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Insulin action and insulinemia are closely related to the fasting complement C3, but not acylation stimulating protein concentration.

OBJECTIVE: An elevated C3 concentration has been reported in people with obesity, type 2 diabetes, hypertension, and dyslipidemia, and has been proposed to play a role in the development of atherosclerosis. We hypothesized that an elevated C3 concentration might be linked to insulin resistance and/or hyperinsulinemia, abnormalities commonly observed in association with the above conditions. RESEARCH DESIGN AND METHODS: Fasting concentrations of C3 and acylation stimulating protein (ASP, C3adesarg), a cleavage product of C3 recently found to stimulate glucose uptake in vitro, were measured in 33 healthy nondiabetic Pima Indians (14 women and 19 men; age 27 +/- 1 and body fat 33 +/- 1%, means +/- SEM). Subjects were characterized for body composition dual-energy X-ray absorptiometry, insulin action (insulin-stimulated glucose disposal [M], hyperinsulinemic glucose clamp), and glucose tolerance (75-g oral glucose tolerance test). RESULTS: Fasting C3 and ASP concentrations were positively correlated (r = 0.43, P < 0.05). Fasting C3 concentration was closely related to percent body fat (r = 0.77), M (r = -0.75), and fasting insulin concentration (r = 0.72) (all P < 0.0001). Fasting C3 concentrations remained significantly related to M and fasting insulin after adjusting for percent body fat (partial r = -0.53 and 0.33, both P < 0.05). In subjects with impaired glucose tolerance, fasting C3 concentrations were higher than in those with normal glucose tolerance--a difference that remained after adjustment for percent body fat and M. We found that fasting ASP concentrations were significantly related to percent body fat (r = 0.37, P < 0.05), but not to M or fasting insulin. CONCLUSIONS: In Pima Indians, fasting C3 concentration is closely related to adiposity, insulin action, and fasting insulin levels and may thus be a mediator for the postulated link between obesity, insulin resistance, hyperinsulinemia, and possibly atherosclerosis.

Absorptiometry, Photon↗

Effects of fasting on tissue amino acid concentrations and urea-cycle enzymatic activities in young pigs.

Weanling pigs were fed a 30% crude protein (CP) diet for 18 d and then assigned to one of three regimens for either 4 or 8 d: 1) fasting, 2) 3% CP, i.e., maintenance or 3) 30% CP after which they were bled, then sacrificed for tissue assessment. Relative to pigs fasted or fed 30% CP, feeding 3% CP resulted in decreased urea-N and NH3-N excretion in the urine. Arginase and ornithine transcarbamoylase (OTC) activities in liver, and arginase activity in kidney cortex were markedly lower in pigs fed 3% CP compared with those either fasted or fed 30% CP. Hepatic arginase and OTC, however, were higher in fasted pigs than in those fed 30% CP. Pigs fed 3% CP had much lower levels of free threonine, tyrosine, cystathionine, taurine and branched-chain amino acids in plasma, liver, kidney, muscle and brain than fasted pigs or those fed 30% CP. Threonine concentration in brain, liver, muscle and plasma increased as length of the fast increased. Fasted pigs had decreased free alanine levels in plasma, and decreased free serine levels in plasma and liver when compared with fed pigs. Inter-organ comparisons provided evidence that both alanine and serine were important gluconeogenic amino acids during fasting. In general, free amino acid levels in brain were similar between fasted pigs and those fed 30% CP. Fasting for 8 d caused a 10-fold elevation in urinary taurine excretion relative to that observed for 4-d fasted pigs.

Amino Acids↗

Effect of sera from fed and fasted pigs on proliferation and protein turnover in cultured myogenic cells.

