International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases.

Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center's series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model's area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.

Unusual morphological damage of Purkinje cells following postnatal BrdU administration in the cerebellar cortex of mouse.

Postnatal development of the cerebellum lasts for weeks in rodents and can be disturbed by systemic 5-bromo-2'-deoxyuridine (BrdU) administration. This thymidine analogue incorporates into the DNA of proliferating cells, and result in more or less serious damage or death granule cells, the most actively dividing neuronal population in the developing cerebellar cortex. Further consequences of postnatal BrdU administration are the interrupted postnatal migration and integrations as well as partial loss of cerebellar Purkinje cells. In the present study, C57B16 mice were administered with 50 µg/g body weight BrdU, one sc. injection daily, between P0 and P11 postnatal days, respectively.Large "cavities" appeared in the cytoplasm of a subpopulation of Purkinje cells by P7 in about one-third of administered animals, their number are size of the cavities (and PCs exhibiting unusual morphology) decreased. EM studies revealed that the unusual Purkinje cells received numerous axonal inputs of unknown origin, first of all on their somatic and dendritic spines. The transitory appearance of a subpopulation of Purkinje cells possessing unusual morphology refers to the influence of other (neuronal, glial, or both) cells on their regular differentiation.

Polymorphisms of beta defensins are associated with the risk of severe acute pancreatitis.

AIMS: Bacterial translocation from the intestinal tract plays an important role in severe acute pancreatitis (AP). Human ß-defensins are a family of antimicrobial peptides present at the mucosal surface. The aim of this study was to investigate the relevance of single nucleotide polymorphisms (SNPs) in the DEFB1 gene and copy number polymorphisms of the DEFB4 genes in AP. METHODS: 124 AP patients (30 with mild and 94 with severe disease) and 100 healthy controls were enrolled in the study. Three SNPs of the DEFB1 gene [G-20A (c.-20G→A), C-44G (c.-44C→G) and G-52A (c.-52G→A)] were genotyped by Custom TaqMan assay. The DEFB4 gene copy number was determined by means of a TaqMan real-time PCR assay. RESULTS: Significantly higher frequencies of the AA genotype of G-20A (c.-20G→A) and the AA genotype of G-52A (c.-52G→A) were observed among the patients with severe AP (SAP) compared with the healthy controls (38 vs. 20 and 41 vs. 18%, respectively). The GG protective genotype of C-44G (c.-44C→G) SNP was much less frequent (1%) among the patients than among the controls (9%). A higher frequency of a lower (<4) copy number of the DEFB4 gene was observed in the patients with SAP compared with the healthy controls (62 vs. 24%, respectively). CONCLUSIONS: The variations in the genes encoding human ß-defensin-1 and -2 may be associated with the risk of SAP. and IAP.

Plasma concentrations of high-mobility group box protein 1, soluble receptor for advanced glycation end-products and circulating DNA in patients with acute pancreatitis.

AIMS: High-mobility group box protein 1 (HMGB1), a late-acting proinflammatory cytokine, is secreted actively by inflammatory cells, and released passively from necrotic cells. From the aspect that both inflammation and necrosis are involved in the pathogenesis in acute pancreatitis, the aim of the study was a joint investigation of the plasma concentrations of HMGB1, its soluble receptor for advanced glycation end-products (sRAGE), and the circulating DNA as a marker of cell death. METHODS: 62 patients with acute pancreatitis (30 mild, 32 severe), 20 patients with sepsis, and 20 healthy controls were enrolled in the study. HMGB1 and sRAGE plasma levels were measured by means of ELISA. Plasma DNA concentrations were estimated by real-time quantitative PCR for the beta-globin gene. RESULTS: The circulating HMGB1 level was significantly higher in patients with severe acute pancreatitis (13.33 +/- 2.11 ng/ml) than in healthy controls (0.161 +/- 0.03 ng/ml) or than in patients with mild pancreatitis (2.64 +/- 0.185 ng/ml). The plasma concentration of sRAGE was highest in patients with sepsis (2,210 +/- 252 pg/ml), while the levels of sRAGE correlated inversely with that of HMGB1 in patients with acute pancreatitis. The plasma DNA level was significantly elevated in patients with severe acute pancreatitis (2,206 +/- 452 ng/ml). CONCLUSION: A complex study of the plasma levels of HMGB1, sRAGE and circulating DNA can be informative in evaluations of acute pancreatitis with different levels of severity.

