Blood Beta-hydroxybutyric Acid Research Articles

Effects of treatment with propylene glycol and cyanocobalamin on disease, milk production and reproductive outcomes of dairy cows diagnosed with hyperketonemia and hypoglycemia

Almost all periparturient dairy cows experience a period of negative energy balance, and despite improvements to fresh cow management, some dairy cows still experience clinical dis­ease associated with the periparturient period (Duffield et al., 2009; Taylor et al., 2004). Hyperketonemia (HK) remains an im­portant production and animal welfare concern (McArt et al., 2012; Tatone, Duffield, Capel, et al., 2016; Tatone, Duffield, LeB­lanc, et al., 2016), and recently several handheld meters which measure beta-hydroxybutyric acid (BHBA) have been validated in dairy cows and can be used to detect pre-clinical HK (Bach et al., 2016; Tatone et al., 2015). Several studies have explored the screening of post-parturient cows to detect HK and adminis­ter treatment in order to ward off clinical disease and increase milk production (Capel et al., 2021; Gordon et al., 2017; McArt et al., 2012). However, these studies have been inconsistent in their findings, and treatment may not be economically beneficial for farms with a relatively low incidence of HK (McArt et al., 2014). A 2017 study indicated that cows may have variable production responses to HK treatment based on blood glucose concentra­tion (Gordon et al., 2017). Because blood glucose can also be mea­sured cow-side, measurement of blood glucose concurrent with measurement of blood BHBA may be a means to target treatment to cows that will respond to current treatments. Therefore, our objective was to explore the effects of treatment with propylene glycol and cyanocobalamin in early post-partum cows based on both HK and glycemic status. We hypothesized that improve­ments to health, milk production, and reproduction would be greatest among cows that were hypoglycemic.

Assessment of the Effects of Supplemental Rumen Protected B Vitamins and Choline for Periparturient Cows: A Meta-Analysis of 28 Feeding Studies

There are currently no prescribed requirements for B vitamins or choline for dairy cows during the transition period, but many recent studies have shown a variety of benefits from supplying these nutrients to periparturient cows. The purpose of this research effort was to determine the potential benefit of including a rumen protected blend composed of B vitamins (riboflavin, folic acid, vitamin B12) and choline (RPBlend, Jefo Nutrition Inc., St. Hyacinthe, QC, Canada) for dairy cows during the transition period, based on results from 28 on-farm feeding studies (USA-12, Mexico-7, Canada-4, Chile-3, Australia-1, Brazil-1) conducted between 2011 and 2018. All farms participated in monthly herd management record keeping systems and were selected to participate in studies due to their excellent management. Meta-analyses in which risk differences were determined were used to assess the effects of the supplemental RPBlend on health parameters and reproduction. The effect size was used as the determinant of the possible contribution of RPblend on the yields of milk, energy corrected milk (ECM), fat and protein yields during the first four weeks of lactation. Results showed that the inclusion of RPblend reduced (P the displaced abomasum and milk fever did not diminish (P > 0.10) with the inclusion of the BPBlend. The incidence rate of subclinical ketosis, determined as blood beta hydroxy butyric acid greater than 1.2 mM was lower (P (than those not supplemented. The proportion of cows confirmed pregnant by 100 days in milk was greater for cows given the BPBlend (P 0.10) while the yield of milk protein was greater (P < 0.05) when the cows received the blend. These results suggest that the inclusion of rumen protected B vitamins and choline can assist cow health, reproduction and production at the start of lactation.