The effects of fasting on the ability of swine serum to affect proliferation, protein synthesis and protein degradation in L6 myoblast cell culture bioassays were evaluated. Barrows (15 to 20 kg) were fitted with jugular catheters. Blood samples were collected at four evenly spaced intervals between 0800 and 1700 on collection days. Prefast blood samples were obtained on d 1 and 2 of the study, after which pigs were subjected to a 5-d fast. Fasted samples were obtained on the 1st, 3rd and 5th d of the fast (d 3, 5 and 7 of the study). Serum from each collection day was pooled and tested in the proliferation bioassay for each pig. Prefast and fasted serum pools were formed by pooling prefast days (1 and 2) or fasted days (3, 5 and 7), respectively, from all pigs in a study. These pools were tested in the proliferation and protein turnover bioassays as well as in a Somatomedin-C (SmC) radioimmunoassay. Serum from the fasted collection days showed a decrease in mitogenic activity compared with serum from the two prefast days (P less than .001). At high concentrations, sera obtained from fasted pigs inhibited muscle cell proliferation (P less than .001). Additionally, adding fasted serum to control swine serum (CSS) inhibited the mitogenic activity of CSS in a dose-dependent manner (P less than .025). Therefore, fasted sera showed a decreased ability to promote muscle cell proliferation and, in addition, appeared to contain a factor(s) that inhibits muscle cell proliferation. Fasted serum also caused a 21.6% increase in protein degradation compared with prefast serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fasting plasma C-peptide levels in health and impaired glucose tolerance: relations to blood glucose and relative body weight.

Pancreatic B-cell function was studied as part of a health control examination by measuring fasting plasma C-peptide concentration in 433 44-55 year-old males with normal glucose tolerance. Fasting C-peptide levels were correlated with relative body weight (r = 0.48) and fasting blood glucose concentrations (r = 0.43), yielding a multiple correlation coefficient of 0.56, and the multiple regression equation: FCP (nmol/l) = -0.89 + 0.61 X RBW + 0.16 X FBG (mmol/l). (FCP = fasting plasma C-peptide, RBW = relative body weight, FBG = fasting blood glucose). In 26 subjects with impaired glucose tolerance, fasting plasma C-peptide levels were even more strongly correlated with relative body weight (r = 0.63) and fasting blood glucose concentrations (r = 0.47). Subjects older than 52 years had a significantly higher fasting C-peptide level than younger subjects (p less than 0.01). In the 26 subjects with impaired glucose tolerance, fasting plasma C-peptide levels were not significantly different from those in the 433 men with normal glucose tolerance. However, when compared to a group with normal glucose tolerance matched for relative body weight, the subjects with impaired glucose tolerance had an elevated fasting blood glucose level (p less than 0.01) without difference in C-peptide level, suggesting a reduced insulin sensitivity. It is concluded that, in order to evaluate B-cell secretory function by determining fasting plasma C-peptide concentration, the relative body weight and simultaneous blood glucose concentration should be taken into consideration.

Adult↗

Fecal shedding and rumen growth of Escherichia coli O157:H7 in fasted calves.

Nine weaned calves aged from 8 to 12 weeks were fitted with rumen cannulas and were inoculated by cannula with 10(10) CFU of a five-strain mixture of nalidixic acid-resistant Escherichia coli O157:H7. Six calves were fasted for 48 h on days 15 and 16 and days 22 and 23 after inoculation. Samples of rumen contents and feces were obtained daily to enumerate E. coli O157:H7 populations and to determine rumen volatile fatty acid (VFA) concentrations and rumen pH. Fasting resulted in a marked decrease in rumen VFA concentrations from a mean of 135 mmol/liter before the fast to a mean of 35 mmol/liter during the second day of the fast. However, there was no correlation between daily VFA concentration and daily rumen or fecal numbers of E. coli O157:H7 in any of the calves. Fasting generally had no significant effect on the rumen or fecal numbers of E. coli O157:H7. The exception was a single fasted calf that experienced a 3-log(10) CFU/g increase in fecal shedding during and after the first fast. Despite the consistent changes in VFA concentrations in fasted calves, the fluctuations in rumen numbers of E. coli O157:H7 in the rumen of fasted calves were minimal. At the end of the experiment, E. coli O157:H7 was detected in either the rumen or omasum in two of three control calves at necropsy and in either the rumen or reticulum in five of six fasted calves. E. coli O157:H7 was detected in the colon in two of three control calves and in six of six fasted calves at necropsy. These results suggest that in cattle already shedding E. coli O157:H7, feed withdrawal and the associated changes in rumen pH and VFA concentrations have little effect on fecal shedding and rumen proliferation of E. coli O157:H7.

