearulein (10 mg/kg/h s.c.) was infused for 5 h to induce pancreatitis. Animals were killed after 1, 2, 3, 4 and 5 h of infusion. The PBF was measured, blood samples were withdrawn to determine serum amylase concentration, biopsy samples were taken to measure the protein content and DNA synthesis. Expression of TGF-beta 1 and EGF mRNA was studied by reverse-transcription of polymerase chain reaction (RT-PCR). Caerulein infused caused a time-dependent decrease in DNA synthesis accompanied by gradual decrease of PBF and significant increase in pancreatic weight. The pancreatic protein content and plasma amylase showed progressive rise during 5 h of cearulein infusion. Histology revealed tissue edema, cellular vacuolization and prominent leukocyte infiltration after 3 h of cearulein infusion. TGF-beta 1 mRNA was strongly expressed at each time interval beginning from the 1 h after the start of cearulein infusion. In contrast, EGF mRNA was detected only at 5 h after induction of pancreatitis. We conclude that 1) the development of caerulein-induced pancreatitis results in the inhibition of pancreatic growth and the reduction in PBF accompanied by enhanced expression of TGF-beta 1; 2) The expression of EGF that was observed at the end of the induction of pancreatitis may indicate the initiation of pancreatic repair; 3) TGF-beta 1 seems to lead to subsequent induction of EGF that may stimulate the regeneration of injured pancreas.

Acute Disease↗

PubMed1997

Adaptation of the pancreas to repeated caerulein administration in rats. A morphological and functional study.

We studied the ability of the pancreas in the aspect of histological, biochemical and functional changes (pancreatic blood flow, serum and pancreatic amylase levels, DNA and RNA content and pancreatic mass) to recover from repeated episodes of caerulein-induced acute pancreatitis. The experiment was carried out in three animal groups: group I receiving one infusion of caerulein, group II receiving two infusions of caerulein at the interval of 10 days, and group III with three infusions every 10 days. It was found that histological signs of acute pancreatitis after the first caerulein infusion showed regression after 3 days, and the process of regeneration was almost completed after 10 days. The content of DNA and RNA correlated with the histological picture. At this time interval also the level of amylase was returning to normal. Each subsequent infusion of caerulein resulted in less enhanced tissue destruction, but regeneration started later. Pancreatic blood flow was decreased each time after induction of pancreatitis, whereas normalization was more rapid. The present findings indicate that the pancreas adapts to repeated injury, which is manifested by decreased severity of changes, but the process of regeneration is delayed.

Adaptation, Physiological↗

PubMed1997

Protective effect of calcitonin gene-related peptide against caerulein-induced pancreatitis in rats.

The stimulation of sensory nerves by capsaicin exhibits the protective effect against caerulein-induced pancreatitis whereas deactivation of these nerves aggravates pancreatic damage evoked by overdose of caerulein. Calcitonin-gene related peptide (CGRP) has been identified as the prominent mediator of sensory nerves. The aim of the present study was to examine the influence of CGRP on the course of caerulein-induced pancreatitis (CIP). CIP led to a significant decrease in DNA synthesis and pancreatic blood flow (PBF) by 48% and 50% respectively, as well as a significant increase of pancreatic weight, plasma amylase concentration and development of the histological signs of pancreatic damage expressed as edema, leukocyte infiltration and vacuolization. Treatment with CGRP (2 x 10 micrograms/kg s.c.) attenuated the pancreatic tissue damage in caerulein-induced pancreatitis and completely reversed the deleterious effect of the ablation of sensory nerves on caerulein-induced pancreatitis. We conclude that CGRP exerts protective effect against caerulein-induced pancreatitis and is able to reverse the damage caused by deactivation of sensory nerves. Vasodilatation and preservation of pancreatic blood flow are involved in this effect.

Amylases↗

PubMed1996

Influence of capsaicin-sensitive afferent neurons and nitric oxide (NO) on cerulein-induced pancreatitis in rats.

CONCLUSION: Stimulation of afferent neurons by capsaicin exerts protective activity against cerulein-induced pancreatitis. This action is dependent on endogenous release of nitric oxide (NO). Deactivation of afferent neurons by high doses of capsaicin contributes to the severity of pancreatitis. This action involves mainly decreased pancreatic blood flow (PBF). Afferent nerves and NO cooperate in the maintenance of the integrity of pancreatic tissue. BACKGROUND: Stimulation of capsaicin-sensitive afferent fibers protects gastric mucosa against damage and causes changes in mucosal blood flow. The aim of the present study was to determine the role of stimulation or ablation of capsaicin-sensitive neurons and NO in the course of cerulein-induced pancreatitis in the rat. METHODS: Low and high doses of capsaicin were administered to animals with pancreatitis and to those without pancreatitis. The effect of several parameters was assessed. NO activity was blocked by NG-nitro-L-arginine. RESULTS: We found that a low dose of capsaicin administered intragastrically caused an increase in PBF. A neurotoxic dose of capsaicin caused a decrease in PBF, RNA content, and DNA synthesis. Pancreatitis led to a significant decrease in PBF and DNA synthesis, but an increase in pancreatic weight, protein content, plasma amylase concentration, and neutrophil adherence. Stimulatory doses of capsaicin attenuated the pancreatic tissue damage of pancreatitis, and alteration of PBF, DNA synthesis, and neutrophil adherence. Capsaicin-induced ablation of afferent neurons caused an increase in all indicators of pancreatic damage. Blocking NO enhanced pancreatic damage, and this was reversed by addition of L-arginine.

Animals↗

PubMed1996

Adaptation of pancreas to repeated caerulein-induced pancreatitis in rats.

