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Biomedical subjects

M Smogorzewski

Publications and source records attributed to M Smogorzewski.

86 records · Page 5Linked to original sources
PubMed1990

IgA nephropathy: a long-term progressive study.

Thirty-three cases of idiopathic IgA nephropathy were followed up for an average of 90.8 +/- 8.4 months. Four therapeutic regimens were applied: symptomatic therapy, immunosuppressive drugs, dipyridamole with acetylsalicylic acid and immunomodulating treatment with thymosin. Parameters of kidney function obtained during control and treatment periods were compared in each patient separately. In all cases but one, frequent fluctuations of serum creatinine levels were observed. Cumulative kidney survival ratio for 5, 10 and 15 years amounted to 1.00, 0.90 and 0.82, respectively. There was no apparent response to thymosin, aspirin and dipyridamole therapy. Immunosuppressive drugs are recommended in cases with steadily progressive disease, when serum creatinine concentration surpasses 2.5 mg/dl.

Adolescent↗
PubMed1989

Effects of verapamil on the abnormalities in fatty acid oxidation of myocardium.

The oxidation of long (LCFA) and short chain fatty acids (SCFA) by myocardial mitochondria is impaired in CRF due to reduced activity of carnitine palmitoyl transferase (CPT) and of enzymes in the beta-oxidation sequence in mitochondrial matrix. It was proposed that PTH, through its ability to augment entry of calcium into cells, enhances calcium uptake by the myocardium leading to calcium accumulation which in turn affects mitochondrial function. A calcium channel blocker may therefore correct these derangements. The present study examined the effects of verapamil on LCFA and SCFA oxidation and on CPT activity of myocardial mitochondria and on 45Ca uptake by, and calcium content of, myocardium obtained from CRF rats and rats treated with PTH, with and without administration of verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in the oxidation of LCFA and SCFA by and of CPT activity of myocardial mitochondria and a significant increase in 45Ca uptake by, and content of, the myocardium. Simultaneous administration of verapamil reversed all these derangements. Administration of verapamil alone to normal rats for 4 or 21 days did not cause significant changes in these parameters. The results of our studies are consistent with the notion that the alterations in myocardial oxidation of LCFA and SCFA in CRF or after PTH treatment are related to PTH-induced calcium accumulation in the heart, and could be reversed by a calcium channel blocker. The data could provide a rational therapeutic approach for the management of uremic myocardiopathy.

Animals↗
PubMed1989

Abnormal norepinephrine uptake and release in brain synaptosomes in chronic renal failure.

Abnormalities in the function of the central nervous system exist in chronic renal failure (CRF) and some of these derangements may be related to excess parathyroid hormone (PTH) which causes a rise in brain calcium. The latter may affect metabolism of neurotransmitters such as norepinephrine (NE) in brain synaptosomes. We measured NE content, uptake and release in brain synaptosomes of CRF rats and studied whether excess PTH affects these parameters. Synaptosomes from rats with 21 days of CRF compared to those from normal animals have higher calcium content (11.4 +/- 0.92 vs. 7.1 +/- 0.50 nmol/mg protein, P less than 0.01) and lower Na-K ATPase activity (6.5 +/- 0.81 vs. 11.4 +/- 0.76 mumol Pi/mg protein/hr, P less than 0.01). NE content (11.0 +/- 0.60 vs. 13.6 +/- 0.55 pmol/mg protein/hr, P less than 0.01), uptake (46 +/- 4.5 vs. 110 +/- 5.9 pmol/mg protein times 50 min, P less than 0.01) and release (2.0 +/- 0.2 vs. 5.1 +/- 0.47 pmol/mg protein times 10 min, P less than 0.01). Parathyroidectomy (PTX) in CRF rats kept normocalcemic reversed these abnormalities in brain synaptosomes; indeed calcium content, Na-K ATPase activity and NE content, uptake and release in synaptosomes from PTX-CRF rats were not different from those seen in normal rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Effect of chronic renal failure and parathyroid hormone on phospholipid content of brain synaptosomes.