Role of blood beta-hydroxybutyric acid estimation as a diagnostic marker of feline hepatic lipidosis

Feline hepatic lipidosis (FHL), characterised by an accumulation of triglycerides in the cytoplasm of hepatocytes, is a common and potentially fatal liver disorder in cats. Hepatic lipidosis in cats can develop due to any condition that will impair nutrient uptake and is often presented with non-specific clinical signs. The present study describes the diagnosis of FHL based on clinicobiochemical, ultrasonographic, and cytological changes and evaluates the diagnostic utility of blood beta-hydroxybutyric acid (βHBA) estimation in FHL. Anorexia, weight loss, lethargy, vomiting, dehydration, and jaundice were the common clinical findings in cats with hepatic lipidosis. Serum biochemical evaluation revealed elevations in alkaline phosphatase (ALP), triglycerides, glucose, and total bilirubin. Ultrasonography revealed an enlarged hyperechoic liver. Fine-needle aspiration cytology of the liver revealed mild to severe vacuolation in the cytoplasm of hepatocytes. Blood beta-hydroxybutyric acid levels were found higher in cats with hepatic lipidosis than in healthy cats and cats with other hepatic disorders. Therefore, βHBA estimation, being a quick and non-invasive method, could be considered as a diagnostic marker in the early diagnosis of FHL.

The effect of blood BHBA level on fertility in sheep

The aim of this study was the effect of pre-synchronization blood BHBA level on pregnancy rates of sheep in the non-breeding season. For this purpose, 100 Merino/Merino crossbred ewe, aged 2-4 years, who have given one birth before, were used in the study. For synchronization purposes, progesterone containing sponges 60 mg Medroxyprogesteron acetate (MPA) analogue, were administered intravaginally for 14 days. BHBA (betahydroxybutyric acid) measurement was made by drawing blood in each animal on the day of administration. 500-700 IU PMSG was injected at the time of sponge withdrawal. Oestrus was observed 24 hours after sponge withdrawal with the help of teaser ram. Animals which was in estrus were hand mated. Pregnancy status was recorded with the help of ultrasound using the transrectal probe in the interval 35-45 days after mating. All of the synchronized animals were determined to be in estrus and their mating were performed. As a result of the pregnancy examination, 57 (57%) of the animals became pregnant and 43 (43%) did not become pregnant. Blood BHBA values were measured in the range of 0.12 mmol/L -0.66 mmol/L (n:100) in present study and the average of BHBA as 0.35±0.083 mmol/L was determined. While blood BHBA level of pregnant animals was found as 0.29±0.005 mmol/L, blood BHBA level of non-pregnant sheep was found to be 0.41±0.073 mmol/L, which was statistically significant (p&amp;lt;0.001). In addition, it was determined that there was a strong negative correlation between blood BHBA level and pregnancy rates in sheep (r = −0.719, p&amp;lt;0.001). As a result, it was concluded that there was no study in the literature about the relationship between the fertility parameters of sheep and the blood BHBA level in the mentioned period, and it was concluded that the presented study made a significant contribution to the literature. It has been concluded that a higher fertility success can be achieved from animals with low BHBA levels, that fertility rates can be increased by regulating the energy balance of animals with high BHBA levels, and that the study can be a criterion to be considered in achieving the target of 3 lambing in 2 years in terms of herd management in sheep breeding.

Effects of Age and Dietary Factors on the Blood Beta-Hydroxybutyric Acid, Metabolites, Immunoglobulins, and Hormones of Goats.

The study was aimed to examine the effects of age and dietary beta-hydroxybutyric acid (BHBA) on blood BHBA and blood health indicators in goat kids. Thirty male goats of five ages (1, 2, 3, 6, and 12 months old) were selected for blood sampling to determine the influence of age. Another 64 goat kids (half males and half females) were weaned at 1 month old and fed with starter diets with control, low, medium, and high BHBA doses (0, 3, 6, and 9 g/animal/day, respectively). Six goats per treatment were selected for blood analysis at 2 and 3 months of age. There were significant effects (p < 0.01) of ages on the blood parameters of goat kids. The 6- and 12-month-old goats showed significantly lower blood total protein, globulin, BHBA, IgA, and IgM concentrations than did young goats, while they had a higher albumin-to-globulin ratio than young goats. The blood glucose decreased (p < 0.01) and IgG increased over time (p < 0.01). In blood, growth hormone (GH) and insulin-like growth factor I (IGF-I) were lower (p < 0.01) at 1- and 3-month-old goats than 12-month-old goats. The high dietary BHBA improved (p < 0.05) the ratio of albumin to globulin of 2-month-old kids compared with control. The blood GH and IGF-I were lower (p < 0.01) in the medium BHBA dose at 2 months of age than control. These results suggested that age greatly impacted blood composition, especially around weaning, and dietary BHBA showed beneficial regulating effects on blood total protein level in young goats.

