Micelle formation and testosterone solubilization by sodium glycocholate.
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Biomedical subjects
Publications and source records attributed to L Martis.
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The disposition kinetics of ethylene oxide, ethylene glycol, and 2-chloroethanol were studied following their intravenous administration to beagle dogs. Plasma concentration of ethylene oxide was found to decline exponentially with a mean rate constant of 0.024 +/- 0.008 min-1 (mean +/- SD) and total body clearance of 20.0 +/- 5.2 ml/kg X min. Ethylene oxide was found to be metabolized mainly to ethylene glycol, which had a mean plasma half-life of 221.0 +/- 77.7 min and a total body clearance of 2.13 +/- 0.58 ml/kg X min. Between 7 and 24% of intravenously administered ethylene oxide was eliminated in the urine as ethylene glycol within 24 h. The elimination half-life and clearance values for 2-chlorethanol were 40.8 +/- 5.7 min and 10.3 +/- 1.7 ml/kg X min, respectively. The pharmacokinetic data gathered in the present investigation suggest that ethylene glycol rather than 2-chloroethanol is the major metabolite of ethylene oxide in the dog.
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A model based on a Michaelis-Menten nonlinear kinetic approach was used to analyze the kinetics of elimination of an intravenously infused lipid emulsion in the dog. The emulsion was administered at doses of 0.3, 3, or 6 g of lipid/kg of body weight. The model was applicable to all data regardless of the kinetic order of the elimination process operating. This can be either zero (linear), mixed, or first order (exponential). Furthermore, it was also found that parameters derived with the model can be used to predict the kinetics of elimination at different dosages. However, it was also shown that elimination parameters for a single bolus dose of lipid emulsion cannot be used to predict the manner in which a continuously infused dose will be eliminated.
A study was performed comparing the elimination kinetics of two soybean oil/egg phosphatide lipid emulsions (10% Travamulsion vs 10% Intralipid) from the vascular compartment of the dog. Elimination kinetics were evaluated after bolus injection and after continuous infusion studies. Evaluation of triglyceride and free fatty acid data indicates the emulsions are similar metabolic substrates. Phospholipid and cholesterol data indicate a possible difference in remnant particle removal. At the higher lipid dosages, remnant particles from Travamulsion injection were removed at a faster rate than those from Intralipid.
OBJECTIVE: To assess the in vitro synthesis rate of hyaluronan (HA) by human peritoneal mesothelial cells and peritoneal fibroblasts in the presence of effluent dialysate from continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: We used primary cultures of human peritoneal mesothelial cells and peritoneal fibroblasts from nonuremic patients to study the effect of interleukin-1beta (II-1beta) and pooled effluent dialysate, from noninfected and infected CAPD patients, on the synthesis of HA by the studied cells. We also tested the effect of the exogenous HA on the synthesis rate of that glycosaminoglycan. We studied the correlation between HA concentration in effluent dialysate and the stimulatory effect of that solution on in vitro synthesis of HA by mesothelium. RESULTS: Peritoneal fibroblasts produce more HA than mesothelial cells. Noninfected effluent dialysates or dialysates from CAPD patients with peritonitis stimulate synthesis of HA by mesothelial cells and fibroblasts. Interleukin-1beta has a stimulating effect, which was synergistic with effluent dialysates, on the synthesis of HA by mesothelium and peritoneal fibroblasts. A weak correlation was demonstrated between the level of HA in effluent dialysate and the stimulatory effect of that dialysate on in vitro synthesis of HA by mesothelial cells. CONCLUSIONS: Peritoneal fibroblasts are a more potent source of HA than are mesothelial cells, but probably the latter are the main source of HA in drained dialysate. Although effluent dialysates contain factors that stimulate the production of HA by mesothelium, there is weak correlation between that stimulatory effect and the actual HA concentration in the dialysate, which, in some patients, might suggest low "responsiveness" of the membrane.
BACKGROUND: Hyaluronan (HA) is a major component of interstitial tissue that participates in fluid homeostasis, response to inflammation, and wound healing. Previous studies have shown that intraperitoneal administration of HA can affect peritoneal fluid transport during short peritoneal dialysis exchanges in anesthetized rats. We sought to investigate the effect of high molecular weight HA on peritoneal permeability in conscious rats during dialysis exchanges up to 8 hours in duration. In addition, we sought to investigate the absorption of HA from the peritoneal cavity, its accumulation in peritoneal tissues, and its metabolism in normal and uremic rats. METHODS: Experiments were performed on male Wistar rats infused with 30 mL peritoneal dialysis solution (Dianeal, Baxter Healthcare; Castelbar, Ireland) containing 10 mg/dL HA or with Dianeal alone (control). Peritoneal fluid removal (net ultrafiltration), permeability to glucose, creatinine, and total proteins, and tissue and blood levels of HA were determined in separate groups of rats at 1,2, 4, 6, and 8 hours after intraperitoneal infusion. Hyaluronan appearance and disappearance from plasma were also studied for 24 hours in separate groups of normal and uremic rats. RESULTS: Net ultrafiltration was significantly greater (27%) in rats infused with HA at 4, 6, and 8 hours (p < 0.01) compared to controls. Transperitoneal equilibration of protein was reduced by 27% (p < 0.001) at 4 hours and by 30% (p < 0.01) at 8 hours. During the 8-hour exchange, peritoneal clearance of creatinine increased by 27% (p < 0.01), whereas the clearance of total protein decreased by 27% (p < 0.005). After 8 hours, 25.7% +/- 3.1% of the administered HA was absorbed from the peritoneal cavity, peritoneal tissue HA concentration was increased by 117% (p < 0.001), and plasma HA levels increased by 435% (p < 0.001). Plasma HA levels returned to normal within 24 hours after intraperitoneal administration in both healthy and uremic rats. CONCLUSIONS: Hyaluronan added to dialysis fluid is absorbed from the peritoneal cavity and accumulates in peritoneal tissues. Hyaluronan supplementation produces changes in peritoneal permeability, leading to higher net ultrafiltration and peritoneal creatinine clearance, whereas total protein clearance decreases. The HA that is absorbed from the peritoneal cavity appears to be rapidly metabolized in both healthy and uremic rats.
