Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis

The objective of this study is to investigate the effects of an acute necrotizing pancreatitis (ANP), without biliary obstruction, on the migrating motor complex (MMC), small bowel bacterial overgrowth (SBBO), bacterial translocation (BT) and infection of the pancreas simultaneously. Rats were divided into four groups: mild pancreatitis, control, ANP and sham operated control. Jejunal myoelectrodes were used to measure MMCs. Blood, peritoneal fluid, bile, and abdominal organs were harvested for microbial culturing 72 h after induction of pancreatitis. The splenic portion of the pancreas was taken for histology. During ANP the MMC cycle length was significantly increased from 14.1 +/- 0.2 to 22.4 +/- 1.9 min (P < 0.05). The duodenum of ANP rats was in contrast with the other groups characterized by Enterobacteriacae (> 3 log 10 CFU g-1 in seven of 12 rats, P < 0.05). A positive correlation (r = 0.78, P < 0.01) existed between duodenal Gram-negative and anaerobic flora and the MMC cycle. Correlation between MMC cycle length and BT to the pancreas was positive as well (r = 0.70, P < 0.01). A positive correlation (r = 0.85, P < 0.01) was found between the severity of pancreatitis and duodenal bacterial overgrowth. During ANP without biliary obstruction, the jejunal MMC is disturbed and consequently SBBO occurs. The correlation between the severity of pancreatitis, the disturbance of the MMC and SBBO suggests an important pathophysiological role of the proximal small bowel in the infection of pancreatic necrosis.     

Validation of esophageal pressure occlusion test after paralysis

Measurements of respiratory mechanics are frequently made in ventilated infants and children. Esophageal pressure measurements (P_es using a balloon on a catheter have been used to partition the respiratory mechanics into lung and chest wall components. Appropriate positioning of this balloon is crucial to obtain accurate estimates of pleural pressure. Traditionally, in spontaneously breathing subjects the balloon position is assessed with an occlusion test. In ventilated subjects, it is not always possible to perform an occlusion test prior to paralysis, and even if such a test is performed it may not be relevant under conditions of positive pressure ventilation. We have assessed a positive pressure occlusion test that is suitable for paralyzed subjects. By occluding the airway opening and applying gentle pressure to the abdomen or rib cage, positive swings in pressure can be measured by both P_es and airway opening pressure (P_ao). We compared traditional occlusion tests measured in 16 spontaneously breathing puppies to the positive pressure occlusion test performed after paralysis. In 2 pups we were unable to obtain a reasonable traditional occlusion test (>15% difference between P_es and P_ao) but we obtained 10 traditional occlusion tests in each of the remaining 14 pups (2.1–14 kg). In 11 of these animals Ape, was within 10% of P_ao. This compared well to positive pressure occlusion test using abdominal pressure performed after paralysis, where Apes was within 10% of ΔP_ao in 10 animals. In 9 of these pups occlusion tests were also performed by applying pressure on the rib cage, where ΔP_es was within 10% of ΔP_ao in 6 animals. These results suggest that it is possible to perform accurate occlusion tests in paralyzed subjects by abdominal or rib cage compression with the airway occluded. Pediatr Pulmonol. 1994; 17:56–62. © 1994 Wiley-Liss, Inc.     

Acute volaemic changes modify the gastroduodenal resistance to the flow of saline in anaesthetized dogs

The effect of acute and sequential volaemic changes on the gastroduodenal flow of saline was assessed in 23 anaesthetized dogs following two different experimental protocols. Hypervolaemia, by i. v. infusion of saline, induced a gradual decrease on gastroduodenal flow which amounted to 76% below control values (P < 0.001) when volaemic expansion attained 5% of body weight. This effect was volume dependent (17% increase on gastroduodenal flow per volume of infused saline equivalent to 0.5% of body weight, P < 0.001), lasted for at least 90 minutes after infusion was completed and was also obtained by expanding previously bled animals. Hypovolaemia due to bleeding was followed by an increase on gastroduodenal flow of about 88% above control values (P < 0.05) when haemorrhage was equal to 3% of body weight. This effect was also volume dependent (23 % increase on gastroduodenal flow per volume of blood shed equivalent to a 0.5% of body weight, P < 0.01) and was reversed after blood volume was restored. These modifications in the resistance of the gastroduodenal segment to the flow of liquid due to acute volaemic changes suggest that the extracellular fluid volume modulates the contractile activity of the gastroduodenal portion of the gut possibly to set a gastroduodenal handling of liquid adequate to cope with volaemic imbalances.     

Short-term suppression of plasma free fatty acids fails to improve insulin sensitivity when intramyocellular lipid is elevated.