Full model selection using regression trees for numeric predictions of biomarkers for metabolic challenges in dairy cows

Dairy cows suffer poor metabolic adaptation syndrome (PMAS)11PMAS: Poor metabolic adaptation syndrome. during early post-calving periods caused by negative energy balance. Measurement of blood beta-hydroxy butyric acid (BHBA)22BHBA: beta-hydroxy butyric acid. and blood non-esterified fatty acids (NEFA)33NEFA: non-esterified fatty acids. allow early and accurate detection of negative energy balance. Machine learning prediction of blood BHBA and blood NEFA using milk testing samples represents an opportunity to identify at-risk animals, using less labor than direct blood testing methods. Routine milk testing on modern dairies and computer record keeping provide an immense amount of data which can then be used in machine learning models. Previous research for predicting blood metabolites using Fourier-transform infrared spectroscopy (FTIR)44FTIR: Fourier-transform infrared spectroscopy. milk data has focused mainly on individual models rather than a comparison among the models. Full model selection is the process of comparing different combinations of pre-processing methods, variable selection, and statistical learning algorithms to determine which model results in the lowest prediction error for a given dataset. For this project we used a full model selection approach with regression trees (rtFMS)55rtFMS: full model selection approach with regression trees. . rtFMS uses the cross-validated performance of different model configurations to feed a regression tree for selecting a final model. A total of 384 possible model configurations (algorithms, predictors and data preprocessing options) for each outcome (blood BHBA and blood NEFA) were considered in the rtFMS technique. rtFMS allows direct comparison of multiple modeling approaches reducing bias due to empirical knowledge, modeling habits, or preferences, identifying the model with minimal root mean squared prediction error (RMSE)66RMSE: root mean squared prediction error. . An elastic net regression model was selected as the best performing model for both biomarkers. The input data for blood BHBA predictions were FTIR milk spectra, with a second derivative pre-processing, and a filter with 212 wave numbers, obtaining RMSE = 0.354 (0.328−0.392). The best performing model for blood NEFA had input data of FTIR milk spectra, with a second derivative pre-processing, and a filter with 212 wave numbers filter along with the time of milking, obtaining RMSE = 0.601 (0.564−0.654). The comparison of multiple modeling strategies, conducted by rtFMS, present an option for improved FTIR prediction models of blood BHBA and blood NEFA by reducing error due to human bias. The implementation of rtFMS to design future prediction models can guide model inputs and features. Our prediction models have the potential to increase early detection of metabolic disorders in dairy cows during the transition period.

On field diagnostic and prognostic indicators of pregnancy toxaemia in goats

Periparturient mortality in goats have a great economic impact on the livelihood of marginal farmer. Pregnancy toxaemia in small ruminants occur as a result of negative energy balance consequent to enhanced requirement for glucose by the developing foetuses in the last trimester (last 6 to 4 weeks) of gestation. Among the does treated for various medical conditions at Veterinary University Peripheral Hospital, Madhavaram Milk Colony, Chennai – 51 during the period October 2016 – September 2018, 72 does in their last six weeks of gestation carrying twins / triplets and presented with the history of off feed were subjected to determination of blood beta hydroxybutyric acid (BHBA) level by means of a portable blood ketone and glucose monitoring system and qualitative urinalysis using urine dip stick. Does with beta hydroxybutyric acid level > 0.8 mmol/L and < 1.6 mmol/L were classified as sub clinical pregnancy toxaemic group (n = 12) and beta hydroxybutyric acid level > 1.6 mmol/L were classified as clinical pregnancy toxaemic group (n = 12). The control animals were selected from adult Tellicherry does in the age group of 2 to 4 years maintained at Livestock Farm Complex (LFC), Madhavaram Milk Colony, Chennai – 600 051. The pregnancy toxaemic does were resorted to treatment with intravenous glucose therapy (5 per cent Dextrose), parenteral therapy of Vitamin B1, B6 & B12 and oral administration of glycerine @ 25 ml twice daily. All the twelve does of sub clinical pregnancy toxaemic group recovered completely with a cure rate of 100 per cent while in the clinical pregnancy toxaemic group the cure rate was only 33 per cent. On field reliable diagnostic indicators of pregnancy toxaemia include blood β-hyroxybutyric acid concentration (≥ 0.8 mmol/L) and presence of ketone body, glucose and protein in urine while hypergly­caemia in advanced pregnancy toxaemic does indicate foetal death.

