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BACKGROUND & AIMS - The mechanism by which gastric mucosa becomes more resistant to damage by repeated aspirin administration is not known. Transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) prevent drug-induced gastric injury. The aim of this study was to determine whether gastroduodenal tissue levels of TGF-alpha and EGF protein were altered during adaptation to aspirin-induced injury in monkeys and rats in vivo.
METHODS - Animals were given aspirin daily for up to 28 days. Gross mucosal injury was assessed by computerized image analysis in rats and by endoscopy in monkeys. Mucosal concentrations of TGF-alpha and EGF were quantitated by radioimmunoassays from endoscopic biopsy samples in monkeys and from scraped mucosa in rats.
RESULTS - Long-term administration of aspirin caused a significant increase in gastric and duodenal tissue levels of TGF-alpha in monkeys and rats; the increased levels of TGF-alpha significantly correlated with the decrease in aspirin-induced injury. No change in the gastroduodenal tissue levels of EGF was observed. Adaptation was not associated with any significant change in basal gastric acid secretion in monkeys and occurred despite a significant decrease in gastric mucin in rats.
CONCLUSIONS - Adaptation of the gastric mucosa to the damaging effect of aspirin is associated with a significant and specific increase in TGF-alpha protein in the gastroduodenum.
Twenty-five lactose-maldigesting and lactose-intolerant African Americans, ranging in age from 13 to 39 y, were given gradually increasing amounts of lactose in milk over a period of time until the maximum lactose dose tolerated was determined. Seventeen (77%) of the 22 subjects who completed the study tolerated > or = 12 g lactose and 5 (23%) tolerated < 12 g. Breath-hydrogen tests done on each subject with the maximum dose of lactose tolerated showed that only four (18%) had a breath-hydrogen concentration < 5 ppm above fasting concentration. This study suggests that the majority of African-American young adults who claim intolerance to moderate amounts of milk can ultimately adapt and tolerate > or = 12 g lactose in milk (the equivalent of 8 oz of full-lactose milk) with minimal or no discomfort if milk is ingested in gradually increasing amounts. The mechanism of adaptation is assumed to be an increased tolerance to colonic lactose-fermentation products.
The rate of gluconeogenesis from lactate increased in perfused livers after exposure of rats to cold for 5 days, and it returned to the control rate after 20 days [M. Shiota, T. Tanaka, and T. Sugano. Am. J. Physiol. 249 (Endocrinol. Metab. 12): E281-E286, 1985.]. The relationship between the increased gluconeogenic activity and its zonal distribution in liver lobules was studied in cold-exposed rats that had been starved for 24 h by examination of preparations enriched for periportal hepatocytes (PP-H) and for perivenous hepatocytes (PV-H), which had been isolated by the digitonin-collagenase perfusion technique. In the control group, the rate of gluconeogenesis from lactate or alanine was three times higher in PP-H than in PV-H. The rate of gluconeogenesis from these substrates in PP-H was not changed by exposure of rats to cold. The rates of PV-H increased to the level in PP-H after 5 days of exposure of rats to cold and then returned to the control rates after 20 days. The rate of gluconeogenesis from fructose was not altered in either preparation of cells by cold treatment of rats. The change in gluconeogenic capacity in PV-H caused by exposure of rats to cold was unrelated to changes in the activity of the malate-aspartate shuttle and of pyruvate kinase. The increased capacity in mitochondrial respiration was observed in both preparations of cells by cold treatment of rats for 5 days. The activity of phosphoenolpyruvate carboxykinase was higher in PP-H than in PV-H in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Nutrient effects on cholesterol fractional synthesis rates (FSR) in infancy by stable isotope determination have not been studied. We hypothesized that FSR is significantly reduced with high dietary cholesterol and phytoestrogen intake and increased with low dietary cholesterol and phytoestrogen intake. We prospectively studied 33 term male infants exclusively fed human milk (high cholesterol, low phytoestrogen, n = 12), cow milk-based formula (low cholesterol, low phytoestrogen, n = 8), soy milk-based formula (zero cholesterol, high phytoestrogen, n = 7), or soy milk-based formula modified to contain cholesterol (low cholesterol, high phytoestrogen, n = 6) during the first 4 mo of life. Cholesterol FSR was determined from rate of incorporation of deuterium into erythrocyte membrane cholesterol, and urinary isoflavone excretion (an index of dietary phytoestrogen exposure) was measured by gas chromatography-mass spectrometry. Significant differences in cholesterol FSR were found. FSR (%/d) was lowest in human milk (2.62 +/- 0.38), highest in soy milk-based formula (9.40 +/- 0.51), and intermediate in cow milk-based and modified soy milk-based formula (6.90 +/- 0.48 and 8.03 +/- 0.28, respectively), p < 0.0001. Cholesterol FSR was significantly lower in modified soy milk-based compared with soy milk-based formula, p < 0.05. We also show for the first time that dietary phytoestrogens are absorbed and excreted by the infant fed soy protein-based formula. Urinary isoflavone excretion was inversely related to cholesterol FSR, but it was not significantly related to serum cholesterol concentration. We conclude that the type of infant nutrition and dietary cholesterol are major factors influencing cholesterol fractional synthesis rates in infancy.
