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PubMed1990

A study of the fasting diabetic patients during the month of Ramadan.

Twenty two Muslim diabetic patients on oral hypoglycaemic agents were studied during the fasting month of Ramadan to determine the effect of fasting on their diabetic control. All the patients completed their fast during the month. Their mean (+/- standard deviation) blood glucose, serum fructosamine and body weight before the fasting month were 10.7 +/- 4.6 mmol/l, 6.64 +/- 3.64 mmol/l and 60.5 +/- 12.6 kg and by the end of the fasting month were 10.9 +/- 4.4 mmol/1,4.34 +/- 1.08 mmol/l and 59.8 +/- 12.3 kg respectively. There was no significant difference between the blood glucose levels but there were significant reductions in the mean body weight and fructosamine values (p = 0.01 and p = 0.03 respectively). The mean decrease in body weight and fructosamine were 0.7 +/- 1.3 kg and 2.29 +/- 3.09 mmol/l respectively. There were also statistically significant differences between the mean daily calorie content before the fasting and during the fasting month (1480 +/- 326 vs 1193 +/- 378 Cal/day - p less than 0.005) and between the mean daily carbohydrate content (389 +/- 298 vs 187 +/- 46 gm/day - p less than 0.005). In conclusion, fasting was safe for diabetic patients on oral hypoglycaemic agents and it was associated with weight reduction and improvement in the overall diabetic control. This was most likely due to decrease in food intake.

Adult↗
PubMed1989

Increased translatable mRNA and decreased lipogenesis are responsible for the augmented secretion of lipid-deficient apolipoprotein E by hepatocytes from fasted rats.

We examined the mechanism through which fasting selectively increases the secretion of apoE while it decreases the secretion of all lipoprotein lipids (Davis, R. A., Boogaerts, J. R., Borchardt, R. A., Malone-McNeal, M., and Archambault-Schexnayder, J. (1985) J. Biol. Chem. 260, 14137-14144). Livers were obtained from rats that were fed chow plus drinking water (control) and drinking water only (fasted) for three days. Livers were extracted for both total and poly(A) RNA. Using full length, nick-translated 32P-labeled cDNA probes for both apoE and beta-actin, the relative abundance was determined by slot blot hybridization assays. There was 2-fold more apoE mRNA in the livers of fasted rats. Furthermore, translation of poly(A) RNA using a reticulocyte lysate showed a similar 2.3-fold increase in the synthesis of immunoprecipitable [35S]methionine-labeled apoE. The 2-fold increase in translatable apoE mRNA correlates with a similar increase in apoE secretion. We also characterized the form of apoE secreted by hepatocytes from fasted cells. Cells were labeled with [35S]methionine, and the medium was separated by agarose 0.5m column chromatography. The majority of the apoE secreted cells from both control and fasted rats eluted in fractions that contained no detectable lipid. Furthermore, almost all of the increased apoE secreted by fasted cells was in these lipid-deficient fractions. The isoform distribution of apoE secreted by cells from both groups consisted of six major apoE isoforms. Consistent with previous results, treatment with neuraminidase transformed the acidic forms into the three most basic, suggesting that the three most acidic isoforms contain varying amounts of sialic acid. The isoform pattern of apoE secreted by cells from fasted rats was significantly enriched in two acidic isoforms, while it was significantly decreased in the major basic isoform. Moreover, when oleic acid (1 mM) was added to the culture medium to stimulate lipogenesis, the amount of apoE secreted with lipid increased as did the more basic isoforms. These data suggest that the secretion of lipid-deficient apoE by cells from fasted rats is the result of increased mRNA and a concomitant reduction in lipogenesis. Furthermore, the parallel shift of both the amount of apoE secreted associated with lipid as well as its isoform pattern to a more basic one by oleic acid suggests that the lipid availability plays a role in determining the lipid complement and sialic acid content of apoE secreted by the hepatocyte.

Acetates↗
PubMed1989

[The effect of single and intermittent fasting on cholesterolemia in rats of various ages].

Experiments studying the influence of single and repeated fasting on cholesterolaemia were performed in rats of both sexes and of our own breed (Wistar) aged 5, 10, 14 and 21 days of postnatal life and in adult rats. Cholesterol was determined by means of Lachema (CSSR) tests. The single fasting was realized in such way that one half of standard litter was separated from mother and nest for a period of 24 hours. Adult rats did not receive an appropriate diet for the same period. The repeated fasting was carried out as follows: in three successive days half of the litter was separated from mother for a period of 18 hours. For the remaining 6 hours the rats were returned to mother into the nest. Isolation was in both cases performed under optimal thermal conditions. Blood was taken by decapitation. Changes in total cholesterolaemia during ontogenesis (maximum up to 14 days of postnatal life) were confirmed. Fasting was found out to cause a significant decrease in cholesterolaemia in the first three age categories and in adult rats. In rats aged 21 days neither single nor repeated fasting caused a significant change in plasma cholesterol contents. In the first three age groups repeated fasting has a demonstrably higher effect, i.e. the decrease in cholesterolaemia is higher after this type of fasting than after the single one. The results are compared with our previous studies concerning the influence of fasting on the development of organism.

Aging↗
PubMed1987

Metabolic effects of short-term fasting in obese hyperglycaemic humans and mice.

The aim of this study was to investigate the metabolic effects of short-term fasting in obese diabetic patients and to correlate the observed changes with the activity of hepatic key enzymes in an animal model of obesity-associated diabetes (ob/ob mice, C57BL/6J strain). In obese diabetic patients (ODP), a 72-h fast (causing slight change in body weight) decreased fasting glycemia by 3.82 +/- 0.79 mmoles/l and significantly improved glucose tolerance (OGTT) while reducing basal and stimulated insulinemia, whereas in obese non-diabetic patients (ONDP) only a small decrease in fasting glycemia (1.24 +/- 0.51 mmoles/l) occurred. This suggests that in ODP hyperphagia is a factor contributing to maintain hyperglycaemia and glucose intolerance (in the face of hyperinsulinaemia, indicating insulin resistance). In fed obese hyperglycaemic mice (OHM), which are a good model of the human obesity-associated diabetes, hepatic fructose-1,6-diphosphatase (F16Pase) and glucose-6-phosphatase (G6Pase), involved in glucose production, showed increased activity (+52 and +200 per cent, respectively) compared to control mice (CM), and the ratios of F16Pase and G6Pase to the opposing enzymes phosphofructokinase (PFK1) and glucokinase (GK), i.e. the F16Pase/PFK1 and G6Pase/GK ratios, were increased by 38 and 101 per cent, respectively, suggesting increase in gluconeogenesis and perhaps in glycogenolysis. In the 48-h fasted OHM, F16Pase activity was decreased (-30 per cent) compared to the fed animals, while the activity of G6Pase showed a smaller and statistically not significant change (-22 per cent). In contrast, in the CM a 48-h fasting was associated with a trend toward increased F16Pase (+22 per cent) and G6Pase (+173 per cent). However, since PFK1 and GK decreased to a similar extent in OHM and CM, the F16Pase/PFK1 and G6Pase/GK ratios, basally elevated in the OHM, did not change with fasting, whereas in the CM they showed a striking elevation (+71 and +274 per cent, respectively). The basally elevated F16Pase/PFK1 and G6Pase/GK ratios (functionally linked to glucose production) in the OHM may contribute to maintain hyperglycaemia; in these mice, the lack of further increase in the glucose production-related F16Pase/PFK1 and G6Pase/GK ratios (which occurs in CM) with fasting might allow that the interruption of the afflux of dietary carbohydrates ameliorates the glycaemic level. Similar mechanisms might occur also in the ODP.

Adult↗
PubMed1988

Regulation of acetyl-coenzyme A carboxylase. II. Effect of fasting and refeeding on the activity, phosphate content, and aggregation state of the enzyme.