Animals↗

The association between cardiorespiratory fitness and impaired fasting glucose and type 2 diabetes mellitus in men.

BACKGROUND: Several studies show an inverse association between self-reported physical activity and type 2 diabetes. It is not known whether physical activity or cardiorespiratory fitness is associated with the onset of objectively determined impaired fasting glucose and type 2 diabetes. OBJECTIVE: To determine whether cardiorespiratory fitness, an objective marker of physical activity, is associated with risk for impaired fasting glucose and type 2 diabetes. DESIGN: Population-based prospective study. SETTING: Preventive medicine clinic. PATIENTS: 8633 nondiabetic men (of whom 7511 did not have impaired fasting glucose) who were examined at least twice. MEASUREMENTS: Cardiorespiratory fitness (determined by a maximal exercise test on a treadmill), fasting plasma glucose level, and other clinical and personal characteristics and incidence of impaired fasting glucose and type 2 diabetes. RESULTS: During an average follow-up of 6 years, 149 patients developed type 2 diabetes and 593 patients developed impaired fasting glucose. After age, cigarette smoking, alcohol consumption, and parental diabetes were considered, men in the low-fitness group (the least fit 20% of the cohort) at baseline had a 1.9-fold risk (95% CI, 1.5- to 2.4-fold) for impaired fasting glucose and a 3.7-fold risk (CI, 2.4- to 5.8-fold) for diabetes compared with those in the high-fitness group (the most fit 40% of the cohort). The risk for impaired fasting glucose was elevated in older men and those with a higher body mass index. Age, body mass index, blood pressure, triglyceride level, and a history of parental diabetes were also directly related to risk for type 2 diabetes. CONCLUSIONS: Low cardiorespiratory fitness was associated with increased risk for impaired fasting glucose and type 2 diabetes. A sedentary lifestyle may contribute to the progression from normal fasting glucose to impaired fasting glucose and diabetes. Risk for type 2 diabetes was elevated in older persons and those with higher body mass index, blood pressure, and triglyceride levels and a parental history of diabetes.

Adult↗

How to minimize missing those subjects with high 2HR plasma glucose but 'normal' fasting plasma glucose levels?

Among the subjects with 'normal' fasting plasma glucose (PG) levels (< 7.0 mmol/L), some of them are actually suffering from impaired glucose tolerance and diabetes, which can only be diagnosed by 2hr PG levels. We aim to find out a proper clinical approach in order to minimize missing those subjects with high 2hr PG but 'normal' fasting PG levels. We analyzed data collected from a previously published population-based prevalence survey for glucose intolerance in 1486 Hong Kong Chinese subjects who had no past history of diabetes. Of the 1468 subjects, there were 138 subjects (9.4%) having "missed glucose intolerance". Compared to the diabetic subjects (fasting plasma glucose > or = 7.0 mmol/L) after adjustment for age, the subjects with missed glucose intolerance had similar characteristics except lower glycemic level. Compared to the normal subjects (fasting plasma glucose < 7.0 mmol/L) after adjustment for age, subjects with missed glucose intolerance had more obesity (both general and central), more hypertension, worse glycemic status and lipid profile in both men and women. There were 38 subjects (2.6%) having impaired fasting glucose. Of these 38 subjects, 24 (63.2%) had missed glucose intolerance. The detection of missed glucose intolerance increased from 9.7% of overall male subjects to 23.1% in men with hypertension to 52.9% in men with both hypertension and family history of diabetes. Similarly, the detection of missed glucose intolerance increased from 9.0% of overall female subjects to 25.7% in women with obesity to 45.2% in women with both obesity and hypertension. If only fasting plasma glucose is performed, 4% of subjects will be diagnosed to have diabetes or impaired fasting glucose while up to 10% of subjects having impaired glucose tolerance or diabetes will be missed in Hong Kong Chinese. The latter 2 groups of subjects have similar cardiovascular risk factors to those with fasting PG > or = 7.0 mmol/L. We recommend that for those with a family history of diabetes, hypertension or obesity, an oral glucose tolerance test instead of fasting plasma glucose should be used in the first place for the diagnosis of glucose intolerance. For those with impaired fasting glucose, a routine follow-up oral glucose tolerance test should also be performed. This clinical approach may improve the detection of those subjects with glucose intolerance, who will be otherwise missed by using fasting plasma glucose alone.

