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Biomedical subjects

L Martis

Publications and source records attributed to L Martis.

At least 55 records · Page 3Linked to original sources

Interactions of cells from peritoneal dialysate with mesothelial cells and fibroblasts in culture.

Peritoneal mesothelial cells and fibroblasts were co-cultured in vitro with peritoneal white blood cells (PWBC) obtained from CAPD patients, after an overnight exchange with 0.5% Dianeal or 2.5% Dianeal. Unstimulated PWBC inhibited proliferation of mesothelial cells and fibroblasts. Upon stimulation with lipoposaccharides (LPS), PWBC from the 0.5% dextrose exchange, enhanced the growth of mesothelial cells and fibroblasts, whereas when stimulated with LPS, PBWC from the 2.5% dextrose exchange increased only proliferation of fibroblasts.

Cell Division↗

Amino acid solutions for CAPD: rationale and clinical experience.

Protein-calorie malnutrition is present in a sizable proportion of dialysis patients. In CAPD patients, constant glucose absorption from dialysate may displace other calorie sources, such as protein, and may suppress the appetite, thus contributing to malnutrition. Use of amino acids in place of glucose as the osmotic agent has been studied extensively. Ultrafiltration and small-molecule clearance similar to that with glucose can be achieved with amino acid solutions, but nitrogenous waste produced by amino acids limits the extent to which they can replace hypertonic glucose. Side effects of CAPD with amino acids appear to be minor and easily manageable. Most studies have found at least some nutritional benefit of amino acid solutions in addition to that of lowering the glucose load. Short-term studies of amino acid solutions for dialysis indicate that they may improve protein nutrition in malnourished CAPD patients.

Amino Acids↗

Calcium mass transfer in peritoneal dialysis patients using 2.5 mEq/l calcium dialysate.

Standard peritoneal dialysate has a relatively high calcium concentration of 3.5 mEq/l. Peritoneal dialysis patients thus gain calcium from the dialysate which contributes to the risk of hypercalcemia. Dialysate with 2.5 mEq/l calcium is now available. Theoretically, using dialysate with this calcium content, calcium transfer should be negative (from the patient into the dialysate) when the patient is hypercalcemic, and positive when the patient is normocalcemic or hypercalcemic. Thus, 2.5 mEq/l calcium dialysate may allow larger doses of calcium carbonate to be prescribed. We compared calcium mass transfer (CMT) in 17 stable peritoneal dialysis patients using 3.5 and 2.5 mEq/l calcium dialysate. A solution of 2.05 l, 1.5 g/dl dextrose was dwelled for 4 hours. Calcium was measured in the drained dialysate and serum (total and ionized). Mean CMT was 0.7 +/- 0.5 mEq/exchange using 3.5 mEq/l calcium dialysate and -0.9 +/- 0.9 mEq/exchange using 2.5 mEq/l calcium dialysate (p less than 0.0001). At the time of the CMT studies, the mean serum ionized calcium levels were identical for the two groups (2.6 mEq/l). CMT correlated inversely with serum total calcium, serum ionized calcium, and drained dialysate volume. During hypercalcemia calcium transfer was from the dialysate to the patient when 3.5 mEq/l calcium dialysate was used, but from the patient to the dialysate when 2.5 mEq/l calcium dialysate was used. We conclude that 2.5 mEq/l calcium dialysate is effective in removing calcium and will be helpful in preventing hypercalcemia when large doses of oral calcium compounds are prescribed as a phosphate binder.

Adult↗

Short-term effects of low-calcium dialysis solutions on calcium mass transfer, ionized calcium, and parathyroid hormone in CAPD patients.

Patients on CAPD using calcium carbonate (CaCO3) as phosphate binder might benefit from low-calcium (Ca) concentration dialysis solutions; however, no data are available for the effects of this regimen on Ca metabolism. We studied 10 patients on stable CAPD regimens with standard dialysis solutions (Ca 7 mg/dL) who were taking CaCO3 to control hyperphosphatemia (mean daily doses 4.5 +/- 2.4 g). Hypercalcemic episodes had been recorded in 6 patients. Standard dialysis solutions were replaced with solutions containing 5 mg/dL of Ca. Calcium and phosphate peritoneal mass transfer (MT), serum concentrations of total Ca, ionized Ca (Ca++), phosphate, intact PTH, and mid-molecular PTH, were evaluated before and 48 hours after change of dialysate. The switch to low-Ca solutions was accompanied by significant changes in calcium mass transfer (Ca MT) (+9.84 +/- 48.22 versus -96.74 +/- 48.32 mg/day, p less than .001). Ca MT was significantly (p less than .05) correlated with the serum/dialysate Ca gradient. There was no difference in phosphate MT. Serum Ca++ significantly (p less than .05) decreased from 5.20 +/- 0.32 to 4.88 +/- 0.36 mg/dL, and intact PTH significantly increased (81.5 +/- 139 versus 112.4 +/- 168 pg/mL, p less than .05). It is concluded that dialysis solutions with Ca 5 mg/dL result in a negative peritoneal Ca MT and can be useful to prevent and treat hypercalcemia in CAPD patients taking CaCO3 as phosphate binder. A careful monitoring of ionized calcium, PTH, and phosphate is suggested when an extensive and long-term use of this solution is considered.

