Bromsulphthalein Clearance Research Articles

Effect on liver function of acetonaemia and the fat cow syndrome in cattle

The effect of fatty infiltration on liver function was studied in 29 dairy cows aged 6 +/- 0.4 (SEM) years with primary acetonaemia, secondary acetonaemia or the fat cow syndrome. The average interval from calving at diagnosis was 16.4 +/- 2.0 days and the animals had been anorexic for a mean of 5.6 +/- 0.8 days. Fatty infiltration of the liver occurred well before calving and was associated with severe clinical illness and intercurrent infections. The percentage of fatty infiltration in the liver (mean 53.1 +/- 2.8 per cent) was significantly correlated with both the degree of clinical illness (P less than 0.001) and the period of anorexia (P less than 0.05). Alterations in uptake, conjugation and excretion at the hepatocyte level were determined by measuring bromsulphthalein clearance, and plasma total bilirubin and total bile acid concentrations. Values for all three were positively correlated with the extent of fatty infiltration. Plasma albumin, urea and glucose concentrations were reliable indicators of the liver's synthetic function and together with plasma aspartate aminotransferase, iditol and glutamate dehydrogenase were correlated with the degree of hepatic lipidosis.

Liver function of dairy cows in late pregnancy and early lactation

The possibility that alterations in liver function may occur during late pregnancy as well as after calving has been investigated in healthy dairy cows and the results compared with those from non-pregnant non-lactating cows. There were significant alterations in plasma total bilirubin, glucose, total ketone body and urea concentrations, in bromsulphthalein clearance and in plasma aspartate aminotransferase and creatine kinase activities in periparturient cows compared with non-pregnant non-lactating cows. Of these, only the alterations in glucose, ketone bodies and urea concentrations and bromsulphthalein half-time and retention were markedly different before calving. The degree of fatty infiltration of the liver was significant two weeks before as well as two weeks after calving which differed from previous reports. It seems likely that the changes in the liver in dairy cows are functional and reversible and related to the metabolic demands of late pregnancy and early lactation. The results suggest that such changes in the liver occur well before calving.

The liver in sarcoidosis.

Neddle biopsies of the liver were performed in 121 cases of sarcoidosis. Granulomas compatible with sarcoidosis were seen in 24 percent of the cases. Liver function tests (serum alkaline phosphatase, serum aspartate aminotransferase, serum alanine aminotransferase, and bromsulphthalein clearance test) were performed on 325 patients with sarcoidosis and on 132 with non-sarcoid erythema nodosum (EN). Pathological findings were seen especially in patients with extensive EN, without any correlation with the disease responsible for the eruption. Hepatic granulomas were found more often in patients with sarcoid changes in lung parenchyma than in those with bilateral hilar adenitis only. There were no other definite correlations between hepatic granulomas and other clinical and laboratory findings. The incidence of pathological results in this study was clearly lower than, e.g., in the USA, thus reflecting the good prognosis of sarcoidosis in the Scandinavian countries.

Hepatogenous photosensitization its induction and study in guinea pigs

Guinea pigs were photosensitized by administering low, repeated doses of carbon tetrachloride, and also by ligation of the common bile duct. Photosensitizing doses of CCl 4 produced a reduction in bromsulphthalein clearance and release of aspartate amino transferase (AST) and alanine aminotransferase (ALT) into the plasma. After bile duct ligation BSP clearance was reduced, and there were increases in plasma AST, ALT, total bilirubin and alkaline phosphatase. In both cases the photosensitive response was an immediate erythema elicited by a narrow waveband radiation in the long ultraviolet and visible part of the spectrum. Phylloerythrin was detected in the urine of both groups of photosensitized animals and also in plasma after bile duct ligation.

Biochemical and metabolic function of the canine liver after four hours preservation.

AbstractCanine livers were stored for four hours with either hypothermia alone, hypothermia and low flow electrolyte perfusion, hypothermia low flow plasma perfusion, or normothermic dilute blood perfusion. The livers were evaluated by a subsequent two hour normothermic dilute blood test perfusion. Pressure flow relationships were of value in assessing the adequacy of the storage, and correlated well with glucose production and ultrastructural appearances. Livers stored with plasma perfusion seemed to be the most satisfactory. Anaerobic utilization of fructose was a more sensitive index of cellular damage than oxygen uptake in manometric studies. Bromsulphthalein clearance during the test perfusion was of limited value.