Adult↗

Stimulation of tumor growth in adult rats in vivo during an acute fast.

These experiments investigate an increase in tumor growth that occurs in adult rats in vivo during an acute fast. The effects of feeding, fasting, and underfeeding on the growth of Morris hepatomas 5123C and 7288CTC in Buffalo rats and of Walker carcinoma 256 and Jensen sarcoma in Sprague-Dawley rats were studied. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fasting or underfeeding. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Fasting increased the rate of growth of the tumors 3 to 4 times over that measured in fed rats. This effect began during the first day of fasting and ended abruptly on refeeding. After refeeding tumor growth slowed to the rate in fed rats. Tumors from fed or fasted rats were not different in cellularity or dry weight/g wet weight. A positive growth response in the tumor required lipolysis and ketosis in the host. No stimulation was observed during an acute fast in either immature rats or in mature rats whose weights had been reduced by underfeeding. These animals have small fat stores and show no increase in arterial blood free fatty acid or ketone body concentrations during an acute fast. Finally, underfeeding of adult rats raised the blood concentrations of these nutrients to values that were intermediate between those in fasted and fed rats. Tumor growth rates in these rats were intermediate between those in fasted and fed rats. The results support the proposal that an increase in availability of free fatty acids and/or ketone bodies is the stimulus that increases the rate of tumor growth during an acute fast.

Animals↗

Effects of duration of fast and animal age on the gastrointestinal absorption of plutonium.

The fraction of plutonium absorbed after oral administration of Pu(VI) to 24-h-fasted mice was 19 X 10(-4), 13-fold higher than in fed mice, 1.4 X 10(-4). We have investigated the relevance of the high gastrointestinal (GI) absorption value for the 24-h-fasted animals in setting drinking water standards for humans. When fasting was initiated at the beginning of the active phase of the mouse's daily activity cycle (when they would normally eat), plutonium GI absorption rose from 2.8 X 10(-4) at zero-time to a level typical of the 24-h-fasted mouse after only 2 h of fasting. In contrast, in mice allowed to eat for 4 h into their active phase prior to initiation of the fast (meal-fed mice), 8 h of fasting were required before GI absorption rose to a level similar to that of the 24-h-fasted mouse. The fraction of plutonium retained after gavage administration of Pu(VI) to 1-day-old rats was 74 X 10(-4), 70-fold higher than the value for fed adults. Retention after GI absorption in neonates remained 30- to 70-fold higher than in adults until weaning. One week after weaning, the fraction absorbed and retained by fed weanling rats was the same as that for fed adults, 1 X 10(-4). Drinking water standards for plutonium have been set based on GI absorption values for fed adult animals. The 10- to 100-fold increases in plutonium absorption in young and fasted animals reported by ourselves and others, and the rapid rise to fasted levels of absorption at the start of the animal's active phase, indicate that consideration should be given to elevated levels of plutonium absorption in young and fasted individuals.

Aging↗

Effect of fasting on plasma metabolites and hormones in lactating dairy cows.