Acetyl-CoA carboxylase isolated from freeze-clamped livers of fed rats has relatively low phosphate content (5.0 mol of Pi/mol of subunit) and high specific activity (3.5 units/mg in the absence of citrate). The enzyme from rats fasted for 12, 18, 24, and 48 h exhibited decreasing specific activities of 2.75, 1.85, 1.7, and 0.9 units/mg, respectively. Citrate activated all preparations of carboxylase, with most activation observed with the least active preparation. There was no significant change in the sensitivity of the enzyme to citrate since half-maximal activation was observed at 0.2 mM for carboxylase from fed as well as fasted rats. With the decrease in activity as a function of fasting, there was a concomitant increase in the phosphate content of carboxylase, with values of 5.3, 5.6, 6.7, and 7.6 mol of Pi/mol of subunit obtained for preparations from rats fasted for 12, 18, 24, and 48 h, respectively. Refeeding the fasted rats resulted in increased specific activity of carboxylase (3.4 units/mg) and decreased phosphate content (5.1 mol of Pi/mol of subunit). Moreover, dephosphorylation by [acetyl-CoA carboxylase]-phosphatase 2 activated the carboxylase from 48-h fasted rats to a value of 2.9 units/mg, assayed in the absence of citrate, indicating that the low activity of carboxylase from fasted rats was due to its increased phosphate content. Superose 6 chromatography showed that the enzyme exists in two polymeric forms, a highly active polymer of greater than or equal to 40 subunits and less active octamer. The former predominates in livers of fed rats, whereas the latter predominates in livers of fasted rats. The octamer could be converted to the highly active polymer by dephosphorylation. These observations indicate that fasting/refeeding results in phosphorylation/dephosphorylation of acetyl-CoA carboxylase with concomitant depolymerization/polymerization of the protein and ultimately decreasing or increasing its specific activity.

Acetyl-CoA Carboxylase↗
PubMedDate not supplied

Insulin clearance and microsomal glutathione-insulin transhydrogenase in perfused livers of fed and fasted rats.

Clearance of exogenous insulin measured in perfused livers from rats fed ad lib or fasted X 24 or X 48 h was correlated with changes in activity and distribution of the insulin-degrading enzyme glutathione-insulin transhydrogenase measured in microsome fractions, post-perfusion. For comparison with endogenous insulin removal (Endocr. Res. Commun. 7: 231, 1980), a single-pass perfusion mode was used and clearance of insulin at levels (less than or equal to 15 ng/ml) typically observed in perfused rat liver-pancreases during glucose stimulation was studied. Similar to the endogenous data, exogenous insulin removal followed an ogival pattern during fasting. In the fed state, clearance was relatively low, corresponding to a hepatic extraction of approximately 29%. Insulin extraction increased nearly 2-fold after a 24 h fast to approximately 48% (p less than .01), declining to approximately 30% (p less than .025) when fasting was prolonged (X 48 h). At portal insulin concentrations greater than 8 ng/ml (approximately 200 microUnits/ml), clearance tended to decrease in all 3 nutritional states, with apparent saturation of the insulin capturing mechanism being strongest in the 24 h fasted state. In conjunction with these changes in whole organ insulin removal, GSH-insulin transhydrogenase nonlatency, viz., nonlatent activity in intact microsomes relative to total activity in disrupted microsomes, did not change during the first 24 h of fasting; whereas the proportion of nonlatent activity was significantly decreased (p less than .01) after 48 h. Homogenate activity remained essentially constant during the initial fasting period, and declined by approximately 16% (p less than .01) after 48 h of fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

The usefulness of a rapid method for total fast hemoglobins determination in screening for diabetes control.

