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Biomedical subjects

M Smogorzewski

Publications and source records attributed to M Smogorzewski.

At least 73 records · Page 4Linked to original sources
PubMed1992

Impaired phagocytosis in chronic renal failure is mediated by secondary hyperparathyroidism.

Patients with chronic renal failure (CRF) display impaired phagocytosis by the polymorphonuclear leucocytes (PMNL), and these cells have elevated basal levels of cytosolic calcium ([Ca2+]i) and reduced ATP content. It has been suggested that these changes in PMNL metabolism and function are mediated by the state of secondary hyperparathyroidism of CRF. To examine the role of excess PTH in these derangements of PMNL, we studied [Ca2+]i, ATP and phagocytic ability of PMNL in five groups of rats including: CRF, CRF normocalcemic parathyroidectomized (CRF-PTX), CRF and normal animals treated with verapamil (CRF-V), and normal-V, respectively. The level of [Ca2+]i in the PMNL of CRF rats (149 +/- 2.7 nM) was significantly (P less than 0.01) higher and the ATP content (4.2 +/- 0.17 nmol/5 x 10(6) PMNL) significantly lower (P less than 0.01) than in normal (108 +/- 2.4 nM; 9.5 +/- 0.15 nmol/5 x 10(6) PMNL), CRF-PTX (103 +/- 2.9 nM; 9.2 +/- 0.19 nmol/5 x 10(6) PMNL), CRF-V (107 +/- 2.2 nM; 9.0 +/- 0.2 nmol/5 x 10(6) PMNL) and normal-V (106 +/- 1.8 nM; 9.2 +/- 0.2 nmol/5 x 10(6) PMNL), despite sustained elevation in blood PTH in the CRF-V group. Phagocytosis was significantly (P less than 0.01) impaired in CRF animals (5.6 +/- 0.25 micrograms oil/10(7) PMNL/min) but was normal in CRF-PTX (9.3 +/- 0.21 micrograms oil/10(7) PMNL/min) and CRF-V (9.5 +/- 0.22 micrograms oil/10(7) PMNL/min) rats. The values of phagocytosis in normal and normal-V rats were 9.6 +/- 44 and 9.6 +/- 0.18 micrograms oil/10(7) PMNL/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Decreased O2 consumption by PMNL from humans and rats with CRF: role of secondary hyperparathyroidism.

Bactericidal ability of polymorphonuclear leukocytes (PMNL) is impaired in chronic renal failure (CRF). This function of PMNL is mediated by the generation of oxidizing radicals and the latter event requires O2 consumption by these cells. The present study examined both basal and FMLP-stimulated rise in cytosolic calcium ([Ca2+]i) and O2 consumption of PMNL from normal subjects and hemodialysis patients and from CRF rats, and evaluated the potential role of secondary hyperparathyroidism of CRF on these properties of PMNL. Basal levels of [Ca2+]i were significantly higher, and FMLP-induced increments in [Ca2+]i were significantly lower in PMNL of both humans and rats with CRF than in normals. Basal and FMLP-stimulated O2 consumption were significantly lower in CRF subjects and rats than in normals. These derangements were prevented by prior parathyroidectomy of CRF rats or by their treatment with verapamil from day one of CRF. Also, therapy of rats with pre-existing CRF with this drug reversed the abnormalities in [Ca2+]i and in O2 consumption of PMNL. The data indicate that: (1) CRF is associated with derangements in the homeostasis of [Ca2+]i of PMNL and their oxygen consumption, (2) these abnormalities are, most likely, mediated by the state of secondary hyperparathyroidism of CRF, and (3) verapamil, which blocks the PTH-induced entry of calcium into cells, and prevents as well as reverses these PMNL dysfunctions. These results implicate the excess PTH of CRF in the genesis of the defective bactericidal function of PMNL, and assign a new dimension to PTH toxicity in CRF.

Adult↗
PubMed1992

On the mechanisms of impaired phagocytosis in phosphate depletion.