Metabolic and pathophysiologic changes of secondary ketosis were studied. Plasma samples were obtained from a group of 8 mature, lactating dairy cows before, during, and after a 48-hour fast. These samples were analyzed for glucose, free fatty acids (FFA), lactic acid, ketone bodies, glucocorticoids, insulin, and growth hormone concentrations. In the prefasting period, metabolites and hormones remained constant. Lactic acid and glucocorticoids also remained stable during the entire experiment, except on the 1st day after termination of the fast, when glucocorticoids increased significantly (P less than 0.05). Glucose values decreased significantly (P less than 0.01) with the onset of fasting, began to rise halfway through the fast, and were elevated following termination of the fast. Plasma glucose concentration returned to normal by the end of the experiment. Plasma FFA concentrations increased during the early portions of the fast and decreased thereafter. Plasma ketone body concentration responded similarly, but the change occurred approximately 12 hours after the plasma FFA changes. A value determined as ketotic was reached during the fast (14.6 +/- 1.3 mg/dl). Insulin concentrations remained low during the fast and increased after fasting. Plasma growth hormone concentration increased to a new plateau in response to fasting and then decreased somewhate after fasting was ended.

Animals↗

The influence of fasting on the disposition of warfarin in rats.

A study was undertaken to investigate the influence of fasting on the disposition of warfarin in rats. Fasting consisted of withholding solid food, but not water, immediately following warfarin (3 or 10 mg/kg s.c.) administration until sacrifice at different time intervals (3, 6, 12, 24 and 30 hours). Control animals were fed ad libitum. Total and unbound warfarin concentrations were measured in plasma and liver supernatant as well as unchanged warfarin and its metabolites in urine. The disposition of unbound warfarin was found to be markedly affected by fasting, especially at the 3 mg/kg dose: the disappearance rate of unbound warfarin from plasma was accelerated in fasted animals in contrast to that of total warfarin. In addition, unbound warfarin was cleared from plasma at a more rapid rate than total warfarin in both control and fasted animals. At the 10 mg/kg dose, the disposition of total and unbound warfarin was little affected by fasting. The concentration of unbound warfarin in the liver supernatant of fasted rats given warfarin, 3 mg/kg, was significantly increased at 6 and 24 hours of fasting. Plasma free fatty acids were significantly elevated starting at 6 hours, but no such difference was noticed with liver homogenate, except at 24 hours. The 24-hour urinary excretion of unchanged warfarin was higher in fasted rats, but fasting failed to produce any change in the excretion of warfarin metabolites. The results of the present investigation indicate that short periods of fasting influence the disposition of unbound warfarin without apparently modifying its biotransformation and further show the importance of plasma protein binding on the pharmacokinetics of warfarin.

Animals↗

Body fatness and waist circumference are independent predictors of the age-associated increase in fasting insulin levels in healthy men and women.

OBJECTIVE: Elevated levels of fasting insulin increase the risk for coronary artery disease. In this study, we considered the independent contributions of age, total body fatness, abdominal fat distribution, peak aerobic capacity, leisure time physical activity, dietary intake, and fasting glucose levels to the age-associated increase in fasting insulin levels in healthy men and women. DESIGN: A cross-sectional analysis. SUBJECTS: A total of 427 healthy men and 293 healthy women age 18 to 90 years. MEASUREMENTS: Plasma glucose and insulin levels were measured in the fasted state and subjects were characterized for body fatness from underwater weighting, abdominal fat distribution from the waist circumference, peak VO2 from a treadmill test to exhaustion, leisure time physical activity from a structured interview and dietary intake from a 3-day food diary. The independent predictors of fasting insulin levels were determined by stepwise multiple regression analysis. RESULTS: Fasting insulin concentrations increased with age in both men (0.09 +/- 0.02 pmol/yr, unadjusted slope +/- SEE) and women (0.14 +/- 0.03 pmol/yr). In men, the major independent predictors of fasting insulin levels were percent body fat (r2 = 28%, P < 0.001) and waist circumference (r2 = 3% P < 0.001). Age, glucose concentration, and peak VO2 were small (1% each), but independent contributors to the variance in insulin levels. In women, the waist circumference (r2 = 18%, P < 0.001) and the fasting glucose concentration (r2 = 7%, P < 0.001) were the independent correlates of fasting insulin concentrations. CONCLUSIONS: Our data suggest that total adiposity and central body fat distribution are significant determinants of the increase in fasting insulin levels, whereas age, dietary intake, and levels of aerobic fitness and physical activity appear to be less important contributors to the variation in fasting insulin concentrations in healthy men and women.