The role of NF-kappaB activation in the pathogenesis of acute pancreatitis.

Acute pancreatitis is an inflammatory disease of the pancreas which, in its most severe form, is associated with multi-organ failure and death. Recently, signalling molecules and pathways which are responsible for the initiation and progression of this disease have been under intense scrutiny. One important signalling molecule, nuclear factor kappaB (NF-kappaB), has been shown to play a critical role in the development of acute pancreatitis. NF-kappaB is a nuclear transcription factor responsible for regulating the transcription of a wide variety of genes involved in immunity and inflammation. Many of these genes have been implicated as central players in the development and progression of acute pancreatitis. This review discusses recent advances in the investigation of pancreatic and extrapancreatic (lungs, liver, monocytes and macrophages, and endothelial cells) NF-kappaB activation as it relates to acute pancreatitis.

Effects of bile acids on pancreatic ductal bicarbonate secretion in guinea pig.

BACKGROUND AND AIMS: Acute pancreatitis is associated with significant morbidity and mortality. Bile reflux into the pancreas is a common cause of acute pancreatitis and, although the bile can reach both acinar and ductal cells, most research to date has focused on the acinar cells. The aim of the present study was to investigate the effects of bile acids on HCO(3)(-) secretion from the ductal epithelium. METHODS: Isolated guinea pig intralobular/interlobular pancreatic ducts were microperfused and the effects of unconjugated chenodeoxycholate (CDC) and conjugated glycochenodeoxycholate (GCDC) on intracellular calcium concentration ([Ca(2+)](i)) and pH (pH(i)) were measured using fluorescent dyes. Changes of pH(i) were used to calculate the rates of acid/base transport across the duct cell membranes. RESULTS: Luminal administration of a low dose of CDC (0.1 mM) stimulated ductal HCO(3)(-) secretion, which was blocked by luminal H(2)DIDS (dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid). In contrast, both luminal and basolateral administration of a high dose of CDC (1 mM) strongly inhibited HCO(3)(-) secretion. Both CDC and GCDC elevated [Ca(2+)](i), and this effect was blocked by BAPTA-AM (1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid), caffeine, xestospongin C and the phospholipase C inhibitor U73122. BAPTA-AM also inhibited the stimulatory effect of low doses of CDC on HCO(3)(-) secretion, but did not modulate the inhibitory effect of high doses of CDC. CONCLUSIONS: It is concluded that the HCO(3)(-) secretion stimulated by low concentrations of bile acids acts to protect the pancreas against toxic bile, whereas inhibition of HCO(3)(-) secretion by high concentrations of bile acids may contribute to the progression of acute pancreatitis.

Recovery of exocrine pancreas six months following pancreatitis induction with L-arginine in streptozotocin-diabetic rats.

The aim of the present work was to investigate the laboratory and morphologic alterations in the pancreas 6 months after pancreatitis induction with L-arginine (Arg) in normal and streptozotocin (STZ)-diabetic rats. The amylase content of the pancreas was significantly decreased in the Arg-treated groups vs. the control group. No significant changes were observed in the DNA, soluble protein and lipase contents of the pancreas. In the STZ-treated groups, the serum glucose level was significantly elevated, whereas the serum immunoreactive insulin (IRI) level was significantly decreased vs. the control group. In these treated groups, the amylase content of the pancreas was also significantly decreased, but that of trypsinogen was significantly elevated vs. the control group. Histologic sections revealed periductal fibroses, adipose tissue and tubular complexes in the Arg-treated rats, but centroacinar hyperplasia was not observed in these groups. No alterations were observed on histological examination in the diabetic rats vs. normal rats 6 months following pancreatitis induction. In conclusion, a major restitution of the pancreatic enzyme content, but moderate histologic alterations were detected 6 months following pancreatitis induction with Arg. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this long-term study, but not to modify the recovery of the exocrine pancreas 6 months following Arg-induced pancreatitis.