Phosphate depletion (PD) impairs the phagocytic ability of polymorphonuclear leukocytes (PMNL). This derangement has been attributed to the low ATP content of PMNL in PD. The mechanisms responsible for the low ATP content are not well defined. Phosphorus deficiency, per se, and/or other cellular metabolic consequences of PD such as a rise in cytosolic calcium ([Ca2+]i) could be responsible. Indeed, PD is associated with a rise in [Ca2+]i in other cells, and such an event may inhibit mitochondrial ATP production. It is also not evident whether the impaired phagocytosis in PD is due to low ATP content and/or a rise in the [Ca2+]i of PMNL. The study presented here examined levels of [Ca2+]i, ATP content, and the phagocytic ability of PMNL from PD and pair-weighed (PW) rats and evaluated the potential beneficial effect of treatment with verapamil (V), which may prevent a rise in [Ca2+]i and the consequent effects on ATP content and the phagocytosis of PMNL. The resting levels of [Ca2+]i of PMNL from PD rats (148 +/- 3.9 nM) were significantly (P less than 0.01) higher, and the ATP contents (4.8 +/- 0.2 nmol/5 x 10(6) PMNL) were significantly (P less than 0.01) lower than in PW (111 +/- 2.8 nM and 9.3 +/- 0.3 nmol/5 x 10(6) PMNL), PW-V (114 +/- 2.2 nM and 9.3 +/- 0.28 nmol/5 x 10(6) PMNL), and PD-V (112 +/- 1.8 nM and 6.6 +/- 0.19 nmol/5 x 10(6) PMNL) animals. Despite the normal [Ca2+]i in the PMNL of PD-V rats, their ATP contents were still significantly (P less than 0.01) lower than those of PW or PW-V rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1992

Reduced activity of Na(+)-K+ ATPase of pancreatic islets in chronic renal failure: role of secondary hyperparathyroidism.

The activity of Na(+)-K+ ATPase of pancreatic islets modulates their insulin secretion. The study presented here examined the activity of this enzyme in pancreatic islets of chronic renal failure (CRF) rats in an effort to further delineate the mechanisms of impaired insulin secretion in CRF. The Vmax of Na(+)-K+ ATPase, but not its Km, and the ATP content are significantly reduced in islets of CRF rats that have elevated levels of parathyroid hormone (PTH). These derangements are prevented by prior parathyroidectomy of CRF rats (low blood levels of PTH) or by their treatment with the calcium channel blocker verapamil; these latter rats have sustained elevation of blood levels of PTH. The data indicate that the chronic excess blood levels of PTH in CRF initiates events (augmented entry of calcium) that lead to the reduction in ATP content and in Vmax of Na(+)-K+ ATPase of pancreatic islets. Reducing the blood levels of PTH by parathyroidectomy or blocking the action of PTH on calcium entry into cells by verapamil prevents these derangements. The results suggest that chronic inhibition of Na(+)-K+ ATPase may participate in the processes underlying the impaired insulin secretion in CRF.

Animals↗
PubMed1992

Mechanism of organ dysfunction in phosphate depletion: a critical role for a rise in cytosolic calcium.

Phosphate depletion (PD) is associated with multiorgan dysfunction. It has been proposed that this phenomenon is due to two metabolic derangements: (a) there is a reduction in ATP content of cells and hence reduced availability of energy-rich phosphate compounds, and (b) there is a decrease in 2,3-diphosphoglycerate in red blood cells, a change that would increase the affinity of hemoglobin to oxygen resulting in tissue hypoxia. Recent studies have demonstrated that PD is associated with a significant elevation in basal levels of cytosolic calcium [Ca2+]i in many cells. This is due to an increased entry into and decreased extrusion of calcium out of cells. This rise in [Ca2+]i plays a major role in organ dysfunction in PD and in the genesis of decreased ATP content of cells.

Animals↗
PubMed1992

[Comparison of the effects of sodium fluoride and calcidiol on the remodeling of the endosteal surface of the rib cortex in dogs after administration of prednisone].

The effects were compared of sodium fluoride and calcidiol on the remodeling of the rib cortical-endosteal surface of dogs treated with prednisone for long time periods. The study used a histomorphometric and tetracycline labeling methods. It was found that administration of sodium fluoride with calcidiol and calcium carbonate limited in a higher degree than the treatment with calcidiol and calcium carbonate the development of the osteoporotic changes induced by glucocorticoids. This included reduced enhancement of the bone resorption surface, increased bone formation surface and osteoid thickness connected with acceleration of mineralization rate. The changes induced by sodium fluoride had a favorable effect on the ratio of the resorption to the formation process at the sites of bone remodeling.