Adolescent↗

Visceral adiposity, fasting plasma insulin, and lipid and lipoprotein levels in Japanese Americans.

OBJECTIVE: To examine the associations among visceral and subcutaneous adiposity, body-mass-index (BMI), fasting plasma insulin, lipid, and lipoprotein levels. DESIGN: Cross-sectional observational study. SUBJECTS: Non-diabetic second- (Nisei, n = 290) and third-generation (Sansei, n = 229) Japanese Americans. MEASUREMENTS: Intra-abdominal (IAF) and subcutaneous abdominal fat (SAF) area were measured using computed tomography. Fasting plasma insulin, lipid, and lipoprotein levels were measured using standard methods. RESULTS: Higher fasting insulin was significantly related to greater mean IAF and SAF area, plasma triglycerides, total HDL and HDL2 cholesterol in men and women of both generations. In a multiple linear regression analysis model among Nisei adjusted for gender, age, SAF, antihypertensive medication use, smoking, alcohol use, and exercise energy expenditure, IAF area and fasting insulin level were independently correlated with plasma triglycerides (IAF r = 0.22, fasting insulin r = 0.23), total HDL (IAF r = -0.29, fasting insulin r = -0.28), HDL2 (IAF r = -0.30, fasting insulin r = -0.27), and HDL3 cholesterol (IAF r = -0.19, fasting insulin r = -0.19). Among Sansei, similar associations were seen, except that fasting insulin was unrelated to total HDL or HDL3 cholesterol. These effects differed by gender in several instances. CONCLUSIONS: Both visceral adiposity and fasting insulin level are significantly and independently related to adverse levels of lipids and lipoproteins in both generations of nondiabetic Japanese Americans. The association between adverse lipid profile and visceral obesity is not mediated solely through detrimental effects of intra-abdominal fat deposition on fasting insulin level.

Adipose Tissue↗

Xenobiotics released from fat during fasting produce estrogenic effects in ovariectomized mice.

The pesticide residues 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2,2-trichloroethane (o,p'-DDT) and beta-hexachlorocyclohexane (beta-HCH) act as weak estrogens, producing uterotrophic responses in ovariectomized rodents and stimulating human breast cancer cells in culture. Such activity suggests that these compounds may act as tumor promoters in estrogen-responsive tissues. Organochlorine compounds such as o,p'-DDT and beta-HCH are concentrated in body fat. The present report tests whether sufficient compound can be released from fat depots to produce estrogenic effects in uteri of ovariectomized mice. Adult animals were "loaded" with test compound by three daily injections of vehicle (DMSO), 17beta-estradiol (E2), beta-HCH, or o,p'-DDT. Uterotrophic effects were assessed at 24 h after the last loading dose of test compound and at 2 weeks after the loading regimen, with or without a prior 2-day period of fasting. The initial 3-day treatment with either beta-HCH or o,p'-DDT doubled the relative dry weight of the uterus: 102 +/- 8.6 mg/kg body weight (BW) and 104 +/- 4.4 mg/kg BW for beta-HCH and o,p'-DDT, respectively, compared to 49 +/- 1.9 mg/kg BW for vehicle-treated animals. E2-treated animals had uterine dry weights of 228 +/- 11 mg/kg BW. After 2 weeks without further treatment, a 2-day fast produced a decrease in body mass of 4.1 g/animal (fasted, 25.9 +/- 1.89 g versus fed, 30.0 +/- 2.82 g). Animals that had been loaded with beta-HCH and fasted had uterine weights (88 +/- 12 mg/kg BW) significantly greater (P < 0.05) than those of vehicle-loaded, fasted animals (51 +/- 2.9 mg/kg BW) or of beta-HCH-loaded, fed animals (59 +/- 4.6 mg/kg BW). The uterine weights of the fasted and fed o,p'-DDT-loaded or E2-loaded animals were not different from those of control weights. The difference between wet and dry weights showed that fasting of beta-HCH-loaded animals also increased water imbibition in the uterus; there was no effect from fasting in the other groups. Generally, epithelial cell height reflected the same responses as uterine weight with the exception that cell heights of beta-HCH-loaded, fed animals were slightly higher (P < 0.05) than corresponding controls, indicating that there may have been some active compound available to the tissues even without fasting. The effects of fasting show that during periods of lipolysis beta-HCH can be released in quantities sufficient to stimulate estrogen target tissues, suggesting a novel mechanism linking obesity and the progression of estrogen-responsive tumors. The lack of effect from fasting in o,p'-DDT-loaded animals indicates that these compounds are differentially mobilized from fat depots.