AIMS: Metabolic responses to manipulation of the plasma free fatty acid (FFA) concentration were assessed in six healthy men via cross-over design to determine whether FFAs independently influence insulin sensitivity. METHODS: Intramyocellular lipid (IMCL) was measured by proton magnetic resonance spectroscopy and insulin sensitivity via frequently sampled intravenous glucose tolerance test (IVGTT) after 67 h of two identical low carbohydrate/high fat (LC) diets which were used to elevate IMCL and plasma FFAs. To uncouple the influence of FFAs and IMCL on insulin sensitivity, FFAs were suppressed 30 min prior to and during IVGTT in one treatment [LC + nicotinic acid (NA)] by NA ingestion. RESULTS: Vastus lateralis IMCL was significantly elevated in LC (13.3 +/- 1.1 x 10(-3)) and LC + NA (13.5 +/- 1.1 x 10(-3)) (P < 0.01 for both), but was not different between conditions (P > 0.05). Plasma FFAs were raised in LC (0.79 +/- 0.08 mmol/l) and LC + NA (0.80 +/- 0.11 mmol/l) (P < 0.01 for both) and were significantly reduced by NA ingestion prior to (0.36 +/- 0.05 mmol/l, P < 0.01) and during IVGTT (P < 0.05) in LC + NA. Despite marked differences in plasma FFA availability, insulin sensitivity and glucose tolerance were not different between LC and LC + NA (P > 0.05 for both). CONCLUSIONS: Plasma FFAs appear to exert no immediate effect on insulin sensitivity/glucose tolerance independent of their action on intracellular lipid moieties. Further research is required to elucidate the duration of FFA suppression required to restore insulin sensitivity following lipid-induced insulin resistance.     

Assessment of oxidative DNA damage in the oxyR-deficient SOS chromotest strain Escherichia coli PQ300.

The SOS chromotest is a simple short-term genotoxicity assay measuring the induction of gene sfiA in Escherichia coli K-12. The recent availability of SOS tester strains with additional mutations in DNA repair or protection systems allows testing of DNA damaging compounds for genotoxic specificity. E. coli PQ300 differs from the standard SOS tester strain PQ37 in that it contains an additional mutation in gene oxyR that renders it more sensitive to oxidative genotoxins. The generation of reactive oxygen intermediates (ROI) by hydroperoxides (H2O2, t-butyl hydroperoxide, cumene hydroperoxide), gamma-radiation, glucose oxidase, and xanthine oxidase resulted in a more vigorous SOS response in strain PQ300 compared to strain PQ37. PQ300 was also more sensitive than PQ37 for the detection of reducing agents such as ascorbic acid, cysteine, and glutathione, which also alter the redox status of the bacterial cells. However, intercalating agents (adriamycin, bleomycin, and mitomycin C) and the UV- and radiomimetic compound 4-nitroquinoline-1-oxide whose DNA damaging potential are known also to involve ROI did not show significant differences between strains PQ37 and PQ300. It is concluded that the oxyR-deficient strain PQ300 is useful for detecting certain classes of genotoxins that change the oxidative/antioxidative balance of tester bacteria in the SOS chromotest.     

Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats

Wilke , W. Lee & Person , A. E. G. 1992. Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats. Acta Physiol Scand 144 , 253–261. Received 26 June 1991, accepted 8 October 1991. ISSN 0001–6772. Department of Physiology, Colorado State University, Fort Collins, Colorado, USA and Department of Physiology and Biophysics, University of Lund, Sweden. Micropuncture experiments were performed on intact and remnant kidneys of male Sprague-Dawley rats before and after angiotensin converting enzyme inhibition with captopril (0.5 mg kg^-1 iv). Partially nephrectomized rats were studied at 2 and 8 weeks post-surgery before the development of systemic hypertension. At 2 weeks, nephrectomized rats had a numerically higher tubular stop-flow pressure than controls (43 ± 2 mmHg vs. 38 ± 2 mmHg; P = 0.08) and a higher post- to pre-glomerular resistance ratio (Re/Ra) (0.40 ± 0.03 vs. 0.31± 0.03; P = 0.08). At 8 weeks, stop-flow pressure and post- to pre-glomerular resistance ratios were similar in remnant and intact kidneys. Captopril had no effect on stop-flow pressure in 2 week post-surgery nephrectomized rats or either control group, but it increased stop-flow pressure in 8 week post-surgery nephrectomized rats (40 ± 2 to 44 ± 2 mmHg, P= 0.04). This increase in stop-flow pressure was associated with an increase in the post- to pre-glomerular resistance ratio (0.33 ± 0.02–0.42 ±0.02, P = 0.009). Stop-flow pressure was positively correlated with the post- to pre-glomerular resistance ratio in 2-week post-surgery nephrectomized rats and their respective controls when combined (r = 0.89, P= 0.0001) and 8-week post-surgery nephrectomized rats and their respective controls combined (r= 0.78, P = 0.0001). Stop-flow pressure was not significantly correlated with mean arterial pressures or welling-point pressures in these groups. We conclude that stop-flow pressure in remnant kidneys of pre-hypertensive rats is primarily determined by the post- to pre-glomerular resistance ratio, and increases in stop-flow pressure and post- to pre-glomerular resistance ratios in remnant kidneys are transient in the absence of systemic hypertension. The role of the renin-angiotensin system in determining the ratio and stop-flow pressure is dependent on time post-nephrectomy. Captopril-induced increases in stop-flow pressure and post- to pre-glomerular resistance ratio at 8 weeks, suggests that its primary effect at that time is not a preferential post-gIomerular vasodilation subsequent to reductions in intrarenal angiotensin II.