Damage To Pancreas Research Articles

Glutamine treatment attenuates the development of organ injury induced by zymosan administration in mice

Glutamine is the most abundant amino acid in the bloodstream. It is important in nucleotide synthesis, is anti-catabolic, has anti-oxidant properties via metabolism to glutathione, may enhance immune responsiveness and possesses immunoregulatory functions. Moreover, it reduces atrophy of intestinal mucosa in animals on total parenteral nutrition and prevents intestinal mucosal injury accompanying small bowel transplantation, chemotherapy and radiation. In the present study, we investigated the effects of glutamine on development of non-septic shock caused by zymosan. Mice received either zymosan (500 mg/kg, administered i.p., as a suspension in saline) or vehicle (saline). Glutamine (1.5 mg/kg i.p.) was administered 1 and 6 h after zymosan administration. Organ failure and systemic inflammation in mice were assessed 18 h after administration of zymosan and/or glutamine. Glutamine-treatment reduced the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan-injection and also attenuated the pancreatic and gut injury. Inflammatory and apoptotic parameters were evaluated to better investigate the effects of the glutamine-administration. So, by immunohistochemical analysis and in vitro assays, we have clearly showed that glutamine reduces: 1) the histological damage in pancreas and gut; 2) the inducible nitric oxide synthase expression; 3) nitrotyrosine and poly (ADP-ribose) formation; 4) TNF-α and IL-1β tissue and plasma levels; 5) FasL localization; and 6) alteration of the balance between Bax and Bcl-2. In addition, at the end of the observation period (7 days), zymosan causes severe illness in the mice characterized by a systemic toxicity, significant loss of body weight and mortality. Glutamine-treatment significantly reduced all these parameters.

Impact of 5-fluorouracil on glucose metabolism and pancreatic pathology in rats

To explore the impact of 5-fluorouracil (5-FU) on glucose metabolism and pancreatic pathology. Twenty Wistar rats were divided into 5-FU group(n=10, chemotherapy was administered intraperitoneally to animals at a dose of 20 mg/kg daily for continuous 5 days) and control group (n=10, sodium chloride was administered intraperitoneally to animals with the same dose at the same time ). Glucose tolerance was evaluated 2 and 7 days following 5-FU treatment by serial measurement of blood glucose before and after an oral glucose load. Plasma insulin concentration was determined by radioimmunoassay. Pancreatic pathology was examined with morphological method and the ultrastructural changes of β cells were observed by transmission electron microscope. Fasting blood glucose level was significantly higher in the 5-FU group than that in the control group [(7.6±0.9) mmol/L vs. (4.6±0.6) mmol/L at day 2; (8.9±1.0) mmol/L vs. (4.7±0.6) mmol/L at day 7, P<0.01]. Insulin releasing test indicated that the early phase insulin response to glucose load was significantly diminished in animals treated with 5-FU at day 2. Insulin level was significantly lower in the 5-FU group than that in the control group at 30 min (P<0.01). The peak secretion time of plasma insulin in 5-FU group was at 60 min, similar to the control group; and plasma insulin level decreased more slowly. Plasma insulin level was higher in 5-FU groups than in control groups on 120 min and 180 min. At day 7, Insulin level was lower in the 5-FU group than that in the control group on 60 min, and the peak secretion time of plasma insulin was delayed to 120 min. Plasma insulin level was significantly increased in 5-FU group than that in control group on 180 min(P<0.01). No gross histopathological damage to the pancreas was observed at day 2 and 7 following administration of 5-FU. The structural changes of mitochondria were mainly the quantities of secretory granule diminished at day 7 under transmission electron microscope. Dilated rough endoplasmic reticula, swollen mitochondria, and the presence of adipose drops in lysosomes were found in few cells. 5-FU-induced hyperglycemia appears to be mediated in part by a relatively deficient insulin secretion to glucose stimulation. A relative deficiency in insulin secretion following 5-FU treatment appears to be related to β cells function impairs with islet cell ultrastructural changes induced by 5-FU.

