Long-Lasting Effect of Infant Rats Endotoxemia on Heat Shock Protein 60 in the Pancreatic Acinar Cells: Involvement of Toll-Like Receptor 4

Introduction. Lipopolysaccharide endotoxin (LPS) is responsible for septic shock and multiorgan failure, but pretreatment of rats with low doses of LPS reduced pancreatic acute damage. Aim. We investigated the effects of the endotoxemia induced in the early period of life on Toll-like receptor 4 (TLR4), heat shock protein 60 (HSP60) and proapoptotic Bax, caspase-9 and -3 or antiapoptotic Bcl-2 protein expression in the pancreatic acinar cells of adult animals. Material and Methods. Newborn rats (25 g) were injected with endotoxin (Escherichia coli) for 5 consecutive days. Two months later, pancreatic acinar cells were isolated from all groups of animals and subjected to caerulein stimulation (10−8 M). Protein expression was assessed employing Western blot. For detection of apoptosis we have employed DNA fragmentation ladder assay. Results. Preconditioning of newborn rats with LPS increased TLR4, Caspase-9 and -3 levels, but failed to affect basal expression of HSP60, Bax, and Bcl-2. Subsequent caerulein stimulation increased TLR4, Bcl-2, and caspases, but diminished HSP60 and Bax proteins in pancreatic acinar cells. Endotoxemia dose-dependently increased TLR4, Bax, HSP60, and both caspases protein signals in the pancreatic acini, further inhibiting antiapoptotic Bcl-2. Conclusions. Endotoxemia promoted the induction of HSP60 via TLR4 in the infant rats and participated in the LPS-dependent pancreatic tissue protection against acute damage

Effect of Intraduodenal Bile and Na-Taurodeoxycholate on Exocrine Pancreatic Secretion and on Plasma Levels of Secretin, Pancreatic Polypeptide, and Gastrin in Man

The effect of intraduodenally administered cattle bile (CB) and Na-taurodeoxycholate (TDC) on basal pancreatic secretion and plasma levels of secretin, pancreatic polypeptide (PP), and gastrin were investigated on two separate days in 10 fasting volunteers. Doses of 2-6 g CB and 20&600 mg TDC were given intraduodenally at 65-min intervals. Volume, bicarbonate, lipase, trypsin, amylase, and bilirubin were measured in 10-min fractions of duodenal juice, and GI peptides determined by radioimmunoassay. CB and TDC enhanced significantly and dose-dependently volume, bicarbonate and enzyme secretion, and plasma secretin and PP levels. In contrast, plasma gastrin showed only a marginal increase. We conclude that the hydrokinetic effect of intraduodenal CB and TDC is at least partially mediated by secretin. Gastrin could be ruled out as a mediator of the ecbolic effect, whereas other GI peptides, primarily CCK, and/or neural mechanisms must be considered possible mediators. Both pathways may also play a role in the PP release

The Role of Bile in the Regulation of Exocrine Pancreatic Secretion

As early as 1926 Mellanby (1) was able to show that introduction of bile into the duodenum of anesthetized cats produces a copious flow of pancreatic juice. In conscious dogs, Ivy & Lueth (2) reported, bile is only a weak stimulant of pancreatic secretion. Diversion of bile from the duodenum, however, did not influence pancreatic volume secretion stimulated by a meal (3,4). Moreover, Thomas & Crider (5) observed that bile not only failed to stimulate the secretion of pancreatic juice but also abolished the pancreatic response to intraduodenally administered peptone or soap

A Prospective Study of Aspirin Use and the Risk of Gastrointestinal Bleeding in Men

Data regarding the influence of dose and duration of aspirin use on risk of gastrointestinal bleeding are conflicting.We conducted a prospective cohort study of 32,989 men enrolled in the Health Professionals Follow-up Study (HPFS) in 1994 who provided biennial aspirin data. We estimated relative risk of major gastrointestinal bleeding requiring hospitalization or a blood transfusion.During 14 years of follow-up, 707 men reported an episode of major gastrointestinal bleeding over 377,231 person-years. After adjusting for risk factors, regular aspirin use (≥2 times/week) had a multivariate relative risk (RR) of gastrointestinal bleeding of 1.32 (95% confidence interval [CI], 1.12-1.55) compared to non-regular use. The association was particularly evident for upper gastrointestinal bleeding (multivariate RR, 1.49; 95% CI, 1.16-1.92). Compared to men who denied any aspirin use, multivariate RRs of upper gastrointestinal bleeding were 1.05 (95% CI 0.71-1.52) for men who used 0.5-1.5 standard tablets/week, 1.31 (95% CI 0.88-1.95) for 2-5 aspirin/week, 1.63 (95% CI, 1.15-2.32) for 6-14 aspirin/week and 2.40 (95% CI, 1.10-5.22) for >14 aspirin/week (P(trend)<0.001). The relative risk also appeared to be dose-dependent among short-term users <5 years; P(trend)<.001) and long-term users (≥5 years; P(trend) = 0.015). In contrast, after controlling for dose, increasing duration of use did not appear to be associated with risk (P(trend) = 0.749).Regular aspirin use increases the risk of gastrointestinal bleeding, especially from the upper tract. However, risk of bleeding appears to be more strongly related to dose than to duration of use. Risk of bleeding should be minimized by using the lowest effective dose among short-term and long-term aspirin users

Mortality Following Clostridioides difficile Infection in Europe : A Retrospective Multicenter Case-Control Study

We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were β-lactams; previous exposure to fluoroquinolones was significantly (p = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome