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Biomedical subjects

C Chaimovitz

Publications and source records attributed to C Chaimovitz.

At least 37 records · Page 2Linked to original sources
PubMed1992

Assessment of combined 24,25(OH)2D3 and 1 alpha (OH)D3 therapy for bone disease in dialysis patients.

An increasing body of experimental data suggests a role for 24,25(OH)2D3 in bone metabolism. The present study was carried out to assess a possible therapeutic role of this vitamin D metabolite in renal osteodystrophy. Twenty-two chronic dialysis patients, most of whom were previously maintained on 1 alpha (OH)D3 therapy, received additional treatment with 10 micrograms/day 24,25(OH)2D3 and were compared to 19 patients receiving 1 alpha (OH)D3 alone. Analysis of transiliac bone biopsies obtained at study entry and following 10-16 months of treatment revealed that the combined therapy produced a decrease in bone turnover. Specifically, the addition of 24,25(OH)2D3 inhibited an increase in trabecular bone volume (BV/TV) and suppressed osteoclastic parameters. Thus BV/TV increased from 26.2 +/- 8.6 to 32.1 +/- 7.5% (p < 0.01) in the 1 alpha (OH)D3 group, but it remained unchanged in the combined therapy group. In contrast, the eroded surface (ES/BS), the osteoclast surface (Oc.S/BS), and the osteoclast numbers were significantly suppressed in patients receiving both 24,25(OH)2D3 and 1 alpha (OH)D3, as compared with those receiving 1 alpha (OH)D3 alone (p < 0.01, p < 0.01, and p < 0.001, respectively). These improvements were independent of changes in 1 alpha (OH)D3 dosage. The extent of bone aluminium deposits was unrelated to the administration of 24,25(OH)2D3 or to its effect. 24,25(OH)2D3 therapy was not associated with any adverse effects.

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Acute phosphate depletion and in vitro rat proximal tubule injury: protection by glycine and acidosis.

The effects of phosphate (PO4) removal from Krebs Henseleit buffer on freshly isolated rat proximal tubules (rPT) were assessed by measuring Ca2+ uptake (nmol/mg protein), cellular adenosine triphosphate (ATP) (nmol/mg), tissue K+ content (nmol/mg) and lactate dehydrogenase (LDH) as an index of cell integrity. Ca2+ uptake increased by 50% in rPT incubated in zero PO4 medium as compared to control (2.6 +/- 0.1 vs. 3.9 +/- 0.19, P less than 0.001) and LDH release increased 2.5-fold from 14.2 +/- 0.6 to 31.6 +/- 1.6%, P less than 0.001. Neither verapamil (200 microM) nor mepacrine (50 microM) reduced Ca2+ uptake or decreased LDH release suggesting that the increased Ca2+ uptake was not occurring through potential operated channels and that phospholipase-induced cell injury was not the cause of increased LDH release. Either glycine (2 mM) or extracellular fluid acidosis (pH 7.06), however, significantly diminished rPT injury and Ca2+ uptake. Specifically, as compared to the increased LDH released in untreated. PO4-depleted rPT, LDH release was diminished significantly by glycine treatment (31.0 +/- 0.9 vs. 15.5 +/- 1.6%, P less than 0.001) or acidosis (30.3 +/- 0.04 vs. 19.2 +/- 0.9%, P less than 0.01). Ca2+ uptake did not increase in glycine treated tubules (2.6 +/- 0.1 vs. 2.8 +/- 0.2 nmol/mg, NS) or in the presence of acidosis (2.6 +/- 0.1 vs. 2.97 +/- 0.17 nmol/mg, NS). ATP concentrations were markedly reduced by PO4 depletion (2.8 +/- 0.2 vs. 4.8 +/- 0.3 nmol/mg, P less than 0.001) and remained at low levels during either acidosis or glycine-induced protection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1991

Metabolism of 25-OH-vitamin D3 by peritoneal macrophages from CAPD patients.

