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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.

Investigations were carried out with 45 normal cows and 45 cows with disturbed carbohydrate metabolism (ketosis). The animals of the groups were all high-producing, and have recently calved, being equated according to the principle of analogues. Studied were the indices that were most characteristic of carbohydrate metabolism--total amount of VFA in the rumen along with individual fractions (acetic, propionic, and butyric acid) and total ketones; blood level of FVA, sugar, and ketone bodies. It was found that in the rumen of normal cows the content of VFA was 564.6 +/- 42.4 mg%, and that of the fractions was: acetic acid-342.2 +/- 14.2 mg%, propionic acid-166.8 +/- 16.3 mg%, butyric acid-56.8 +/- 5.6 mg%, and ketone bodies-6.4 +/- 0.8 mg%. In the blood VFA were 8.2 +/- 1.2 mg%, sugar was 66.3 +/- 1.4 mg%, and ketones were 7.6 +/- 1.8 mg%. With ketosis-affected cows, exhibiting disturbed carbohydrate metabolism these values were: in the rumen-VFA-322.6 +/- 28.4 mg%, acetic acid-120.8 +/- 17.8 mg%, propionic acid-76.4 +/- 12.2 mg%, butyric acid-126.0 +/- 9.5 mg%, and ketone bodies-93.2 +/- 1.8 mg%; in the blood-VFA-72.4 +/- 9.2 mg%, sugar-32.3 +/- 1.9 mg%, and ketone bodies-106.6 +/- 8.6 mg%. Analysis of the results with normal carbohydrate metabolism has revealed that the total amount of VFA in the rumen consisted of 60.6% acetic acid, 29.5% propionic acid, and 10.0% butyric acid.

Studied was the activity of the alkaline phosphatase and the transaminases in the serum of clinically normal and ketosis-affected cows as well as cows with an affected liver. The changes were followed in the activity of SGOT and SGPT that had set in as a result of five-day starving and the injection of prednisolon at the rate of 0.5 mg/kg in the course of four days. The activity of serum alkaline phosphatase in ketosis-affected cows proved unchanged--1.99 +/1 0.35 VE. A moderate increase was established in cows with liver affections-- 3.73 +/- 0.35 VE. The hyperenzymemia in ketosis-affected animals, in animals with liver injuries as well as in cows subjected to starving or prednisolon treatment was substantiated by the higher activity of SGOT. Dependable higher values of SGOT were established in the serum of freshly calved cows as compared to cows of advanced lactation. The higher activity of SGOT in animals with ketosis is associated with the physiologic status, starving, enzyme induction, inadequacy of the cell energy balance--all limiting the possibility of it being ascribed with preference to the tissue proliferation or destruction, which is to be expected with cows having an affected liver.

Pregnant cows in the dry period were given methionine at the rate of 0.5 cent of the dry matter of the ration 20 days before parturition. It was shown that such animals manifest no ketosis and other disturbances in the liver. High-producing, lactating cows that were offered DL-methionine orally at 0.6 per cent in the first 90 day of the lactation period did not likewise develop ketosis and other liver troubles, while animals that were deprived from this amino acid were affected up to 10 per cent. The blood levels of sugar, ketone bodies, total lipids and protein, bilirubin, SGOT, SGPT, LDH, and aldolase were influenced positively by the administration of methionine to high-producing cows. The total amount of amino acids in the blood of lactating cows rose, methionine reaching 80 per cent above the ordinary level when diets containing synthetic methionine were fed to the animals.

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.

Studies were carried out with a total of 40 ketosis-affected cows and 40 normal (control) cows. It was found that with the diseased animals the blood level of sugar was lowered by 45 per cent, that of total protein--by 24 per cent, that of carotene and vitamin A--by more than twice, and that of inorganic phosphorus--by 20 per cent as against the blood indices with the control cows. In the same period the content of ketone bodies in the blood of ths affected cows increased 5 times, and in the urine it rose 6 times. With cows that had ketosis the cases of dystocia and retained placenta were 5 times more, still births were twice more, and the cases of diseased endometrium were 6 times more than those in the control cows. Respectively, cows that had manifested clinical ketosis showed longer independence period (by 22 days), longer service period (by 54 days), lack of estrus (in 20 per cent of the animals), and as many as 33.3 per cent of them failed to conceive and were culled. It was concluded that ketosis had unfavourably affected the normal course of the parturition process ++ and the conception of high-producing cows.

Some of the indices of carbohydrate metabolism were studied in 30 freshly calved, high-producing cows affected with the disease and after they had recovered from ketosis as well as in 25 control cows. Investigated were the volatile fatty acids (VFA), ketone bodies, pH, and the count and composition of infusoria in the rumen content; the sugar, ketone bodies, and VFA in the blood--all being considered the most characteristic indices of carbohydrate metabolism in ruminants. With diseased cows pH in the rumen was 22 per cent lower than in the controls; the total count of infusoria per cu.cm was more than twice lower than the values found after recovery and those in the controls. Diplodinium and Isotricha infusoria were twice as low as the values found in the controls and after recovery. Entodinium infusoria were totally lacking in the rumen content of the affected animals, while the ketone bodies were 13.5 to 15.5 times as high, and VFA were 37 to 49 per cent lower. The level of the individual VFA fractions was altered; it was 2.4 to 2.8 times lower for acetic acid and 1.8 to 1.9 lower for propionic acid, while it was 1.8 to 2.1 times higher for butyric acid. The blood level of sugar in the diseased cows was more than twice lower, while the blood level of ketone bodies was 12 to 13 times higher; it was also higher (8 to 13 times) for VFA as compared with the values shown by normal cows and cows that had recovered from ketosis.