Histopathological changes in the reproductive organs of does with pregnancy toxaemia and their aborted foetuses

Pregnancy toxaemia (PT) is a metabolic disorder affecting does during late gestation. This study describes the histopathological changes in pregnant does and their foetuses experimentally-induced with PT. Eight does in their late pregnancy were induced into PT by reducing the energy intake (Group 1), while 6 does were maintained with adequate energy intake (Group 2). The blood beta-hydroxybutyric acid (BHBA) and glucose concentrations were measured every 5 days throughout the 20-day study period. All does that experienced stillbirth were immediately euthanised, while the does and the full-term, non-aborted foetuses were euthanised on day 20. Samples of umbilical cords, placentas and uteri were collected from the does, while hearts and livers were collected from the foetuses. The samples were subjected to histopathological assessment, and subsequently correlated with the blood BHBA concentration. Stillbirth occurred in 5 (62.5 %) does of Group 1. The remaining does of Group 1 and all does of Group 2 did not experience stillbirth until the end of the experiment. Overall lesions in the umbilical cord were significantly (p < 0.01) more severe in Group 1. Does of Group 1 that experienced stillbirth showed chorionic villi necrosis and homogenous chorionic villi hypomaturity, while the endometrial glands were non-secreting. The stillborn foetuses showed extensive hepatic necrosis. The last concentrations of BHBA and glucose showed significant (p < 0.05) difference between the two groups. The histopathological lesions in the placenta, uterus, and foetal liver were significantly (p < 0.05−0.01) correlated with the blood BHBA concentration. The histopathology lesions could suggest the mechanism of stillbirth in PT and raise concern that it could affect the performance of the off-springs should stillbirth did not occur.

Effect of adding humate to the ration of dairy cows on yield performance

The aim of this study is to investigate the effects of different levels of humate addition to colostrum quality, milk composition, somatic cell count, some blood metabolites and reproductive performance in the period from prepartum 40th to postpartum 60th day. In this study, dairy cows from prepartum 40th to postpartum 60th day were given humate additive which was according to dosed on dry matter consumption basis from (75 g, 150 g). In the study, 26 Swiss Brown cows in the same care and feeding conditions were used in the second lactation. The feeds were weighed to determine the dry matter intake of the individual cows daily. Blood was collected from the vena jugularis at 40, 30, 20 and 10 days before the estimated date of birth, at calving (day 0) and on days 5, 10, 20, 30, 45, and 60 after birth. Colostrum and milk samples were taken in the study. As a result of the study, it has been determined that the use of humate additives has no effect on body condition score, body weight, in milk non-fat milk solid, density, protein, lactose, freezing point, somatic cell count, in blood triglicerides, phosphorus, magnesium, albumin, glucose, blood urea nitrogen. It was found that with the addition of humate additive to the feed, colostrum specific gravity increased, prepartum and postpartum dry matter intake increased, milk yield and the fat percentage increased, serum non-esterified fatty acid and blood beta-hydroxybutyric acid levels decreased, and postpartum serum calcium level increased. It was concluded that 75 g of humate, which is determined based on dry matter consumption, can be added to the rations of the dairy cows at this dose and has positive effects on colostrum quality, milk yield, milk fat ratio, and negative energy balance.