Fermented ginseng protects streptozotocin‐induced damage in rat pancreas by inhibiting nuclear factor‐κB

In this study, we investigated the protective effects of fermented ginseng (FG) on hyperglycemia induced by streptozotocin (STZ) in Sprague Dawley rats. FG was administered orally at dose of 250 (FGL) or 500 mg/kg (FGH) for 20 days starting one week before STZ injection. FG restored the plasma insulin levels by 266% and 334% in FGL and FGH, respectively, and resulting in reduction of plasma glucose concentration. Histological observation indicated that STZ-induced destruction of pancreatic islets was protected by FG. Consistent with this observation, FG reduced protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as determined by Western blotting and RT-PCR, respectively. The molecular mechanism of FG's inhibition of iNOS and COX-2 gene expressions appeared to involve the inhibition of nuclear factor-kappaB (NF-kappaB) activation via prevention of inhibitor kappaB (IkappaB) phosphorylation and degradation. The cytoprotective effects of FG were also mediated through suppression of extracelluar signal-regulated kinase (ERK) and c-JUN N-terminal kinase (JNK) pathways. Collectively, these results suggest that FG might be used to preserve functional beta-cell mass.

Melanoma differentiation-associated protein-5 (MDA-5) limits early viral replication but is not essential for the induction of type 1 interferons after Coxsackievirus infection

Coxsackievirus infections are associated with severe diseases such as myocarditis, meningitis and pancreatitis. To study the contribution of the intracellular viral sensor melanoma differentiation-associated protein-5 (MDA-5) in the host immune response to Coxsackievirus B3 (CVB3) we infected C57BL/6 and 129/SvJ mice lacking mda-5. Mice deficient in MDA-5 showed a dramatically increased susceptibility to CVB3 infection. The loss of MDA-5 allowed the virus to replicate faster, resulting in increased liver and pancreas damage and heightened mortality. MDA-5 was not absolutely required for the induction of type 1 interferons (IFNs), but essential for the production of maximal levels of systemic IFN-alpha early after infection. Taken together, our findings indicate that MDA-5 plays an important role in the host immune response to CVB3 by preventing early virus replication and limiting tissue pathology.

Study on protective effects of lipsomal clodronate on renal injury acute pancreatitis

Objective To investigate the protective effects of lipsomal clodronate on renal injury in rats with severe acute pancreatifis and the assessment of renal injury. Method Totally 48 rats were randomly divided into three group:normal control group (C);SAP group, in which rats were treated with pure liposomal (P);treatment group, in which SAP rats were treated with liposomal clodronate disodium(T). The SAP model of rat was induced by injection of 5 % sodium taurochohte beneath the pancreatic membrane. Rats of normal control group received isovolumetric injections of 0.9% physiological saline solution instead of sodium taurocholate. Blood samples were collected to measure AMS,BUN,Cr,IL-6 and IL-12 at 2 hors, 6 hours after SAP. At the same time, the samples of pancreatic and renal tissues were taken for observing the pathological changes. Results Compared with controlgroup, serious renal and pancreatic damages were found in group P, and the AMS, BUN, Cr levels elevated signifi-candy (P < 0.01). Compared with group P,the renal and pancreatic damages were attenuated in group T, and the levels of Cr and AMS decreased significantly (P < 0.01), and the IL-6, IL-12 were decreased at 2 hours and 6 hours (P < 0.01). The BUN decreased significantly at6 hours (P < 0.05). Conciusions Excessive release of inflammatory mediator play an important role in renal injury in SAP. Lipsomal clodronate disodium can alleviate the damage of pancreas and kidney. Key words: Severe acute pancreatitis; Macrophages; Lipsomal clodronate; Renal injury

