[Proteinuria in the nephrotic range].
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Biomedical subjects
Publications and source records attributed to M Tavernini.
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Six healthy volunteers and six patients with asymptomatic duodenal ulcer disease received placebo or 300 mg nizatidine once at night or twice daily (morning and evening) for a week in a random, cross-over fashion. Steady-state serum nizatidine concentrations and gastric pH were measured over a 24-hour period. No significant differences in the pharmacokinetic indices were observed between the healthy volunteers and patients with duodenal ulcer disease. In patients with duodenal ulcers, significantly lower peak serum concentrations, longer half-life (t1/2) and larger volume of distribution (Vd) were observed after the night doses compared with the daytime doses. The diurnal variation in drug kinetics between the nighttime and daytime doses in the twice daily regimen may be caused by a slower absorption rate, paralleled with a higher extent of distribution. Despite lower serum nizatidine concentrations, gastric pH was higher in the evening than in the daytime; it is speculated that this was due to a time-dependent enhanced distribution of the H2-receptor blocker into the site of action.
Diabetes-associated changes in intestinal uptake of nutrients are modified by isocaloric variations in the type of dietary lipids, and are associated with alterations in the phospholipid and fatty acyl content of the intestinal brush border membrane. The present study was designed to test the hypothesis that diet- and diabetes-associated changes in enterocyte microsomal membrane phospholipids are due to variations in the activity of two phospholipid metabolizing enzymes, 1,2-diacylglycerol:CDPcholine cholinephosphotransferase (CPT) and phosphatidylethanolamine methyltransferase (PEMT). Adult female Wistar rats were fed one of four semisynthetic diets--beef tallow low in cholesterol (BT), beef tallow high in cholesterol (BTC), fish oil low in cholesterol (FO) or fish oil high in cholesterol. In half of the animals, diabetes mellitus was produced by injection of streptozotocin. Jejunal and ileal enterocyte microsomes (EMM) were isolated and analyzed for cholesterol and phospholipids, as well as for CPT and PEMT activities. In control animals, feeding FO reduced EMM total phospholipids including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol. Feeding FO resulted in a greater than 95% reduction in the activity of CPT. Diabetes was associated with increased jejunal EMM total phospholipids including sphingomyelin (SM) and PE, without associated changes in CPT or PEMT. Dietary cholesterol supplementation did not affect EMM total cholesterol or phosphlipid composition in control rats fed BT or FO, but was associated with an increase in EMM cholesterol in diabetic rats fed BT or FO. A decrease in total phospholipids due to a decline in SM, PC and PE in diabetic rats fed FO was not associated with changes in the activities of CPT or PEMT in EMM.(ABSTRACT TRUNCATED AT 250 WORDS)
Previous studies have demonstrated that abdominal irradiation alters intestinal uptake of nutrients. The purpose of this study was to determine the effect of an orally administered synthetic prostaglandin E2, enprostil, given on three occasions shortly prior to a single exposure to 600 cGy external abdominal irradiation, on intestinal active and passive transport processes and villus morphology measured 7 days later. Animals were sham-irradiated (CONT) or were exposed to a single dose of 600 cGy external abdominal irradiation (RAD); two and one mornings before the day of irradiation or sham irradiation, and 1 h before irradiation or sham irradiation enprostil was administered. One half of CONT and RAD groups were dosed orally with enprostil, 5 micrograms/kg body weight, and the other half of the CONT and RAD groups were dosed with placebo. Seven days later the in vitro uptake of glucose, galactose, long-chain fatty acids, and cholesterol was determined