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Biomedical subjects

M L Foegh

Publications and source records attributed to M L Foegh.

At least 109 records · Page 6Linked to original sources
PubMed1985

Prolongation of experimental cardiac allograft survival with thromboxane-related drugs.

A novel receptor antagonist, 3-hydroxymethyl-dibenzo (b,f) thiepin 5,5-dioxide (L-640,035) and the thromboxane synthase inhibitor, sodium (E) -3-(4-[3-pyridylmethyl phenyl]) -2-methyl-acrylate (OKY 1581) were evaluated for their effect in promoting the survival of cardiac allografts in Lewis rats that received cardiac allografts from Lewis x Brown-Norway F1 rats. Neither of these drugs or azathioprine alone significantly prolonged graft survival. However a combination of azathioprine with either of the two drugs significantly increased graft survival. Because L-640,035 inhibits platelet and smooth muscle responses to thromboxane-mimics, and because OKY 1581 is a specific thromboxane synthase inhibitor, we conclude that thromboxane may have a causal role in experimental cardiac allograft rejection in rats.

Animals↗
PubMed1985

Urine immunoreactive thromboxane B2 in rat cardiac allograft rejection.

Increases in urinary excretion of immunoreactive thromboxane B2 (i-TXB2), the stable break-down product of thromboxane A2, have been described in kidney allograft rejection in patients. We investigated these findings by monitoring daily urine i-TXB2 excretion in a heterotopic cardiac allograft rat model using Lewis rats as recipients. In order to obtain differences in allograft survival, a donor was used that was either ACI or LewisxBrown Norway F1 (LxB-NF1). The ACI-to-Lewis model rejected on day 6.2 +/- 0.2 (n = 6). The LxB-NF1-to-Lewis model received, in addition, azathioprine (5 mg/kg/daily) and rejected on day 9.1 +/- 0.8 (n = 9). Urinary i-TXB2 excretion increased significantly in both groups, compared with i-TXB2 values measured following sham surgery or isograft transplantation. Thus increases in urinary i-TXB2 appear to be associated with cardiac allograft rejection.

Animals↗
PubMed1981

Urine i-TXB2 in renal allograft rejection.

Immunoreactive thromboxane B2 (i-TXB2) was measured in daily urine samples from twelve patients after renal transplantation. In 21 of 30 rejection episodes, the increase in i-TXB2 preceded both the increase in serum beta 2-microglobulin (beta 2-MG) and the clinical diagnosis of rejection. In 26 of 30 rejection episodes, the increase in urine i-TXB2 preceded the increase in serum creatinine. The degree of change in i-TXB2 is greater than that of either serum beta 2-MG or creatinine. Urinary i-TXB2 was very high in one patient with deep venous thrombosis, but it did not rise in patients with urinary tract infection, pneumonia, or acute tubular necrosis. Thus, urinary i-TXB2 seems to be an early indicator of clinical renal allograft rejection.

Acute Disease↗
PubMedDate not supplied

Free radicals, arachidonic acid metabolites, and nutrition.

Oxygen reactive species are normally formed in cells and play an essential part of the bactericidal activity of phagocytic cells. The damaging effect of these oxygen reactive species is prevented by the endogenous scavengers SOD, glutathione peroxidase, catalase, circulating transferrin, ascorbic acid, and membrane-bound alpha-tocopherol. However, when excess amounts of oxygen radicals and hydrogen peroxide are formed, as in reperfusion injury or trauma, the endogenous scavengers are insufficient to react with these active molecules. Lipid peroxidation is an important part of the formation of oxygen reactive species. Lipid peroxidation, especially peroxidation of LDL, may have a significant role in atherosclerosis. Thus dietary manipulation of PG and TX formation through either feeding cold water fish oils or plant oils containing high amounts of polyunsaturated fatty acids may be a two-edged sword. Also, the dietary manipulation of arachidonic acid through increasing its precursor linoleate may cause a decrease in the immune response as seen in animal experiments. The marine oils may be regarded as a natural aspirin in that formation of PGs of the bisenoic series will be replaced by the PGs of the trienoic series. This results in the formation of TXA3, which is biologically inactive, and PGI3, which is biologically active like PGI2. This may have no physiologic consequences but it is used to illustrate a possible mechanism for the postulated beneficial cardiovascular effects of these oils. The issues and the mechanisms are controversial and frequently highly speculative. The subject is a boon for the lipid biochemist and nutritionist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Angiopeptin: a treatment for accelerated myointimal hyperplasia?

