Dose-Dependent Beneficial Effect of Ketone Supplement-Evoked Ketosis on Anxiety Level in Female WAG/Rij Rats: Sometimes Less Is More.

While one-third of the population can be affected by anxiety disorders during their lifetime, our knowledge of the pathophysiology of these disorders is far from complete. Previously, it has been demonstrated in male animals that exogenous ketone supplement-evoked ketosis can decrease anxiety levels in preclinical rodent models, such as Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Thus, in this study, we investigated whether intragastric gavage of the exogenous ketone supplement KEMCT (mix of 1,3-butanediol-acetoacetate diester/ketone ester/KE and medium-chain triglyceride/MCT oil in 1:1 ratio) for 7 days can alter the anxiety levels of female WAG/Rij rats using the light-dark box (LDB) test. We demonstrated that a lower dose of KEMCT (3 g/kg/day) increased blood R-ßHB (R-ß-hydroxybutyrate) levels and significantly decreased anxiety levels (e.g., increased the time spent in the light compartment) in female WAG/Rij rats on the seventh day of administration. Although the higher KEMCT dose (5 g/kg/day) increased blood R-ßHB levels more effectively, compared with the lower KEMCT dose, anxiety levels did not improve significantly. We conclude that ketone supplementation might be an effective strategy to induce anxiolytic effects not only in male but also in female WAG/Rij rats. However, these results suggest that the optimal level may be moderately, not highly, elevated blood R-ßHB levels when the goal is to alleviate symptoms of anxiety. More studies are needed to understand the exact mechanism of action of ketone supplementation on anxiety levels and to investigate their use in other animal models and humans for the treatment of anxiety disorders and other mental health conditions.

Exogenous ketone supplementation: an emerging tool for physiologists with potential as a metabolic therapy.

NEW FINDINGS: What is the topic of this review? The integrative physiological response to exogenous ketone supplementation. What advances does it highlight? The physiological effects and therapeutic potential of exogenous ketones on metabolic health, cardiovascular function, cognitive processing, and modulation of inflammatory pathways and immune function. Also highlighted are current challenges and future directions of the field. ABSTRACT: Exogenous oral ketone supplements, primarily in form of ketone salts or esters, have emerged as a useful research tool for manipulating metabolism with potential therapeutic application targeting various aspects of several common chronic diseases. Recent literature has investigated the effects of exogenously induced ketosis on metabolic health, cardiovascular function, cognitive processing, and modulation of inflammatory pathways and immune function. This narrative review provides an overview of the integrative physiological effects of exogenous ketone supplementation and highlights current challenges and future research directions. Much of the existing research on therapeutic applications - particularly mechanistic studies - has involved pre-clinical rodent and/or cellular models, requiring further validation in human clinical studies. Existing human studies report that exogenous ketones can lower blood glucose and improve some aspects of cognitive function, highlighting the potential therapeutic application of exogenous ketones for type 2 diabetes and neurological diseases. There is also support for the ability of exogenous ketosis to improve cardiac metabolism in rodent models of heart failure with supporting human studies emerging; long-terms effects of exogenous ketone supplementation on the human cardiovascular system and lipid profiles are needed. An important avenue for future work is provided by research accelerating technologies that enable continuous ketone monitoring and/or the development of more palatable ketone mixtures that optimize plasma ketone kinetics to enable sustained ketosis. Lastly, research exploring the physiological interactions between exogenous ketones and varying metabolic states (e.g., exercise, fasting, metabolic disease) should yield important insights that can be used to maximize the health benefits of exogenous ketosis.

Adenosine Receptors Modulate the Exogenous Ketogenic Supplement-Evoked Alleviating Effect on Lipopolysaccharide-Generated Increase in Absence Epileptic Activity in WAG/Rij Rats.