Adult↗

In vitro dissolution and in vivo bioavailability of commercial levothyroxine sodium tablets in the hypothyroid dog model.

The objective of this study was to determine whether a correlation exists between the rate of in vitro dissolution and bioavailability of levothyroxine sodium (T4) tablets. Dissolution versus time profiles for Synthroid, the Flint brand of levothyroxine sodium, and two competitors' tablets (brands A and B) were generated using an official dissolution apparatus (USP), and 0.05 M phosphate buffer (pH 7.4) as the medium. These tablets were also utilized in single-dose crossover bioavailability studies in the hypothyroid dog model (n = 6). The average areas under the serum T4 concentration versus time curve from 0 to 8 h (AUC) for Synthroid, brand A, and brand B were 8.22, 6.32, and 8.70 ng-h/mL per dose (micrograms per kg body weight), respectively. Respective peak serum concentrations (Cmax) for each tablet formulation were 1.26, 1.07, and 1.36 ng/mL per dose. The corresponding dissolution rates, expressed as t50%, were 20.5, 3.06, and 14.1 min, respectively. Data analysis indicated no correlation between dissolution kinetic parameters and the bioavailability parameters AUC and Cmax. However, a linear relationship was observed between dissolution kinetics and both the time to reach maximal serum concentration (tmax) and the observed absorption rate constant (ka).

Animals↗

Calcium carbonate as a phosphate binder: is there a need to adjust peritoneal dialysate calcium concentrations for patients using CaCO3?

The widespread use of calcium carbonate as a phosphate binder is limited by its tendency to develop hypercalcemia in some patients using effective dosages needed to control hyperphosphatemia. Most common continuous ambulatory peritoneal dialysis (CAPD) regimens using dialysis solutions containing 3.5 mEq/L of calcium result in net absorption of calcium from the dialysis solution and, hence limit the amount of oral calcium that can be administered. Peritoneal dialysis solutions with reduced calcium levels are needed for effective use of CaCO3 to control hyperphosphatemia in some dialysis patients.

Calcium↗

Tissue distribution and excretion of tri-(2-ethylhexyl)trimellitate in rats.

The disposition kinetics of tri-(2-ethylhexyl)trimellitate (TEHTM), a new plasticizer for polyvinyl chloride (PVC) plastic, was studied in rats following intravenous administration of [14C-carbonyl]tri-(2-ethylhexyl)trimellitate using an oil in water emulsion as the vehicle. The distribution half-life, elimination half-life, and clearance values estimated from the plasma concentration of radioactivity data obtained following iv administration of 10.5 mg/kg of TEHTM (59.9 muCi/kg), were 46.2 min, 5.34 d, and 40.5 ml/kg X h, respectively. Following iv dosage of 15.6 mg/kg of TEHTM (28.0 muCi/kg), significant accumulation of radioactivity was found in the liver, lungs, and spleen, with liver accounting for 72% of the administered dosage at 24 h. Excretion of TEHTM and its biotransformation products was slow, with 21.3% of the administered radioactivity found in the feces and 2.8% in the urine during the 14-d collection period. Biliary excretion seems to be the major route of elimination of TEHTM. The pharmacokinetic data gathered in the present investigation are compared to di-(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer for PVC.

Animals↗

Comparison of the elimination of 10 and 20% TRAVAMULSION lipid emulsion from the blood of beagle dogs.

Metabolic utilization of fat emulsions containing 20% lipid and 10% lipid were compared using beagles. The key parameter measured was elimination of the lipid from the bloodstream, which serves as an indication of the emulsion's availability for metabolism. Nonlinear kinetic analysis was used in this determination. Blood concentrations of free fatty acids, phospholipid, and cholesterol were also measured as additional ways of determining emulsion metabolism. The 10 and 20% emulsions appeared to be equivalent in elimination of the caloric substrate triglyceride from the blood stream. Results also showed an adaptation to emulsion infusion over time at both dosages administered (3 and 6 g/kg of body weight). This was indicated by increased elimination capacity and stabilization of each lipid class measured. However, blood concentrations of phospholipid and cholesterol indicate that the 20% emulsion provides a lesser lipid load for the amount of calories administered when compared to an emulsion containing 10% lipid.

Animals↗

Assessment of the toxicity of cyclohexanone administered intravenously to Wistar and Gunn rats.

