Background The clinical manifestations of bronchial remodeling in asthma and the potential impact of this process on lung function remain unclear. We aimed to determine whether the presence of ...pathologic features of airway remodeling in patients with asthma was associated with steroid responsiveness in the short term. Methods Sixty-three consecutive patients with severe asthma with chronic airflow impairment (post-bronchodilator FEV1 < 80% predicted values) were recruited, clinically characterized, and had an initial bronchoscopy where endobronchial biopsy and BAL were performed. BAL cellular content was reported and reticular basement membrane (RBM) thickness was measured by validated repeated measures. Patients were then treated with 1 mg/kg/d of methyl prednisone, directly administered IV, for 10 days. A threshold of 15% FEV1 improvement was used to discriminate responsive (group 1) and refractory patients (group 2). Results Thirty-eight patients had a steroid responsiveness > 15% (group 1) and a thinner RBM at the biopsy level (5.78 ± 2.0 μm vs 7.60 ± 2.2 μm; P = .001) compared with nonsteroid responsive group 2 patients as defined. The best predictors for being unresponsive were no long-term treatment with oral steroids and increased RBM thickness. The associated receiver operating characteristic curve indicated that RBM thickness could predict steroid responsiveness below 15% with an area under the curve of 0.747 ( P = .0002) at a threshold of 7 μm. Conclusions Features of airway remodeling are associated with limited short-term steroid responsiveness in severe asthma.
In a prospective study, 23 children with infantile spasms received intravenous gammaglobulins in high doses. 19 patients present a West syndrome. 4 older patients were included in the study because ...infantile spasms had preceded their Lennox-Gastaut syndrome. None of the patients had recently undergone corticosteroid therapy. No effect was observed in 15 patients, while transitory clinical and/or electroencephalographic improvement was noted in 3. Complete normalization was obtained in the remaining 5 patients, of whom 4 had severe brain lesions. No correlation existed between the therapeutic results and immunological abnormalities, a deficiency in IgG subclasses in particular. On the whole, the therapeutic results were disappointing. But the existence of some cases in which spectacular electroencephalographic and/or clinical improvement was obtained leads us to suggest that IV gamma-globulins be used as auxiliary treatment in infantile spasms.
Metabolic changes in rats fed a low protein diet during post-weaning growth Claeyssens, S. (Groupe de Biochimie et de Physiopathologie Digestive et Nutritionnelle, Saint Etienne du Rouvray, France); Lavoinne, A; Fresel-Ragot, M ...
Metabolism, clinical and experimental,
07/1990, Volume:
39, Issue:
7
Journal Article
Peer reviewed
Metabolic changes in rats fed a low protein diet were investigated during 3 weeks after weaning using lactalbumin (LP) as dietary protein source. The energy intake was higher and the weight gain ...lower in rats fed the low protein diet (6%, LP group) than in control rats (13% lactalbumin, C group). Low protein diet induced no changes in plasma glucose, free fatty acids, or triacylglycerol concentrations; however, plasma protein and urea concentrations were lower in LP than in C rats. Plasma free T3 was higher in LP than in C rats (+38%, day 21) and insulin progressively decreased during the experimental period (-56%, day 21) without change in glucagon. Liver glycogen and triacylglycerol concentrations (+40% and +180%, respectively, day 21), and cytosolic and mitochondrial redox states increased (+100% and +100%, day 21), and protein concentration was decreased (-15%, day 21). Pyruvate kinase (PK) and malic enzyme activities were higher in LP than in C rats throughout the experiment (+80% and +210%, respectively, day 21), and glucose-6-phosphate dehydrogenase (G6PDH) activity progressively decreased (-65%, day 21). Phosphoenolpyruvate carboxykinase (PEPCK) activity increased after 2 weeks on a LP diet (+35%, day 21) and fatty acid synthetase (FAS) activity increased only during the first week on the diet (+100%, day 7). Such hormonal and metabolic changes appeared to be associated with the development of a futile energy-wasting cycle between pyruvate and phosphoenolpyruvate.
Plasma insulin, glucagon, glucose, free fatty acids and glycerol, hepatic cyclic AMP and glycogen, and liver phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-bisphosphatase (FBPase), glucose ...6-phosphatase (G6Pase) and alanine amino transferase (AAT) activities were examined in adult rats during the first 24 h of either starvation or consumption of a high protein, carbohydrate-free (HP) diet. Under both nutritional conditions, plasma insulin fell within 12 h and remained constant thereafter. Glucagon increased 12 h after the start of the experiment and peaked between 18-24 h. The insulin: glucagon ratio was lower during the last 12 h of the experiment. In both experimental groups, liver cyclic AMP increased progressively and peaked between 15-24 h, but it increase was higher on HP diet than on starvation. Whereas plasma glucose remained low on starvation for 24 h, it returned to normal on consumption of the HP diet. In both groups, liver glycogen fell within 12 h and remained low until the end of experiment. FBPase, G6Pase and AAT did not change on starvation, while they increased toward the end of 1 d HP consumption. During starvation or consumption of the HP diet, PEPCK increased progressively and peaked between 15-24 h, but the increase was greater with the HP diet than with starvation. These findings suggest that in the first 24 hours, the adaptative response of hepatic gluconeogenesis is higher with a HP diet than upon starvation.