It has been previously demonstrated that KEKS food containing exogenous ketogenic supplement ketone salt (KS) and ketone ester (KE) decreased the lipopolysaccharide (LPS)-generated increase in SWD (spike-wave discharge) number in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, likely through ketosis. KEKS-supplemented food-generated ketosis may increase adenosine levels, and may thus modulate both neuroinflammatory processes and epileptic activity through adenosine receptors (such as A1Rs and A2ARs). To determine whether these adenosine receptors are able to modify the KEKS food-generated alleviating effect on LPS-evoked increases in SWD number, an antagonist of A1R DPCPX (1,3-dipropyl-8-cyclopentylxanthine; 0.2 mg/kg) with LPS (50 µg/kg) and an antagonist of A2AR SCH58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine; 0.5 mg/kg) with LPS were co-injected intraperitoneally (i.p.) on the ninth day of KEKS food administration, and their influence not only on the SWD number, but also on blood glucose, R-beta-hydroxybutyrate (R-ßHB) levels, and body weight were measured. We showed that inhibition of A1Rs abolished the alleviating effect of KEKS food on LPS-generated increases in the SWD number, whereas blocking A2ARs did not significantly modify the KEKS food-generated beneficial effect. Our results suggest that the neuromodulatory benefits of KEKS-supplemented food on absence epileptic activity are mediated primarily through A1R, not A2AR.

Effects of a Multicomponent Herbal Extract on the Course of Subclinical Ketosis in Dairy Cows - a Blinded Placebo-controlled Field-study.

A blinded placebo-controlled multi-center on-farm trial was conducted in dairy cows with subclinical ketosis to investigate effects of a multicomponent herbal extract. Blood ketone levels were measured weekly in early lactating cows from 16 Swiss herds. Cows were subclassified based on their initial blood-ß-hydroxybutyrate levels (≥ 1.0 [KET-low, 84 cows] and > 1.2 mmol/L [KET-high, 39 cows]) and randomly distributed to 3 groups treated orally with herbal extract containing Camellia sinensis, Cichcorium intybus, Gentiana lutea, Glycyrrhiza glabra, Taraxacum officinale, Trigonella foenum-graecum, and Zingiber officinale, sodium propionate, or placebo twice a day for 5 days. Milk yield, milk acetone, blood-ß-hydroxybutyrate, glucose, nonesterified fatty acids, gamma-glutamyl transferase, and glutamate dehydrogenase were analyzed over 2 wk. Linear mixed effect models were used for data analysis. No effects were found for nonesterifed fatty acids, gamma-glutamyl transferase, and glucose. Significantly higher glutamate dehydrogenase (29.71 U/L) values were found in herbal extract-treated animals compared to sodium propionate on day 7 (22.33 U/L). By trend, higher blood-ß-hydroxybutyrate levels (1.36 mmol/L) were found in the placebo group of KET-high-cows on day 14 compared to the sodium propionate group (0.91 mmol/L). Milk yields of all treatment groups increased. Milking time and treatment showed a significant interaction for milk acetone: sodium propionate led to an immediate decrease, whereas herbal extracts resulted in a milk acetone decrease from day 7 on, reaching significantly lower milk acetone on day 14 (3.17 mg/L) when compared to placebo (4.89 mg/L). In conclusion, herbal extracts and sodium propionate are both likely to improve subclinical ketosis in dairy cows, however, by different modes of action.

Selected Physiological Effects of a Garcinia Gummi-Gutta Extract in Rats Fed with Different Hypercaloric Diets.

Garcinia gummi-gutta (GGG) rind extract is effective for reducing appetite, body weight and adiposity of obese rodents fed high-fat (HF), high-sugar (HS) or high fat/sugar (HFS)-based diets, but these effects have not been simultaneously evaluated. Thirty obese (~425 g) male Wistar rats were fed for eleven weeks with six hypercaloric diets (4.1 kcal/g; five rats/diet) non-supplemented (HF, HS, HFS), or supplemented (HF+, HS+, HFS+) with GGG extract (5.9%), while rats from the control group (375 g) were fed a normocaloric diet (3.5 kcal/g). Body weight, dietary intake, body fat distribution, and histological and biochemical parameters were recorded. Compared to control rats, non-supplemented and supplemented groups consumed significantly less food (14.3% and 24.6% (−4.3 g/day), respectively) (p < 0.05). Weight loss was greater in the HF+ group (35⁻52 g), which consumed 1.9 times less food than the HS+ or HFS+ fed groups. The HF and HFS groups showed 40% less plasma triacylglycerides and lower glucose levels compared to the HF+. GGG-supplemented diets were associated with lower ketonuria. The HF+ diet was associated with the best anti-adiposity effect (as measured with the dual X-ray absorptiometry (DXA) and Soxhlet methods). The severity of hepatocyte lipidosis was HF > control > HF+, and no signs of toxicity in the testes were observed. The results indicate that GGG is more effective when co-administered with HF diets in obese rats.