Pancreatic Injury in Rabbits with Acute Renal Failure

Background. Acute renal failure (ARF) is a common critical disorder. To decrease the mortality, it is important to prevent ARF from invading other organs in clinical setting. It is not known whether there is a dysfunction in pancreas during the pathogenesis of ARF. This study aimed to investigate the changes of morphology and function on pancreas in ARF rabbits. Methods. Sixty rabbits were randomly divided into four groups. The ARF model of groups 1 and 2 rabbits was established by hypodermic injection of 1% HgCl2 (1.3 mL/kg) and intramuscular injection of 50% glyceritum (10 mL/kg), respectively. The control groups 1 and 2 were injected with same volume of normal saline. After 24 hours, urea and creatinine contents and pancreatic amylase (AMY) activities in serum were measured using an automatic biochemical analyzer; the insulin levels were measured with radioimmunoassay method. Moreover, morphological alterations were examined by light microscopy; free radicals, nitric oxide (NO), and nitric oxide synthase (NOS) in pancreas homogenate were determined. Results. Morphological study showed that there were vacuolar degeneration and necrosis in pancreas of ARF for both groups 1 and 2. Compared with corresponding control group, the AMY activity was significantly elevated, whereas the INS values were decreased significantly in ARF groups 1 and 2. Malonaldehyde, NO, and NOS in pancreas homogenate were significantly increased, and superoxide dismutase activity was decreased. Conclusion. These data suggested that there were morphological damage of pancreas and disturbance of pancreatic secretion function in rabbits with ARF. Free radicals-injury and NO excessive release may explain the observed dysfunction.

Transgenic and other experimental models of pancreas and islet damage

To unravel the cellular and molecular mechanisms involved in beta-cell renewal and expansion throughout life, several different experimental models were devised in the past. A number of experimental approaches and transgenic models have been engineered to trigger specifically pancreatic injury and thus explore regeneration. Globally, three main strategies are followed to induce pancreas damage: surgical, chemical and genetic. Some of the most relevant studies regarding these three approaches are briefly summarized in this short overview. Although significant progress has been achieved in recent years, there is much room for improving our understanding of many fundamental processes regulating beta-cell mass maintenance.

Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats

Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Berberine is one of the main alkaloids of Rhizoma coptidis which has been used to treat diabetes for more than 1400 years in China. The present study was designed to evaluate the protective effects of berberine against β cell damage and antioxidant of pancreas in diabetic rats. Diabetic rats with hyperlipidemia were induced by intraperitoneally injection 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Rats were divided into 7 groups at the end of week 16: untreated control, untreated diabetic, 75, 150, 300 mg/kg berberine-treated diabetic, 100 mg/kg fenofibrate-treated, and 4 mg/kg rosiglitazone-treated. After 16 weeks treatment, serum insulin level, insulin expression in pancreas, and malonaldehyde content, superoxide dismutase activity in pancreatic homogenate were assayed. Pancreas was examined by hematoxylin/eosin staining and transmission electron microscope. Pancreas to body weight ratio, insulin level, insulin sensitivity index, malonaldehyde content and superoxide dismutase activity were altered in diabetic rats, and were near control levels treated with 150, 300 mg/kg berberine. Mitochondrial vacuolization and swelling, dilatation of the endoplasmic reticulum were observed in β cells of diabetic rats. The pancreatic islet area atrophied and secretory granules of β cells decreased in diabetic rats. Slight pathological changes existed in β cells of 150, 300 mg/kg berberine-treated diabetic pancreas. These findings suggest that berberine has protective effect for diabetes through increasing insulin expression, β cell regeneration, antioxidant enzyme activity and decreasing lipid peroxidation.

Silymarin, a flavonoid antioxidant, protects streptozotocin-induced lipid peroxidation and β-Cell damage in rat pancreas

Silymarin, a flavonoid antioxidant, protects streptozotocin-induced lipid peroxidation and β-Cell damage in rat pancreas

Protective effects of N-acetylcysteine against liver injury in rats with severe acute pancreatitis