We have used a simple and rapid method for the determination of total fast hemoglobins (HbA1a+b+c) in 102 diabetics and 36 normal controls. The method was described by Kynoch and marketed by Isolab. It proved to be useful in screening for patients with inadequate metabolic control in whom as a rule, total fast Hb values were higher than 8.5%. Mean Hb A1a+b+c value was significantly higher in the group of diabetics in comparison with normals (9.9 +/- 0.2 versus 6.9 +/- 0.8%). The diabetic patients were separated into four groups according to predetermined criteria of recent metabolic control. Even the patients considered to have a very good diabetes control during the past eight weeks, had supranormal total fast Hb values (7.7 +/- 0.2%). In the patients with good, poor and bad diabetes control, mean total fast Hb levels were respectively 9.3 +/- 0.3, 10.1 +/- 0.3 and 12.5 +/- 0.4%. In normals, there was a positive correlation between individual fasting blood glucose and total fast Hb values and in diabetics, mean blood glucose values correlated with total fast Hb levels. Hb A1a+b+c determinations also correlated with triglyceride values. We could find no significant association between high total fast Hb levels (greater than 8.5%) and the prevalence of retinopathy.

Blood Glucose↗
PubMed1984

Effect of long-term fasting of obese patients on pancreatic exocrine function, gastrointestinal hormones and bicarbonate concentration in plasma.

The CCK- and secretin stimulated pancreatic volume, bicarbonate and enzyme secretion was investigated before and during fasting for 20 days in 12 obese subjects. Pancreatic function tests were performed at the start of the fasting period and on the 10th and 20th day. In an additional and comparable group of 8 obese patients plasma concentrations of cholecystokinin (CCK), gastrin and insulin as well as metabolic parameters (bicarbonate, beta-OH-butyrate and free fatty acids) have been measured before and during total fasting. During three weeks of total fasting the average overweight of the patients undergoing pancreatic function tests was reduced from 49 to 31% (-11.5 +/- 1,5 kg). A significant reduction of volume, bicarbonate, trypsin and amylase secretion occurred already after 10 days of total fasting. After 20 days these parameters were further significantly reduced compared to the 10th day. All mentioned parameters were found at the lower limit of the normal range at the end of the fasting period at 20 days. The only exception being lipase secretion; the decrease of this enzyme was not significant at the 5% level. No significant reduction of basal plasma concentrations could be observed for CCK and gastrin during the course of total fasting. The plasma insulin levels were significantly reduced after 7 days whereas at 10 and 20 days insulin concentration was not significantly lowered compared to day 1. A small but significant decrease in the blood bicarbonate concentration could be observed after 7 days of fasting which remained constant up to the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1982

Fasting: the history, pathophysiology and complications.

An appreciation of the physiology of fasting is essential to the understanding of therapeutic dietary interventions and the effect of food deprivation in various diseases. The practice of prolonged fasting for political or religious purposes is increasing, and a physician is likely to encounter such circumstances. Early in fasting weight loss is rapid, averaging 0.9 kg per day during the first week and slowing to 0.3 kg per day by the third week; early rapid weight loss is primarily due to negative sodium balance. Metabolically, early fasting is characterized by a high rate of gluconeogenesis with amino acids as the primary substrates. As fasting continues, progressive ketosis develops due to the mobilization and oxidation of fatty acids. As ketone levels rise they replace glucose as the primary energy source in the central nervous system, thereby decreasing the need for gluconeogenesis and sparing protein catabolism. Several hormonal changes occur during fasting, including a fall in insulin and T(3) levels and a rise in glucagon and reverse T(3) levels. Most studies of fasting have used obese persons and results may not always apply to lean persons. Medical complications seen in fasting include gout and urate nephrolithiasis, postural hypotension and cardiac arrhythmias.

Adult↗
PubMed1980

Glucose turnover, tolerance and insulin response in wethers, ewes and pregnant ewes in the fed and fasted state.