The active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), is produced mainly by the kidney, but there is evidence for extrarenal production in certain circumstances. We studied whether peritoneal macrophages (PM) from CAPD patients were capable of metabolizing 25-OH-D3 to 1,25(OH)2D3. We found that PM were able to metabolize 25-OH-D3 in vitro; the main product following 16 hours of incubation was 19-nor, 10-oxo, 25-OH-D3 with smaller amounts of 1,25(OH)2D3. However, after shorter incubations of three and five hours a larger portion of 1,25(OH)2D3 was produced. The metabolism of 25-OH-D3 was greatly enhanced in PM harvested during episodes of peritonitis. This property was specific for PM of CAPD patients, and was not found in PM from normal subjects. However, incubation of control PM with peritoneal effluent from CAPD patients resulted in induction of the ability of these cells to metabolize 25-OH-D3. This induction was enhanced by preincubation with peritoneal effluent from CAPD patients suffering from peritonitis. Prostaglandin E2 was found to be involved in this synthesis: addition of PGE2 to normal PM induced metabolism of 25-OH-D3, and incubation of PM from CAPD patients with indomethacin decreased the metabolism of 25-OH-D3. The vitamin D metabolites produced by PM from CAPD patients could have a role in immunological resistance to peritoneal infections.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Oral administration of 24,25(OH)2D3 suppresses the serum parathyroid hormone levels of dialysis patients.

We measured the serum parathyroid hormone (PTH) levels in 20 patients treated with continuous ambulatory peritoneal dialysis before and after oral treatment with 24,25-dihydroxyvitamin D3- 24,25(OH)2D3. This metabolite was given in addition to existing treatment with 1 alpha-OH-D3 and calcium carbonate. Administration of 24,25(OH)2D3 led to a significant decrease in PTH levels (intact molecule) from 382 +/- (SE) 65 to 245 +/- 54 pg/ml in 9 patients whose initial levels were extremely high (p = 0.01). No side effects were observed. On the average, calcium values were unchanged and within the normal range throughout the study period; however, a few episodes of mild asymptomatic hypercalcemia occurred which responded quickly to reduction of the calcium carbonate dosage. The present study suggests that oral administration of 24,25(OH)2D3 combined with 1 alpha-OH-D3 is safe and capable of suppressing the raised serum PTH levels of end-stage renal disease patients without the danger of significant hypercalcemia.

24,25-Dihydroxyvitamin D 3↗
PubMed1991

Acute phosphate depletion dissociates hormonal stimulated second messengers in osteoblast-like cells.

The acute effect (24 h) of either phosphate depletion or phosphate surfeit on hormonal stimulated signal transduction systems was studied in the osteoblastic cell line UMR-106. Elevation of intracellular Ca2+ ([Ca2+]in), induced by different calciotropic hormones (PTH, prostaglandin E2, endothelin) was blunted by acute phosphate depletion, whereas at high inorganic phosphate (Pi) concentrations the rise in [Ca2+]in was augmented. Basal [Ca2+]in was not altered by either Pi depletion or Pi excess. The effect of acute phosphate depletion on hormonal mediated [Ca2+]in rise was not observed in the absence of extracellular Ca2+ suggesting that under these conditions, the release of Ca2+ from intracellular stores, is not affected. Also, nonhormonal calcium entry pathways such as depolarization-activated calcium channels or protein kinase C-activated Ca2+ channels were not affected by acute phosphate depletion. cAMP accumulation in the cells, either through receptor or nonreceptor-mediated mechanisms, increased under low Pi conditions and decreased as Pi concentration in the culture media was progressively increased from 0 to 2 mM during 24 h of incubation. Changes in Pi concentration had no effect on basal cAMP generation by the cells. The facilitative effect of acute Pi depletion on agonist-induced cAMP accumulation could be demonstrated in both the presence and absence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.2 mM). PTH receptor binding assessed with [Nle8 Nle18 Tyr34] bovine PTH (1-34) NH2 was not altered by phosphate depletion. We conclude that exposure of osteoblasts to different Pi environments modulates the second messenger responses to hormones in a reciprocal fashion so that acute phosphate depletion down-regulates [Ca2+]in signals while augmenting cAMP generation and vice versa. Inasmuch as bone resorption processes can be modulated by Ca2+ and cAMP the data presented herein suggest that the altered bone resorptive response to calciotropic hormones (e.g. PTH), under surfeit or deficit of phosphate, is mediated by changes in [Ca2+]in and cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Diversity in peritoneal macrophage response of CAPD patients to 1,25-dihydroxyvitamin D3.