AIM:To investigate the role of nuclear factor-kappa B(NF-κB)activation in liver injury in rats with severe acute pancreatitis(SAP),and to explore the protective effect of N-acetylcysteine(NAC)against SAP-associated liver injury in rats.METHODS:Forty-two Wistar male rats were divided into sham operation group(SO,n = 6),SAP group(n = 18),and SAP + NAC group(NAC,300 mg/kg body wt,n = 18).SO group underwent laparotomy only.SAP model was established by retrograde injection of 50 g/L so-dium taurocholate into the bili-pancreatic duct in Wistar rats.SAP + NAC group were given NAC 300 mg/kg body weight intaperitoneally 2 h before SAP model was established.Rats were sacrificed at 3,6 and 12 h after operation.The liver and pancreas tissues were obtained to observe their pathological changes with light microscopy.The levels of serum ALT and AST were determined at three time points(8 rats for each time point).The expression of TNF-α mRNA was detected by reverse transcription polymerase chain reaction(RT-PCR).The activ-ity of NF-κB in liver was examined by immuno-histochemical methods.RESULTS:The levels of serum ALT and AST increased significantly in SAP group as com-pared with those in SO group at 3,6 and 12 h(ALT:186.67 ± 27.28,321.17 ± 56.14,492.50 ± 69.77 vs 36.83 ± 7.02;AST:255.50 ± 44.15,343.17 ± 43.70,425.33 ± 58.37 vs 41.67 ± 5.35;P 0.05 or 0.01).The level of TNF-α mRNA in SAP group was significantly higher than that in SO group at 3,6 and 12 h(0.37 ± 0.03,0.77 ± 0.04,0.54 ± 0.04 vs 0.24 ± 0.03;P 0.05 or 0.01).The activity of NF-κB was also higher in SAP group than that in SO group at 3 or 6 h(51.95 ± 4.76,24.67 ± 4.93 vs 9.33 ± 2.05;P 0.01 or 0.05).Liver and pan-creas pathological damages were more severe in SAP group than those in SO group under light microscope.In SAP + NAC group,the levels of serum ALT and AST(143.67 ± 16.62,203.33 ± 25.41,301.17 ± 26.82;136.33 ± 26.27,221.50 ± 38.31,310.50 ± 38.17)decreased significantly in comparison with those in SAP group(P 0.05 or 0.01),and the expression of TNF-α mRNA was significantly lower than that in SAP group at the three time points(0.25 ± 0.03,0.50 ± 0.05,0.43 ± 0.03,P 0.05 or 0.01).The activity of NF-κB in SAP + NAC group was lower than that in SAP group at 3 or 6 h(37.60 ± 6.37,12.88 ± 2.66,P 0.05).CONCLUSION:NF-κB activation and TNF-α mRNA up-regulation involve in the pathogen-esis of liver injury in SAP rats.NAC at a dose of 300 mg/kg can alleviate the pathological dam-age to liver,and its mechanism might relate to inhibition of NF-κB activation and reduction of cytokines such as TNF-α.

Is hyperlipasemia in critically ill patients of clinical importance? An observational CT study

To assess morphological alterations of the pancreas by contrast-enhanced computed tomography (cCT) and subclinical cellular damage of the pancreas by measuring pancreatitis-associated protein (PAP) in critically ill patients without prior pancreatic disorder who presented with raised serum lipase levels. Prospective, observational study Mixed surgical/neurosurgical intensive care unit of a German university hospital. One hundred and thirty consecutive critically ill patients without prior damage or disease of the pancreas and an expected length of stay of more than 5 days. Daily serum lipase measurements and daily serum PAP measurements. Contrast-enhanced upper abdominal cCT study in patients with triple increase of serum lipase. Thirty-eight patients showed raised serum lipase levels and qualified for the cCT scan study. In 20 patients cCT scans were performed. Morphological alterations of the pancreas were found in 7 out these 20 patients while serum PAP levels were raised in all patients. Hyperlipasemia is a common finding in critically ill patients without prior pancreatic disorder. While elevated serum PAP levels indicate pancreatic cellular stress morphological alterations of the pancreas are rare and of little clinical importance.

Altered glucose homeostasis and oxidative impairment in pancreas of rats subjected to dimethoate intoxication

The primary objective of this study was to investigate the effect of repeated sublethal doses of dimethoate (DM), an organophosphorus insecticide on glucose homeostasis, oxidative stress induction in pancreas and pancreatic damage in adult rats. Daily oral administration of DM (20 and 40 mg/kg b.w.) for 30 days induced a significant increase in blood glucose levels which was associated with impaired glucose tolerance. DM treatment resulted in elevated levels of pancreatic tissue specific markers such as activities of amylase and lipase in serum and pancreatic tissue indicating pancreatic dysfunction. Further, the activities of DT-diaphorase and NADPH-diaphorase in pancreas of DM treated rats were also found to be elevated. Interestingly, these biochemical dysfunctions were accompanied by a marked dose-related enhancement of lipid peroxidation and ROS levels in the pancreatic tissue indicating significant induction of oxidative damage. Additional evidence such as depletion in reduced glutathione levels and significant alterations in enzymic antioxidant defenses in pancreas among DM treated rats suggested induction of oxidative stress. Taken together, these findings provide experimental evidence that dimethoate at subchronic oral doses has the propensity to impair glucose homeostasis, induce significant pancreatic damage and also provide an account of the associated oxidative damage to pancreatic tissue in adult rats.

Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultra structural changes of pancreatic β-cells in experimental diabetes in rats

Oxidative stress and oxidative damage to tissues are common end points of chronic diseases such as atherosclerosis, diabetes, and rheumatoid arthritis. Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. The aim of the present study was to evaluate the possible protective effects of Murraya koenigii leaves extract against beta-cell damage and antioxidant defense systems of plasma and pancreas in streptozotocin induced diabetes in rats. The levels of glucose and glycosylated hemoglobin in blood and insulin, Vitamin C, Vitamin E, ceruloplasmin, reduced glutathione and TBARS were estimated in plasma of control and experimental groups of rats. To assess the changes in the cellular antioxidant defense system such as the level of reduced glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were assayed in pancreatic tissue homogenate. The levels of glucose, glycosylated hemoglobin, insulin, TBARS, enzymatic and non-enzymatic antioxidants were altered in diabetic rats. These alterations were reverted back to near control levels after the treatment of M. koenigii leaves extract. Transmission electron microscopic studies also revealed the protective nature of M. koenigii leaves on pancreatic beta-cells. These findings suggest that M. koenigii treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress and pancreatic beta-cell damage. The antioxidant effect of the M. koenigii extract was compared with glibenclamide, a well-known hypoglycemic drug.

Alcoholic pancreatitis: mechanisms of viral infections as cofactors in the development of acute and chronic pancreatitis and fibrosis

Acute and chronic pancreatitis is associated with alcohol abuse, but symptomatic pancreatitis develops in only a small proportion of persons (10-20%) who abuse alcohol. This apparent paradox has led to the notion that additional cofactors are involved in the development of alcoholic pancreatitis. Potential cofactors, such as diet and smoking, have been suggested, but there are no compelling epidemiologic data to support this idea. A number of viruses and some bacteria have been shown to infect the pancreas and produce pancreatitis. One important mediator of pancreatitis in persons with a compromised immune system is a viral infection. The increased susceptibility of immunocompromised persons to viral pancreatitis led to the hypothesis, described in this paper, that the well-known immunosuppression associated with alcohol abuse would result in a more severe viral pancreatitis in mice, which are provided ethanol, than in control animals. To test this hypothesis, C57BL/6 mice were infected with a virulent strain of coxsackievirus B3, which preferentially induces pancreatitis, or with a strain that is naturally avirulent. The study findings presented in this paper show that ethanol consumption alone does not produce pancreas damage but results in a more severe and prolonged pancreatitis after infection with a virulent virus and interestingly, after infection with the avirulent strain of virus. This was associated with an increased number of viruses in the pancreas and spleen, which correlated with decreased humoral immune responses to the virus.

Validation of the Scoring System for Standardization of the Pancreatic Donor for Islet Isolation as Used in a New Islet Isolation Center

Background The aim of this study was to evaluate the effectiveness of the Edmonton Donor Scoring System for use in our much less active islet center. Because the ability to recognize an appropriate donor may help to achieve consistent and predictable success of pancreatic islet isolation, it should lead to increased effectiveness and lower cost. Material and Methods Charts of 36 consecutive pancreas donors were reviewed to assess the donor points (DP). DP ranged from 0 to 100 based on donor age, body mass index, cause of death, social and medical history, hospital stay, vasopressor dosages, laboratory tests, cold ischemia time and procurement team, as well as pancreas size, consistency, fat content, damage, and quality of procurement and packing. Results Successful isolation was achieved in 39% of donors (14 of 36), a value similar to that achieved in Edmonton (40%). We used the optimal cutoff value (DP = 79) proposed by the Edmonton group. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66%, 75%, 57%, 82% and 72%, respectively. Successful islet isolation from poor or marginal donors (DP < 49.5 and 50 to 59.5) was 0% and 28.6% respectively; it was 63% and 100% in optimal donors (DP = 80 to 89.5 and 90 to 100). We concluded that islet isolation success correlated with the previously proposed donor scoring system. Conclusions The Donor Scoring System can be successfully implemented regardless of the level of activity of an experienced isolation center. This system permits identification of a suitable donor prior to organ processing. It may guide a center’s donor selection strategy based on its goals and its budget.

