This study was systematically designed to compare bovine serum albumin (BSA) loaded poly(epsilon-caprolactone) (PCL) microparticles based on a 2(3) factorial experiment. The microparticles were prepared by the holt-melt technique without using an organic solvent for polymer solubilization. The influence of the particle size of protein, protein/polymer ratio, and hydrophilic PEG on the surface morphology, particle size as well as the yield of PCL microparticles, encapsulation efficiency of BSA, and in vitro release properties were investigated. The structure of BSA remained its integrity using this technique. The mean particle size of BSA-loaded microparticles were in the range of 12.7 +/- 0.1-16.9 +/- 0.8 microm, and all of the particles were smooth on the surface. The production yield of microparticles and the encapsulation efficiencies were high, and the values were in the range of 94.8 +/- 1.6%-98.1 +/- 1.0% and 94.9 +/- 9.6%-98.6 + 0.3%, respectively. The burst release of BSA was in the range of 8.2 +/- 0.4%-61.0 +/- 0.8%, which strongly depended on the formulation. None of three variables affected the yield of microparticles prepared from eight formulations (p > 0.05). However, the particle size of BSA significantly affected the size and the burst release as well as the cumulative release of protein in these microparticles (p < 0.05). The initial loading of BSA in terms of BSA/PCL ratio and the amount of PEG blended with PCL significantly affected all of the properties, except the yield (p < 0.05). The smaller the particle size of the BSA, the smaller the size of the resulting microparticles. Since the total surface area of the small particles was larger than that of the large particles, this accounted for the high burst release of protein from the microparticles encapsulating triturated-BSA.

Drug Delivery Systems↗

PubMedDate not supplied

N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) (W-7) causes increases in intracellular free Ca2+ levels in bladder female transitional carcinoma (BFTC) cells.

The effect of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) (W-7), a widely used calmodulin inhibitor, on intracellular free Ca2+ levels ([Ca2+]i) in bladder female transitional cancer (BFTC) cells was examined using fura-2 as a Ca2+ dye. W-7 (10-1000 microM) caused an increase in [Ca2+]i in a concentration-dependent manner with an EC50 of 75 microM. The [Ca2+]i response was composed of an initial rise and a sustained plateau without significant decaying during the measurement of 250 seconds. Extracellular Ca2+ removal dramatically decreased the Ca2+ signals by 50-90%. W-7 (100 microM) failed to induce a [Ca2+]i increase in Ca(2+)-free medium after pretreatment with thapsigargin (1 microM), an endoplasmic reticulum Ca2+ pump inhibitor; conversely, W-7 pretreatment abolished the Ca2+ release induced by thapsigargin. Addition of 3 mM Ca2+ increased [Ca2+]i after preincubation with 100 microM W-7 in Ca(2+)-free medium. W-7-induced Ca2+ release was not altered by inhibiting phospholipase C with 2 microM 1-(6-((17b-3-methoxyestra-1,3,5 (10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) (U73122). Together, this study shows that W-7 caused [Ca2+]i increases in human bladder cancer cells by releasing intracellular Ca2+ from the endoplasmic reticulum and also by causing extracellular Ca2+ influx with the later playing a dominant role. The W-7-induced intracellular Ca2+ release was uncoupled to a prior elevation in intracellular levels of inositol 1,4,5-trisphosphate (IP3).

Adenosine Triphosphate↗

PubMedDate not supplied

Metabolism and disposition of diphacinone in rats and mice.

14C-diphacinone (0.2-1.5 mg/kg) was orally administered to rats and mice. Residue distribution in various tissues and radiocarbon elimination in feces and urine were determined. More than 60% of the administered radiocarbon was eliminated in feces and about 10% in urine in 4 days from mice and in 8 days from rats. The greatest amount of radioactivity in tissues of both rats and mice appeared in liver. Brain, muscle, blood, and fat had the lowest residue levels. Metabolites in feces and liver were chromatographically isolated and identified by mass spectrometry. In addition to unchanged diphacinone, four hydroxylated metabolites were identified in feces and liver. Hydroxylation occurred on either or both the indandione or phenyl rings. The positions of the hydroxy groups on the rings were not established.

Animals↗

PubMedDate not supplied

Predialysis glycemic control is an independent predictor of clinical outcome in type II diabetics on continuous ambulatory peritoneal dialysis.

OBJECTIVE: To evaluate the correlation between predialysis glycemic control and clinical outcomes for type II diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Sixty type II diabetic patients on CAPD were classified into 2 groups according to the status of glycemic control. In group G (good glycemic control), more than 50% of blood glucose determinations were within 3.3-11 mmol/L and the glycosylated hemoglobin (HbA1C) level was within 5-10% at all times. In group P (poor glycemic control), fewer than 50% of blood glucose determinations were within 3.3-11 mmol/L or HbA1C level was above 10% at least once during the follow-up duration. In addition to glycemic control status, predialysis serum albumin, cholesterol levels, residual renal function, peritoneal membrane function, and the modes of glycemic control were also recorded. SETTING: Dialysis Unit, Department of Nephrology of a single university hospital. PATIENTS: From February 1988 to October 1995, 60 type II diabetic patients receiving CAPD for at least 3 months were enrolled. MAIN OUTCOME MEASURES: Morbidities before and during the dialysis period, patient survival, and causes of mortality. RESULTS: The patients with good glycemic control had significantly better survival than patients with poor glycemic control (p < 0.01). There was no significant difference in predialysis morbidity between the two groups. No significant differences were observed in patient survival between the patients with serum albumin greater than 30 g/L and those with less than 30 g/L (p = 0.77), with cholesterol levels greater or less than 5.18 mmol/L (p = 0.73), and with different peritoneal membrane solute transport characteristics evaluated by peritoneal equilibration test (p = 0.12). Furthermore, there was no significant difference in survival whether the patients controlled blood sugar by diet or with insulin (p = 0.33). Cardiovascular disease and infection were the major causes of death in both groups. Although good glycemic control predicts better survival, it does not change the pattern of mortality in diabetics maintained on CAPD. CONCLUSIONS: Glycemic control before starting dialysis is a predictor of survival for type II diabetics on CAPD. Patients with poor glycemic control predialysis are associated with increased morbidity and shortened survival.

Aged↗