Brief Periods Of Fasting Research Articles

Abstract #1402115: A Case of Starvation Ketoacidosis in Pregnancy Secondary to Perforated Appendicitis

Starvation ketoacidosis in pregnant patients is a rare but life-threatening condition. There are few case reports in the literature of starvation ketoacidosis of pregnancy with no consensus on treatment. We present a case of starvation ketoacidosis in pregnancy that was successfully treated with dextrose and insulin infusion. A 35-year-old pregnant woman with a history of prior gestational diabetes diagnosed in a previous but not current pregnancy presented at 33 weeks of gestation with severe abdominal and poor oral intake for 3 days prior to admission. On evaluation, the patient was found to have a perforated appendix with peritonitis and was taken to the operating room for open laparotomy. During surgery, she was noted to have an anion gap metabolic acidosis. Arterial blood gas revealed pH of 7.06 (range 7.35-7.45), pCO2 of 43mmHg (range 32-35 mmHg), pO2 of 120 mmHg (range 83-108 mmHg), and bicarbonate of 12 mmol/L (range 22-26 mmol/L). Further blood work demonstrated serum bicarbonate of 14 mmol/L (range 21-30 mmol/L), and an anion gap of 18 (4-16). Beta-hydroxybutyrate was elevated at 58.5 mg/dL (range 0-3 mg/dL), with serum glucose of 134 mg/dL (range 70-99 mg/dL) and normal lactate of 1.3 mmol/L (range 0.5-2.2 mmol/L). Urinalysis demonstrated 2+ ketones (range negative). She was started on a dextrose 5% infusion with insulin infusion at a fixed rate to overcome any inherent insulin resistance and suppress lipolysis. Metabolic parameters were corrected in 12 hours and the patient was extubated in 24 hours. At 48 hours, insulin and dextrose infusions were discontinued. She then underwent cesarian section 1.5 weeks later due to development of pelvic abscess requiring surgical intervention. She delivered a healthy baby girl. Women in late pregnancy are at increased risk for ketosis during even brief periods of fasting. This is due to increased relative insulin resistance and enhanced lipolysis, a protective mechanism to ensure adequate glucose supply to the growing fetus. Prompt recognition of ketosis and timely management are essential to prevent profound acidosis and avoid maternal-fetal mortality. Although there is no consensus on management of starvation ketoacidosis in pregnancy, most case reports suggest carbohydrate administration is the cornerstone of treatment, although insulin administration can be considered if there is concern for marginal insulin reserve or there is treatment failure with carbohydrate administration alone. In our case, given the profound degree of acidosis, simultaneous administration of carbohydrate and insulin was pursued with rapid resolution of the patient’s metabolic derangements.