The pathogenesis of L-arginine-induced acute necrotizing pancreatitis: inflammatory mediators and endogenous cholecystokinin.

This study was aimed at an assessment of the role of oxygen-derived free radicals, cytokines and endogenous cholecystokinin (CCK) in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat. We measured the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn- and Cu, Zn-SOD) in pancreatic tissue, the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and CCK, and evaluated the protective effect of the xanthine oxidase inhibitor allopurinol and a novel CCK receptor antagonist KSG-504. Acute pancreatitis was induced in male Wistar rats by injecting 2x 250 mg/100 g body weight of Arg intraperitoneally in an 1-h interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. 200 mg x kg(-1) allopurinol 30 min before the first Arg treatment or 50 mg x kg(-1) KSG-504 30 min before and 6, 18 and 36 h after the first Arg injection was administered subcutaneously. Rats were killed at 6, 12, 24 and 48 h following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 h after the Arg injection (30,800 +/- 3,813 versus 6,382 +/- 184 U x L(-1) in the control) and normalized at 48 h. The tissue concentration of MDA was significantly elevated at 24 h, and reached the peak value at 48 h (5.00 +/- 1.75 versus 0.28 +/- 0.05 nM x mg(-1) protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 h, and the Cu, Zn-SOD activity was significantly lower at 12 h after the Arg injection as compared with the controls. Both the TNF-alpha and the IL-6 levels were already elevated significantly at 12 h and peak at 24 h versus the controls (19.1 +/- 7.9 U x mL(-1) and 57.6 +/- 11.2 pg x mL(-1) versus 3.1 +/- 0.8 U x mL(-1) and 15.2 +/- 3.1 pg x mL(-1), respectively). No significant changes in plasma CCK levels were observed. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 +/- 2.257 U x L(-1) at 24 h), prevented the increase in tissue MDA concentration (0.55 +/- 0.09 nM x mg(-1) protein at 48 h) and significantly ameliorated the pancreatic edema, necrosis and inflammation at 48 h after Arg administration. KSG-504 administration did not exert any beneficial effect on the development of histopathological changes neither modified the serum amylase or cytokine levels. Oxygen-derived free radicals and cytokines are involved, while endogenous CCK does not seem to play a role in the pathogenesis of Arg-induced acute pancreatitis.

The effect of long-term administration of lorglumide (CR 1409) on rat pancreatic growth and enzyme composition.

The effects of lorglumide (CR 1409), a potent cholecystokinin (CCK) receptor blocker developed recently by the Rotta Research Laboratories, were studied on pancreatic growth and enzyme composition. In secretory studies, the inhibitory effect of 4 mg/kg of lorglumide administered subcutaneously proved to last more than 3 h. The trophic effect of exogenous CCK (600 ng/kg given three times daily for 2 weeks) was significantly decreased by the simultaneous administration of 4 mg/kg of lorglumide. To study the role of endogenous CCK released by feeding while maintaining pancreatic trophism, 4 mg/kg of lorglumide was administered subcutaneously four times daily during the feeding period for 2 weeks. Lorglumide significantly decreased pancreatic weight, pancreatic content of soluble protein, trypsinogen, and chymotrypsinogen, while decreases in DNA, lipase, and amylase failed to reach statistical significance. According to our experiments, high-doses of lorglumide could inhibit not only the trophic effect of exogenous CCK but also the effect of endogenous CCK released by food and lorglumide itself.

The effect of CR 1409, a potent CCK receptor antagonist, on basal and stimulated pancreatic secretion in rat.

