Biomedical subjects

M Fromm

Publications and source records attributed to M Fromm.

131 records · Page 8Linked to original sources

PubMedDate not supplied

Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis.

Intestinal barrier failure and subsequent translocation of bacteria from the gut play a decisive role in the development of systemic infections in severe acute pancreatitis. Glutamine (GLN) has been shown to stabilize gut barrier function and to reduce bacterial translocation in various experimental settings. The aim of this study was to evaluate whether GLN reduces gut permeability and bacterial infection in a model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 50 rats under sterile conditions by intraductal infusion of glycodeoxycholic acid and intravenous infusion of cerulein. Six hours after the induction of pancreatitis, animals were randomly assigned to one of two groups: standard total parental nutrition (TPN) or TPN combined with GLN (0.5 g/kg(-1)/day(-1)). After 96 hours, the animals were killed. The pancreas was prepared for bacteriologic examination, and the ascending colon was mounted in a Ussing chamber for determination of transmucosal resistance and mannitol flux as indicators of intestinal permeability. Transmucosal resistance was 31% higher in the animals treated with GLN- supplemented TPN compared to the animals given standard TPN. Mannitol flux through the epithelium was decreased by 40%. The prevalence of pancreatic infections was 33% in animals given GLN-enriched TPN as compared to 86% in animals receiving standard TPN (P < 0.05). Adding GLN to standard TPN not only reduces the permeability of the colon but decreases pancreatic infections in acute necrotizing pancreatitis in the rat. This confirms previous reports that GLN decreases bacterial translocation by stabilizing the intestinal mucosal barrier. The present findings provide the first evidence suggesting that stabilizing the intestinal barrier can reduce the prevalence of pancreatic infection in acute pancreatitis and that GLN may be useful in preventing septic complications in clinical pancreatitis.

Acute Disease↗

PubMedDate not supplied

Intestinal microcirculation and gut permeability in acute pancreatitis: early changes and therapeutic implications.

Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 c 0.06 vs. 1.98 +/-0.04 nl x min(-1) x cap(-1) [control]; P = NS), whereas mucosal (1.59 +/-0.03 vs. 2.28 +/-0.03 nl x min(-1) x cap((-1))[control]; P <0.01) and subserosal (2.47 +/-0.04 vs. 3.74 +/-0.05 nl x min(-1) x cap((-1))[control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 +/-0.03 vs. 1.98 +/-0.04 nl x min(-1) x cap(-1) [control]; P <0. 01) and colonic (mucosal: 0.59 +/-0.01 vs. 2.28 +/-0.03 nl x min(-1) x cap((-1))[control], P <0.01; subserosal: 1.96 +/-0.05 vs. 3.74 +/-0.05 nl x min(-1) x cap(-1) [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 +/-19 nmol x thr(-1) x cm(-2); mild pancreatitis: 158 +/-23 nmol x hr(-1) x cm(-2); severe pancreatitis: 181 +/-33 nmol x hr(-1) x cm(-2); P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation.

Acute Disease↗

PubMedDate not supplied

The interleukin-2-deficient mouse model.

Interleukin-2-deficient (IL-2(-/-)) mice develop colitis with striking clinical and morphological similarities to ulcerative colitis. Since transport and barrier properties are impaired in ulcerative colitis, we studied transport and barrier functions in IL-2(-/-) mice in order to gain insight for the first time into the general pathomechanisms of disturbed transport and barrier function of the intestine during inflammation. Alternating current impedance analysis was used to determine tissue conductance in the inflamed proximal colon of IL-2(-/-) mice and to discriminate between pure epithelial and subepithelial conductance. Surprisingly, epithelial conductance was not increased but diminished in IL-2(-/-) mice compared to controls (20.2 +/- 1.3 versus 28.8 +/- 2.8 mS/cm(2)). Concomitantly, conductance of the subepithelial tissue layers was decreased in IL-2(-/-) mice as a result of edema and infiltration with inflammatory cells. In the distal colon, electrogenic Na(+) transport (J(Na)) mediated by the epithelial Na(+) channel (ENaC) was measured 8 h after stimulation with 3.10(-9) M aldosterone in vitro as the drop in I(SC) (short circuit current) after addition of 10(-4) M amiloride. In controls, J(Na) was 6.9 +/- 0.9 micromol x h(-1) x cm(-2), whereas it was abolished in IL-2(-/-) mice. In conclusion, the inflamed colon of IL-2(-/-) mice exhibits a severe disturbance in Na(+) uptake via the ENaC in the absence of a barrier defect. Thus, reduced expression of active absorptive transport and not a barrier defect is responsible for the diarrhea in this model of intestinal inflammation. This makes this model suitable for studying the general pathomechanisms of the inflammatory downregulation of intestinal transport proteins.

Aldosterone↗

PubMedDate not supplied

Ultrastructural apoptotic lesions induced in bone marrow after neptunium-237 contamination.

This study describes the ultrastructure of lesions induced by neptunium-237 (237Np), a by-product of uranium in nuclear reactors, in the bone marrow. A group of rats were given a single injection of 237Np-nitrate solution in order to observe the acute toxicity effects of this actinide. Electron microscopy was used to describe the different lesions. Observations included the swelling of the cell membrane, nuclear membrane lyses, abnormal chromatin condensation or nucleus convolution. These ultrastructural alterations of the nucleus and the cellular membrane appeared shortly after treatment. This study demonstrates the toxic effects of neptunium and its implication in the induction of apoptosis in bone marrow.

Animals↗

PubMedDate not supplied

Influence of phase I early clinical trials on the quality of life of cancer patients. A pilot study.

A non-randomized, prospective, two-arm pilot study was conducted to assess the impact of clinical phase I trials with new cytotoxic drugs on the quality of life (QOL) of cancer patients, comparing a 10-item linear analog self-assessment (LASA) and Karnofsky performance scale (KPS) of 18 patients treated in phase I protocols versus 8 patients treated with standard/low efficacy cytotoxic or endocrine 1-2 drug regimens. There was no negative significant influence of treatment in phase I protocols either on LASA and KPS at the times before, during and after study or on changes (delta LASA, delta KPS) occurring with treatment. On the contrary, there was a slight positive influence of treatment within phase I protocols on self-assessed social activity (delta LASA) and on delta KPS when the groups were compared throughout the complete observation period. In addition, within the total study population there was significant positive influence of overall anticancer medication on psychological and social aspects of LASA, as indicated by feeling of well being, mood, level of activity and level of anxiety. Moreover, KPS and questions regarding appetite within LASA correlated with prognosis as measured by survival time, and intra-individual response comparison revealed the dominance of a differentiated reliable response type among our patients.

Activities of Daily Living↗