Glucose turnover parameters were obtained in fed and fasted wethers, ewes and pregnant ewes in their 2nd and 3rd trimesters, using a jugular bolus injection of D-glucose-2-3H. Fasting significantly (P less than 0,05) reduced glucose turnover (c. 40%) in both the wether and the non-pregnant ewe. A somewhat larger difference (c. 54%) between the fed and fasted ewes was found in their 3rd trimester of pregnancy due to an increase when fed (c. 29% higher turnover than in the non-pregnant ewe) rather than a decrease when fasted, since there was no statistical difference (P less than 0,1) between glucose turnover values of pregnant or non-pregnant fasted ewes. Glucose tolerance was estimated from an intrajugular glucose load (1 g/kg0,75 body mass) in these 3 groups of sheep under both fed and fasted conditions, and the resulting insulin response was followed for 4 hr after the injection. Fasting reduced the plasma clearance rate of glucose by c. 63% in both the wether and the non-pregnant ewe while the reduction was somewhat smaller (c. 51%) during the 2nd trimester of pregnancy. Only the pregnant ewe group showed a corresponding reduction in the resulting insulin response of 46% which was similar in magnitude to the diminished clearance, indicating that factors other than insulin are responsible for the reduced glucose clearance associated with fasting in the wether and non-pregnant ewe. Despite similar baseline plasma glucose values the glucose load appeared to distribute in a space that was significantly less than that found in all 3 groups of fed sheep when trace amounts were injected.

Animals↗
PubMed1982

Differences in circulating gluconeogenic substrates during short-term fasting in men, women, and children.

To determine whether the differences in fasting glucose responses in men, women and children could be related to differences in glucoregulatory hormone secretion or availability of circulating gluconeogenic substrates, 20 adults (10 men and 10 women) were fasted for 86 hr and 15 children (6.1 +/- 0.8 yr, mean +/- SE) were fasted for 30 hr. Circulating concentrations of glucose, ketone bodies, potential gluconeogenic substrates and glucoregulatory hormones were determined at frequent intervals. In the postprandial state (1-14 hr fasting), substrate and hormone concentrations were similar in all groups with the exception of plasma glutamine concentrations which were higher in men (640 +/- 20 microM) than in women of children (490 +/- 20 microM and 480 +/- 50 microM, respectively, p less than 0.01 for both). Following 30 hr fasting children had the lowest glucose (53 +/- 3 mg/dl) and alanine (167 +/- 17 microM) concentrations and men had the highest (72 +/- 3 mg/dl and 279 +/- 16 microM, respectively) whereas those of women were intermediate (64 +/- 3 mg/dl and 226 +/- 19 microM. respectively). Following 30 hr of fasting betahydroxybutyrate concentrations were highest in children and lowest in men (the children, 3.7 +/- 0.4 mM; women, 1.7 +/- 0.2 mM and men 0.9 +/- 0.2 mM, p less than 0.02 between all groups). An inverse relationship (p less than 0.001 was observed between beta-hydroxybutyrate and glucose concentrations throughout the fast for each group (r greater than 0.92). Although plasma cortisol concentrations were higher in women and children when compared to those of the men, no differences in growth hormone, glucagon, or insulin concentrations were observed among the three groups studied. Differences in plasma substrate responses to fasting among the groups studied may reflect differences in glucose requirements among men, women and children, as well as the relative availability of both gluconeogenic substrate and ketone bodies.

Adult↗
PubMed1996

Selective innervation of fast and slow muscle regions during early chick neuromuscular development.