A major complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis. Increasing the activity of the peritoneal macrophages, the predominant cell type found in the peritoneal cavity, may be a promising treatment for this infection. The effect of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] on the activity of peritoneal macrophages from CAPD patients and nonuremic controls was studied. 1,25(OH)2D3 had a biphasic effect on superoxide generation in the concentration range of 2.5 10(-9) M to 5 x 10(-6) M with a peak at 2 x 10(-8) M. The addition of 2 x 10(-8) M 1,25(OH)2D3 to nonuremic control macrophages for 24 hours caused a significant twofold increase in superoxide generation in response to phorbol myristate acetate (PMA), from 2.21 + 0.2 to 4.1 + 0.2 nmol/10(6) mac (P less than 0.001), and enhanced the bactericidal activity from 60 + 7% to 85 + 9% (P less than 0.005). CAPD patients were divided into two groups: Group A, patients with high peritonitis incidence (HPI); group B, patients with low peritonitis incidence (LPI). Macrophages from HPI patients show a lower bactericidal activity (37 +/- 5%) and were not affected by 1,25(OH)2D3 after 24 hours of treatment. The increase in macrophage activity was seen only after three days of incubation with the hormone. Macrophages from this group generated a high amount of prostaglandin E2 (PGE2) during the first 24 hours in culture (7.8 +/- 0.52 ng/ml as compared with 0.35 +/- 0.03 ng/ml in the controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗
PubMed1989

Human peritoneal macrophage activity is increased by tuftsin.

Peritonitis caused by Candida albicans is a major complication of continuous ambulatory peritoneal dialysis (CAPD). Increasing the activity of the peritoneal macrophages--the predominant cell type found in the peritoneal cavity--may be of great importance in the prevention and therapy of peritonitis. Therefore, the activating effect of tuftsin was studied on human peritoneal macrophages from CAPD patients. Tuftsin induced a biphasic effect on macrophage activity within a range of 2 X 10(-9)-2 X 10(-6) M, with a maximal activity of 2 X 10(-7) M. At this concentration, tuftsin enhanced by twofold cell association with radiolabelled candida (from 2 +/- 0.2 to 4 +/- 0.2 candida per macrophage) and superoxide anion production in response to exposure to candida (from 150 +/- 20 to 300 +/- 20 nmoles/mg). These results suggest the potential use of tuftsin as a therapeutic drug.

Adult↗
PubMed1989

Inhibition of growth of Chlamydia trachomatis by the calcium antagonist verapamil.

Treatment of BGM (African Green Monkey kidney) cells with the calcium antagonist Verapamil resulted in a reduced yield of chlamydial infectious particles. The inhibitory effect was concentration-dependent, the maximal effect being achieved at 200 microM-Verapamil, which produced a 99.99% reduction of infectious particle yield. Electron microscopy showed that control Chlamydia trachomatis-infected BGM cells contained typical large inclusions in which most of the particles were elementary bodies, whereas Verapamil-treated infected cells contained small inclusions consisting predominantly of reticulate bodies. The findings indicate a possible therapeutic use of this calcium antagonist as an anti-chlamydial drug.

Animals↗
PubMed1989

Active urea transport in toad skin is coupled to H+ gradients.

Active transport of urea exists inwardly through the skin of the toad Bufo viridis and is enhanced by adapting the toads to hypertonic saline solutions. In this paper, we report our studies on the energy coupling of this active transport system. We have shown previously that this system is independent of sodium transport. We thus studied the possibility of coupling to proton transport by studying the following: 1) the effect of acidifying the epithelium by means of CO2 and protonophores, 2) the effect of alkalinizing the epithelium with the anion-exchange inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and by removal of chloride from the serosal medium, 3) the effect of inhibiting the proton-translocating ATPase of the skin, 4) dependence on mucosal pH. We found that 1) acidification of the epithelium by means of 5% CO2 and the protonophores carbonyl cyanide m-chlorophenylhydrazone (CCCP) and nigericin inhibited urea influx; 2) alkalinization of the epithelium by means of the disulfonic stilbene DIDS and by removal of serosal chloride increased urea influx; 3) inhibition of the proton-translocating ATPase of the skin by means of 1,3-dicyclohexylcarbodiimide (DCCD), N-ethylmaleimide (NEM), and sodium orthovanadate inhibited urea transport; 4) urea influx was unaffected by alkalinizing the external medium to 8.5 or by acidifying to 6.5; it was significantly suppressed by a mucosal pH of 5.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Nephrotic syndrome associated with transitional cell carcinoma of the bladder.

We describe the occurrence of a nephrotic syndrome in association with transitional cell carcinoma of the bladder. The proteinuria disappeared several weeks after removal of the tumor. Light and electron microscopy were compatible with a minimal-change lesion, but immunofluorescence showed linear immunoglobulin deposition. Immunoglobulins eluted from the tumor reacted specifically with the kidney and vice versa. We conclude that antibody formation against a specific component of basement membrane common to both kidney and tumor gave rise to the nephropathy in this case.

