PubMed Health⌕ Search

Biomedical subjects

M Neumeister

Publications and source records attributed to M Neumeister.

At least 19 recordsLinked to original sources
PubMed2001

Limited use of cyclosporin A in skeletal muscle ischemia--reperfusion injury.

Reperfusion injury is propagated by an inflammatory-mediated tissue edema and damage after reestablishment of vascular flow following an initial ischemic insult. In the field of transplantation, cyclosporin A(CsA) provides protection against chronic graft rejection through lymphocyte immunosuppression. Evidence for an independent protective effect of CsA against ischemia-reperfusion (IR) injury during organ transfer has prompted studies showing the benefit of CsA in various ischemia-exposed visceral organs. The authors hypothesized that CsA administration may similarly benefit IR injury after skeletal muscle amputations. To determine the effects of CsA on IR injury the authors induced 4 hours of ischemia on the gracilis muscle in a rat model. CsA (15 mg per kilogram orally) was administered in two experimental groups: (1) preischemic (N = 6): 48, 24, and 3 hours before ischemia; and (2) postischemic (N = 6): 30 minutes after induction of ischemia. The effects of CsA on IR muscle injury were observed in each of the experimental groups as well as a control group (N = 6) exposed to similar ischemia and administered a saline vehicle. Muscle viability (nitro blue tetrazolium staining) and muscle edema (wet-to-dry weight ratio) were assessed 24 hours after reperfusion. The preischemic CsA-treated gracilis muscle group demonstrated improved muscle viability (39.1 +/- 4.8%) when compared with the ischemic control muscle group (23.8 +/- 7.1%; p = 0.039). Furthermore, the preischemic CsA-treated muscle group demonstrated decreased edema (1.137 +/- 0.095 times the contralateral nonischemic muscle) when compared with the control ischemic muscle group (1.248 +/- 0.045 times the contralateral nonischemic muscle; p = 0.011). Although a trend toward improved muscle viability (32.1 +/- 4.2%) and decreased edema formation (1.200 +/- 0.062 times the contralateral nonischemic muscle) was observed in the peri-ischemic CsA-treated group when compared with the control ischemic muscle group, these differences were not significant. These observations confirm the beneficial effects of preischemic CsA therapy observed in organ transplantation research and suggest limited clinical use of peri-ischemic CsA therapy for patients with musculoskeletal amputations.

Animals↗
PubMed2000

Hepatic fibrosis and cytochrome P450: experimental models of fibrosis compared to AHR knockout mice.

Hepatic fibrosis is characterized by abnormal collagen deposition resulting from increased collagen synthesis and decreased collagen degradation. Cytochrome P450 mediates major drug metabolizing enzyme activity in the liver and this activity is reduced in hepatic fibrosis. In this study we assess cytochrome P450 and CYP 1A mRNA in livers of animals that have been induced to hepatic fibrosis using the heterologous serum induced model of fibrosis in rats compared to controls. Fibrosis was confirmed by assessing the collagen in liver sections as quantified by Sirius red/Fast green staining, a quantitative measure of fibrosis as well as by visualization of the hepatic fibrosis. Collagen levels in the liver sections of heterologous serum induced fibrotic rats was increased by 33% compared to controls and a typical fibrotic pattern was seen. Messenger RNA was prepared from heterologous serum induced fibrotic rats and compared to controls. CYP 1A2 was assessed using a specific probe and the CYP 1A2 level was significantly reduced in the heterologous serum induced fibrotic rats compared to controls. These results further suggest that cytochrome P450 is reduced in the presence of hepatic fibrosis. Thus, in three well established experimental models of hepatic fibrosis which had clearly developed hepatic fibrosis (as shown by Sirius red/Fast green staining), cytochrome P450 mediated enzyme activity, or specifically, CYP 1A messenger RNA is decreased. We then investigated a transgenic mouse, deficient in the arylhydrocarbon hydroxylase receptor (AHR), which has undetectable levels of CYP 1A messenger RNA. We quantitated the collagen in liver sections obtained from AHR knockout mice compared to controls, as an indication of the presence of hepatic fibrosis. Collagen concentration was significantly increased by 53% (P<0.0005) in sections from Ahr-/- (knockout) mice compared to wild-type controls. Collagen in livers of the Ahr+/- heterozygous mice was not different from wild-type controls. The increase in collagen concentration in liver sections is an indication of fibrosis in Ahr-/- mice. Collagen protein deposition was also elevated in liver sections from bile duct ligated rats (by 44%) compared to sham operated controls, was elevated in liver sections from heterologous serum induced fibrosis in rats (33%) compared to controls, and was elevated in liver sections from yellow phosphorous induced hepatic fibrosis (74%) compared to vehicle treated controls. In conclusion, these results indicate that cytochrome P450 and specific subtypes of P450, the CYP 1A subgroup, are significantly reduced in three experimental models of hepatic fibrosis when there is evidence of increased collagen deposition in the livers. These results also indicate that mice that are deficient in CYP 1A have elevated levels of hepatic collagen protein, an indication of hepatic fibrosis.

Journal Article↗
PubMed1999

Induction of heat-shock protein 72 in rat skeletal muscle does not increase tolerance to ischemia-reperfusion injury.

Ischemia-reperfusion injury is implicated in the failure of free flap and replant surgeries and is associated with the pathogenesis of a wide variety of clinical diseases including stroke, myocardial infarction, spinal injury, and compartment syndromes. We used a skeletal muscle flap model to test if the induction of heat-shock protein 72 (HSP72) by mild hyperthermia provides tolerance against ischemia-reperfusion injury. Immunocytochemistry and Western blot analysis verified increased production of HSP72 in the gracilis muscle of globally heated rats. Neutrophil accumulation in the microvasculature and postischemic muscle survival after ischemia-reperfusion were unaltered by preischemic hyperthermia, indicating HSP72 induction is not sufficient to provide resistance against severe injury in skeletal muscle.

Adaptation, Physiological↗