Grapefruit Derived Flavonoid Naringin Improves Ketoacidosis and Lipid Peroxidation in Type 1 Diabetes Rat Model.

BACKGROUND: Hypoglycemic effects of grapefruit juice are well known but the effects of naringin, its main flavonoid on glucose intolerance and metabolic complications in type 1 diabetes are not known. OBJECTIVES: To investigate the effects of naringin on glucose intolerance, oxidative stress and ketonemia in type 1 diabetic rats. METHODS: Sprague-Dawley rats divided into 5 groups (n = 7) were orally treated daily with 3.0 ml/kg body weight (BW)/day of distilled water (group 1) or 50 mg/kg BW of naringin (groups 2 and 4, respectively). Groups 3, 4 and 5 were given a single intra-peritoneal injection of 60 mg/kg BW of streptozotocin to induce diabetes. Group 3 was further treated with subcutaneous insulin (4.0 IU/kg BW) twice daily, respectively. RESULTS: Stretozotocin (STZ) only-treated groups exhibited hyperglycemia, polydipsia, polyuria, weight loss, glucose intolerance, low fasting plasma insulin and reduced hepatic glycogen content compared to the control group. Furthermore they had significantly elevated Malondialdehyde (MDA), acetoacetate, ß-hydroxybutyrate, anion gap and significantly reduced blood pH and plasma bicarbonate compared to the control group. Naringin treatment significantly improved Fasting Plasma Insulin (FPI), hepatic glycogen content, malondialdehyde, ß-hydroxybutyrate, acetoacetate, bicarbonate, blood pH and anion gap but not Fasting Blood Glucose (FBG) compared to the STZ only-treated group. CONCLUSIONS: Naringin is not hypoglycemic but ameliorates ketoacidosis and oxidative stress. Naringin supplements could therefore mitigate complications of diabetic ketoacidosis.

Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU.

OBJECTIVE: Patients with a chronic alcohol use disorder presenting to the ICU may be deficient in important vitamins and electrolytes and are often prescribed a "banana bag" as a reflexive standard of therapy. The difficulty of diagnosing Wernicke's encephalopathy in the critical care setting is reviewed. Furthermore, whether the contents and doses of micronutrients and electrolytes in standard banana bags meet the needs of critically ill patients with an alcohol use disorder is assessed based on available evidence. DATA SOURCE: MEDLINE/PubMed (1966 to June 2015) database search, the Cochrane Database of Systematic Reviews, and manual selection of bibliographies from selected articles. STUDY SELECTION AND DATA EXTRACTION: Articles relevant to Wernicke's encephalopathy, vitamin and electrolyte deficiencies in patients with alcohol use disorders, and alcoholic ketoacidosis were selected. Articles were narratively synthesized for this review. DATA SYNTHESIS: Of these deficiencies, thiamine is the most important for the practicing clinician to assess and prescribe replacement in a timely manner. Based on a pharmacokinetic assessment of thiamine, the banana bag approach likely fails to optimize delivery of thiamine to the central nervous system. Folic acid and magnesium may also merit supplementation although the available data do not allow for as strong a recommendation as for prescribing thiamine in this setting. There is no available evidence supporting the prescription of a multivitamin. CONCLUSIONS: Based on the published literature, for patients with a chronic alcohol use disorder admitted to the ICU with symptoms that may mimic or mask Wernicke's encephalopathy, we suggest abandoning the banana bag and utilizing the following formula for routine supplementation during the first day of admission: 200-500 mg IV thiamine every 8 hours, 64 mg/kg magnesium sulfate (approximately 4-5 g for most adult patients), and 400-1,000 µg IV folate. If alcoholic ketoacidosis is suspected, dextrose-containing fluids are recommended over normal saline.