Animals↗
PubMed1991

Reduced phospholipid contents of brain synaptosomes in phosphate depletion.

The effects of 6 wk phosphate depletion (PD) and pair-weight feeding (PW) without and with treatment with verapamil (PD-V and PW-V, respectively) on phospholipid (PL) and cholesterol content and on resting levels of cytosolic calcium concentration ([Ca2+]i) of brain synaptosomes of rats were examined. PD was associated with significantly (P less than 0.01) lower synaptosomal content of total PL, phosphatidylinositol (PI), phosphatidylserine (PS), and phosphatidylethanolamine (PE) and with significant (P less than 0.01) elevation in [Ca2+]i. Verapamil treatment of PD rats prevented the rise in [Ca2+]i of brain synaptosomes and the fall in PI and caused significant (P less than 0.01) improvement in the synaptosomal content of PS and PE; values of PS and PE in PD-V rats, however, were still significantly (P less than 0.01) lower than those of PD rats. Verapamil treatment of PW rats did not affect synaptosomal content of the various PL or resting levels of [Ca2+]i. Cholesterol content of brain synaptosomes of the various groups was not significantly different, but cholesterol-to-total PL ratios were significantly (P less than 0.01) higher in PD and PD-V rats than in PW or PW-V animals. Results indicate that PD affects metabolism of total phospholipids, PI, PS, and PE of brain synaptosomes, and these derangements are due to reduced availability of phosphorus and to the rise in [Ca2+]i. The data are consistent with the proposition that PD-induced changes in PL render the synaptosomal membrane more permeable to calcium, an event that may lead to a rise in [Ca2+]i.

Animals↗
PubMed1991

Phosphate depletion increases cytosolic calcium of brain synaptosomes.

Phosphate depletion (PD) is associated with a rise in resting levels of [Ca2+]i in pancreatic islets. It is not known whether this derangement occurs in other cells, and the mechanisms by which PD affects [Ca2+]i have not been delineated. This study examined the effect of PD on [Ca2+]i of brain synaptosomes and evaluated potential mechanisms that may lead to rise in their [Ca2+]i. [Ca2+]i levels in synaptosomes of PD rats (460 +/- 18.3 nM) were higher (P less than 0.01) than those of pair-weighed (PW) rats (358 +/- 12.5 nM). Verapamil treatment of PD rats (PD-V) normalized [Ca2+]i in their synaptosomes (361 +/- 8.5 nM). In verapamil-treated PW rats (PW-V), synaptosomal [Ca2+]i (359 +/- 8.3 nM) was not affected. ATP content and Na(+)-K(+)-ATPase activity of synaptosomes were lower (P less than 0.01) in PD rats than in PW, PD-V, and PW-V rats. The values of these parameters from the latter three groups were not different. Km of synaptosomal Ca2(+)-ATPase was not affected by PD but Vmax of this enzyme (2.5 +/- 0.33 mumol Pi.mg protein-1.h-1) was lower (P less than 0.05) than in PW (5.4 +/- 0.66 mumol Pi.mg protein-1.h-1), PD-V, and PW-V rats. Our data indicate that PD raises [Ca2+]i in brain synaptosomes and suggest that PD increases calcium entry into synaptosomes. This would inhibit mitochondrial ATP production, with a consequent fall in ATP content of synaptosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Impaired phagocytosis in dialysis patients: studies on mechanisms.

Dialysis patients have increased susceptibility to infection and this is, in part, due to impaired phagocytic and bactericidal activities of polymorphonuclear leukocytes (PMNL). The mechanisms responsible for the reduced phagocytosis are not known. Dialysis patients have elevated blood levels of parathyroid hormone (PTH), and available data indicate that PMNL is a target cell for PTH. Chronic exposure to excess PTH may cause accumulation of calcium in PMNL which in turn could adversely affect cellular events leading to their dysfunction. We studied phagocytosis, resting levels of cytosolic calcium [( Ca2+]i), ATP content and the rise in [Ca2+]i in response to ligation of Fc gamma RIII receptors with 3G8 monoclonal antibody in PMNL from 37 dialysis patients and 48 normal subjects. The PMNL from the dialysis patients displayed impaired phagocytosis, elevated resting levels of [Ca2+]i, decreased ATP content and a smaller rise in [Ca2+]i in response to various doses of 3G8 monoclonal antibody as compared to values obtained in PMNL of normal subjects. Our results suggest that derangements in cellular metabolism and possibly an abnormality in Fc gamma RIII interaction with antibody and/or the consequences of such interaction are responsible, at least in part, for the impaired phagocytosis of PMNL of dialysis patients. Our data are consistent with the notion that excess PTH may play an important role in the processes leading to impaired phagocytosis.