PSUN240 A Case of Euglycemic DKA in Pregnancy

Abstract Background Euglycemic diabetic ketoacidosis (EKDA) is a rare diagnosis of exclusion occurring in a state of decreased hepatic production of glucose due to fasting state or enhanced urinary excretion of glucose. Pregnancy predisposes a woman to a state of accelerated starvation, where even short periods of fasting can lead to increased lipolysis and subsequent ketosis. DKA can develop quickly at lower serum glucose concentrations when triggers such as stress, pump malfunction, infection are present. EDKA is particularly important to recognize and treat in pregnant patients, as this increases risk of fetal demise. Diagnostic criteria of EKDA are elevated beta-hydroxybutyrate in serum or urine, decreased serum bicarbonate, glucose > 200 mg/dL, anion gap metabolic acidosis.Clinical case:26-year-old female G1P2 at 29-weeks’ gestation, with a medical history of type 1 diabetes mellitus on insulin pump, hypothyroidism, prior pregnancy complicated by pre-eclampsia presented as a transfer from an outside hospital after a low-impact motor vehicular accident. Patient was transferred with concern for DKA. At the time of presentation patient had been using her insulin pump per home settings, was NPO for at least 24 hours due to nausea and mild abdominal pain. BP was 140/77 mmHg, HR 114 beats/min, 97.6F, RR 16 with SpO2 99% on RA. Patient was alert and oriented, not in acute distress. Labs were notable for beta-hydroxybutyrate of 3.3 mmol/L, lactate 1.0 mmol/L, HbA1c 7.3%, TSH 3.16 mIU/L, Na 136 mmol/L, K 4 mmol/L, Cl 105 mmol/L, serum bicarbonate 18 mmol/L, glucose 97 mg/dL, creatinine 0.49 mg/dL, eGFR >90 mL/min/1.73m2, anion gap of 13 mmol/L. Patient was found to be in euglycemic DKA and was started on IV insulin with fluid resuscitation per protocol. Endocrinology was consulted as labs demonstrated worsening, with Na 135 mmol/L, serum bicarbonate 17 mmol/L, glucose 166 mg/dL. At this point patient had just started tolerating PO intake, no fetal distress was observed. We recommended continuation of treatment for a total of 24 hours, with subsequent normalization of labs and resolution of nausea. Patient was transitioned to home insulin pump with recommendation to snack frequently between meals and was discharged home with outpatient follow up. Upon follow up, patient did not experience recurrence of DKA but had been induced at 33 weeks due to pre-eclampsia, successfully giving birth to a live baby girl with Apgar scores of 5/6. Conclusions EDKA is a rare but easily missed diagnosis that is important to treat particularly in a pregnant patient, as risks of fetal demise are high. Serum or urine ketones should be checked in any hospitalized diabetic patient regardless of symptoms or other laboratory indicators. Triggers of EKDA in a state of pregnancy can include brief periods of fasting, infection, stress, and dehydration. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Preoperative fasting protects mice against hepatic ischemia/reperfusion injury: mechanisms and effects on liver regeneration

We show that brief periods of fasting induce functional changes similar to those induced by long-term dietary restriction in mice, and these changes include protection from ischemia/reperfusion (I/R) injury. In this study, we investigated the mechanisms of protection induced by fasting, and we determined the effect on liver regeneration after partial hepatectomy. Partial hepatic ischemia (75 minutes) was induced in ad libitum fed mice and in 1- to 3-day-fasted mice, and one-third or two-thirds hepatectomy was performed in ad libitum fed mice and 3-day-fasted mice. Preoperative fasting for 2 or 3 days significantly decreased hepatocellular I/R injury. Hepatic gene expression of heme oxygenase 1 (HO-1), superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (Gpx1), and glutathione reductase (GSR) was significantly up-regulated in 3-day-fasted mice at the baseline and 6 hours after reperfusion. After reperfusion, p-selectin and interleukin-6 (IL-6) levels were significantly lower, and superoxide radical generation, lipid peroxidation, and neutrophil influx were significantly attenuated in 3-day-fasted mice. Preoperative fasting did not affect liver regeneration after one-third hepatectomy. Hepatic gene expression of IL-6 and transforming growth factor β1 was significantly higher in 3-day-fasted mice before and after one-third hepatectomy. Tumor necrosis factor α expression significantly increased after one-third hepatectomy in 3-day-fasted mice. After a 3-day fast and two-thirds hepatectomy, liver regeneration and subsequent postoperative recovery were compromised. In conclusion, up-regulation of the stress response gene HO-1 and the antioxidant enzymes SOD2, Gpx1, and GSR at the baseline and a better response after reperfusion likely underlie the protection induced by fasting against hepatic I/R injury. Preoperative fasting may be a promising new strategy for protecting the liver against I/R injury during liver transplantation and minor liver resections, although its effect on extended hepatectomy warrants further exploration.

Anticipatory Behavior in Blood Glucose Control: Using Meal Prior Probabilities to Prepare for Future Meal Disturbances

AbstractAutomatic regulation of blood glucose in patients with Type 1 Diabetes is challenged by unknown or unannounced food consumption. Yet we know most food is ingested in discrete meals, spaced by brief periods of fasting. Treating meals as discrete events, this paper proposes a set of prior probabilities relating distinct meals independently of daily patterns. Using these prior probabilities, closed-loop blood glucose control can attain anticipatory behavior, implicitly lowering glucose levels when patients should be hungry and meals are most likely to occur. This improves overall performance and individual meal responses. The benefits occur because blood glucose prediction, which anticipates future food intake, can achieve near zero mean errors even over a long prediction horizon. As a side effect, such predictors can easily be tuned or tested against unrestricted out-patient data which, by definition, contains unknown meals. We validate our approach in both prediction and control of blood glucose levels. We see improved prediction accuracy over 1-4 hour horizons and a significant reduction in the blood glucose risk index for simulated closed-loop control.