Efecto agudo del baño con citrato sobre la alcalemia postdiálisis / Acute effect of citrate baths on post-dialysis alkalemia

INTRODUCCIÓN: La corrección de la acidosis metabólica provocada por la insuficiencia renal se consigue aportando bicarbonato durante la diálisis. Para evitar la precipitación de carbonato cálcico y magnésico que se produce en el líquido de diálisis (LD) al añadir bicarbonato, es necesario añadir un ácido, habitualmente acetato, que no está exento de efectos secundarios. Así, el citrato se presenta como una alternativa ventajosa al acetato, aunque sus efectos agudos no se conocen con precisión. OBJETIVO: Evaluar el efecto agudo sobre los parámetros del equilibrio ácido base y del metabolismo calcio-fósforo con la utilización de un líquido de diálisis con citrato en lugar de acetato. MATERIAL Y MÉTODOS: Estudio prospectivo y cruzado realizado en veinticuatro pacientes (15 hombres y 9 mujeres). Todos los pacientes se dializaron con monitor AK- 200-Ultra-S con líquido de diálisis SoftPac®, elaborado con 3 mmol/l de acetato y con SelectBag Citrate®, con 1 mmol/l de citrato, libre de acetato. Se extrajeron pre y post-diálisis: gasometría venosa, calcio (Ca), calcio iónico (Cai), fósforo (P) y hormona paratiroidea (PTH). RESULTADOS: Encontramos diferencias (p < 0,05) cuando utilizamos el baño con citrato (C) frente a acetato (A) en los valores postdiálisis de: pH (C: 7,43 (0,04) vs. A: 7,47 (0,05)), bicarbonato (C: 24,7 (2,7) vs. A: 27,3 (2,1) mmol/L), exceso de base (BEecf) (C: 0,4 (3,1) vs A: 3,7 (2,4) mmol/L), calcio corregido (Cac) (C: 9,8 (0,8) vs A: 10,1 (0,7) mg/dl) y Cai (C: 1,16 (0,05) vs A: 1,27 (0,06) mmol/L). No encontramos diferencias en ninguno de los parámetros medidos prediálisis. CONCLUSIÓN: La diálisis con citrato consigue un mejor control de equilibrio ácido base postdiálisis disminuyendo/evitando la alcalemia postdiálisis y un menor aumento de calcio corregido (Cac) y Cai. Este hallazgo es de especial interés en pacientes con factores predisponentes a arritmias, pacientes con insuficiencia respiratoria, retención de carbónico, calcificaciones y hepatopatía avanzada

Introduction: Correcting metabolic acidosis provoked by renal failure is achieved by supplying bicarbonate during dialysis. To prevent the precipitation of calcium and magnesium carbonate produced in the dialysis fluid (DF) when bicarbonate is added, it is necessary to add an acid(normally acetate), which involves secondary effects. Consequently, citrate is presented as an advantageous alternative to acetate, although its acute effects are not known with precision. Objective: Our objective was to assess the acute effect of using a DF with citrate instead of acetate on the parameters of acid-base balance and of phosphorus-calcium metabolism. Material and methods: We carried out a prospective, cross-over study on 24 patients (15 males and 9 females). All the patients were dialysed using an AK 200 ULTRA-S monitor with SoftPacRDF, prepared with 3 mmol/l of acetate, and with SelectBag CitrateR, with 1 mmol/l of acetate freecitrate. Before and after dialysis we extracted: venous blood gases, calcium (Ca), ionized calcium (Cai), phosphorus (P) and parathyroid hormone (PTH).Results: We found differences (P<.05) when we used a dialysate with citrate (C) compared with using acetate (A) in the post-dialysis values of pH (C: 7.43 [0.04] vs A: 7.47 [0.05]), bicarbonate(C: 24.7 [2.7] vs A: 27.3 [2.1] mmol/L), base excess of extracellular fluid (BEecf) (C: 0.4 [3.1] vs A: 3.7[2.4] mmol/L), corrected calcium (cCa) (C: 9.8 [0.8] vs A: 10.1 [0.7] mg/dl) and Cai (C: 1.16 [0.05] vsA: 1.27 [0.06] mmol/L). We found no differences in any of the parameters measured before dialysis. Conclusion: Dialysis with citrate achieves better post-dialysis acid-base balance, lowering/avoiding post-dialysis alkalemia and producing a lower increase in corrected calcium (Cac) and Cai. This finding is of special interest for patients with predisposing factors to arrhythmia and patients with respiratory failure, carbon dioxide retention, calcifications or advanced hepatopathy (AU)

[Starvation is a rare cause of metabolic ketoacidosis].