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.

Investigations were carried out with a total of 276 high-producing and clinically healthy cows that had freshly calved on 11 farms, being divided into groups according to the extent to which ketonuria was present if al all. Whole blood and blood serum were sampled to determine the ketone bodies, blood sugar, erythrocyte and leukocyte counts, hemoglobin, inorganic phosphorus, Ca, Mg, total protein, carotene, and activity of the GOT and GPT enzymes as well as the activity of lactic acid dehydrogenase, alkaline phosphatase, aldolase, and leucine aminopeptidase. Studied were the body temperature, the pulse rate, and the respiration rate. It was found that on farms with ketosis in cows ketonuria was manifested most often after the ketone bodies in the blood rose to 10-12 mg%. At the same time the blood sugar level was lowered and as a rule it showed reverse correlation with the levels of ketonemia and ketonuria. In such cows there was a lowering trend with the Ca and carotene contents and the erythrocyte count, and the respiration rate was higher. There were no changes in the body temperature, pulse rate, leukocyte count, Ca, Mg, hemoglobin, protein, and the activity of aldolase. The activity of the other enzymes mentioned was higher, and it correlated positively with the rise of ketonemia and ketonuria. With diseased cows the activity of alkaline phosphatase only was shown to be lower, negatively correlating with ketonuria.

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.

The total lipids and cholesterin were determined in the serum of 26 normal cows in an advanced lactvery. It was found that the rise of the total lipids in the diseased cows was negligible and was statistically significant only with regard to those that have recently calved, which showed the lowest values. No conceivable differences were established after recovery. The drop of the total cholesterin in the fresh and ketosis-affected animals was not accompanied by substantial changes in the coefficient of esterification; these variations disappeared with recovery. Anologous were the changes in the ester cholesterin the rise of which was visible after recovery although statistically insignificant. The changes observed were characteristic of the glucose deficiency present in ketosis-affected cows.

The investigation confirms hypoglycaemia and hyperketonaemia as typical for ketosis. A reverse correlation has been found between the level of blood sugar and that of ketone bodies. The changes observed in both blood sugars and ketones have not been shown to manifest any definite relation to the feeding regime, which may not have been perfectly balanced but has supplied metabolizable energy and digestible protein for maintenance and production in excess. Five-day starving of freshly calved, clinically normal cows may cause a dependable drop of the blood sugar level and rise of the ketone bodies to an extent that vary from that observed in ketosis-affected cows showing no clinical picture characteristic of the disease. The glycaemic reaction observed with the glucose-tolerance and the adrenaline tests shows that there is no apparent differences in the carbohydrate metabolism and the glycosynthetic capacity of the liver between diseased and clinically normal animals. The use of the two tests as auxiliary clinical methods has not been effective in registering the deviations in the status of the adrenal cortex and the pituitary gland.

Studied was the bilirubin equilibrium in 62 normal cows, 52 cows with clinical ketosis, 31 cows with diffuse liver injury, and 14 cows that went off food for five days. A moderate rise of the total bilirubin of mixed type was found in ketosis-affected cows. Statistically significant proved the changes in the free fraction, however, there were no persuasive data that they were due to superproduction of bilirubin. Changes in the total bilirubin similar to those in cows with ketosis were established also in cows subjected to starvation, substantiated by the adequate rise of the free and the bound fraction. The hyperbilirubinemia in cows with diffuse liver injuries was found to be of a mixed type, with a very clear transposition in the bilirubin fractions. The direct: indirect ratio of bilirubin in this case was higher than unit, and the percent participation of the indirect fraction was brought down to 42.5. Apparently, the symptoms of liver affections were beyond the frames of what was found in the cows with ketosis. With the use of tests for the demonstration of urobilin and urobilinogen in the urine no dependable idea could be found of the status of the pigment fraction in the liver of ketosis-affected cows or the fact that this fraction was involved to a considerable extent. Discussed is the possibility of linking the state of hyperbilirubinemia in cows with ketosis with some energy deficiency with regard to the plasma glucosis and the liver glycogen.

Biochemical and histological investigations were carried out with cows affected with ketosis in a subclinical and clinical form. Parellel studies were performed with normal (control) cows originating from the herds with the ill animals and manifesting the same physiologic status. It was found that the blood level of glucose in the diseased cows was lowered more than 2.6 times, and the content of ketone bodies was higher-- it was increased 4.6 times, that of total lipids was 2.6 times higher, and that of free fatty acids was 3.5 times higher as compared to the same indices in the controls. The blood content of pyruvate in the affected cows was also increased. The liver glycogen in these animals was lowered from 2.1 to 4.1 times. The activity of glucose-6-phosphatase was lower, and that of glucose-6-phosphatedehydrogenase was higher as against the same indices shown by normal cows.