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Biomedical subjects

C Chaimovitz

Publications and source records attributed to C Chaimovitz.

104 records · Page 6Linked to original sources

Exaggerated natriuretic response to volume expansion in patients with primary biliary cirrhosis.

Fluid retention and ascites are rarely seen in patients with primary biliary cirrhosis (PBC). This contrasts with the conspicuous tendency of patients with Laennec's cirrhosis to retain salt and water. In an attempt to clarify this clinical observation, renal handling of sodium was studied during extracellular volume expansion (ECVE) and maximal suppression of antidiuretic hormone in five patients with PBC. These PBC patients were compared with two control populations: five edema-free patients with Laennec's cirrhosis and nine healthy volunteers. The natriuretic and diuretic response to ECVE was significantly greater in the patients with PBC as compared with the two control groups. CH2O for given rates of urine flow were similar in PBC patients as compared with normal subjects. The data suggest that a supranormal rejection of sodium at the proximal tubule in response to ECVE underlies the exaggerated natriuresis of PBC. The augmented elimination of salt during ECVE in patients with PBC may explain the rarity of ascites and edema in this variety of cirrhosis.

Adult↗

Mechanism of acute hypercalcemic hypertension in the conscious rat.

Acute hypercalcemia in the conscious, unanesthetized rat, achieved by a 30-minute infusion of CaCl2 (serum calcium level, 12.8 +/- 0.6 mg/dl) resulted in significant elevation of mean arterial pressure (from 112 +/- 2 mm Hg to 129 +/- 3 mm Hg, p less than 0.001). This pressor response was associated with a significant increase in systemic vascular resistance, from 0.45 +/- 0.02 mm Hg/(ml/min)/kg body weight to 0.50 +/- 0.02 mm Hg/(ml/min)/kg body weight (p less than 0.05), but it caused no alteration in cardiac index. The pressor response to acute hypercalcemia does not appear to be mediated by vasopressor hormones or attenuated by vasodepressor hormones since inhibition of the renin-angiotensin system (nephrectomy), catecholamines (central and peripheral 6-hydroxydopamine), vasopressin (vascular antagonist), prostaglandins (indomethacin), and parathyroid hormone (parathyroidectomy) did not significantly alter the pressor response to infusion of CaCl2 in spite of similar serum calcium levels in all groups of animals. Rather, the pressor response to acute hypercalcemia seems to be mediated by a direct action of calcium ion on smooth muscle and perhaps myocardial cell contractility, since pretreatment with the calcium channel blockers verapamil or nifedipine blocked the pressor response to acute hypercalcemia.

Acute Disease↗

Potential use of tuftsin in treatment of candida peritonitis in a murine model.

A major complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis caused by Candida albicans. Increasing the activity of the peritoneal macrophages, the predominant cell type found in the peritoneal cavity, may be a promising treatment for this infection. Tuftsin was found to increase thioglycollate-elicited mouse peritoneal macrophage activity. 2x10(-7) M tuftsin enhanced two-fold cell association with radiolabelled candida, superoxide aniom production, and killing activity. Thus, a model consisting of mice undergoing peritoneal dialysis was developed in order to study the use of tuftsin as a therapeutic drug against peritoneal candidiasis. Administration of tuftsin (50 micrograms/mouse) before candidiasis induction with a lethal dose of candida (7x10(8) candida per mouse) improved mouse survival up to 70%, compared with 10% in the control group. The potential of tuftsin as a treatment for candidiasis was shown when the infection was induced with a sublethal dose of candida. Daily intraperitoneal injections of tuftsin (50 micrograms) to the sublethally infected mice caused a significant decrease in the number of candida recovered from the peritoneal cavity and from the blood (from 700 +/- 190 to 110 +/- 26 CFU/ml and from 100 +/- 26 CFU/ml to 17 +/- 8 CFU/ml, respectively). In addition, a larger number of peritoneal macrophages with greater phagocytic and killing activity were found in the tuftsin-treated mice. The effect of tuftsin may promote its potential use in the therapy of peritonitis in patients undergoing chronic peritoneal dialysis.

Animals↗

Losses of 25-hydroxyvitamin D in peritoneal fluid: possible mechanism for bone disease in uremic patients treated with chronic ambulatory peritoneal dialysis.