PPARA/RXRA signalling regulates the fate of hepatic non-esterified fatty acids in a sheep model of maternal undernutrition

Maternal undernutrition during late gestation accelerates body fat mobilization to provide more energy for foetal growth and development, which unbalances metabolic homeostasis and results in serious lipid metabolism disorder. However, detailed regulatory mechanisms are poorly understood. Here, a sheep model was used to explore the regulatory role of PPARA/RXRA signalling in hepatic lipid metabolism in undernutrition based on RNA sequencing and cell experiments. KOG function classification showed that lipid transport and metabolism was markedly altered in an undernourished model. In detail, when compared with the controls, fatty acid transport and oxidation and triglyceride metabolism were up-regulated in an undernourished model, while fatty acid synthesis, steroid synthesis, and phospholipid metabolism were down-regulated. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis demonstrated that PPARA/RXRA signalling pathway was altered. Moreover, PPARA signalling associated genes were positively correlated with hepatic non-esterified fatty acid (NEFA) levels, while retinol metabolism associated genes were negatively correlated with blood beta-hydroxybutyric acid (BHBA) levels. Results of primary hepatocytes showed that NEFAs could activate PPARA signalling and facilitate fatty acid oxidation (FAO) and ketogenesis, while BHBA could inhibit RXRA signalling and repress FAO and ketogenesis. Excessively accumulated NEFAs in hepatocytes promoted triglyceride synthesis. Furthermore, activation of PPARA/RXRA signalling by WY14643 and 9-cis-retinoic acid could enhance FAO and ketogenesis and reduce NEFAs accumulation and esterification. Our findings elucidate the regulatory mechanisms of NEFAs and BHBA on lipid metabolism as well as the potential role of the PPARA/RXRA signalling pathway in hepatic lipid metabolism, which may contribute to exploring new strategies to maintain lipid metabolic homeostasis in human beings.

THE EFFECT OF PREPARTUM ANTIOXIDANT ADMINISTRATIONS ON BLOOD BHBA CONCENTRATION IN COWS

Objective: The presented study was aimed that investigation effect of the prepartum antioxidant administration on blood Beta-hydroxybutyric acid ( BHBA) concentrations at day 7th postpartum in Holstein dairy cows. Antioxidants are defined as substances that delay or inhibits oxidative damage . Oxidant s such as reactive oxygen species (ROS) are created as a consequence of adenosine triphosphate (ATP) production in mitochondria. Oxidants can cause tissue damage by damaging cells' macromolecules, such as DNA, proteins, and lipids. Lipids are the most sensitive macromolecule against oxidative damage. Oxidative stress can both disrupt the mechanism of insulin and induce more lipolysis. And so, ROS overproduction can enhance non ‐ esterified fatty acids (NEFA) and BHBA production . Material and Method: Eighty multiparous Holstein breed pregnant dairy cows were used in this study. The cows were divided into two groups as treatment (G1; n=40) and control groups (G2; n=40) . In the G1, solutions containing of vitamins (A, D, E) and trace elements (Cu, Zn, Se, Mn) were performed intramuscularly at 21±5 and 10±5 days before expected parturition (280 days). In the G2, it was performed the same amounts of saline injections as a placebo . Result and Discussion: Blood BHBA levels were found that lower in the G1 group (0.73±0.20 mmol/L) compared to the G2 group (0.84±.29 mmol/L) . In conclusion, it was determined that prepartum antioxidant administrations decrease blood BHBA concentration in the postpartum period in dairy cows.