The effect of a specific cholecystokinin (CCK) receptor blocker from Rotta Research Laboratorium (Monza/Milano, Italy), CR 1409 (Lorglumide), on pancreatic secretion was investigated. CR 1409 caused a rightward and parallel shift in the dose-response curve of CCK-8-stimulated pancreatic protein secretion in anesthetized rats, demonstrating a competitive mechanism of inhibition. The mean pA2 value, showing the 50% inhibitory dose of CR 1409, was 6.4. CR 1409 proved to be about 1,000 times more potent as a CCK receptor blocker than proglumide, the first glutaramic acid analogue with anti-CCK potential. In conscious rats, pancreatic protein and water secretion were significantly diminished for about 2 h in response to 300 micrograms/kg of CR 1409 given subcutaneously during diversion of pancreatic juice, demonstrating inhibition of endogenous CCK by this new glutaramic acid derivative. By contrast, during reintroduction of precollected pancreatic juice into the duodenum, when the release of CCK is almost totally eliminated, pancreatic secretion was not modified by the same dose.

The anti-CCK effect of glutaramic acid derivatives in anesthetized and conscious rats.

The effects of specific gastrin-cholecystokinin (CCK) receptor blockers (proglumide and a new, more potent product of Rotta Research Laboratorium, CR-1392) on pancreatic secretion were studied. Proglumide and CR-1392 caused a rightward and parallel shift, respectively, in the dose-response curve of CCK8 stimulated pancreatic protein secretion in anesthetized rats, demonstrating a competitive-like mechanism of inhibition. The mean PA2 values, demonstrating the 50% inhibitory dose of proglumide and CR-1392 were 3.7 and 5.7, respectively; i.e., CR-1392 proved to be about 100 times more potent than proglumide. In conscious rats, protein output and the volume of pancreatic juice were significantly decreased for about 2 h in response to 150 mg/kg of proglumide or 3 mg/kg of CR-1392 administered s.c. during diversion of pancreatic juice, demonstrating inhibition of endogenous CCK by glutaramic acid derivatives. Indeed, during reintroduction of precollected pancreatic juice into the duodenum, when the release of CCK is known to be almost totally eliminated, pancreatic secretion was not significantly modified by the same doses.

Effect of a liquid meal given as a bolus into the jejunum on human pancreatic secretion.

Major features of pancreatic secretion stimulated by a meal depend on intestinal phase mechanisms. However, an intrajejunal (i.j.) meal infusion is widely used for the treatment of inflammatory pancreatic diseases when the resting of the gland is desired. This study was undertaken to compare the effects of an intragastric (i.g.) and an i.j. complete fluid (Lundh) test meal on pancreatic enzyme secretion. Eight men (mean age, 43 years; range, 31-48) free from pancreatic disease were studied. Pancreatic secretion was measured via a multiple-lumen tube by aspiration of the duodenal juice. After a fasting period, the Lundh test meal was placed in the stomach or the upper jejunum. After the i.g. administration of the test meal, the aspirated duodenal juice was reinfused into the jejunum. The effect of atropine infusion (0.5 microg/kg/h) on the pancreatic enzyme secretion was studied. The pancreatic amylase, trypsin, and lipase outputs were determined. The plasma levels of cholecystokinin (CCK) and of gastrin were measured by bioassay and radioimmunoassay, respectively. The trypsin, amylase, and lipase secretions increased significantly after either an i.g. or an i.j. test meal intake. The trypsin, amylase, and lipase outputs were significantly decreased during the i.j. perfusion as compared with i.g. administration. The gastrin levels increased significantly after i.g., but remained unchanged after i.j. administration. The CCK release attained its maximum 40 and 60 min after the i.g. and i.j. test meal, respectively. However, the CCK release was significantly lower during the i.j. administration as compared with i.g. perfusion. An atropine infusion significantly reduced the i.g. and i.j. test meal-stimulated enzyme outputs. An i.j.-administered meal stimulates the pancreatic enzyme secretion, but this effect is significantly lower than that which occurs on i.g. administration. The i.j. meal-stimulated secretion of pancreatic enzymes is subject to both cholinergic and peptidergic regulation. The deficiency of gastrin and the delayed and decreased CCK release are believed to account for the reduced enzyme output.