The effects of 21 days of chronic renal failure (CRF) with and without excess parathyroid hormone (PTH) and those of 21 days administration of intact PTH on phospholipids and cholesterol contents of rat brain synaptosomes were examined. CRF and PTH treatment were associated with a significant (P less than 0.01-0.02) reduction in the synaptosomal contents of total phospholipids, phosphatidylinositol (PI), phosphatidylserine (PS), and phosphatidylethanolamine (PE). Parathyroidectomy (PTX) prior to the induction of CRF prevented the decrements in the synaptosomal contents of total phospholipids, PI, PS, and PE. The synaptosomal contents of these phospholipids in CRF-PTX rats were not different from those in normal rats despite CRF. There were no significant changes in the cholesterol content of the synaptosomes in the various experimental groups of animals. The data show that CRF affects synaptosomal metabolism of total phospholipids, PI, PS, and PE, and these derangements are due to the state of secondary hyperparathyroidism of renal failure. The decrements in the content of PI, PS, and PE could be, at least in part, responsible for the previously reported abnormalities in the neurotransmitter functions of brain synaptosomes in CRF and could underlie some of the abnormalities in central nervous system dysfunction in uremia.

Animals↗
PubMed1989

Immunogenicity of allogeneic pancreatic islet grafts: the effect of in vitro culture and the site of transplantation.

Freshly isolated or cultured for 14 days rat allogeneic pancreatic islets were transplanted either intramuscularly or intratesticularly. After 14 days, the specific recipients' antigraft humoral and cellular immunity evaluated by means of leukoagglutination assay and indirect splenocyte migration inhibition test, respectively. Islet preculture resulted in significant decrease of humoral and in absence of cellular antigraft immunity irrespectively of site of transplantation. Intratesticular grafting did not evoke cellular response after transplantation of both fresh and cultured islets. However, antibody production after intratesticular transplantation of fresh islets remained unaffected. It may be concluded that preculture of rat pancreatic islets affects their immunogenicity. Moreover, testis appears to be a suitable immunoprivileged site for islet grafting.

Animals↗
PubMed1989

Rapid separation and quantitation of major phospholipids in biological samples by combined high-performance liquid chromatography and automated phosphorus analyzer.

Phospholipids extracted from tissue samples were separated by an isocratic high-performance-liquid-chromatographic (HPLC) method and simultaneously quantitated by an automated phosphorus analyzer. Results from various tissues were compared with previously published data obtained by thin-layer chromatography (TLC). Liver, heart, skeletal muscle, kidney and brain cortex synaptosomes from rats were examined. Optimal separation of major phospholipids of these tissues was achieved in a single HPLC run using a mobile phase of acetonitrile, methanol and sulfuric acid 100:2.1:0.05 (v:v:v). Recoveries of pure phospholipids injected onto the column averaged 75-80%. Similar recoveries were obtained with heart and skeletal muscle phospholipids, whereas liver, kidney and synaptosomes yielded lower recoveries (50-66%), suggesting the presence of other phospholipids in these tissues which did not elute from the column. The composition of total and individual phospholipids varied among the tissues and was generally similar to previously reported findings with TLC. The intraassay coefficients of variation ranged from 5 to 11%. We conclude that this technique is a reliable, rapid, and reproducible method for separation and quantitation of the major phospholipid species of tissues and subcellular fractions.

Animals↗
PubMed1988

Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle.

Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in 45Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker.

Animals↗
PubMed1988

Fatty acid oxidation in the myocardium: effects of parathyroid hormone and CRF.