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OBJECTIVE: To assess effects of the inflammatory cytokines (IL-1-beta, TNF-alpha, TGF-beta 1) and dialysate effluent on synthesis of hyaluronic acid by human peritoneal mesothelial cells (HMC) in in vitro culture. METHODS: Dialysate effluent was collected after the overnight dwell of Dianeal 1.5% from patients during CAPD training. HMC were obtained from omentum from nonuremic donors or were harvested from the dialysate effluent from CAPD patients. Synthesis of hyaluronic acid was studied on monolayers of HMC, which were deprived of serum 48 hours prior to experiment. Effects of cytokines were tested in a medium with low serum concentration (0.1%) or in medium mixed (1:1 v/v) with the autologous dialysate. Hyaluronic acid level in medium was measured with radioimmunoassay. RESULTS: Cytokines enhanced synthesis of hyaluronic acid by HMC, and the strongest effect was induced by IL-1. Effluent dialysate stimulates synthesis of hyaluronic acid stronger than 10% FCS. Effluent dialysate and IL-1 synergistically enhance synthesis of hyaluronic acid by HMC. CONCLUSION: Effluent dialysate from CAPD patients stimulates production of hyaluronic acid by HMC and acts synergistically with cytokines.
OBJECTIVE: Some patients develop a mild acidemia during treatment with amino acid-based peritoneal dialysis solutions due to hydrogen ion produced by metabolism of lysine, arginine, and methionine. In this study we modified the formulation of such a solution by reducing these amino acids and adding anionic amino acids so as to provide minimal net acid production. DESIGN: A modified formula (MF) was compared to a conventional formula (CF) of the solution in a randomized cross-over study in 12 stable continuous ambulatory peritoneal dialysis patients. Patients were given each solution for 14 days without a wash-out period. Each patient replaced one or two dextrose dialysis exchanges with amino acid solution, depending upon oral protein intake and body weight. Total intake (oral protein plus amino acids absorbed) was equivalent to 1.1-1.3 g protein/kg body weight/day. Plasma bicarbonate and urea were assessed at the beginning and end of each 14-day period. RESULTS: In the group as a whole, without regard to the order in which the solutions were given, patients had a decrease in serum bicarbonate with CF and an increase in bicarbonate when they received MF. Similar trends were observed regardless of the order in which the solutions were administered. Serum urea did not differ between the two solutions. CONCLUSION: The results suggest that patients are less prone to develop acidemia when receiving MF as opposed to CF. Further studies will be necessary to determine the long-term effects and the relative nutritional benefits of the two solutions.
OBJECTIVE: To assess the effect of insulin on the Na+/K(+)-ATPase expression and activity in human peritoneal mesothelial cells (HPMC). METHODS: HPMC were isolated from the omental tissue of non-uremic patients, grown to confluence and rendered quiescent by serum deprivation for 24 hours. The activity of Na+/K(+)-ATPase was determined by measuring the ouabain-sensitive 86Rb uptake. To assess whether the effect of insulin was related to changes in [Na+]i the sodium influx was measured with 22Na and the activity of Na+/K(+)-ATPase was assessed in the presence of amiloride. Expression of Na+/K(+)-ATPase alpha 1,alpha 2 and beta 1-subunit mRNAs was determined by RT/PCR. RESULTS: Exposure of HPMC to insulin resulted in a time- and dose-dependent increase in the Na+/K(+)-ATPase activity. After 60 minutes the ouabain-sensitive 86Rb uptake (cpm/10(4) cells) was increased from 6650 +/- 796 in control cells to 9763 +/- 1212 in HPMC exposed to 100 mU/mL insulin (1.5-fold increase; n = 4, P < 0.05). In addition, incubation of HPMC with 100 mU/mL insulin resulted in a time-dependent increase in the 22Na influx. Pre-exposure of HPMC to 1mM amiloride reduced the activity of Na+/K(+)-ATPase but did not block the stimulatory effect of insulin. RT/PCR analysis revealed that HPMC constitutively expressed alpha 1- and beta 1-subunit mRNAs while the alpha 2-subunit mRNA was barely detectable. Exposure of HPMC to insulin for up to 24 hours was not associated with any changes in the expression of either alpha 1, alpha 2 or beta 1-subunit. CONCLUSION: Insulin stimulates the Na+/K(+)-ATPase activity in HPMC in a time- and dose-dependent manner. This effect appears to mediated by an increase in [Na+]i and is not related to alterations in Na+/K(+)-ATPase subunit mRNAs expression.