Adenosine Triphosphate↗
PubMed1991

Chronic parathyroid hormone excess in vivo increases resting levels of cytosolic calcium in brain synaptosomes: studies in the presence and absence of chronic renal failure.

It has been suggested that excess parathyroid hormone (PTH) in chronic renal failure (CRF) or chronic administration of PTH to normal rats caused derangements in norepinephrine and phospholipid metabolism of brain synaptosomes, because of an increase in their resting levels of cytosolic calcium which may induce a decrease in synaptosomal content of ATP. In the study presented here, the resting levels of cytosolic calcium in brain synaptosomes were measured in six groups of rats including: (1) normal rats; (2) rats with CRF of 21-days duration; (3) normocalcemic parathyroidectomized rats with CRF of 21-days duration; (4) rats with CRF of 21-days duration treated with verapamil from day 1 of CRF; (5) normal rats treated with verapamil for 21 days; and (6) normal rats treated with PTH for 21 days. Resting levels of cytosolic calcium of brain synaptosomes of CRF rats (437 +/- 18.0 nM) and normal rats treated with PTH (428 +/- 5.6 nM) were significantly (P less than 0.01) higher than those of normal rats (345 +/- 9.0 nM), normal rats treated with verapamil (354 +/- 8.7 nM), CRF rats treated with verapamil (361 +/- 12.9 nM), or CRF-parathyroidectomized rats (363 +/- 8.2 nM). There were no significant differences between the values of the last three groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Effect of chronic renal failure on Ca2+ ATPase of brain synaptosomes.

Chronic renal failure (CRF) is associated with a sustained rise in the concentration of cytosolic calcium [( Ca2+]i) of brain synaptosomes. This was attributed to secondary hyperparathyroidism where the excess blood levels of parathyroid hormone (PTH) augment calcium entry into synaptosomes. However, for such an effect of PTH to cause a sustained rise in [Ca2+]i, calcium extrusion out of synaptosomes should be impaired. The study presented here examined the effect of CRF with and without (CRF-PTX) excess PTH and the treatment of CRF rats with verapamil (V) on the Vmax and Km for calcium of synaptosomal Ca2+ ATPase, an enzyme that plays an important role in pumping calcium out of the synaptosomes. The Vmax of synaptosomal Ca2+ ATPase in CRF rats was significantly (P less than 0.01) lower than that of normal, CRF-PTX, CRF-V, and normal-V rats. However, the values in CRF-V were still below normal (P less than 0.05). There were no significant differences in the Km for calcium of synaptosomal Ca2+ ATPase among the five groups of animals. [Ca2+]i was significantly (P less than 0.01) higher in synaptosomes of CRF rats than in normal, CRF-PTX, CRF-V, and normal-V animals, and the values among the latter four groups were not different. The data demonstrate that the activity of synaptosomal Ca2+ ATPase is reduced in CRF rats, and this derangement is related to the excess PTH. This derangement in Ca2+ ATPase activity plays an important role in the genesis of the sustained elevation of synaptosomal [Ca2+]i in CRF.

Animals↗
PubMed1991

Effect of potassium chloride on cytosolic calcium of brain synaptosomes of rats with chronic renal failure.

Norepinephrine (NE) release from brain synaptosomes is dependent in major part on an adequate rise in cytosolic calcium ([Ca2+]i). A smaller or a greater calcium signal (delta [Ca2+]i) or delta[Ca2+]i/basal [Ca2+]i ratio in response to stimuli may interfere with NE release from brain synaptosomes. In order to further evaluate the mechanism of reduced NE release from brain synaptosomes in chronic renal failure (CRF), we examined the changes in synaptosomal [Ca2+]i in response to KCl in normal, CRF, and normocalcemic, parathyroidectomized (PTX) CRF rats (CRF-PTX) and in CRF rats treated with verapamil (CRF-V). CRF rats displayed significantly (p less than 0.01) higher basal levels of [Ca2+]i and a higher delta[Ca2+]i and delta [Ca2+]i/basal [Ca2+]i ratio than in the other three groups of rats. These parameters were not different among normal, CRF-PTX and CRF-V rats. The data are consistent with the notion that the higher calcium signal and the higher ratio between signal and the basal [Ca2+]i in response to a stimulus in CRF are deleterious to synaptosomal function and are responsible, in part, for the reduced NE release by these structures in CRF.