Extensive smooth muscle cell proliferation is the major event leading to the narrowing or occlusion of the lumen of the coronary arteries of patients undergoing heart transplantation or percutaneous transluminal coronary angioplasty. The smooth muscle cell proliferation in transplant atherosclerosis may be initiated by immunologic events, allowing the vascular smooth muscle cells to respond with migration and proliferation to circulating growth factors as well as chemoattractants and growth factors released by inflammatory cells and smooth muscle cells themselves. The somatostatin analog angiopeptin is a cyclic octapeptide that has different binding affinities for different somatostatin receptors compared with the parent compound itself. The antiproliferative effects of angiopeptin have been demonstrated in vitro in several tumor cell lines. In a rabbit model of heterotopic heart transplant-accelerated coronary atherosclerosis, angiopeptin has been shown to attenuate myointimal hyperplasia. Further studies in simpler models of myointimal hyperplasia have shown that angiopeptin will inhibit smooth muscle cell proliferation after vascular injury. Further, angiopeptin inhibits thymidine uptake in vitro in pig coronary arteries. Angiopeptin also exerts its inhibitory effect at a very early stage after injury: an 8-hour delay of treatment abolishes the inhibitory effect of angiopeptin on smooth muscle cell proliferation (intimal hyperplasia). On the basis of the experimental data, clinical studies of the inhibitory effect of angiopeptin on prevention of transplant atherosclerosis in heart transplant patients and prevention of restenosis after coronary artery angioplasty are ongoing, as well as are studies in patients undergoing saphenous vein coronary artery bypass surgery.

Animals↗
PubMedDate not supplied

Effects of estrogen on vein grafts.

The effect of estrogen on veins was evaluated in vitro and in vivo in three species. 17 beta-estradiol did not significantly alter 3H-thymidine uptake in vitro in segments from either canine femoral or human saphenous veins. In vivo in a rabbit carotid vein graft model, 17 beta-estradiol administration did not affect the development of intimal hyperplasia but was associated with a higher rate of graft thrombosis. These data suggest that the effects of estrogen on veins differs from the effects reported in arteries. These differences were seen both in vitro in veins taken from their normal location and in vivo in veins placed in the arterial circulation.

Adult↗
PubMedDate not supplied

Effect of estradiol on accelerated atherosclerosis in rabbit heterotopic aortic allografts.

Migration and proliferation of vascular smooth muscle cells are early and major events in the formation of atherosclerotic lesions. We report on an aorta transplant model in rabbits wherein myointimal proliferation is inhibited by 17-beta-estradiol. The abdominal aortas of outbred white New Zealand rabbits were harvested and allografted to the carotid artery of the recipient. The animals, which were fed either a normal or a high-cholesterol (0.5%) diet, were killed 3 weeks later. The degree of myointimal proliferation was measured with a digitized system attached to a light microscope. The myointimal hyperplasia was expressed as the cross section area of the intima/the area of the intima + the area of the media x 100. Transmission electron micrographs were obtained for all vessels. Intimal thickening was shown mainly to consist of proliferating smooth muscle cells. The cholesterol diet resulted in significantly higher serum total cholesterol levels compared to animals on a normal diet (p < 0.0001) but did not affect serum high-density lipoprotein-cholesterol or serum triglyceride levels. The cholesterol diet was also associated with a greater but not significant amount of intimal thickening. Treatment with 17-beta-estradiol significantly decreased both serum triglyceride concentration (p < 0.05) and myointimal thickening (p < 0.01) in cholesterol-fed animals. Transmission electron microscopy showed that the endothelial cells appeared structurally normal in the estradiol-treated animals. Further, estradiol prevented the appearance of vacuolized macrophages. Thus estradiol may decrease myointimal thickening by preserving the endothelium and preventing macrophage appearance in the intima.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Disposition and tissue distribution of angiopeptin in the rat.

The disposition and tissue distribution of angiopeptin, a long-acting octapeptide analogue of somatostatin, were studied in rats following single iv and sc administration of the drug. Similar plasma levels and excretion values of angiopeptin were observed by using radioimmunoassay and radiolabeling techniques. Angiopeptin was absorbed fairly rapidly, with a mean peak plasma level of 25 +/- 4.1 ng/ml at 10-15 min after administration. The kinetics of angiopeptin following sc administration closely resembled those following iv administration due to rapid absorption. The pharmacokinetics of angiopeptin can be described by a two-compartment model. The plasma half-life of the drug ranged from 2.6-2.9 hr when administered sc and 1.98-2.5 hr when given iv. Distribution of angiopeptin was rapid, with the highest concentration appearing in the liver. Half-lives in the liver and bile were short. Most of the drug was excreted in the feces via the bile, while approximately 10% was excreted in the urine. Angiopeptin was also found to be secreted in the saliva. TLC and HPLC of blood, urine, feces, and bile samples did not reveal the presence of any metabolites. In conclusion, the in vivo fate of angiopeptin is characterized by little or no hepatic metabolism and rapid biliary excretion.

Amino Acid Sequence↗