Biopsy↗
PubMed1989

Peritonitis in continuous ambulatory peritoneal dialysis patients in southern Israel.

We report our experience of peritonitis in a group of continuous ambulatory peritoneal dialysis (CAPD) patients in the south of Israel during a 3-year period. During this period, 51 patients were treated with CAPD, comprising a total of 999 patient months of treatment. One hundred and forty-three episodes of peritonitis occurred in 42 patients. When the patients were divided into high risk and low risk groups, the overall incidence was one episode every 5.7 months in the high risk group and one episode every 13.2 months in the low risk group. Gram-positive organisms accounted for 62.2% of the infections, and coagulase negative Staphylococcus for 35% of infections. The recurrence rate was 12%. Catheter removal was required in seven patients, and three patients were transferred to hemodialysis because of recurrent infections. We conclude that CAPD is a safe and viable modality of treatment for end-stage renal disease in our patient population.

Adult↗
PubMed1988

Renal cortical mitochondrial transport of calcium in chronic uremia.

Calcium overload of tubular cells may occur in uremia, and may be the underlying functional abnormality in the continued deterioration of renal function in chronic renal failure. In order to study this question further, the effect of chronic uremia on the calcium transport properties and respiratory rates was examined in mitochondria (Mi) isolated from the cortex of the remnant kidneys of subtotally nephrectomized rats (SNX) and sham operated controls (C). Plasma calcium concentration was similar in both groups of rats, but a significant hyperphosphatemia was seen in SNX, 8.6 +/- 0.6 mg%, as compared to 7.2 +/- 0.2 mg% in C (P less than 0.001). Mi calcium and phosphate concentrations (nmol/mg protein) were significantly elevated in SNX, 49.9 +/- 7.9 and 35.1 +/- 4.2, respectively, in SNX compared to C, 21.2 +/- 4.2 and 21.4 +/- 2.7, respectively (P less than 0.01). Mi respiratory control ratio and ADP/O were similar in both experimental groups. Kinetic parameters for calcium uptake (Ca2+ concentrations in the medium of 1.25 to 16 microM) revealed initial velocities 1.5-fold higher in SNX Mi than in C. Mi retention of calcium in the presence of medium Ca2+ concentrations up to 500 microM was studied. Calcium retention was reduced in SNX: the Mi were unable to retain calcium at concentrations of 250 microM. The addition of ruthenium red to the medium substantially improved calcium retention by the uremic Mi. Chronic parathyroidectomy did not correct either the increased calcium uptake or the poor retention of uremic Mi.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Active urea transport by the skin of Bufo viridis: amiloride- and phloretin-sensitive transport sites.

Urea is actively transported inwardly (Ji) across the skin of the green toad Bufo viridis. Ji is markedly enhanced in toads adapted to hypertonic saline. We studied urea transport across the skin of Bufo viridis under a variety of experimental conditions, including treatment with amiloride and phloretin, agents that inhibit urea permeability in the bladder of Bufo marinus. Amiloride (10(-4) M) significantly inhibited Ji in both adapted and unadapted animals and was unaffected by removal of sodium from the external medium. Phloretin (10(-4) M) significantly inhibited Ji in adapted animals by 23-46%; there was also a reduction in Ji in unadapted toads at 10(-4) and 5 x 10(-4) M phloretin. A dose-response study revealed that the concentration of phloretin causing half-maximal inhibition (K1/2) was 5 x 10(-4) M for adapted animals. Ji was unaffected by the substitution of sucrose for Ringer solution or by ouabain. We conclude 1) the process of adaptation appears to involve an increase in the number of amiloride- and phloretin-inhibitable urea transport sites in the skin, with a possible increase in the affinity of the sites for phloretin; 2) the adapted skin resembles the Bufo marinus urinary bladder with respect to amiloride and phloretin-inhibitable sites; 3) we confirm earlier observations that Ji is independent of sodium transport.

Amiloride↗
PubMed1988

Effect of chronic renal failure on respiratory muscle strength.