Animals↗
PubMed1991

Cytosolic calcium is normally distributed in brain synaptosomes of normal and chronic renal failure rats.

Available data indicate that the basal levels of cytosolic calcium ([Ca2+]i) varies widely in polymorphonuclear leukocytes and in thymocytes. The present study examined whether a similar phenomenon exists in other cells. We measured the basal level of [Ca2+]i in brain synaptosomes of normal and chronic renal failure (CRF) rats. We find these levels (278-439 mM) vary widely in both normal rats and in CRF animals (350-495 mM) as well. However, despite these wide variations, the values followed normal distribution in both groups of animals. The data are consistent with the proposition that the values of [Ca2+]i in many cells display wide variations among a particular species and the levels are most likely predetermined genetically for each animal.

Animals↗
PubMed1990

Verapamil corrects abnormalities in norepinephrine metabolism of brain synaptosomes in CRF.

Abnormalities in norepinephrine (NE) metabolism of brain synaptosomes occur in chronic renal failure (CRF), and this has been attributed to the parathyroid hormone (PTH)-induced accumulation of calcium in synaptosomes. The present study examined the effect of treatment with the calcium-channel blocker verapamil on NE content, release, and uptake, on Na(+)-K(+)-ATPase activity, and on calcium content of brain synaptosomes from rats with 21 days of CRF. Verapamil treatment of normal rats for 21 days did not affect synaptosomal NE content, release, or uptake, Na(+)-K(+)-ATPase activity, or calcium content. Rats with 21 days of CRF displayed a significant (P less than 0.01) reduction in their synaptosomal NE content, release, and uptake, an increase in Na(+)-K(+)-ATPase activity, and a significant (P less than 0.01) increase in calcium content of synaptosomes. The treatment of CRF rats with verapamil normalized synaptosomal NE content and release and Na(+)-K(+)-ATPase activity, produced a significant (P less than 0.01) improvement in NE uptake, and prevented the accumulation of calcium in synaptosomes. The data of the present study are consistent with the notion that the abnormalities in synaptosomal NE metabolism and Na(+)-K(+)-ATPase in CRF are mainly the result of PTH-induced accumulation of calcium in synaptosomes and could be prevented by a calcium-channel blocker.

Animals↗
PubMed1990

Effect of verapamil on CRF-induced abnormalities in phospholipid contents of brain synaptosomes.

Chronic renal failure is associated with significant reductions in total phospholipids, phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine of brain synaptosomes. These derangements in synaptosomal phospholipid metabolism were attributed to the state of secondary hyperparathyroidism of chronic renal failure (CRF) and the parathyroid hormone-induced accumulation of calcium in synaptosomes. This study examined whether a calcium channel blocker, verapamil, would prevent this synaptosomal calcium accumulation and correct the abnormalities in synaptosomal phospholipids in CRF. Verapamil treatment of normal rats for 21 days did not affect synaptosomal content of calcium or phospholipids. CRF of 21 days' duration was associated with a significant (P less than 0.01) increase in synaptosomal calcium (10.2 +/- 0.5 vs 7.4 +/- 0.6 nmol/mg protein) and a significant reduction (P less than 0.01) in total phospholipids (397 +/- 12 vs 529 +/- 19 nmol phospholipid P/mg protein), phosphatidylinositol (2.7 +/- 0.22 vs 4.6 +/- 0.27 nmol phospholipid P/mg protein), and phosphatidylserine (37 +/- 1.9 vs 83 +/- 5.2 nmol phospholipid P/mg protein). Simultaneous treatment of CRF rats with verapamil for 21 days reversed the synaptosomal abnormalities in calcium and phospholipid contents. Our data support the notion that the effect of excess parathyroid hormone of CRF on synaptosomal phospholipids is mainly due to the parathyroid hormone-induced calcium accumulation.

Animals↗