in the four groups (CONT with and without enprostil, and RAD with and without enprostil). In CONT, enprostil was associated with increased jejunal uptake of glucose and ileal uptake of galactose. In RAD given enprostil, there was increased jejunal uptake of galactose but reduced ileal uptake of glucose and galactose. The expected radiation-associated decline in jejunal galactose uptake was prevented with enprostil. In CONT given enprostil, there was increased jejunal uptake of fatty acid (FA) 14:0 and 16:0 but reduced uptake of FA 18:0, 18:1, and 18:2; enprostil had no effect on lipid uptake in the ileum in CONT.(ABSTRACT TRUNCATED AT 250 WORDS)
Previous studies have demonstrated that external abdominal irradiation alters intestinal nutrient transport and brush border membrane (BBM) phospholipid content. This study was undertaken to assess the possible protective effect of oral dosing of enprostil, a synthetic E2 prostaglandin, on the BBM marker enzyme and lipid composition of non-irradiated control (CONT) animals and of rats exposed seven days perviously to a single dose of 600 cGy external abdominal irradiation (RAD). Half the CONT and RAD animals were orally dosed with enprostil 5 mcg/kg body weight, two and one mornings before the day of irradiation, and one hour before 600 cGy; the remaining half were dosed with placebo according to the same schedule. BBM were isolated and purified from the animals seven days post-irradiation for analysis of marker enzymes and lipid composition. Radiation was associated with a decline in jejunal and ileal BBM activity of sucrase. Enprostil was associated with a decline in the ratio of alkaline phosphatase/sucrase in jejunal BBM from irradiated rats, despite its preventing a radiation-associated decline in BBM sucrase activity. Radiation was associated with changes in ileal BBM phospholipids, and these alterations were not prevented with enprostil. Furthermore, enprostil given to non-radiated control rats altered BBM composition, such as increased jejunal and ileal lysophosphatidylethanolamine, and lowered ileal BBM sphingomyelin and phosphatidylethanolamine. Thus, enprostil failed to protect the intestine from the effects of abdominal irradiation on BBM phospholipids, but did partially prevent the effect of abdominal irradiation on jejunal sucrase activity.
Previous studies have indicated that saturable, Na+-bile acid coupled transport is absent in the ileum throughout most of the suckling period and that the maturation of ileal bile acid uptake which occurs during weaning results primarily through an increase in functional bile acid carriers within the ileal brush border membrane. This study was undertaken in weanling and adult rabbits to establish the effect of maturation on the active ileal and passive jejunal and colonic uptake of 8 bile acids. The in vitro uptake of a range of concentrations of cholic (C), taurocholic (TC), glycocholic (GC), chenodeoxycholic (CDC), taurochenodeoxycholic (TCDC), glycochenodeoxycholic (GCDC), deoxycholic (DC) and taurodeoxycholic (TDC) acid was determined. Active ileal uptake of C, TC, GC, DC and TDC was greater in adult than in weanling animals, whereas uptake of CDC, TCDC and GCDC was similar in both groups. The relative permeability for passive uptake of bile acids into the jejunum and colon was similar in young and adult rabbits. Jejunal mucosal surface area was similar in the two groups, but was greater in the ileum in the adult than in the weanling rabbits due to an increase in villus height, width, and number of villi per unit serosal length. However, the age-associated differences in active bile acid uptake were not explained simply on the basis of these differences in ileal mucosal surface area or the concentration of bile acids in the intestinal lumen. Thus, maturation of the rabbit from weanling to adulthood does not influence the relative passive permeability of the jejunum or colon to bile acids, but does increase active ileal uptake of conjugated and unconjugated cholic acid and deoxycholic acid, but not chenodeoxycholic acid.