In 10 patients with chronic renal failure (CRF), undergoing hemodialysis, we studied respiratory muscle strength and endurance. The data obtained was compared with those acquired from 10 age-, sex-, weight- and height-matched normal volunteers. Maximal static inspiratory pressures (PImax) measured at residual volume and maximal static expiratory pressure (PEmax) measured at total lung capacity were significantly lower in the CRF group, 58.2 +/- (SD)24.9 and 50.8 +/- (SD)24.2% of predicted, respectively (p less than 0.005, p less than 0.01). There was a significant correlation between PImax and PEmax (r = 0.827, p less than 0.001), indicating similar involvement of both inspiratory and expiratory muscle groups. Maximal voluntary ventilation (MVV), although 84.4% of the predicted value in the CRF group, was significantly lower than in the control group, where it was 114% of predicted (p less than 0.001). MVV also correlated significantly with PImax and PEmax (r = 0.764, p less than 0.001 and r = 0.807, p less than 0.001, respectively). All but one CRF patient had elevated erum inorganic phosphorus levels, and a significant correlation was found between the serum inorganic phosphorus levels and PImax and PEmax (r = 0.718, p less than 0.001). These data indicate that there is an impairment of respiratory muscle strength and endurance in patients with CRF which may predispose the patient to respiratory muscle fatigue.

Adult↗
PubMed1988

The involvement of calcium ions in the effect of 1,25-dihydroxyvitamin D3 on HL-60 cells.

1,25-Dihydroxyvitamin D3 (1,25[OH]2D3) was found to suppress growth of human leukemic cells (HL-60), and to induce the differentiation of these cells to monocyte-like cells. The purpose of the present study was to examine the role of calcium ions in the effects of 1,25(OH)2D3 on HL-60 cells. Incubation of the HL-60 cells with 1,25(OH)2D3 (10(-7) M) for 4 days caused a significant inhibition of 50% of cell growth. The number of differentiated cells increased simultaneously from 24 x 10(3) +/- 2 x 10(3) in the controls to 658 x 10(3) +/- 32 x 10(3) in the 1,25(OH)2D3 (10(-7) M)-treated cells. The role of calcium ions in the effects of 1,25(OH)2D3 on HL-60 cells was first studied by changing the available calcium in the medium and by measuring the effect of 1,25(OH)2D3 on intracellular Ca2+ levels. Limitation of the available Ca2+ by means of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or verapamil enhanced the inhibitory effect on proliferation and decreased the number of differentiated cells obtained by 1,25(OH)2D3 alone. These effects could be abolished by restoring the Ca2+ levels. The role of the intracellular free Ca2+ ions in the effect of 1,25(OH)2D3 was further illustrated by measuring the intracellular Ca2+ levels. The intracellular free Ca2+ concentration in 1,25(OH)2D3 (10(-7) M)-treated HL-60 cells rose significantly from 117.0 +/- 6.3 nM in the untreated HL-60 cells to 145.0 +/- 7.5 nM in the treated cells (p less than 0.02). Addition of verapamil moderated the increase in intracellular free Ca2+ (125.0 +/- 5.2 nM) obtained by 1,25(OH)2D3 alone. Thus the elevation of intracellular free Ca2+ caused by 1,25(OH)2D3 treatment may be involved in the effect of the hormone on the HL-60 cells.

Calcitriol↗
PubMed1988

Vitamin D-deficiency in the elderly: treatment with ergocalciferol and hydroxylated analogues of vitamin D3.

The purpose of the present work was to study the effect of vitamin D and its metabolites in correcting hypovitaminosis D in the elderly. Thirty elderly people (mean age 78.4 years) participated in this study. They all had low serum levels of 25-hydroxyvitamin D (25-OH-D), of 24,25-dihydroxyvitamin D [24,25(OH)2D] and of 1,25-dihydroxyvitamin D [1,25(OH)2D]. These low levels did not increase in nine subjects after oral administration of vitamin D2 (3,000 IU/day for 12 weeks). However, administration of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) to 12 other subjects (0.5 micrograms/day for 8 weeks) led to a significant increase in the serum levels of 1,25(OH)2D. The other vitamin D metabolite levels remained unchanged. A significant increase in the levels of all three main vitamin D metabolites was obtained following administration of 25-hydroxyvitamin D3 (25-OH-D3) to a third group of nine subjects (25 micrograms/day for 1 week). These results suggest that vitamin D nutrition in elderly people insufficently exposed to the sun could be maintained by regular administration of 25-OH-D, whereas the administration of native vitamin D (ergocalciferol) in the doses used was inadequate for vitamin D nutrition.

24,25-Dihydroxyvitamin D 3↗