A 79-year-old woman with no medical history was admitted under the diagnosis of stroke. Two months prior she had a fractured tibia, complicated by osteomyelitis. Physical examination showed dehydration and malnourishment. Chest X-ray revealed pneumonia and laboratory data revealed signs of infection, dehydration and normoglycaemic metabolic acidosis with elevated P-3-hydroxybutyrate. The case presents a starvation- (weight loss ~ 13 kg) and infection-induced non-diabetic metabolic ketoacidosis treated with intravenous supplementation of isotonic saline, potassium, bicarbonate and insulin.

An unusual case of Butcher's Broom precipitating diabetic ketoacidosis.

BACKGROUND: Herbal medicines are readily available and commonly perceived to be relatively harmless. Butcher's Broom is used in various medicinal preparations and contains substances having α-adrenergic-stimulating properties. OBJECTIVE: Our aim was to report a case of toxicity associated with Butcher's Broom in a diabetic patient. CASE REPORT: A 39-year-old woman developed diabetic ketoacidosis 5 days after beginning therapy with Butcher's Broom for mild ankle swelling. Her diabetic ketoacidosis was complicated by hyperkalemia and acidosis with a pH of 7.02. After management with intravenous fluid, insulin, and calcium gluconate, her condition stabilized and she was discharged several days later. CONCLUSIONS: This case represents a small but potentially serious public health concern in a diabetic woman taking Butcher's Broom.

Oxidative stress indices in the erythrocytes from lactating cows after treatment for subclinical ketosis with antioxidant incorporated in the therapeutic regime.

The present investigation was carried out to assess the erythrocytic oxidative stress indices such as lipid peroxides level and activities of antioxidant enzymes such as superoxide dismutase and catalase, and some hematological parameters after treatment of subclinically ketotic lactating cows with antioxidants, vitamin E and selenium, incorporated in conventional treatment regimen. The study was carried out using lactating cows reared in small dairy herds in and around Bhubaneswar. Out of 250 urine samples examined, 42 cows were diagnosed positive for subclinical ketosis with an overall incidence of 16.8%. Blood samples were collected on day 0 (before treatment) and treatment was initiated on day 1 and the second sampling was carried out on day 7. The hematological parameters improved significantly following treatment as compared to pre-treatment level (day 0). A significant (P < 0.05) improvement was observed on day 7 with respect to hemoglobin level (8.66 +/- 0.23 vs. 9.12 +/- 0.14 gm/dl) and packed cell volume (29.7 +/- 0.56 vs. 31.1 +/- 0.50%) in the group given routine treatment along with antioxidants. The comparison of mean lipid peroxides level before (day 0) and after treatment (day 7) revealed a significant difference in group I (routine treatment, P < 0.05) and group II (routine treatment plus antioxidants, P < 0.01). The maximum reduction in SOD activity was recorded in group II animals after treatment with conventional regimes along with supplemented antioxidants (1.29 +/- 0.08 against 1.89 +/- 0.15 units/ mg of Hb, P < 0.01). The mean value of SOD activity recorded in group III animals kept as non-treated positive control (PC) on day 7 (2.59 +/- 0.14 units/mg of Hb) was significantly (P < 0.05) higher than the mean level recorded on day 0 (1.91 +/- 0.31 units/mg of Hb). An almost similar trend was observed in erythrocytic catalase activity where there was a significant (P < 0.05) reduction in catalase activity in the group II (RT+A) but there was no significant increase in catalase activity in non-treated positive control (PC) animals.

Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate.

A patient with severe pyruvate carboxylase deficiency presented at age 11 weeks with metabolic decompensation after routine immunization. She was comatose, had severe lactic acidemia (22 mM) and ketosis, low aspartate and glutamate, elevated citrulline and proline, and mild hyperammonemia. Head magnetic resonance imaging showed subdural hematomas and mild generalized brain atrophy. Biotin-unresponsive pyruvate carboxylase deficiency was diagnosed. To provide oxaloacetate, she was treated with high-dose citrate (7.5 mol/kg(-1)/day(-1)), aspartate (10 mmol/kg(-1)/day(-1)), and continuous drip feeding. Lactate and ketones diminished dramatically, and plasma amino acids normalized, except for arginine, which required supplementation. In the cerebrospinal fluid (CSF), glutamine remained low and lysine elevated, showing the treatment had not normalized brain chemistry. Metabolic decompensations, triggered by infections or fasting, diminished after the first year. They were characterized by severe lactic and ketoacidosis, hypernatremia, and a tendency to hypoglycemia. At age 3(1/2) years she has profound mental retardation, spasticity, and grand mal and myoclonic seizures only partially controlled by anticonvulsants. The new treatment regimen has helped maintain metabolic control, but the neurological outcome is still poor.