Responsiveness of the reproductive axis to a single missed evening meal in young adult males

The male reproductive axis is responsive to energetic deficits, including multiday fasts, but little is known about brief periods of fasting (<24 hours). Reduced testosterone in low-energy balance situations is hypothesized to reflect redirection of resources from reproduction to survival. This study tests the hypothesis that testosterone levels decrease during a minor caloric deficiency by assessing the effects of a single missed (evening) meal on morning testosterone in 23 healthy male participants, age 19-36. Participants provided daily saliva and urine samples for two baseline days and the morning following an evening fast (water only after 4 PM). Testosterone, cortisol, and luteinizing hormone were measured with enzyme immunoassays. Fasting specimens had significantly lower overnight urinary luteinizing hormone (P = 0.045) and morning salivary testosterone than baseline (P = 0.037). In contrast to morning salivary testosterone, there was a significant increase in overnight urinary testosterone (P = 0.000) following the evening fast, suggesting an increase in urinary clearance rates. There was a marginal increase in overnight urinary cortisol (P = 0.100), but not morning salivary cortisol (P = 0.589). These results suggest the male reproductive axis may react more quickly to energetic imbalances than has been previously appreciated.

Regulation of glutamate metabolism and insulin secretion by glutamate dehydrogenase in hypoglycemic children

In addition to its extracellular roles as a neurotransmitter/sensory molecule, glutamate serves important intracellular signaling functions via its metabolism through glutamate dehydrogenase (GDH). GDH is a mitochondrial matrix enzyme that catalyzes the oxidative deamination of glutamate to α-ketoglutarate in a limited number of tissues in humans, including the liver, the kidney, the brain, and the pancreatic islets. GDH activity is subject to complex regulation by negative (GTP, palmitoyl-coenzyme A) and positive (ADP, leucine) allosteric effectors. This complex regulation allows GDH activity to be modulated by changes in energy state and amino acid availability. The importance of GDH regulation has been highlighted by the discovery of a novel hypoglycemic disorder in children, the hyperinsulinism-hyperammonemia syndrome, which is caused by dominantly expressed, activating mutations of the enzyme that impair its inhibition by GTP. Affected children present in infancy with hypoglycemic seizures after brief periods of fasting or the ingestion of a high-protein meal. Patients have characteristic persistent 3- to 5-fold elevations of blood ammonia concentrations but do not display the usual neurologic symptoms of hyperammonemia. The mutant GDH enzyme shows impaired responses to GTP inhibition. Isolated islets from mice that express the mutant GDH in pancreatic β cells show an increased rate of glutaminolysis, increased insulin release in response to glutamine, and increased sensitivity to leucine-stimulated insulin secretion. The novel hyperinsulinism-hyperammonemia syndrome indicates that GDH-catalyzed glutamate metabolism plays important roles in 3 tissues: in β cells, the regulation of amino acid–stimulated insulin secretion; in hepatocytes, the modulation of amino acid catabolism and ammoniagenesis; and in brain neurons, the maintenance of glutamate neurotransmitter concentrations.

Caloric intake versus temporal pattern of food intake

Aging Clin Exp Res, Vol. 16, No. 6 423 In 2003, Anson et al. (1) published some surprising findings: when C57BL/6 mice were given unlimited access to food one day and fasted the next day, from age 9 through 38 weeks, their total caloric intake was similar to that of mice with continuous access to food (i.e., ad libitum-fed), and this “every other day feeding” regime had beneficial effects on both carbohydrate metabolism and resistance of neurons to injury. In fact, the beneficial effects were even more pronounced with mice on the “every other day feeding” regime than with mice whose daily caloric intake was restricted to 60% of that of mice with continuous access to food. The authors suggested that “every other day feeding” may extend life by means other than reducing caloric intake, but their research provided no such information, since the duration of “every other day feeding” was only 29 weeks and the mice were about 9 months of age at the end of the study. Moreover, Duffy et al. (2) reported that longterm “every other day feeding” of mice did result in a 40% reduction in caloric intake. However, it must be noted that all experimental paradigms in caloric restriction studies have involved fasting periods of varying durations, depending on the study design (3). Thus, the anti-aging action that has been attributed to caloric restriction might instead relate to the occurrence of periodic fasting. This possibility certainly warrants further study. Indeed, an attempt was made in our laboratory to address this issue by comparing the effects of caloric restriction in rats whose daily allotment of food was provided in a single meal at 15:00 h or in two daily meals at 07:00 h and 15:00 h (4). Both of these procedures resulted in the same increase in longevity, leading us to conclude that energy intake rather than temporal pattern of food intake is the factor responsible for life extension. However, these findings do not conclusively eliminate the role of periodic fasting, since even in this twice-a-day feeding paradigm daily brief periods of fasting are likely. Caloric intake versus temporal pattern of food intake