Despite a good control of serum phosphate levels, bone disease still occurs in patients treated with chronic ambulatory peritoneal dialysis (CAPD). The purpose of this study was to determine if 25-hydroxyvitamin D (25-OH-D) penetrates through the peritoneal membrane and whether chronic peritoneal dialysis may thereby decrease the serum 25-OH-D levels. In 10 CAPD-treated patients the serum 25-OH-D was 8.8 +/- 1.1 ng/ml, which is significantly lower than in the hemodialysis-treated group (15.5 +/- 2.3 ng/ml) and lower than in healthy controls (30.3 +/- 3.6 ng/ml). The mean total daily loss of 25-OH-D in the peritoneal fluid was 1,491 +/- 260 ng/day. The serum 25-OH-D binding capacity was significantly lower in the CAPD group than in normal controls. The mean daily loss of 25-OH-D binding capacity in the dialysate was 153 +/- 28 nmol/day. We conclude that permeability of the peritoneal membrane to middle-size proteins leads to loss of 25-OH-D binding protein, and this increases loss of 25-OH-D. Low levels of 25-OH-D in plasma may aggravate the symptoms of osteodystrophy of renal failure in patients treated with CAPD.

25-Hydroxyvitamin D 2↗

Effect of bicarbonate-based dialysis solutions on intracellular pH (pHi) and TNFalpha production by peritoneal macrophages.

OBJECTIVE: To compare the effect of Dianeal and two newly-formulated bicarbonate-based peritoneal solutions on intracellular pH (pHi), tumor necrosis factor-alpha (TNFalpha) mRNA level, and TNFalpha secretion by peritoneal macrophages (PMphi). DESIGN AND MEASUREMENTS: Peritoneal macrophages were isolated from dialysates collected after overnight dwells in peritonitis-free continuous ambulatory peritoneal dialysis patients. Dialysis solutions contained 1.5% or 4.25% dextrose. HCO3 concentrations of bicarbonate-(TB) and bicarbonate/lactate-buffered (TBL) solution were 38 mM and 25 mM, respectively. TBL also contained lactate at a concentration of 15 mM. pCO2 levels were 78 mmHg and 51 mmHg, respectively. In all experiments pCO2 was carefully maintained at a stable level. The pHi was measured by spectrofluorometry in BCECF-loaded PMphi exposed to different dialysis solutions or Hank's balanced salt solution. TNFalpha levels were measured by ELISA in the supernatant of lipopolysaccharide- (LPS) stimulated PMphi after their incubation in different solutions for 15 and 30 minutes. TNFalpha mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR) of total RNA extracted from LPS-stimulated PMphi after their incubation in different solutions for 30 minutes. beta-actin mRNA was used as the control. RESULTS: Dianeal caused a profound drop in pHi to below 6.2. Following an initial drop, pHi stabilized after 4 minutes at levels of 6.96 and 6.8 after incubation in TB and TBL, respectively. In comparison to the control solution, a fall of 11% and 21% in TNFalpha secretion was seen after incubation in TB for 15 and 30 minutes, respectively, and 15% and 26% after incubation in TBL. Under identical conditions, Dianeal (Baxter, McGaw Park, IL, U.S.A.) caused 59% and >95% suppression of TNFalpha secretion. Accordingly, TNFalpha mRNA level in PMphi was severely depressed by Dianeal but no detectable inhibition was observed following incubation for 30 minutes in TB and TBL. When dextrose concentration in TB and TBL was increased from 1.5% to 4.25%, TNFalpha secretion by PMphi was not suppressed by more than 49%, even after 30 minutes incubation. Moreover, suppression of TNFalpha mRNA levels could not be detected with TB or TBL even at high dextrose concentrations. CONCLUSIONS: In contrast to Dianeal, both bicarbonate-based solutions caused only a mild drop in pHi of PMphi. We postulate this effect to be responsible for the improved capacity of PMphi to secrete TNFalpha when incubated in bicarbonate-based solutions compared to Dianeal. Reflecting its known cytotoxicity, dextrose in high concentrations diminishes the protective effect of TB and TBL on immune function of PMphi. TBL is as effective as TB in preventing the deleterious effect of Dianeal on PMphi function.

Bicarbonates↗