Chinese hamster ovary (CHO) cells were exposed to a 43 degrees C, 15-min heat shock to study the relationship between protein synthesis and the development of thermotolerance. The 43 degrees C heat shock triggered the synthesis of three protein families having molecular weights of 110,000, 90,000, and 65,000 (HSP). These proteins were synthesized at 37 and 46 degrees C. This heat shock also induced the development of thermotolerance, which was measured by incubating the cells at 46 degrees C 4 h after the 43 degrees C heat treatment. CHO cells were also exposed to 20 micrograms/ml of cycloheximide for 30 min at 37 degrees C, 15 min at 43 degrees C, and 4 h at 37 degrees C. This treatment inhibited the enhanced synthesis of the Mr 110,000, 90,000, and 65,000 proteins. The cycloheximide was then washed out and the cells were incubated at 46 degrees C. HSP synthesis did not recover during the 46 degrees C incubation. This cycloheximide treatment also partially inhibited the development of thermotolerance. These results suggest that for CHO cells to express thermotolerance when exposed to the supralethal temperature of 46 degrees C protein synthesis is necessary.
Albino rats were born and raised in one of three cyclic (12L: 12D) lighting conditions: (1) 5 lux for 9 weeks, (2) 800 lux for 9 weeks, or (3) 800 lux for 9 weeks, followed by 5 lux for 3 weeks (800:5). After the treatment, the following were determined: (i) retinal function as measured by the electroretinogram (ERG); (ii) retinal morphology, including rod outer segment (ROS) length and outer nuclear layer area; (iii) rhodopsin levels in whole retina and ROS preparations; (iv) fatty acid profile of ROS membranes and (v) retinal antioxidant levels. After 9 weeks, rats raised in 800 lux sustained an irreversible loss of photoreceptors which could not be reversed by then placing them in 5 lux. However, these rats displayed significant alterations in all other parameters measured after the 3 weeks in dim cyclic light. ERGs showed a 60% increase of b-wave maximum amplitude in 800:5 rats at 12 weeks over the value at the time of their change to a dim environment, while a-wave amplitude in 800:5 rats increased more than 2.5 times. This increase can be explained by a combination of increased ROS length and increased ROS membrane concentration of rhodopsin during the three weeks in 5 lux. Polyunsaturated fatty acids predominated in the ROS of 5 lux rats and 800:5 rats, but not in 800 lux animals. Measurements of retinal glutathione enzyme activity and vitamin E and C levels were relatively low in 800:5 rats. Some rats from the 800:5 group were exposed to 2000 lux for 24 hr. Retinas of these rats sustained 50% loss of photoreceptors from this exposure. Comparisons are made to previous studies concerning the effect of cyclic light environments on the retinas of albino rats.
Masking effects are a common feature of daily rhythmicity in invertebrates; and, particularly with respect to activity/rest cycles in arthropods and mollusks, there are numerous examples of masking in response to external environmental stimuli. Internal masking, in which endogenous processes modulate circadian patterns, has also been documented in a few species. In general, however, because of the absence of appropriate experimental investigations on masking, the functional significance (in an ecological sense) of masking effects is not understood.