Evaluation of pancreatic exocrine function by secretin-enhanced magnetic resonance cholangiopancreatography.

AIM: To assess the feasibility and usefulness of secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) for evaluation of pancreatic exocrine function. METHODOLOGY: S-MRCP was performed in 20 patients with mild (n = 8) or severe (n = 12) chronic pancreatitis (according to the grade of exocrine pancreatic insufficiency indicated by the Lundh test) and in 10 volunteers without pancreatic disease. MRCP images were evaluated before and 10 minutes after the intravenous administration of 0.5 IU/kg secretin. The changes in pancreatic tissue T2 signal intensity and duodenal filling after the injection of secretin were determined by means of S-MRCP. The S-MRCP findings were then compared with those of the Lundh test. RESULTS: The pancreatic T2 signal intensity showed a significant elevation after secretin administration in the volunteers and in the patients with mild or severe chronic pancreatitis. This elevation was significantly lower in patients with mild and severe chronic pancreatitis than in the volunteers (66.85+/-15.77 and 24.45+/-5.85 vs. 200.0+/-45.07, respectively). After administration of secretin. the diameter of the duodenum was significantly increased in all three groups. This duodenal filling was significantly reduced in patients with mild or severe exocrine pancreatic insufficiency as compared with the volunteers (4.12+/-1.33 and 1.70+/-0.77 vs. 15.38+/-1.73, respectively). There was no significant difference in pancreatic T2 signal intensity changes or in duodenal filling in patients with mild or severe exocrine pancreatic insufficiency. There were significant correlations between the pancreatic T2 signal intensity changes and the duodenal filling and the results of the Lundh test (r = -0.616 and -0.78). CONCLUSION: These results demonstrate that the administration of secretin increases the T2 signal intensity of the pancreatic tissue and the diameter of the duodenum to different extents in normal subjects and in patients with chronic pancreatitis. This suggests that S-MRCP can provide information of value in the assessment of an exocrine pancreatic insufficiency.

Pancreatic secretory responses in L-arginine-induced pancreatitis: comparison of diabetic and nondiabetic rats.

The aim of this work was to study cholecystokinin-octapeptide (CCK-8)-stimulated pancreatic secretion after the induction of pancreatitis with L-arginine (ARG) in rats with or without streptozotocin (STZ) diabetes. One, 3, 7, and 14 days after pancreatitis induction, rats were surgically prepared with pancreatic duct and femoral vein cannulae under urethane anesthesia. Graded doses of CCK-8 ranging from 9 to 2,400 ng/kg/30 min were administered intravenously. In the control group, the step-wise increasing doses of CCK-8 resulted in a characteristic dose-response curve for the pancreatic volume, protein and amylase secretion (maximal volume, protein and amylase output at 600 ng/kg/30 min of CCK-8: 157 +/- 20.2 microl/30 min, 28.3 +/- 1.18 mg/30 min, and 3,750 +/- 92 IU/30 min, respectively). In rats with pancreatitis, the pancreatic volume (both basal and maximal) and amylase secretion were significantly elevated on day 1 versus the control group; then on days 3,7, and 14, the pancreatic secretory volume and amylase were progressively and significantly decreased versus the control group. However, the protein output was continuously decreased versus the control group on days 1, 3, 7, and 14. In diabetic rats, the maximal volume and protein and amylase output were all significantly decreased versus the control group throughout the experiment. In the diabetes + pancreatitis group, the maximal volume and protein and amylase output were all significantly increased versus the diabetes group on days 1, 3, 7, and 14. These results indicate that in the early phase of ARG-induced pancreatitis, the pancreatic secretion is characterized by increases in secretory volume and amylase, with a simultaneous decrease in protein output. Simultaneous diabetes seems to moderate the CCK-8-stimulated secretory changes in both the early and late phases after ARG-induced pancreatitis.