Adipose Tissue↗

Posterior fast atrioventricular node pathways: implications for radiofrequency catheter ablation of atrioventricular node reentrant tachycardia.

OBJECTIVES: This study sought to present evidence that fast atrioventricular (AV) node pathways with posterior exit sites may participate in typical AV node reentry. BACKGROUND: Catheter ablation of the slow AV node pathway in the posteroseptal right atrium is the preferred therapeutic approach in patients with AV node reentrant tachycardia. Despite the success achieved with this approach, electrophysiologic changes consistent with fast pathway ablation are occasionally observed. One potential explanation is the presence of an aberrant posterior fast pathway. METHODS: The location of fast and slow AV node pathways was determined by atrial activation mapping along the tricuspid valve annulus during tachycardia and was further confirmed by the effect of radiofrequency catheter ablation. RESULTS: Seven patients with AV node reentrant tachycardia had evidence of a posterior fast pathway near the coronary sinus os. Abolition of anterograde and retrograde fast pathway conduction followed radiofrequency ablation in the posteroseptal region in six patients. Consistent with fast pathway ablation, the AH interval increased from 70 +/- 24 to 195 +/- 35 ms (mean +/- SD), and tachycardia was no longer inducible. Selective slow pathway ablation was performed in one other patient with a posterior fast pathway. CONCLUSIONS: Functionally fast AV node pathways may be located in the posteroseptal right atrium, where slow pathway modification is performed. These data delineate the limitation of an anatomically guided slow pathway ablative approach and emphasize the importance of detailed mapping and localization of the retrograde fast pathway exit site before ablation. Failure to recognize the presence of posterior fast AV node pathways may account for sporadic examples of AV block, complicating posteroseptal ablation in patients with AV node reentry.

Adult↗

Estimating the fasting triglyceride concentration from the postprandial HDL-cholesterol and apolipoprotein CIII concentrations.

Hypertriglyceridemia is an important risk factor for atherosclerosis. In the fasting state, the triglyceride (TG) concentration is correlated significantly with the high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein CIII (apoCIII) concentrations. A postprandial change is evident in TG, but negligible in HDL-C and apoCIII. We investigated whether the fasting TG concentration could be estimated from the postprandial HDL-C and apoCIII concentrations. We measured the TG, HDL-C, and apoCIII concentrations at seven points a day in 58 inpatients. Multiple regression analysis showed that the actual fasting TG concentration was strongly correlated with the TG concentration estimated from the fasting HDL-C and apoCIII concentrations (ln[TG](fasting)=0.0140[apoCIII](fasting)-0.724[HDL-C](fasting)-0.142, r=0.852, p<0.001). This equation was also fit to the fasting data from 163 outpatients (r=0.883, p<0.001). Although the TG concentration increased by up to 28.2%, the HDL-C and apoCIII concentrations changed little during the day. When we substituted the postprandial HDL-C and apoCIII concentrations for the respective fasting values in this equation, there were still strong positive correlations (r=0.794-0.840) between the actual and estimated fasting TG concentrations throughout the day. In conclusion, the fasting TG concentration can be estimated from the postprandial HDL-C and apoCIII concentrations.