The electrical properties of adult motoneurons are well matched to the contractile properties of the fast or slow muscle fibers that they innervate. How this precise matching occurs developmentally is not known. To investigate whether motoneurons exhibit selectivity in innervating discrete muscle regions, containing either fast or slow muscle fibers during early neuromuscular development, we caused embryonic chick hindlimb muscles to become innervated by segmentally inappropriate motoneurons. We used the in vitro spinal cord-hindlimb preparation to identify electrophysiologically the pools of foreign motoneurons innervating the posterior iliotibialis (pITIB), an all-fast muscle, and the iliofibularis (IFIB), a partitioned muscle containing discrete fast and slow regions. The results showed that the pITIB and the fast region of the IFIB were exclusively innervated by motoneurons that normally supply fast muscles. In contrast, the slow region of the IFIB was always innervated by motoneuron pools that normally supply slow muscles. Some experimental IFIB muscles lacked a fast region and were innervated solely by "slow" motoneurons. In addition, the intramuscular nerve branching patterns were always appropriate to the fast-slow nature of the muscle (region) innervated. The selective innervation was found early in the motoneuron death period, and we found no evidence that motoneurons grew into appropriate muscle regions, but failed to form functional contacts. Together, these results support the hypothesis that different classes of motoneurons exhibit molecular differences that allow them to project selectively to, and innervate, muscle fibers of the appropriate type during early neuromuscular development.

Animals↗
PubMed2002

Can Swedish interactive thresholding algorithm fast perimetry be used as an alternative to goldmann perimetry in neuro-ophthalmic practice?

OBJECTIVE: To assess the potential role of Swedish Interactive Thresholding Algorithm (SITA) Fast computerized static perimetry, compared with that of Goldmann manual kinetic perimetry (GVF), for reliably detecting visual field defects in neuro-ophthalmic practice. BACKGROUND: Automated visual field testing is challenging in patients with poor visual acuity or severe neurological disease. In these patients, GVF is often the preferred visual field technique, but performance of this test requires a skilled technician, and this option may not be readily available. The recent development of the SITA family of perimetry has allowed for shorter automated perimetry testing time in normal subjects and in glaucoma patients. However, its usefulness for detecting visual field defects in patients with poor vision or neurological disease has not been evaluated. DESIGN AND METHODS: We prospectively studied 64 consecutive, neuro-ophthalmologically impaired patients with neurologic disability of 3 or more on the Modified Rankin Scale, or with visual acuity of 20/200 or worse in at least one eye. Goldmann manual kinetic perimetry and SITA Fast results were compared for each eye, with special attention to reliability, test duration, and detection and quantification of neuro-ophthalmic visual field defects. We categorized the results into 1 of 9 groups based on similarities and reliabilities. Patient test preference was also assessed. RESULTS: Patients were separated into 2 groups, those with severe neurologic deficits (n = 50 eyes) and those with severe vision loss but mild neurologic dysfunction or none at all (n = 50 eyes). Overall, GVF and SITA Fast were equally reliable in 77% of eyes. Goldmann manual kinetic perimetry and SITA Fast showed similar visual field results in 75% of all eyes (70% of eyes of patients with severe neurologic deficits and 80% of eyes with poor vision). The mean +/- SD duration per eye was 7.97 +/- 3.2 minutes for GVF and 5.43 +/- 1.41 minutes for SITA Fast (P<.001). Ninety-one percent of patients preferred GVF to SITA Fast. CONCLUSIONS: We found the SITA Fast strategy of automated perimetry to be useful in the detection, and accurate in the quantification of central visual field defects associated with neuro-ophthalmic disorders. Our results suggest that for the general ophthalmologist or neurologist, visual field testing with SITA Fast perimetry might even be preferable to GVF, especially if performed by a marginally trained technician, even in patients with severely decreased vision or who are neurologically disabled.

Adolescent↗
PubMed1991

Expression of a fast myosin heavy chain mRNA in individual rabbit skeletal muscle fibers with intermediate oxidative capacity.

In situ hybridization (ISH) of myosin heavy chain (MHC) mRNA, immunofluorescent detection of MHC protein, and oxidative enzyme histochemistry were performed on the same fibers in serially sectioned rabbit skeletal muscle. By combining these three techniques quantitatively, on a fiber-by-fiber basis, fibers that expressed mRNA complementary to a fast MHC cDNA pMHC24-79 of unknown subtype (Maeda et al., 1987) were classified into fiber types with respect to slow myosin expression and oxidative capacity. As expected, slow fibers had low hybridization to pMHC24-79. Fast fibers were divided into three subtypes. mRNA from the low oxidative fibers (fast-glycolytic, IIB) did not hybridize with pMHC24-79. Fast fibers whose mRNA hybridized best to pMHC24-79 were mainly in the intermediate range of oxidative capacity (probably IIX). The fast fibers with the highest oxidative capacity had low hybridization to this MHC mRNA (probably IIA). Thus, pMHC24-79 was identified as a clone of a fast isomyosin, tentatively designated as the fast IIX with intermediate oxidative capacity. The expression of more than a single species of fast and slow isomyosin mRNAs in classically defined fiber type was considered in interpreting these results.