Prognostic role of 99mTc-HM-PAO-leukocyte scintigraphy in acute pancreatitis and in patients with pancreatic pseudocysts.

Fifty-five leukocyte scintigraphies were performed. Thirty-five patients (group 1) with acute pancreatitis in the early phase and 20 patients (group 2) with pancreatic chronic pseudocysts following acute pancreatitis were tested. The clinical features, laboratory parameters, and Ranson classifications were registered during hospitalization. In group 1, most of the cases with a severe clinical outcome gave positive leukocyte scintigraphic results (10/12). Leukocyte accumulation was also detected in patients with mild acute pancreatitis (4/23), but at a lower frequency. In the acute phase, significant differences in laboratory parameters (sedimentation rate and leukocyte count) were found in the leukocyte scintigraphy-positive versus-negative cases. The scintigraphic activity correlated with the sedimentation rate, leukocyte count, fever, and duration of hospitalization. In group 2 there were five cases with a positive leukocyte scan. A pancreatic abscess was found in four of them during surgery. In seven patients with a normal scintigram, surgery revealed a noninfected pancreatic pseudocyst. Leukocyte infiltration of the pancreas can be demonstrated by leukocyte scintigraphy. A positive leukocyte scan indicated a severe course of acute pancreatitis. The method also seems useful for differentiation between infected and noninfected chronic pancreatic pseudocysts.

Oxidative stress changes in L-arginine-induced pancreatitis in rats.

The important role of oxygen radicals in acute experimental pancreatitis was demonstrated by study of the changes in the antioxidant system in the blood, liver, kidney, and pancreas of rats after the administration of a large quantity of L-arginine (L-Arg). The changes in lipid peroxidation and in reduced and oxidized glutathione were followed, as well as the activities of peroxide-decomposing enzymes (glutathione peroxidase and catalase) and H2O2-producing superoxide dismutases. The results demonstrated that "oxidative stress" develops and acute pancreatitis appears rapidly after L-Arg treatment. Oxidative stress symptoms are expressed 24 h after the final treatment. Slow restitution of the studied antioxidant system can be demonstrated as early as after 48 h.

Experimental acute pancreatitis results in increased blood-brain barrier permeability in the rat: a potential role for tumor necrosis factor and interleukin 6.

Pancreatic encephalopathy is a severe complication of acute pancreatitis. Proinflammatory cytokines may play a role in the development of multi-organ failure during pancreatitis. In the present study, we measured the changes in the blood-brain barrier (BBB) permeability concomitantly with the determination of serum tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels in rats before, as well as 6, 24 and 48 h after the beginning of intraductal taurocholic acid-induced acute pancreatitis. Cytokine concentrations were measured in bioassays with specific cell lines (WEHI-164 for TNF and B-9 for IL-6), while the BBB permeability was determined for a small (sodium fluorescein, molecular weight (MW) 376 Da), and a large (Evans' blue-albumin, MW 67000 Da) tracer by spectrophotometry in the parietal cortex, hippocampus, striatum, cerebellum and medulla of rats. The serum TNF level was significantly (P < 0.05) increased 6 and 24 h after the induction of pancreatitis, while the IL-6 level increased after 24 and 48 h. A significant (P < 0.05) increase in BBB permeability for both tracers developed at 6 and 24 h in different brain regions of animals with acute pancreatitis. We conclude that cytokines, such as TNF and IL-6, may contribute to the vasogenic brain edema formation during acute pancreatitis.

Induction of heat shock proteins fails to produce protection against trypsin-induced acute pancreatitis in rats.