This study was undertaken in young and growing rabbits to establish the of feeding a high- (2%) cholesterol diet (HC) on the intestinal in vitro uptake of a homologous series of saturated fatty acids, dodecanol, cholesterol, and bile acids. In the jejunum there was an increase in the uptake of myristic acid and dodecanol in HC as compared with animals fed Purina Chow, whereas in the ileum the uptake of stearic acid, cholesterol, and taurocholic acid was reduced. There was increased jejunal uptake of medium-chain length fatty acids, increased incremental change in free energy (integral of delta Fw----l), increased uptake of palmitic, taurocholic acid, and glycocholic acid and reduced uptake of myristic acid and dodecanol in animals fed the high-cholesterol diet for 10 days followed by Purina Chow for 18 days (HC-chow), as compared with HC. There was also increased ileal uptake of palmitic acid in HC-chow as compared with HC but reduced ileal uptake of stearic acid, cholesterol, taurocholic acid, and glycocholic acid. In the colon, there was increased uptake of stearic acid and dodecanol in HC-C as compared with HC, but reduced uptake of cholesterol, taurocholic acid and glycocholic acid. These changes in lipid uptake were not explained by alterations in the mucosal surface area or in the animals' body weight gain. It is proposed that early feeding experiences with a high-cholesterol diet may alter the normal development of intestinal transport of lipids with increased jejunal permeability to medium-chain fatty acids and increased effective resistance of the intestinal unstirred water layer.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was undertaken in the young and growing rabbit to establish the effect of feeding a high-cholesterol (2%) diet on the intestinal in vitro uptake of glucose, galactose, leucine, and cholic acid. Three groups of animals were fed standard Purina chow for 14, 28, and 42 days. A fourth group was fed chow for 14 days followed by high-cholesterol diet for 10 days followed by chow for 4 days. A fifth group was fed chow for 14 days followed by the high-cholesterol diet for 10 days followed by chow for 18 days. Short-term feeding with a high-cholesterol diet reversed the normal developmental decline in the jejunal uptake of some nutrients (e.g., glucose), enhanced the age-related uptake of other nutrients (e.g., galactose and leucine), but had no effect on others (e.g., jejunal uptake of cholic acid). Two weeks after stopping the high-cholesterol diet, there was enhanced jejunal uptake of all nutrients. Colonic uptake of glucose, galactose, and leucine was unresponsive to the effects of early development or of a high-cholesterol diet, whereas the colonic uptake of cholic acid did increase. This altered uptake is not explained by nonspecific mechanisms such as changes in body weight gain, intestinal mass, or effective resistance of the intestinal unstirred water layer. In summary, early feeding of rabbits for a short interval with a high-cholesterol diet is associated with transport changes that may persist, progress, or appear for the first time when the animals are switched from the high-cholesterol diet back to chow. Thus, early feeding with a high-cholesterol diet alters the normal development of intestinal transport function.
In order to achieve possible greater therapeutic efficacy, ranitidine 300 mg bid (R2) may be given rather than 300 mg qhs (R1), or nizatidine 300 mg bid (N2) may be given rather than 300 mg qhs (N1). A randomized placebo-controlled crossover study was performed in six healthy volunteers (four males, two females) who ranged in age from 23 to 43 years, comparing R1, R2, N1 and N2 versus placebo (P), measuring 24 h intragastric pH by the aspiration technique, gastric juice pepsin and prostaglandin E2 (PGE2) concentrations, as well as serum gastrin concentrations. In all treatment groups, 24-h intragastric pH was higher than with P; the 24 h and daytime (0800-2200 h) pH was higher with N2 than with N1, but not with R2 versus R1. The percentage pH > or = 3 was greater with N2 than with N1 during the daytime. Night-time (2200-0800 h) and 24 h pepsin concentrations were higher in R2 than in R1, were similar in N1 and N2, and were lower in these treatment groups than in P. The gastric juice PGE2 concentration at night-time, but not at daytime, was increased in the four treatment groups compared with P. Despite the higher pH values at night-time in the treatment groups, the night-time concentrations of serum gastrin were unchanged, and yet during the daytime the higher values of pH were associated with increased gastrin concentrations when R2 or N2 were given, but not with R1 and N1. There was a negative correlation between intragastric juice pH and pepsin concentration during the daytime, and a positive correlation between pH and PGE2 concentration during the night-time. The slopes and y-axis intercepts between pH and pepsin or PGE2 concentrations differed between the placebo and the treatment groups, suggesting that these H2-receptor antagonists may have an effect on lowering pepsin and raising PGE2 concentrations in addition to their effects on pH. As the percentage of time over the 24 h period and night-time periods when the pH was greater than 3 was not different between ranitidine and nizatidine, the two regimens will likely have similar clinical efficacy.