Animals↗
PubMed2004

Experience with focused abdominal sonography for trauma (FAST) in 313 pediatric patients.

PURPOSE: The use of focused abdominal sonography for trauma (FAST), which detects free fluid in the abdomen and pelvis, for the assessment of blunt abdominal trauma is gaining acceptance worldwide and has been described extensively in the general medical literature. The precise application of this technique in pediatric patients, however, has yet to be established. The aim of this study was to assess the utility of FAST in pediatric trauma patients by comparing the results of this technique with those of CT and explorative laparotomy (ELAP). METHODS: We retrospectively reviewed the medical records and sonographic examinations of pediatric patients who had sustained multiple traumatic injuries for which they were treated at our hospital during a 20-month period. For all patients, FAST had been the initial screening examination for blunt abdominal trauma. We compared the FAST findings, which had been recorded as positive or negative, with the findings on CT or ELAP, which were considered definitive. RESULTS: A total of 313 patients (204 boys and 109 girls) with a mean age of 7.1 years were included in the study. The FAST finding had been negative in 274 patients, of whom 201 had had no clinical signs of abdominal injury and had been managed conservatively without complications. CT had been performed in 109 patients and ELAP in 11. FAST had yielded 3 false-negative and 2 false-positive results. The sensitivity, specificity, and accuracy of FAST were 92.5%, 97.2%, and 95.5%, respectively. CONCLUSIONS: FAST is an effective tool in screening pediatric trauma patients for blunt abdominal trauma.

Abdominal Injuries↗
PubMed1993

Two types of neonatal-to-adult fast myosin heavy chain transitions in rat hindlimb muscle fibers.

Adult fast myosin heavy chain (MHC) isoforms are accumulated in fibers of rat hindlimb skeletal muscle which initially contain neonatal MHC at birth. The specific factors controlling these transitions are not known, but in rat and mouse muscle tissue the transition between the neonatal and adult fast MHC proteins does not appear to require continuous innervation. We have reinvestigated the role of innervation in the neonatal-to-adult fast MHC protein and mRNA transitions that occur in developing rat fast-twitch muscles using immunohistochemistry and S1 nuclease mapping. We find that neonatal MHC-containing developing fibers exhibit different responses after denervation at birth regarding the disappearance of neonatal MHC and the accumulation of adult fast MHC isoforms. Immunohistochemistry shows that one fiber population loses neonatal MHC and accumulates adult fast IIB (or possibly IIX) MHC over a period of 2-3 weeks, whereas in the other population neonatal MHC does not decrease nor does the adult fast IIA isoform accumulate to high levels. The results of S1 analysis of mRNAs show that the levels of neonatal MHC mRNA do not decrease in muscles denervated at birth. We also demonstrate that in young adult rats this mRNA is reexpressed in denervated or paralyzed muscles. Since the appearance of IIB mRNA has been previously shown to be nerve-independent (S.D. Russell, N. Cambon, B. Nadal-Ginard, and R.G. Whalen, 1988, J. Biol. Chem. 263, 6370-6374), these results suggest that fibers containing neonatal MHC in rat hindlimb muscles at birth are already differentiated (i.e., preprogrammed) to accumulate either the adult fast IIA or IIB MHC isoforms and that the neonatal-to-adult MHC transitions occurring in these two fiber populations are controlled by different mechanisms.