1211-P: No Significant Change of Glucagon Level by Empagliflozin in Diabetic Mice

Introduction: It is indicated that sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucose lowering agents, may increase a level of glucagon, and simultaneously, compete with their antiglycemic effect. Aim: To elucidate the alteration of glucagon concentration and blood glucose level during administration of SGLT2i, Empagliflozin (EMPA) was administered to diabetic mice with homozygous (gcg−/−) or heterozygous (gcg+/−) deficiency of glucagon gene. Methods: After induction of diabetes using 150 mg/kg of streptozotocin, gcg−/− and control gcg+/− mice of 12-14 weeks old were administered 30 mg/kg/day of EMPA for 3-5 weeks. Casual blood glucose, fasting blood glucose, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), blood glucagon, blood insulin, blood beta-hydroxybutyric acid were evaluated. Additionally, metabolic parameters including respiratory exchange ratio (RER), activity, feeding, and drinking, were monitored utilizing a home-cage chronic laboratory animal monitoring system (CLAMS). Results: Glucagon concentration in control gcg+/− mice were not altered by induction of diabetes or administration of EMPA. In gcg−/−, blood glucagon was not detected. The OGTT of diabetic gcg+/− and gcg−/− revealed that the area under the curve (AUC) of blood glucose in mice treated with EMPA were decreased compared with that without EMPA (p&amp;lt;0.05). However, reduction ratios of the AUC showed no significant difference between gcg+/− and gcg−/−. In ITT, there was no significant difference in the reduction rate of glucose levels between mice treated with or without EMPA. CLAMS revealed no significant difference induced by EMPA in metabolic parameters: RER, activity, food intake, and drinking. Conclusion: Administration of EMPA for almost one month in mice did not induce noticeable change in glucagon level or metabolic parameters. The gcg deficiency did not have any impact on glucose lowering effect of EMPA. Disclosure H. Shimoda: None. Y. Seino: None. T. Himeno: None. R. Inoue: None. M. Motegi: None. T. Hayami: None. E. Asano: None. S. Asano: None. M. Kato: None. Y. Yamada: None. E. Miura-Yura: None. M. Kondo: None. S. Tsunekawa: None. Y. Kato: Speaker's Bureau; Self; Merck &amp; Co., Inc. K. Kato: None. Y. Hayashi: Speaker's Bureau; Self; Astellas Pharma Inc., Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd. J. Nakamura: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceu. Co. Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. H. Kamiya: Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., MSD K.K., Novartis Pharma K.K., Novo Nordisk Oharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K.

Effect of rearing system on pre-weaning growth, rumen development and its influence on post-weaning performance of lambs

Abstract. Twenty-four 21-day-old Balouchi male lambs were equally divided into two groups. Twelve subjects were artificially reared (AR), twelve others were ewe reared (ER) and used as control. AR in comparison of ER lambs maintained higher concentrations of blood beta- Hydroxybutyric acid (BHBA); however glucose concentration was not affected by rearing system. Unlike the DNA content and cell size, the RNA concentration and ribosomal capacity (Cs) of AR groups were significantly (P&lt;0.05) higher than that of ER lambs. Rearing system did not affect morphologic characteristics of rumen wall except thickness of keratinized layer that was thickest in AR, 20 % less than in ER lambs (P&lt;0.05). Stomach weight and capacity in AR animals were significantly (P=0.05) higher than ER lambs. Neither post-weaning growth rate nor feed conversion efficiency were affected (P&gt;0.05) by rearing method. Also there were no differences with respect to slaughter and dissection data between groups in postweaning phase. In conclusion, the results of this study showed that naturally rearing system gave rise to developmental and carcass characteristics similar to those observed in artificial raised lambs.