Caloric Restriction Results in Phospholipid Depletion, Membrane Remodeling, and Triacylglycerol Accumulation in Murine Myocardium

Herein, we utilize the power of shotgun lipidomics to demonstrate that modest caloric restriction results in phospholipid depletion, membrane remodeling, and triacylglycerol (TAG) accumulation in murine myocardium. After brief periods of fasting (4 and 12 h), substantial decreases occurred in the choline and ethanolamine glycerophospholipid pools in murine myocardium (collectively, a decrease of 39 nmol of phospholipid per milligram of protein at 12 h representing approximately 25% of total phospholipid mass and approximately 20 cal of Gibbs free energy per gram wet weight of tissue). Remarkably, the selective loss of long-chain polyunsaturated molecular species was present in the major phospholipid classes thereby altering the physical properties of myocardial membranes. No decrease in TAG mass was present in myocardium during fasting, but rather myocardial TAG increased during 12 h of refeeding nearly 3-fold returning to baseline levels only after 24 h of refeeding. No alterations in other examined lipid classes were present during fasting. In contrast to these lipid alterations in myocardium, no decreases in phospholipid mass were present in skeletal muscle myocytes and a dramatic decrease in skeletal muscle (or skeletal muscle associated) TAG mass was prominent after 12 h of fasting. These results identify phospholipids as a rapidly mobilizable energy source during modest caloric deprivation in murine myocardium, while triacylglycerols are a major source of energy reserve in skeletal muscle. Collectively, these results demonstrate dramatic alterations in the membrane composition of mildly fasted mammalian myocardium that identify the unanticipated plasticity of myocardial phospholipids to adapt to modest chemical and physical perturbations.

Feeding-induced stimulation of luteinizing hormone secretion in male rhesus monkeys is not dependent on a rise in blood glucose concentration.

Recent studies have suggested a role for glucose availability in the central control of reproductive function. Various experimental paradigms have shown that a large pharmacological reduction in circulating or cellular glucose levels can suppress LH secretion, ovulation, and reproductive behavior. In contrast, states of undernutrition, which are also associated with a suppression of reproductive function, are accompanied by very mild changes in circulating glucose levels. In monkeys, 1 day of fasting leads to a significant suppression of LH secretion before any significant change in blood glucose levels, and by 2 days of fasting, circulating glucose levels only decrease by about 20%. Refeeding a normal meal after 2 days of fasting results in a restoration of euglycemia and a rapid stimulation of LH secretion. To test the hypothesis that physiological changes in glucose levels occurring during brief periods of fasting and refeeding can modulate LH secretion, we provided monkeys that had been fasted for 2 days with meals that differed in the ability to raise blood glucose levels. Meals consisting of mixed nutrients, carbohydrate only, or protein and fat were provided to monkeys through indwelling gastric cannulas. Mixed nutrient infusions and carbohydrate infusions caused a rise in blood glucose as well as a robust stimulation of LH secretion. However, protein and fat meals also stimulated LH secretion, even though no rise in blood glucose concentrations occurred. Thus, the restoration of pulsatile LH secretion when fasted animals are refed is not dependent on an elevation in circulating glucose levels. These results do not support the hypothesis that physiological changes in circulating glucose levels play a necessary role in mediating the changes in LH secretion that occur with fasting and refeeding. Alternatively, these results support the hypothesis that the availability of metabolizable fuels, regardless of their nature, provides a critical cue that regulates the central drive to the reproductive axis under physiological conditions of fasting and feeding.