Animals↗
PubMed1995

Thermodynamic investigation of hirudin binding to the slow and fast forms of thrombin: evidence for folding transitions in the inhibitor and protease coupled to binding.

Temperature dependent studies of the interaction of the clotting enzyme thrombin with the potent natural inhibitor hirudin reveal a large negative heat capacity change of -1.7(+/- 0.2) kcal/mol per K associated with the formation of the thrombin-hirudin complex, independent of the allosteric state of the enzyme. Binding of N-terminal fragments of hirudin (hir1-49 and hir1-43) is characterized by heat capacity changes of -1.2(+/- 0.1) and -0.9(+/- 0.1) kcal/mol per K, respectively. The magnitude of these heat capacity changes is unprecedented for protease-inhibitor interactions. A thermodynamic analysis based on observed heat capacity and entropy changes predicts that binding is accompanied by substantial coupled folding transitions in both hirudin and thrombin. In the absence of a structure of free thrombin, analysis of differences in the predicted number of residues which fold upon binding hirudin and its fragments leads to the following structural model: three surface loops in thrombin (W60d, W148 and fibrinogen binding loops) are disordered in the free state and fold upon formation of the thrombin-hirudin complex. Molecular dynamics simulations, run over a time scale of 5 ps, are consistent with the hypothesis of large scale coupled folding transitions in both hirudin and thrombin upon formation of the complex. Comparison of the thermodynamics for the interaction of hirudin with the slow and fast forms of thrombin allows dissection of the coupling free energy for allosteric switching. The coupling free energy for the slow-->fast transition increases linearly, in absolute value, with temperature. The coupling enthalpy and entropy terms for hirudin were found to be delta Hoc = 12(+/- 1) kcal/mol and delta Soc = 47(+/- 4) cal/mol per K. Preferential interaction with the fast form is therefore due to the balance of two opposite forces, both quite large in magnitude. The contribution of enthalpic effects opposes the slow-->fast transition and stabilizes binding to the slow form. The contribution of entropic effects favors the slow-->fast transition and stabilizes binding to the fast form. In the physiological temperature range the entropic effects prevail and result in preferential binding of hirudin to the fast form. The region of thrombin recognizing the N-terminal domain of hirudin contains most of the residues that are energetically linked to the slow-->fast transition. This region is part of the "allosteric core" of thrombin and includes the W60d loop, shaping the specificity site S2, and the Na+ binding loop connecting the last two beta-strands of the B chain.

Allosteric Regulation↗
PubMed1994

Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers.

The relationship between myonuclear number, cellular size, succinate dehydrogenase activity, and myosin type was examined in single fiber segments (n = 54; 9 +/- 3 mm long) mechanically dissected from soleus and plantaris muscles of adult rats. One end of each fiber segment was stained for DNA before quantitative photometric analysis of succinate dehydrogenase activity; the other end was double immunolabeled with fast and slow myosin heavy chain monoclonal antibodies. Mean +/- S.D. cytoplasmic volume/myonucleus ratio was higher in fast and slow plantaris fibers (112 +/- 69 vs. 34 +/- 21 x 10(3) microns3) than fast and slow soleus fibers (40 +/- 20 vs. 30 +/- 14 x 10(3) microns3), respectively. Slow fibers always had small volumes/myonucleus, regardless of fiber diameter, succinate dehydrogenase activity, or muscle of origin. In contrast, smaller diameter (< 70 microns) fast soleus and plantaris fibers with high succinate dehydrogenase activity appeared to have low volumes/myonucleus while larger diameter (> 70 microns) fast fibers with low succinate dehydrogenase activity always had large volume/myonucleus. Slow soleus fibers had significantly greater numbers of myonuclei/mm than did either fast soleus or fast plantaris fibers (116 +/- 51 vs. 55 +/- 22 and 44 +/- 23), respectively. These data suggest that the myonuclear domain is more limited in slow than fast fibers and in the fibers with a high, compared to a low, oxidative metabolic capability.

Animals↗