We tested the hypothesis that depletion of intracellular glutathione (GSH) during heat shock results in protein thiol oxidation, thereby increasing thermal sensitivity. Depletion of GSH was accomplished using a combination of diethylmaleate and buthionine sulfoximine and protein sulfhydryls were measured using two independent methods. Chinese hamster ovary (CHO) cells were solubilized in polyacrylamide gel electrophoresis (PAGE) sample buffer containing 3-(N-maleimido-propionyl) biocytin, separated by sodium dodecyl sulfate (SDS)-PAGE, electroluted onto nitrocellulose, and visualized via avidin-alkaline phosphatase staining. A second method utilized 5,5'-dithiobis(2-nitrobenzoic acid) to measure protein solubilized in SDS. The results indicate that when CHO cells are heated at 43 degrees C GSH depletion can increase thermal sensitivity but does not cause nonspecific protein thiol oxidation at this temperature or at 37 degrees C.
To assess compensation for the absence of the exercise-induced fall in insulin, dogs underwent 150 min of treadmill exercise with insulin infused intraportally with (IC + Glc; n = 7) or without (IC; n = 6) glucose clamped. Glucose production (Ra), gluconeogenic conversion (Conv), and intrahepatic gluconeogenic efficiency (Eff) were assessed with tracers ([3H]glucose, [14C]alanine) and arteriovenous differences. Glucose fell by 6 +/- 4 and 11 +/- 2 mg/dl at 30 min of exercise and by 8 +/- 2 and 36 +/- 5 mg/dl at 150 min in IC + Glc and IC. Glucagon rose by 16 +/- 8 and 55 +/- 17 pg/ml by 30 min of exercise and by 18 +/- 6 and 93 +/- 22 pg/ml by 150 min in IC + Glc and IC. Norepinephrine was unaffected by the glycemic decrement in IC, whereas epinephrine was greater for the last 60 min of exercise. Ra rose by an average of 0.9 +/- 0.3 and 3.7 +/- 0.2 mg.kg-1.min-1 in IC + Glc and IC. Conv rose by 91 +/- 39 and 325 +/- 75% in IC + Glc and IC at 150 min of exercise, and Eff rose by 87 +/- 57 and 358 +/- 99%. The compensatory Ra exceeded the maximum possible gluconeogenic rate, indicating that glycogenolysis was also stimulated. In summary, in the absence of the exercise-induced fall in insulin 1) glycemia falls approximately fourfold faster; 2) minimal glycemic decrements elicit a large and rapid increase in Ra; 3) this compensation involves a glycogenolytic and gluconeogenic response; 4) the accelerated gluconeogenic rate is due, in large part, to stimulation of Eff; and 5) the compensatory Ra is likely mediated, in part, by glucagon. Hence, although the fall in insulin is essential for normal glucoregulation during exercise, a highly sensitive counterregulatory response prevents severe hypoglycemia. The remarkable sensitivity of the liver to small changes in glycemia implies that the normal coupling of the exercise-induced increase in Ra to glucose utilization may be signaled by small, nearly imperceptible changes in glucose.
The purpose of this investigation was to measure lower leg compliance before, during and after a 10-day period of bedrest at head-down tilt to test the hypothesis that leg compliance and the capacity for venous pooling is increased by the adaptation to stimulated microgravity. Venous occlusion plethysmography with multiple proximal occlusion pressures was used to obtain compliance measurements in six male subjects. Calf circumference decreased significantly during the tilt (corresponding to a decrease in cross sectional area of 7%) and had not returned to baseline seven days after the end of tilt. Compliance post-tilt was significantly greater than pre-tilt, probably mainly due to a reduction in muscle mass. This study supports the need for investigations to define: (a) the degree of protection against orthostatic hypotension that can be achieved by maintaining leg muscle mass and tone, and (b) efficient and specific exercise programs to prevent loss of muscle mass and function-particularly during spaceflight.