Modulation of reproductive hormone secretion by nutritional intake: stress signals versus metabolic signals.

States of chronic undernutrition can cause a profound suppression of reproductive function. To begin to determine the time course and the nature of the mechanism by which undernutrition suppresses the activity of the reproductive axis we have examined the effects of brief periods of fasting on reproductive hormone secretion in men and male rhesus monkeys. In monkeys there is a significant suppression of pulsatile luteinizing hormone (LH) and testosterone secretion after a single day of fasting, that is apparent within the first 4 h after a meal is missed. The suppression of pulsatile LH secretion on a day of fasting does not appear to be caused by the psychological stress experienced when monkeys are deprived of their daily meal in that monkeys who are maintained in a metabolically fed state (by feeding a large excess of food on the day prior to fasting), but are deprived of a meal and displayed behavioural agitation associated with fasting, have no suppression of LH secretion. The suppression of LH secretion on a day of fasting cannot be reversed by naloxone infusion, indicating that increased secretion of opioid peptides is not the primary mechanism causing the decrease in the central drive to the reproductive axis during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of luteinizing hormone secretion during short-term fasting in male rhesus monkeys: the role of metabolic versus stress signals.

One day of fasting leads to a significant suppression of pulsatile LH secretion in adult male rhesus monkeys that is evident within the first 4-6 h after a missed meal. Restricting food intake may suppress the central drive to the reproductive axis via metabolic signals occurring during the transition from a fed, energy storing state to a fasted, energy mobilizing state or via signals associated with the "psychological stress" imposed by withholding food. To distinguish between these two general types of signals, we chose the experimental strategy of providing monkeys with a great excess of calories on the day before fasting (i.e. overfeeding on the day before fasting) in order to maintain them in a metabolically fed state on the following day when they were fasted, without preventing the psychological stress associated with fasting. We reasoned that if metabolic signals are responsible for causing the fasting-induced suppression of LH secretion, overfeeding on the day before fasting would prevent the fasting-induced suppression of LH secretion. Eight adult male rhesus monkeys with indwelling venous catheters were studied on three occasions: on a day of normal feeding (receiving approximately 30 pellets of monkey chow at 1100 h on the day of the study), on a day of fasting after a day of normal feeding, and on a day of fasting after a day of overfeeding (receiving one meal of 100 pellets on the day before the study). Pulsatile LH secretion on a day of fasting after a day of normal feeding (0.4 +/- 0.2 pulses/6 h, measured from 1200-1800 h) was significantly suppressed, P < 0.05, compared to a day of normal feeding (1.8 +/- 0.3 pulses/6 h). In contrast, on a day of fasting after a day of overfeeding there was no significant difference in LH secretion measured from 1200-1800 h (1.5 +/- 0.3 pulses/6 h) compared to a day of normal feeding. Overfeeding the day before fasting prevented the normal fasting-induced suppression of plasma T3 concentrations and delayed the normal fasting-induced decline in plasma insulin concentrations. Overfeeding did not prevent the display of agitated behavior that we have previously documented in monkeys when they are fasted. These results support the hypothesis that the signal(s) which suppresses normal LH secretion after brief periods of fasting is related to the metabolic status of the body during the transition from a fed to a fasted state, rather than a function of the psychological state imposed by withholding food.

Suppression of luteinizing hormone secretion during short-term fasting in male rhesus monkeys: the role of metabolic versus stress signals