[Use of sodium acetate in feed rations in ketotic cows]. / Pouzití octanu sodného v krmných dávkách ketózních krav.

On a farm where the ration of cows contained 88.0 g of butyric acid, an experimental group of cows (n = 8), producing milk containing 7.9 mg or more acetone per litre, was studied for 14 days for the effect of a 250 g supplement of sodium acetate to the ration (combined with single i.m. administration of vitamins A, D2 and E) on selected metabolism parameters and on milk production. As distinct from the control group of cows (n = 8) from the same farm which produced milk containing 3.9 mg or less acetone per litre and which were fed without sodium acetone supplements, a tendency of increased alkaemia of the organism was suggested in the experimental cows. This tendency manifested itself during the trial in increased pH values, increased base excess (BE) and standard bicarbonate (SB) in the blood, and in an increase in the pH value and net acido basic secretion in urine. A decrease was recorded in the concentration of the acetone + acetacetic acid sum, the same as beta-hydroxybutyric acid in blood and the sum of acetone and acetacetic acid in milk (P less than 0.01). An insignificant increase of the activity of gammaglutamyl transpeptidase (GMT) was recorded in the blood serum of the experimental cows and a significant increase occurred in the content of potassium (up to P less than 0.01) and urea (up to P less than 0.01) in urine. The supplement of sodium acetate to the feed ration did not influence the degree of ketonuria and the finding of urobilinogen in urine.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinico-experimental and clinical studies of a ketomethine preparation in sheep and cows]. / Kliniko-eksperimentalni i klinichni prouchvaniia na preparata ketometin pri ovtse i kravi.

Some of the clinical parameters of the preparation ketomethyne, containing propylene glycol, methyonine, and Co bichloride, were comparatively studied with the analogous preparation ursoketin at oral application to sheep and cows. It was found that ketomethyne raised more slowly the level of blood sugar than ursoketin, but maintained it by 24-35 per cent higher than the initial level from the 6th to the 24th hour following treatment. The oral application of ketomethyne had no unfavourable effect on the rumen activity, the general clinical indices body temperature, pulse, respiration), the hematologic indices as hemoglobin and erythrocyte and leukocyte count, and the appetite. Similarly to ursoketin, ketomethyne was not readily taken by animals as judged by what was noted with ruminants in cases where the preparation was given as a supplement to the ordinary amounts of feed (concentrates). It was more successfully offered to the large ruminants when 5 to 8 kg silage and the preparation at the rate of 400-500 cm3 were admixed. With cows having paraclinical signs of ûetosis (hypoglycemia and ketonuria) the oral administration of ketomethyne at 500 cm3 in the course of four consecutive days produced favourable effects (up to 100 per cent). On such basis, therefore, the use of the preparation is worthwhile in the prevention of ketosis in sheep and cows or in their treatment.

[Therapeutic and prophylactic action of monensin and nicotinic acid in cows with subclinical ketosis]. / Prouchvane na lechebnoto i profilaktichnoto deistvie na monenzina i nikotinovata kiselina pri kravi sus subklinichna ketoza.

Experiments were carried out with sheep and cows on the basis of a limited feed ration--the giving of concentrates was discontinued, and the ration of alfalfa hay was replaced with meadow hay and a monensine supplement (at the rate of 20-25 mg for sheep and 250 mg for cows, daily), and nicotinic acid (at 0.8 g and 6.0 g, respectively). Observations revealed that in the course of 6-7 weeks in succession the drop of blood sugar was reduced, and monensine led to a rise of the alkali reserves of the blood by 27 to 41 per cent. Cows with ketonuria (from ++ up to + positive results with the nitroprusside tests) and hydroglycaemia (blood sugar up to 30 mg) were treated with monensine at the rate of 125 mg, in the morning and in the evening or with nicotinic acid at 3 g and the same frequency for 6-7 consecutive days. The symptoms receded to a greater extent (12.1 to 60 per cent) as compared to the process of self-healing for the same time period. In this respect the effect of monensine was better manifested. It was demonstrated that the prophylactic use of these drugs inhibited to a minimum the manifestation of hypoglycaemia and ketonuria.