The toxicity of cyclohexanone, used as a solvent cement in polyvinyl chloride medical devices, was assessed in Wistar and Gunn rats. The Gunn rat was used because it has a negligible activity of UDP glucuronosyltransferase toward bilirubin and certain other aglycones. Cyclohexanone was administered iv for 28 consecutive days to Wistar and Gunn rats in two doses (50 and 100 mg/kg), using solutions containing 0.25 and 0.50 g per 100 ml, respectively, at a constant volume of 20 mg/kg. Saline (0.9% NaCl) was used as the control. Daily observations for signs of toxicity showed no adverse effects in Wistar or Gunn rats injected with either dose. Daily weight changes of control and test animals were similar. Ophthalmologic examinations revealed no treatment-related structural lesions. No adverse effects were noted when the data from the hemogram or clinical chemistry parameters were evaluated. Gross pathological and histopathologic assessment showed no alterations due to cyclohexanone treatment. Urinary excretions of total and glucuronide conjugates of cyclohexanol were similar for Wistar and Gunn rats; less than 1% was excreted as free cyclohexanone and cyclohexanol. It is concluded that the Gunn rat is capable of forming glucuronides of cyclohexanol and that cyclohexanone at these doses has a negligible toxic potential.

Animals↗

Comment on the carcinogenic potential of di(2-ethylhexyl) phthalate.

Analysis of the carcinogen bioassay of di(2-ethylhexyl) phthalate (DEHP) has shown that the designated maximum tolerated dose was exceeded in the low- and high-dose groups of male rats, in the high-dose group of female rats, and in the low- and high-dose groups of female mice. Significant differences in tumor incidence among small populations of laboratory animals within the testing facility further confounded interpretation of the bioassay. Critical data on food consumption, nutritional status, clinical signs, clinical pathology, and intestinal microorganisms are lacking. This review concludes that because of major deficiencies in the available data, the studies cannot be interpreted as showing a carcinogenic effect due to DEHP alone. Epigenetic mechanisms to explain the biologic effects are examined.

Animals↗

Biotransformation of sevoflurane in dogs and rats.

Sevoflurane, 3% and 4% in oxygen was administered to four dogs for 3 hours. Sevoflurane was metabolized to inorganic fluoride and hexafluoroisopropanol. Serum fluoride concentrations reached peak values during 2 to 3 hours into anesthesia and averaged 18.5 micrometer/L (n = 2) and 20.0 +/- 4.8 (mean +/- SD) micrometer/L (n = 4) following 3% and 4% sevoflurane exposure, respectively. They returned to normal values within 24 hours after anesthesia. Hexafluoroisopropanol was excreted in the urine as glucuronide conjugate. Its elimination was essentially complete within 48 hours after the end of exposure to sevoflurane. During inhalation of 4% sevoflurane, blood concentration of the anesthetic reached an average apparent steady state of 0.765 +/- 0.10 micrometer/L (n = 4). No anesthetic was detected in blood 24 hours after this exposure. Rats were anesthetized with 2% sevoflurane for 2 and 4 hours. Immediately after anesthesia, observed mean (n = 6) serum fluoride concentrations were 2.9 +/- 0.5 micrometer/L and 2.5 +/- 0.6 micrometer/L, respectively. Hepatic microsomal enzyme induction produced by pretreatment with either phenobarbital or polychlorinated biphenyls (PCBs) resulted in an approximately 5-fold increase in serum fluoride concentrations following anesthesia with sevoflurane when compared to noninduced rats exposed to sevoflurane. A comparison of serum fluoride concentrations between the rat and dog indicates that the amount of sevoflurane metabolized is lower in the rat than in the dog, and the fluoride concentrations observed in both animal species during sevoflurane anesthesia are not expected to produce nephrotoxicity.

Anesthetics↗

Pharmacokinetics of carbamazepine in monkeys following intravenous and oral administration.

The pharmacokinetics of carbamazepine were evaluated in four male rhesus monkeys. A 20-mg/kg dose was administered by intravenous (5-min) infusion and orally (nasal-gastric intubation) in a propylene glycol-ethanol-water solvent. Plasma and urine determinations were performed by GLC. All semilogarithmic intravenous curves exhibited an irregular decay behavior in the first 3-hr period, followed by a linear disappearance phase (T 1/2 equals 1.0-2.4 hr). Urinary excretion measurements confirmed the short elimination half-life and showed that less than 1% of the dose was excreted unchanged. Oral studies also yielded a short elimination half-life (1.0-1.60 hr), which was confirmed by urinary excretion measurements. The oral curves were analyzed pharmacokinetically. The fraction of the dose reaching the systemic circulation ranged between 58 and 87%. Measurable (but insignificant) amounts of drug were found in the feces after intravenous and oral administrations.

Administration, Oral↗