One day of fasting leads to a significant suppression of pulsatile LH secretion in adult male rhesus monkeys that is evident within the first 4-6 h after a missed meal. Restricting food intake may suppress the central drive to the reproductive axis via metabolic signals occurring during the transition from a fed, energy storing state to a fasted, energy mobilizing state or via signals associated with the "psychological stress" imposed by withholding food. To distinguish between these two general types of signals, we chose the experimental strategy of providing monkeys with a great excess of calories on the day before fasting (i.e. overfeeding on the day before fasting) in order to maintain them in a metabolically fed state on the following day when they were fasted, without preventing the psychological stress associated with fasting. We reasoned that if metabolic signals are responsible for causing the fasting-induced suppression of LH secretion, overfeeding on the day before fasting would prevent the fasting-induced suppression of LH secretion. Eight adult male rhesus monkeys with indwelling venous catheters were studied on three occasions: on a day of normal feeding (receiving approximately 30 pellets of monkey chow at 1100 h on the day of the study), on a day of fasting after a day of normal feeding, and on a day of fasting after a day of overfeeding (receiving one meal of 100 pellets on the day before the study). Pulsatile LH secretion on a day of fasting after a day of normal feeding (0.4 +/- 0.2 pulses/6 h, measured from 1200-1800 h) was significantly suppressed, P < 0.05, compared to a day of normal feeding (1.8 +/- 0.3 pulses/6 h). In contrast, on a day of fasting after a day of overfeeding there was no significant difference in LH secretion measured from 1200-1800 h (1.5 +/- 0.3 pulses/6 h) compared to a day of normal feeding. Overfeeding the day before fasting prevented the normal fasting-induced suppression of plasma T3 concentrations and delayed the normal fasting-induced decline in plasma insulin concentrations. Overfeeding did not prevent the display of agitated behavior that we have previously documented in monkeys when they are fasted. These results support the hypothesis that the signal(s) which suppresses normal LH secretion after brief periods of fasting is related to the metabolic status of the body during the transition from a fed to a fasted state, rather than a function of the psychological state imposed by withholding food.

Restoration of Pulsatile Luteinizing Hormone Secretion after Fasting in Rhesus Monkeys (Macaca mulatta): Dependence on Size of the Refeed Meal*

In men and adult male rhesus monkeys brief periods of fasting (i.e. 1-2 days) can often lead to a suppression of hypothalamic-pituitary-testicular axis activity, marked by decreased circulating concentrations of LH, FSH, and testosterone. Refeeding a normal meal can rapidly restore normal secretory patterns of LH and testosterone. To learn more about the nature of the signal that links reproductive hormone secretion to nutrient intake, we examined whether the degree of restoration of pulsatile LH and testosterone secretion after a brief period of fasting is influenced by the size of the refeed meal. Adult male rhesus monkeys had indwelling venous catheters surgically implanted and were maintained on swivel/tether systems for remote collection of blood samples. Monkeys were fasted for 1 day and then on the following day they were refed one of five meals which varied in size and calorie content (i.e. 0 Cal/0 pellets Purina monkey chow; 100 Cal/5 pellets; 200 Cal/10 pellets; 300 Cal/15 pellets; or 600 Cal/30 pellets). Blood samples were collected from 0800-2400 h at 20-min intervals on the days of refeeding and assayed for LH and testosterone content. After a day of fasting, the frequency of pulsatile LH secretion the following morning was very low (0.56 +/- 0.1 pulses/3 h, measured from 0800-1100 h). When monkeys were not refed (i.e. were subjected to a second day of fasting; 0 pellet group) LH pulse frequency remained low [2.88 +/- 0.72 pulses/13 h, measured from 1100-2400 h (equivalent to 0.66 pulses/3 h)] throughout the day and evening hours. Refeeding monkeys 5, 10, 15, and 30 pellets caused a progressive stimulation of pulsatile LH secretion (3.17 +/- 0.54, 3.67 +/- 0.56, 5.5 +/- 0.67, and 6.38 +/- 0.53 pulses/13 h, respectively). Like LH pulse frequency, mean circulating LH and testosterone concentrations progressively increased as the size of the refeed meal was increased. For all three parameters (i.e. LH pulse frequency, mean LH concentration, and mean testosterone concentration) there was a significant, P less than or equal to 0.001, linear trend with increasing meal size. These findings indicate a very strong relation between the level of nutritional intake and the level of central drive to the reproductive axis during nutritional recovery from fasting, and suggest a physiological parameter that responds in a progressive fashion to increasing food intake serves as the signal to link central drive to the reproductive axis to changes in nutrient intake.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolic Cues for the Onset of Puberty

The hypothesis that the timing of puberty is at least in part stimulated by some 'metabolic signal' that tells the central control system of the reproductive axis that the body is becoming large enough, and that there are enough metabolic fuel stores, to support reproductive function has received considerable attention over the past several decades. However, direct experimental support for the hypothesis that mild metabolic changes, such as those that occur slowly during development, are actually capable of modulating reproductive function has been lacking. Our recent studies have shown that very brief periods of fasting in both male rhesus monkeys and men can modify the pulsatile release of LH and testosterone. In monkeys, missing a single meal is associated with a suppression of mean plasma LH, FSH and testosterone concentrations, and with a slowing of the frequency of pulsatile LH secretion. Current studies are aimed at identifying the specific metabolic signals which cause these changes. It is hoped that the results of these studies will eventually help to answer the question of whether normal metabolic changes occurring during development play a role in timing puberty onset.