[Hyperglycemic and therapeutic action of nontranquilizing doses of xylazine in healthy sheep and cows and in cows with subclinical ketosis]. / Prouchvane khiperglikemichnoto i lechebnoto deistvie na netrankvilizirashte dozi ksilazin pri zdravi ovtse i kravi i pri kravi sus subklinichna ketoza.

Experiments with 19 sheep and 26 cows revealed that subcutaneous and muscular injection of xylasine (Rompun - Bayer at 0.04 to 0.08 mg/kg body mass) led to a dependable increase in the level of blood sugar by 50-220 per cent for a period of 1 to 3 hrs. At the 6th to the 24th hour the amount of blood sugar came back to normal. In cows with subclinical ketosis (ketonuria ++ to +++ after Lastradet's test) and hypoglycaemia (blood sugar 29.7 +/- 4.6 mg%) the injection of xylasine (0.05-0.08 mg/kg body mass) increased the level of blood sugar by 169 to 185 per cent, which remained at a comparatively high level up to the 24th hour. Ketonuria dropped, however, full dusapperance of ketone bodies in the urine was observed in 7 per cent of the treated animals only. It is believed that although there was a pronounced hyperglycaemic effect of the preparation it cannot be applied alone for the treatment of ketosis-affected cows. It is important as an additional means, particularly with animals affected with the nervous form of the disease.

[Bovicystan treatment of subclinical ketosis in cows]. / Lekuvane na subklinichnata ketoza pri kravi s bovitsistan.

Experiments with normal animals (10 sheep and 15 cows) revealed that the intravenous injection of bovicystan led to a considerable and dependable rise of the blood sugar for 2 to 36 hours the peak being at the 6th hour. The treatment of 95 freshly calved cows on 8 farms with signs of subclinical ketosis (ketonemia 22.4 +/- 1.9 mg%, ketonuria up to dilution of 1:2-1:16 and hypoglycemia 26.7 +/- 2.6 mg%) resulted in a 92.6 per cent total curative effect, consisting in the full inhibition of ketonuria, drop of the ketone bodies in the blood up to 16.5 +/- 1.2 mg%, on an average, and rise of the blood sugar up to 47.7 +/- 1.2 mg%, on an average. In 27.4 per cent of the treated cows ketonuria disappeared after the first injection, in 50.5 per cent - after the second one, and in 14.7 per cent only did ketonuria faded after the third injection of the preparation within a period of 24 hours. At the 48th hour following the last introduction of bovicystan there was an increase in the blood serum level of carotene and lactose, and a decrease in the level of inorganic phosphorus. One to three weeks after treatment with bovicystan in some 27.6 to 33.0 per cent of the cows on 2 of the farms signs of subclinical ketosis reappeared.

Treatment of alcoholic acidosis: the role of dextrose and phosphorus.

We have made serial metabolic observations in 18 acute episodes of alcoholic ketoacidosis in ten patients. Data from patients treated with only saline initially were compared to data from patients who received modest amounts of intravenous dextrose (7.0 to 7.5 gm/hr). More rapid improvement in the acidotic state was seen in the latter group (P less than .001). The quicker decline in absolute levels and ratio of beta-hydroxybutyrate to acetoacetate when glucose was given suggests that this treatment induced mitochondrial oxidation of the reduced form of nicotinamide adenine dinucleotide (NADH). Since phosphorus is a critical cofactor necessary for NADH oxidation and the glucose-induced correction of the acidosis was associated with a rapid decline in serum phosphorus from an initial mean of 6.79 +/- .82 mg/100 ml SEM to 0.96 +/- 0.12 mg/100 ml in 24 hours, we propose that glucose enhanced the mitochondrial capacity to oxidize NADH by increasing hepatocyte phosphorus. This effect combined with decline in free fatty acid levels results in reversal of acidosis. Our data suggest that glucose provides the safest, most effective treatment for this disorder; addition of either insulin or bicarbonate is usually unnecessary.