Heat shock proteins (HSPs) are necessary in the synthesis, degradation, folding, transport, and translocation of different proteins. It is well known that the increased expression of HSPs may have a protective effect against cerulein-induced pancreatitis in rats or against choline-deficient ethionine-supplemented diet model pancreatitis in mice. The aim of this study was to investigate the potential effects of HSP preinduction by cold or hot water immersion on trypsin-induced acute pancreatitis in rats. Trypsin was injected into the interlobular tissue of the duodenal part of the pancreas at the peak level of HSP synthesis, as determined by Western blot analysis. The rats were sacrificed by exsanguination through the abdominal aorta 6 h after the trypsin injection. The serum amylase activity, the tumor necrosis factor-alpha, interleukin-1, and interleukin-6 levels, the pancreatic weight/body weight ratio, and the pancreatic contents of DNA, protein, amylase, lipase, and trypsinogen were measured. A biopsy for histology was taken. Hot water immersion significantly elevated the HSP72 expression, while cold water immersion significantly increased the HSP60 expression. Cold water immersion pretreatment ameliorated the pancreatic edema in trypsin-induced pancreatitis, however this was not due to the HSP60. Hot water immersion pretreatment did not have any effect on the measured parameters in trypsin-induced pancreatitis. The findings suggest that the induction of HSP60 or HSP72 are not enough to protect rats against the early phase of this localized necrohemorrhagic pancreatitis model.

Bacterial contamination of the uterus after parturition and its effect on the reproductive performance of cows on large-scale dairy farms.

The bacteriological status of the uteri of 150 cows was examined on 14 large-scale dairy farms 10 to 20 d after parturition and then twice again in 2-wk intervals during uterine involution. The degree of bacterial contamination and the proportion of the infected uterus as well as the composition of the isolated flora were determined. The antibiotic sensitivity of the important bacterium strains was also studied. The relationship between the reproductive data and bacterial contamination of the uteri was analyzed, and the influence of certain environmental and genetic factors on the rate of infection was examined. The proportion of cows having moderate or more serious uterine infection remained above 30 % at the end of involution on more than 35 % of the farms. Infections were caused mainly by streptococci, E. coli and corynebacteria. The bacterium strains showed broad resistance against commericially available antibiotics. There were significant differences in the length of time from the parturition to the first insemination and conception among cows at the various farms. There was a significant correlation between these differences and the bacteriological status of the uteri. Reproductive data were the lowest in the group of cows infected with Corynebacterium pyogenes. The rate of the infected uteri was considerably higher after the third parturition and in cows producing less than 20 l of milk per day. No connection was found between the bacteriological status of the uteri and the breed, type of housing, and season of the parturitions.

[Contact litholysis of common bile duct calculi. Study of 44 patients]. / Litholyse de contact des calculs de la voie biliaire principale. Etude chez 44 malades.

OBJECTIVES: Endoscopic sphincterotomy has become a generally accepted method for extracting common bile duct stones in high risk or cholecystectomized patients. However, stone extraction is impossible by the usual methods in 5 to 10% of cases. The purpose of this study was to evaluate the effect of a recently developed solvent system in patients with large bile duct stones. METHODS: Forty four patients (15 men and 29 women, median age of years) underwent contact dissolution after unsuccessful Dormia extraction. Solvents were administered via a nasobiliary catheter in 41 patients following papillotomy and through a T-tube in 3 patients. Solvent mixtures (26 mM ethylene diamine tetraacetic acid, 40 mM sodium deoxycholate and 30% dimethyl sulfoxide in an alkaline aqueous solution; and a 70/30 dimethyl sulfoxide/methyl tert-butyl ether mixture) were infused continuously and alternatively for 2 hours. RESULTS: Bile duct stones disappeared in 13-24 hours of infusion in 11 patients. In 29 patients, a clear reduction in stone volume occurred, allowing complete endoscopic extraction of the fragments. In 4 patients, the size of the stone did not change. Only mild and transient side-effects including abdominal pain (68%), nausea (72%), vomiting (52%), diarrhea and sleepiness (50%) were observed. CONCLUSION: Direct dissolution therapy could be an effective method for the non-surgical management of large bile duct stones in selected patients when intra- or extracorporeal lithotripsy is unsuccessful.