Posttraumatic Hypocaloric Parenteral Nutrition – Development and Clinical Application

The use of hypocaloric parenteral nutrition (HPN) is very common in surgical medicine because it allows for a standardized peripheral venous supply of nutrients. HPN causes very little stress to the posttraumatically labile carbohydrate metabolism-this applies to the use of glucose as well as to sugar substitutes: For example, mean glucose concentrations in serum on glucose administration of 2-3 g/kg/day are between 5.5 and 8.4 mmol/l. The mean dose of amino acids of 1.0-1.2 g/kg/day commonly used in HPN leads to a 50-67% improvement in the N-balance compared to an exclusive water/electrolyte supply or the administration of 2 g of carbohydrates per kg and day. Even a high caloric nutritional therapy leads to no significantly improved N-balances on the first posttraumatic days. HPN is recommended after major surgery and severe trauma in order to better estimate the individual metabolic reaction to nutritional supply prior to any consumption-orientated parenteral nutrition. HPN is also important as an adjunct to early-phase enteral nutrition. Its value after moderate surgical interventions is questionable because studies have yet to confirm HPN's clinical efficacy. HPN should not be used after minor surgery or brief periods of fasting. A possible, but as yet uncertified indication for HPN is the longer-term nutrition of very obese patients.

Hypoglycaemia in infantile malnutrition.

SummaryThe incidence, the clinical significance and the factors predisposing to hypoglycaemia were studied in 84 malnourished infants. Predisposing factors were young age, intestinal infections, extreme wasting of the body, the deficit in weight exceeding 25 % as compared to normal infants of the same length, and even brief periods of fasting. Older oedematous infants, if not extremely marasmic, were not hypoglyc‐aemic. Malabsorption of carbohydrate does not play a leading role in eliciting hypoglycaemia, since severe hypoglycae‐mia was also observed in cases in whom the ability to split disaccharides was preserved.The prominent clinical symptoms at blood sugar levels between 25 and 0 mg/ 100 ml were pallor and apnoeic spells, while convulsions were exceptional. There was a prompt response to intravenous glucose, and recurring attacks were generally prevented by frequent feeding and by the administration of corticoids. Some cases exhibiting very low blood sugar levels remained asymptomatic. Fasting blood sugar levels were found to be of great prognostic significance.

Effects of food, fast and alcohol on serum uric acid and acute attacks of gout

The interrelationship of the effects of brief periods of fasting and of alcohol on uric acid metabolism has been investigated in nine gouty patients and in two normouricemic subjects. There were appreciable elevations in serum urate concentration after one and two day fasts, which were accompanied by increases in both serum beta-hydroxybutyrate and blood acetoacetate. The rise in serum urate could be accounted for in most cases by a diminution in the urinary output of uric acid, which was presumably the result of inhibition, by the elevated ketone levels, of urate excretion by the tubules. The administration of from 68 to 100 gm. of ethyl alcohol together with a low purine diet produced only minor changes in serum urate levels and urinary excretion of uric acid. Larger doses of alcohol (112 to 135 gm.) given with food led to significant increases in blood lactate concentration, diminution in urinary uric acid output and hyperuricemia. When the same (smaller) amounts of alcohol which had been found to be without effect on serum urate levels were taken during brief periods of fasting, there was an elevation in serum urate levels which was slightly greater than that observed after fasting alone. This was accompanied by greater increases in blood lactate than observed after the administration of alcohol with food, and greater increases in serum beta-hydroxybutyrate than observed after an equivalent period of fasting alone. It appears that the combination of fasting and ethyl alcohol may be additive or mutually potentiating with respect to the effects of each of these factors on uric acid metabolism. Eight of the nine patients experienced one or more acute attacks of gout during the course of these studies. In the majority of cases the onset of the attack appeared to be related to rapid fluctuations in serum urate levels induced by fasting or by fasting together with alcohol ingestion. Serum urate levels tended to remain stable during and immediately after these attacks, giving little or no indication of the changes which had preceded the onset of acute gouty-arthritis. Although treatment with probenecid in two cases produced the expected uricosuria, it did not prevent the increase in serum urate induced by fasting and alcohol. The patient with gout should be cautioned to avoid prolonged fasting and other situations which produce rapid changes in serum urate concentration. However, our gouty patients do not go out to fast, but to drink. Unfortunately the alcoholic bout often continues in the absence of food, thus resulting in a combination of metabolic changes which often lead to an acute attack.