Growth dependence on insulin‐like growth factor‐1 during the ketogenic diet

To examine the influence of the ketogenic diet (KD) on linear growth and insulin-like growth factor I (IGF-I) levels in children with pharmacotherapy-resistant epilepsy. A prospective study was designed to evaluate growth, serum IGF-I levels, blood beta-hydroxybutyric acid (beta-OHB), and seizure frequency before and during KD in 22 children (median age 5.5 years). Growth was assessed by measurements of weight, height, body mass index (BMI), and height velocity. Standard deviation scores (SDS) were calculated for all measured parameters as well as for serum IGF-I to eliminate the influence of age- and sex-related differences among patients. Fourteen of the 22 patients responded to the KD. Weight, height, BMI, and height velocity decreased significantly during the KD. We found that the KD had profound influence on growth and IGF-I levels. No correlation was found between seizure response and growth alterations. Height velocity correlated negatively with beta-OHB during the KD. The slope of the regression of height velocity against IGF-I decreased significantly during the KD. Height velocity was most affected in those with pronounced ketosis, which implies that, in clinical practice, the level of ketosis should be related to outcomes in seizure response and growth. Our data indicate that growth disturbances and the decreased sensitivity of growth to similar IGF-I levels during KD are independent of seizure reduction. The metabolic status induced by KD may be the mechanism underlying both alterations of linear growth and seizure reduction.

Platelet alpha 2-adrenoceptor and adenylate cyclase in patients with anorexia nervosa and bulimia.

Platelets alpha 2-adrenoceptors were studied in 24 patients with anorexia nervosa shortly after admission to the hospital and after 10% weight gain. Twenty patients with bulimia and 24 healthy age- and sex-matched normal subjects also were studied. Receptor number was significantly increased in patients with bulimia and anorexia nervosa. After 10% weight gain, the receptor number almost normalized in anorexia nervosa patients. Kd values were increased in all patients groups at all times of study. In patients with bulimia or anorexia nervosa, both initially and after weight gain, the maximal effect of prostaglandin E1 (PGE1) on platelet cAMP production was greatly increased, while the half-maximally effective dose was unchanged. Also, the maximal inhibitory effects of epinephrine and clonidine on PGE1-stimulated platelet cAMP production were greater, while the half-maximal dose of both alpha 2-agonists was unchanged. Metabolic and endocrine indicators of starvation were present in both bulimic and anorexia nervosa patients initially. Blood beta-hydroxybutyric acid was elevated, and plasma T3 values and the orthostatic response of plasma norepinephrine (delta NA) were reduced, while cortisol was elevated (only in anorexia nervosa patients). Among these parameters, only delta NA significantly correlated with the actions of PGE1 and epinephrine on cAMP production. In conclusion, the activity of the sympathetic nervous system was reduced in patients with anorexia nervosa and bulimia. This reduction was accompanied by an increased capacity and a decreased affinity of platelet alpha 2-receptors and an increased PGE1 stimulatory and epinephrine inhibitory effects on cAMP production.

Metabolic Effects of Nicotinic Acid in Acute Insulin Deficiency in the Rat

To investigate the role of increased free fatty acid (FFA) mobilization in the hyperglycemia, ketonemia, hyperlipemia and fatty liver produced by acute insulin deficiency, nicotinic acid was used to inhibit FFA mobilization in rats given guinea pig anti-insulin serum (AIS). Effects on concentration of plasma FFA, blood glucose and betahydroxybutyric acid (BHBA), and plasma and liver lipids were studied acutely after nicotinic acid administration and during six and twenty-four hours of treatment with this compound. Nicotinic acid produced an immediate fall in plasma FFA and a lesser but significant decrease in blood glucose when given two hours after AIS. When treatment was begun simultaneously with administration of AIS and repeated every four hours, plasma FFA and plasma and liver lipids were kept at normal control levels or lower for at least six hours, and blood BHBA for eighteen hours. Blood glucose remained at 70 per cent of values in untreated rats for eighteen hours, yet exceeded control levels during this time. At twenty-four hours there were no important differences between treated and untreated animals in any parameter except plasma triglycerides. This change was possibly related to a rebound of FFA levels in the nicotinic acid treated group. The effects of nicotinic acid on plasma FFA, blood BHBA and plasma and liver lipids are most likely due to inhibition of FFA release from adipose tissue. Increased FFA mobilization in acute insulin deficiency could thus explain the increase in concentration of these substances during the first several hours after AIS administration. The mechanism of action of nicotinic acid and the influence of plasma FFA levels on glucose concentration is less clear.