Aged↗

Establishment of a time-resolved fluoroimmunoassay for measuring plasma insulin-like growth factor I (IGF-I) in fish: effect of fasting on plasma concentrations and tissue mRNA expression of IGF-I and growth hormone (GH) in channel catfish (Ictalurus punctatus).

A time-resolved fluoroimmunoassay (TR-FIA) was established and validated that allows for the determination of plasma concentrations of insulin-like growth factor I (IGF-I) in three domestically cultured fishes: channel catfish (Ictalurus punctatus), hybrid striped bass (Morone chrysopsxM. saxatilis), and rainbow trout (Oncorhynchus mykiss). Sensitivity of the assay was 0.20 ng/ml. Intra- and inter-assay coefficients of variation (CV) were <7 and <12%, respectively. Serial dilutions of plasma from each species were parallel to the standard curve. Recovery of IGF-I from spiked plasma samples was >90% for all three species of fishes. The IGF-I TR-FIA was biologically validated via its use to determine the effect of fasting on circulating IGF-I levels in channel catfish. Fasting-induced changes in plasma growth hormone (GH), hepatic IGF-I mRNA expression, and pituitary GH mRNA expression were also determined. Fasted channel catfish lost 5.6 and 15.6% body mass after 2 and 4 weeks of fasting, respectively. Plasma IGF-I concentrations were depressed (P<0.05) relative to fed controls following 2 and 4 weeks of fasting. Plasma GH concentrations were not different (P>0.05) in fasted fish after 2 weeks, but significantly increased (P<0.05) by 4 weeks of fasting. Hepatic IGF-I mRNA expression after 2 and 4 weeks of fasting was reduced (P<0.05) relative to fed controls. Pituitary GH mRNA expression was similar (P>0.05) between 2-week-fasted catfish and fed controls, but was increased (P<0.05) in 4-week-fasted catfish. The IGF-I TR-FIA was sensitive, accurate, and precise for all three species of fishes, and provided a low-cost, and non-radioisotopic method for quantifying plasma IGF-I levels in fed and fasted channel catfish.

Animals↗

Time course of the GH/IGF axis response to fasting and increased ration in chinook salmon (Oncorhynchus tshawytscha).

Body growth in vertebrates is chiefly regulated by the GH/IGF axis. Pituitary growth hormone (GH) stimulates liver insulin-like growth factor-I (IGF-I) production. During fasting, plasma IGF-I levels decline due to the development of liver GH resistance, while GH levels generally increase. In mammals, decreased insulin during fasting is thought to cause liver GH resistance. However, the sequence of events in the GH/IGF axis response to fasting is not well characterized, especially in non-mammalian vertebrates. We assessed the time course of the GH/IGF axis response to fasting and increased ration in chinook salmon. Fish were placed on Fasting, Increased, or Control rations, and sampled daily for 4 days and at more widely spaced intervals through 29 days. Plasma IGF-I, GH, insulin, and 41 kDa IGF binding protein (putative salmon IGFBP-3), and liver IGF-I gene expression were measured. Control and Increased ration fish did not differ strongly. Plasma IGF-I and 41 kDa IGFBP were significantly lower in Fasted versus Control fish from day 4 onward, and liver IGF-I gene expression was significantly lower from day 6 onward. Liver IGF-I gene expression and plasma IGF-I levels were correlated. Plasma insulin was lower in Fasted fish from day 6 onward. There was a trend toward increased GH in Fasted fish on days 1-2, and GH was significantly increased Fasted fish from day 3 onward. Fasted GH first increased (days 1-3) to a plateau of 10-20 ng/ml (days 4-12) and then increased dramatically (days 15-29), suggesting that the GH response to fasting had three phases. The early increase in GH, followed by the decrease in plasma IGF-I after 4 days, suggests that GH resistance developed within 4 days.

Animals↗