Ultrastructural Clues for the Protective Effect of Ascorbic Acid and N-Acetylcysteine against Oxidative Damage on Caerulein-Induced Pancreatitis

Background: Oxygen free radicals (OFR) have been implicated in the induction of acute pancreatitis (AP). Aims: The aim of this study was to determine the effect of ascorbic acid and N-acetylcysteine (NAC), potent antioxidants, against oxidative stress in AP. Methods: AP was induced by two i.p. injections of caerulein at 2-hour intervals (50 µg/kg BW). One group received additionally an antioxidant mixture composed of L(+)-ascorbic acid (14.3 mg/kg BW) and NAC (181 mg/kg BW) i.p. The rats were sacrificed 12 h after the last injection. Oxidative stress markers were evaluated. Light-microscopic and ultrastructural examination was performed. Results: Formation of vacuoles, mitochondrial damage, and dilatation of rough endoplasmic reticulum, margination and clumping of chromatin were major ultrastructural alterations in AP group. Ascorbic acid + NAC prevented these changes. Small vacuoles were present within the cytoplasm of some of the acinar cells. Pancreas damage was accompanied by an increase in tissue malondialdehyde (MDA) levels (p < 0.05), whereas a decrease was seen in catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and total glutathione (GSH) levels (p < 0.005). Ascorbic acid + NAC decreased MDA levels but increased CAT, SOD, GPx activities and GSH levels (p < 0.005). Conclusion: These results suggest that ascorbic acid + NAC is potentially capable of limiting pancreatic damage produced during AP via protecting fine structure of acinar cells and tissue antioxidant enzyme activities.

Expression of Nestin and Pancreatic Fibrosis in a Spontaneous Chronic Pancreatitis Model (Male WBN/Kob Rats)

Purpose: Although the causes of human chronic pancreatitis are quite diverse, there are many aspects of its onset that are currently unclear. WBN/Kob rat serve as a model of spontaneous chronic pancreatitis that presents with impaired internal and external pancreatic secretion in males only, and causes fibrosis and inflammatory cells infiltration consisting mainly of monocytes in the pancreas starting at age 12 weeks. The purpose of this study is examining the mechanism of the onset and development of pancreatitis. Methods: The animals used in this study consisted of 8-, 10- and 12-week-old male WBN/Kob rats and male Wistar rats (control). Total RNA was extracted from the pancreas followed by competitive hybridization using a Rat Oligo Microarray. In addition, real-time RT-PCR, MassARRAY and immunohistostaining were carried out on genes highly expressed with the microarray. Results: Nes was highly expressed at 10, 12 weeks as compared with the control. Increased expression was observed at age 10 and 12 weeks as compared with the control in real-time RT-PCR as well. A similar trend was also observed in analyses using MassARRAY. According to the results of immunohistostaining, nestin was stained primarily in spindle cells observed surrounding pancreatic acinar cells, and was thought to be expressed in pancreatic stellate cells. Conclusions: The activation of pancreatic stellate cells has attracted attention in fibrosis associated with chronic pancreatitis. Pancreatic stellate cells have been reported to be stained by nestin during pancreas damage induced by pancreatic duct ligation. Increases in expression of Nes starting at 10 weeks observed in the study rats. This expression is thought to be localized primarily in pancreatic stellate cells, thereby suggesting a correlation among increased expression of nestin, activation of pancreatic stellate cells and pancreatic fibrosis.