The aim of this work was to find by which mechanisms an increased availability of plasma free fatty acids (FFA) reduced carbohydrate utilization during exercise. Rats were fed high-protein ...medium-chain triglycerides (MCT), high-protein long-chain triglycerides (LCT), carbohydrate (CHO) or high-protein low-fat (HP) diets for 5 weeks, and liver and muscle glycogen, gluconeogenesis and FFA oxidation were studied in rested and trained runner rats. In the rested state the hepatic glycogen store was decreased by fat and protein feeding, whereas soleus muscle glycogen concentration was only affected by high-protein diets. The percentage decrease in liver and muscle glycogen stores, after running, was similar in fat-fed, high-protein and CHO-fed rats. The fact that plasma glucose did not drastically change during exercise could be explained by a stimulation of hepatic gluconeogenesis: the activity of phosphoenolpyruvate carboxykinase (PEPCK) and liver phosphoenolpyruvate (PEP) concentration increased as well as cyclic adenosine monophosphate (AMPc) while liver fructose 2,6-bisphosphate decreased and plasma FFA rose. In contrast, the stimulation of gluconeogenesis in rested HP-, MCT- and LCT-fed rats appears to be independent of cyclic AMP.
Pertinent hepatic metabolites and enzymes were examined in rats fed a high carbohydrate (HC) diet and during the first 24 h of either starvation or feeding a high protein (HP) diet. Consumption of ...the HC diet induced slight but definite 24-h oscillations in hepatic concentrations of cyclic AMP, glycogen, glucose 6-phosphate, fructose 2,6-bisphosphate, fructose 1,6-bisphosphate and phosphoenolpyruvate, as well as the activities of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase and phosphoenolpyruvate carboxykinase. The transition to starvation or the HP diet induced, within 12 h, concurrent increases in cyclic AMP and phosphoenolpyruvate and decreases in glycogen, glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate and fructose 1,6-bisphosphate. These changes were associated with a decrease in the ratio of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and an increase in phosphoenolpyruvate carboxykinase. These results suggest that the activity of the fructose 6-phosphate/fructose 1,6-bisphosphate cycle is similar during the first 24 h of starvation or HP consumption.
Plasma hormones, glucose and free fatty acids, liver glycogen and two key enzymes of glycolysis and gluconeogenesis were examined in adult rats during a 40-day period of high protein feeding. Plasma ...insulin fell within 1 day but returned to normal after 4 days. Glucagon changed more slowly, reaching a maximum on day 4 and declined to near the control value within 24 days. Consequently, the insulin to glucagon ratio was lower on days 1, 4 and 8 and was nearly normal on day 24. With respect to hepatic enzymes, phosphoenolpyruvate carboxykinase activity rose sharply on the 1st day and remained elevated for 40-day period; the L-isozyme of pyruvate kinase, although unchanged on the 1st day, decreased thereafter and from day 8 on represented 15--20% of control. Circadian variations in these parameters were also measured in rats adapted to the high protein diet. In such animals, the diurnal change in plasma hormones was less marked but tended to be inverted with respect to controls; the insulin/glucagon ratio was highest during daylight on high protein and in late night on the control diet. Over 24 hours, pyruvate kinase activity was related directly and phosphoenolpyruvate carboxykinase inversely to the hormone ratio. We concluded that in rats adapted to high protein, as in controls, the diurnal balance between glycolysis and gluconeogenesis is probably regulated by the same factor, namely the insulin/glucagon ratio.
Gluconeogenesis from dihydroxyacetone (DHA), glycerol, lactate, pyruvate or alanine was studied in the absence or in the presence of glucagon in hepatocytes isolated from starved rats or from rats ...fed a high protein diet for 2-48 h. In both groups, gluconeogenesis from DHA, glycerol, lactate and pyruvate exhibited similar changes over 48 h; the rates of glucose production increased progressively until 24 h and then plateaued. During the early phase (2-11 h), gluconeogenesis from DHA and glycerol were higher than gluconeogenesis from lactate and pyruvate. During the first 24 h of the experiment, gluconeogenesis from alanine displays a kinetic similar to that from lactate or pyruvate. After feeding a high protein diet for 24 to 48 h, gluconeogenesis from alanine was slightly higher than that in starved rats and paralleled the increase in alanine aminotransferase activity. Glucagon stimulated gluconeogenesis from DHA up to 48 h, but with glycerol this effect occurred only during the early phase (2-11 h). Glucagon stimulated gluconeogenesis from lactate, pyruvate or alanine by 1.35-fold throughout the experimental period. These findings suggest that the development of gluconeogenesis during starvation or after feeding a high protein diet displays different kinetics, depending on the substrate used and on the level of entry in the gluconeogenic pathway: triose phosphates or pyruvate.
PDF