Fatty acids constitute an important substrate utilized by the myocardium as a major fuel for energy production; certain data suggest that oxidation of long chain fatty acids (LCFA) may be impaired in uremia, and such a derangement could, in part, contribute to the myocardiopathy of uremia. The latter is associated with secondary hyperparathyroidism and PTH has been shown to affect myocardial metabolism. The present study evaluated in rats the effects of four days administration of PTH and 21 days of chronic renal failure (CRF) with and without excess PTH on oxidation of alpha-ketoglutarate, beta-hydroxybutyric acid, LCFA and short chain fatty acids (SCFA). PTH impaired oxidation of alpha-ketoglutarate, LCFA, SCFA, but not of beta-hydroxybutyric acid and reduced the activity of carnitine palmitoyl transferase (CPT). Inactivation of the PTH abolished its effects. CRF rats with intact parathyroid glands also had impaired oxidation of LCFA and CTP activity. Carnitine contents of myocardium were not altered. The data show that PTH excess in normal rats is associated with impaired oxidation of LCFA and SCFA, and secondary hyperparathyroidism in CRF animals impairs oxidation of LCFA. This effect is due to: 1) reduction in the activity of CPT, a key enzyme for the transport of LCFA to mitochondrial matrix for beta-oxidation; and 2) impairment in beta-oxidation. The data provide for new and additional pathway through which excess PTH and CRF can affect myocardial metabolism.

Animals↗
PubMed1988

Chronic renal failure, parathyroid hormone and fatty acids oxidation in skeletal muscle.

Fatty acids are an important source of skeletal muscle energy, and certain data suggest oxidation of long-chain fatty acids (LCFA) may be impaired in uremia. This abnormality may in part be responsible for uremic myopathy. Uremia is associated with hyperparathyroidism and PTH affects muscle metabolism; PTH enhances muscle proteolysis and impairs muscle bioenergetics, and it is possible that PTH also affects fatty acids oxidation. The present study examined in rats the effects of 4 days administration PTH and of 21 days of chronic renal failure (CRF) with and without excess PTH on oxidation of LCFA and short-chain fatty acids (SCFA). Both 1-84 and 1-34 PTH impaired oxidation of LCFA but not of a SCFA (beta-hydroxybutyric acid) and reduced the activity of carnitine palmitoyl transferase (CPT). Inactivation of the PTH abolished its effects. CRF rats with intact parathyroid glands had also impaired oxidation of LCFA and of CPT activity. Parathyroidectomy in CRF rats normalized these abnormalities. Carnitine contents of muscle were not altered. The data show that PTH excess in normal or in CRF rats is associated with impaired oxidation of LCFA and this effect is due to reduction in the activity of CPT, a key enzyme for the transport of LCFA to mitochondrial matrix for beta-oxidation. The data demonstrate another toxic effect of PTH on muscle in CRF and provide an additional pathogenic mechanism for uremic myopathy.

Animals↗
PubMed1986

The influence of the H-2 receptor antagonist ranitidine on cadaver kidney allograft function.

To assess the influence of ranitidine on kidney allograft function a double-blind, placebo-controlled clinical study in 42 cadaver kidney recipients has been performed. Patients received ranitidine or placebo for 1 month. Four years after transplantation 81% of the patients in the control group were alive; 67% in the control and 71% in the ranitidine group with functioning grafts. These differences were statistically not significant. However, a slightly more intensive steroid therapy was given to keep the ranitidine patients adequately immunosuppressed. Ranitidine thus can be safely used in kidney graft recipients. Because of a lack of gastrointestinal complications in both groups, no conclusions can be drawn regarding the prophylactic value of ranitidine.

Adolescent↗
PubMed1985

Niridazole as an adjunct to "conventional" immunosuppression in kidney allograft transplantation. Long-term follow up.

To assess the value of niridazole as adjuvant immunosuppressant to conventional steroid and azathioprine therapy, a prospective randomized clinical study in 26 cadaver kidney recipients had been performed. No beneficial effect was observed on the kidney graft survival with the addition of niridazole. Neither was there any additional immunosuppressive action demonstrated in the serum of the patients in this group. On the basis of our limited clinical experience niridazole can not be recommended as an adjunct agent for kidney graft recipients.

Adult↗