The role of imaging studies in pancreatic injury due to blunt abdominal trauma in children

Background The role imaging studies play in the choice of treatment in traumatic pancreas damage remains unclear. This study was performed to gain insight into the role of radiological studies in children 16 years of age or younger admitted to our hospital with pancreatic damage due to a blunt abdominal trauma. Method Retrospectively, the radiological as well as patient clinical records were reviewed of all children admitted to our hospital between 1975 and 2003 with a pancreatic lesion due to blunt abdominal trauma. Results Thirty-four children with ages ranging from 3 to 14 years old were admitted with traumatic pancreas damage. Initially 33 children were treated conservatively for the pancreatic damage and only one had immediate surgery of the pancreas with a Roux-y pancreaticojejunostomy. Five other children had immediate surgery for other reasons. Overall, five children proved to have a pancreas transection on CT scans or during laparotomy. One child had a pancreas hematoma and 28 a pancreas contusion. In total 15 children developed a pseudocyst (44%), nine of which resolved spontaneously while six were treated by intervention. None of the children had residual morbidity, and there were no deaths. Considering the pancreas, the 11 available CT's were re-evaluated by two radiologists independently. Grade 3 pancreas damage (distal transection of the pancreatic duct) was diagnosed in five patients by radiologist A and four patients by radiologist B (80% match); Grade 1 was diagnosed in, respectively six and one patients (15% match). An US was performed on 19 children with 82 follow-up examinations, mostly for follow-up of the pseudocysts. Conclusion Traumatic pancreas damage is a rare and difficult diagnosis. There is no straightforward answer for diagnostic imaging in blunt abdominal trauma in children. The diagnostic relevance of CT is limited. CT in combination with MRCP may be a better option for exclusion of pancreatic duct lesions.

Ligustrazine alleviates acute renal injury in a rat model of acute necrotizing pancreatitis

To evaluate the effect of ligustrazine, a traditional Chinese medicine, on renal injury in a rat model of acute necrotizing pancreatitis (ANP). A total of 192 rats were randomly divided into three groups: control (C group), ANP without treatment (P group), and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6, 12 h subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. T group was infused sodium taurocholate as above, and 0.6% ligustrazine was then administered via the femoral vein. Serum urea nitrogen (BUN) and creatinine (Cr) concentrations were measured for the evaluation of renal function. The effects of ligustrazine on the severity of renal injury were assessed by renal function, TXA(2)/PGI(2) and histopathological changes. Renal blood flow was determined by the radioactive microsphere technique (RMT). Compared with control group, the renal blood flow in P group was decreased significantly. Serious renal and pancreatic damages were found in P group, the BUN and Cr levels were elevated significantly, and the ratio of TXA(2) to PGI(2) was increased at 2, 6 and 12 h. Compared with P group, the blood flow of kidney was elevated significantly at 6 and 12 h after induction of ANP, the renal and pancreatic damages were attenuated, and the BUN and Cr levels were decreased significantly, and the ratio of TXA(2) to PGI(2) was decreased at 6 and 12 h in T group. Microcirculatory disorder (MCD) is an important factor for renal injury in ANP. Ligustrazine can ameliorate the condition of MCD and the damage of pancreas and kidney.

ゲノミクス・プロテオミクスを中心に‐ｏｍｉｃｓへの電気泳動法の応用 自然発症慢性膵炎モデルラット（雄性ＷＢＮ／Ｋｏｂ）の網羅的遺伝子解析

WBN/Kob rat serve as a model of spontaneous chronic pancreatitis that presents with impaired internal and external pancreatic secretion in males only, and causes fibrosis and inflammatory cells infiltration consisting mainly of monocytes in the pancreas starting at age 12 weeks. In this study, a comprehensive genetic analysis was conducted using an Oligo Microarray for the purpose of determining the mechanism of pancreatitis. The expression of the secretory stress proteins of Reg1, Reg3a, and Pap was thought to be involved in the onset of chronic pancreatitis in male WNB/Kob rats. The involvement of PRSS1was suggested with respect to the onset of human chronic pancreatitis. Since Prss1 was also highly expressed in the study rats, studies including SNP analysis are considered to be useful in the future. The activation of pancreatic stellate cells has attracted attention in fibrosis associated with chronic pancreatitis. Pancreatic stellate cells have been reported to be stained by nestin during pancreas damage induced by pancreatic duct ligation. Increases in expression of Nes starting at 12 weeks observed in the study rats as well is considered to constitute an interesting finding. Arg2 has been reported to be involved in NO production. Therefore, it is an interesting finding expression of Arg2 increased at 8 weeks in the male WBN/Kob rats. Pancreatic fibrosis tends to cause replacement of fatty tissue over time in male WBN/Kob rats. Since adipsin is involved in the differentiation into adipocytes, the increased expression of Adn in these rats was considered to be an interesting finding.