Induction by caerulein of acute pancreatitis with tissue damage and acinar cells loss is followed by recovery. We studied biochemical, histological and functional regeneration of pancreatic tissue after repeated acute pancreatitis. Pancreatitis was evoked in rats by s.c. infusion of caerulein (10 micrograms/kg/h) for 5 h. After infusion, rats were divided into three groups. First group was infused with caerulein one time, in the second group infusion of caerulein was repeated 10 days later. The third groups was infused with caerulein for the 3rd time 10 days after the 2nd infusion. Rats were sacrificed at time sequence of 0, 12, 24, 48, 72 hours and at 5th, and 10th day after last infusion of caerulein. Pancreatic blood flow (PBF) was measured using laser Doppler flowmeter. Plasma and pancreatic amylase, pancreatic weight, RNA and DNA contents, and histological changes were determined. We found that DNA and RNA content, as well, as histological changes in 1st group showed progressive regeneration after 3 days. Regeneration after 1st time caerulein-induced pancreatitis was almost completed within 10 days and amylase content in the tissue and plasma amylase level returned to normal values. Each subsequent infusion of caerulein caused significantly less pronounced destruction of the pancreatic tissue, however, the regeneration occurred progressively later than after the 1st or 2nd infusion. Tissue repair after the 2nd infusion reached peak at 5th day while after 3rd infusion at 10th day. PBF dropped after 1st caerulein induced pancreatitis by about 50% but with repeated caerulein induced pancreatitis lower decreases in PBF were observed and they returned in shorter time back to control value. These results indicate that the pancreas is able to adapt to repeated injury and this is manifested by cumulative decrease of pancreatic damage after each repetition of induction of acute pancreatitis and correlated with the preservation of PBF, however, the pancreatic tissue regeneration is significantly delayed.

Acute Disease↗

PubMed1995

The role of capsaicin-sensitive sensory neurons and nitric oxide in regulation of gastric mucosal growth.

Capsaicin and nitric oxide (NO) cause potent vasorelaxation which is important in gastroprotective activity against damage but the mechanisms underlying these effects have not been elucidated. This study investigated the influence of capsaicin-induced functional ablation of afferent neurons and inhibition of NO production on the gastric mucosal growth in normal conditions, after 48 h fasting and subsequent refeeding. We found that ablation of sensory neurons by capsaicin pretreatment (100 mg/kg over 3 days) reduced by around 45% the mucosal blood flow (MBF), as measured by laser Doppler flowmetry, in normal fed and refed rats, while by 15% only in fasted animals. This last group of animals had significant decrease in the MBF even in control conditions as compared to that recorded in fed animals. This drop in MBF after capsaicin-induced denervation was accompanied by a significant decrease in DNA synthesis (by 40% in control group and 35% in refed rats) and was less pronounced in the group of fasted rats (23%). Ablation of sensory neurons resulted in the decrease in the stomach weight and RNA content in regular feed and refed but not in 48 h fasted group of animals. Treatment with NG-nitro-L-arginine (L-NNA; 2 x 20 mg/kg daily s.c.), a selective blocker of NO synthase, significantly suppressed the MBF in all three groups of animals tested but this suppression was less pronounced when compared to capsaicin pretreatment. This inhibitory effect of L-NNA on MBF was fully antagonized by L-arginine (2 x 100 mg/kg daily s.c.). L-NNA injection s.c. reduced the DNA synthesis (36% control group, 38% refed animals, 18% fasted rats), stomach weight, RNA and DNA content in all tested groups of rats. This inhibition was reversed by the addition of L-arginine. The combination of capsaicin and L-NNA decreased the MBF significantly and the inhibition was stronger than the effect of each substance given alone. In normal fed and refed rats, the neurotoxic dose of capsaicin together with L-NNA significantly decreased the DNA synthesis, stomach weight, RNA and DNA content but these effects were smaller than the sum of the effects of each agent given alone. We conclude that both the capsaicin-induced denervation and the suppression of endogenous NO by L-NNA inhibit the growth of the gastric mucosa by the mechanism involving, at least in part, the suppression of gastric mucosal blood flow.

Animals↗

PubMedDate not supplied

Epidermal growth factor protects against pancreatic damage in cerulein-induced pancreatitis.

Epidermal growth factor (EGF) exhibits gastroprotective and ulcer-healing action. These observations prompted us to determine the influence of EGF on cerulein-induced pancreatitis (CIP) in the rat. Acute pancreatitis was induced by subcutaneous infusion of cerulein (10 microg/kg/h) for 5 h. Initially EGF was administrated twice at doses of 1, 5, 10 or 100 microg/kg s.c. (first injection 30 min prior to cerulein infusion, and the second injection 2.5 h after the start of cerulein infusion) and from this part of study 10 microg/kg was chosen for the next experiments. CIP led to a significant decrease in DNA synthesis and a reduction in pancreatic blood flow (PBF) by 42 and 30%, respectively, as well as a significant increase in pancreatic weight, plasma amylase concentration, plasma interleukin-1beta (IL-1beta) level and the development of the histological signs of pancreatic damage with marked edema, leukocyte infiltration and vacuolization of acinar cells. Treatment with EGF attenuated the pancreatic tissue damage in CIP as manifested by partial reversal of the drop in DNA synthesis and improvement of pancreatic histology. Moreover, EGF administration attenuated the fall in PBF and significantly reduced the cerulein-evoked increase in pancreatic weight. Also plasma amylase and IL-1beta were decreased in rats treated with EGF. We conclude that: (1) EGF exerts a protective effect against CIP, and (2) the beneficial activity of EGF in CIP seems to depend on the increase in pancreatic cell proliferation, the reduction in cytokine generation and the attenuation of the fall in PBF.

Acute Disease↗