Alterations in adrenal cortical function in fasting obese subjects

The effect of short periods of starvation on adrenal function was evaluated in a group of obese females. Normal plasma cortisol levels were maintained during the fast period, while urinary excretion of 17-hydroxycorticoids, 17-ketosteroids, and unconjugated 11-hydroxycorticoids fell. Evidence indicates that a reduction of cortisol secretion occurs during brief periods of fasting. In addition, the measurement of urinary 11-hydroxycorticoids may be a rapid and efficient method for differentiating exogenous obesity from Cushing's syndrome.

Societies and Academies

LONDON. Royal Society, Nov. 5.—Sir F. Gowland Hopkins and K. A. C. Elliott: The relation of glutathione to cell respiration with special reference to hepatic tissue. The relative capacity of various mammalian tissues to reduce the disulphide form of glutathione under anaerobic conditions has been determined. The course of the oxidation of the thiol group during the survival respiration of the hepatic tissue of various animals has been followed. That the concentration of certain metabolites in the liver is wholly, or in part, responsible for the maintenance and amount of reduction is shown by the effects of administering or withholding food. In general the initial marked delay in the disappearance of the – SH group during aeration is observed only in the liver of well-fed animals; after relatively brief periods of fasting it is much lessened and may not be observed. If extra glutathione in the disulphide form be added to the freshly excised tissue before aeration, the existence of residual active hydrogen is revealed. In spite of vigorous aeration the concentration of – SH then rises during the earlier periods of survival, though ultimately the whole is oxidised. The amount of this extra pressure-head of hydrogen consistently differs in the livers of different species. The origin of the active hydrogen which reduces the disulphide grouping is at present unknown. The transport of hydrogen to molecular oxygen by the path in question, though representing but a small part of the total respiration, may, therefore, prove to represent a specialised and significant aspect of tissue oxidations.—Lord Rutherford and C. D. Ellis: The origin of γ-rays. Calculations are made of the probability of escape of the α-particles from radium C and of the average tune of transition of the γ-particle for different energies of the γ-ray. The strongest γ-ray group, which corresponds to the emission of a β- or γ-ray of energy l.426 × 106 volts, represents an abnormal mode of transition compared with other groups. The time of transition is very long, and it may be, as suggested by R. H. Fowler, that the transition is radiationless, the surplus energy being directly transferred to one or more of the outer electrons of the atom. Many of the lines in the β-ray spectrum may be a result of similar radiationless transitions. In explanation of the complicated γ-ray spectrum of radium C it is suggested that more than one α-particle in the nucleus may occupy the same energy level.—A. V. Hill: Myothermic experiments on the frog's gastrocnemius. An arrangement is described by which the ‘initial’ heat set free in the contraction of a frog's gastrocnemius can be measured in absolute units. A single fine thermocouple of constantan-iron is employed, the ‘hot’ junction lying inside the muscle. It may be applied to single twitches, to groups of twitches, or to tetani up to 25 seconds in duration. The mean value of Tl/H, the isometric heat coefficient in a twitch, is 13.4. This is twice the mean value found in sartorii. The difference is due to the fact that in gastrocnemii the fibres, or parallel fibre bundles, run, on the average, only half the length of the muscle. A modification is described of the method recently suggested by Bozler of “calibrating” by condenser discharges. This is far simpler and more accurate than the old method employing an alternating current. The specific heats of muscle and blood have been determined. For a given water content they are the same. The density of a tissue depends upon the amount of solid it contains. This provides a simple and accurate method of measuring, without the labour of drying and weighing, the percentage of solid in a muscle.