A Review of Factors Affecting Blood Biochemistry in the Pig

SUMMARY Lack of information on the clinical biochemistry of the conventional pig compared with many other species is due, among other factors, to the present economic policy of culling or isolating unthrifty animal's without preliminary biochemical investigation, and the animal's intractability which makes blood and urine sampling difficult. This paper discusses the effects of some normal environmental factors such as age, sex, breed and particularly diet, as well as some disease conditions, on the levels of some organic serum components such as protein, urea, cholesterol, certain enzymes including alkaline phosphatase, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, glutamate and sorbitol dehydrogenases, arginase, carbamoyl transferase and lactate dehydrogenase, several of which are in current use in the diagnosis of liver disease and muscle dystrophy in other species. Bromsulphthalein clearance and urine analysis for common abnormalities are also discussed. It is concluded, on somewhat slender evidence, and taking into account the effects of age, diet, etc., that liver function can best be assessed routinely by S-GOT, OCT, possibly LDH and to a lesser degree by S-GPT, and kidney function by analysis of urine for abnormalities, and blood or serum for urea. Limited work indicates the possible value of BSP clearance for liver function, but intractability of the species renders this less useful as a routine test. Estimations of serum proteins and cholesterol do not appear to offer much useful information in assessing liver and kidney function. It is concluded that further basic studies must be carried out, more specifically on alkaline phosphatase, glutamate and sorbitol dehydrogenases in order to make it possible to recommend a larger battery of routine tests for liver function, and that estimations of serum urea, urinary protein and phenolsuiphonphthalein clearances should be investigated in connection with kidney function.

Experimental Chronic Copper Toxicity in Sheep: Biochemical and Haematological Studies during the Development of Lesions in the Liver

Summary Eight sheep were dosed repeatedly with copper sulphate in order to induce chronic copper poisoning. This object was achieved in 7 animals and several had repeated haemolytic episodes. Raised blood copper levels were found only immediately before or during haemolysis and both plasma copper and red cell copper fractious were increased at this time. An increase in the concentration of sorbitol dehydrogenase, arqinase andglutamate-oxaloacetate transaminase was detected in the serum one week after the start of dosing and by 2 weeks 5 animals also showed an increased serum glutamate dehydrogenase concentration. Subsequently the enzyme levels fluctuated and in some instancesfell to near the pre-dosing range. A marked increase in serum enzyme activity occurred immediately prior to the haemolytic crisis. Serum bilirubin leveb followed a similar trend and the highest values were recorded during haemolytic episodes. Reduced bromsulphthalein clearance occurred several weeks before haemolysis and particularly low rates of clearance were recorded in the 2 weeks prior to haemolytic crises. Haemolysis was associated with neutrophilia, Heinz body formation and high blood urea levels. Post mortem markedly elevated copper levels were found in the liver and kidneys and slightly elevated copper levels were found in the spinal cord. Liver zinc levels were raised, kidney iron levels were markedly increased but spinal cord iron levels were decreased.

The kinetics of organic anion excretion by the liver in acute intermittent porphyria.

1. The kinetics of disappearance from the blood of three organic anions were studied in patients with acute intermittent porphyria. Indocyanine green (ICG) and [14C]bilirubin were cleared normally in this disease, whereas bromsulphthalein (BSP) was cleared at less than the normal rate. The first exponential component of the BSP clearance curve was normal in acute intermittent porphyria, but the second exponential component declined less rapidly than in normals. The abnormality was greater in symptomatic than in asymptomatic patients, but both groups were significantly different from normals. 2. The data are discussed in terms of a previously published model of BSP metabolism. The findings suggest normal BSP uptake initially by the liver with increased regurgitation of dye into the blood and decreased excretion of BSP from the liver cell into the bile. 3. In contrast to human acute intermittent porphyria, plasma clearance of BSP was greatly increased in experimental porphyria. This was associated with an increased level of BSP conjugating enzyme in the liver in experimental porphyria. 4. The BSP retention in acute intermittent porphyria, along with certain other findings, raises the question of the existence of an ‘oestrogen effect’ in this disease, but further studies will be required to determine whether the mechanism of BSP retention is identical to that produced by oestrogen.

The Experimental Intoxication of Sheep with Sporidesmin, A Metabolic Product of Pithomyces chartarum: III.—Some Changes in Cellular Components and Coagulation Properties of the Blood, in Serum Proteins and in Liver Function

SUMMARY Sporidesmin was administered to sheep at the rate of 0.5 mg., 0.8 mg. and 1.0 mg./kg. bodyweight. The blood cellular picture was followed in sheep dosed at the intermediate and higher levels. While no significant change was noted in the erythrocyte values during the course of the experiments, a diphasic increase of neutrophil leucocytes was observed and its probable significance is discussed. Changes in blood “prothrombin” time and clot retraction were noted, but it is considered unlikely that these changes play a significant role in the course of the disease. Serum protein levels were followed in sheep dosed with 1.0 mg./kg. and the changes found gave good indication of progressing liver injury. The elevated levels of total serum protein found were mainly due to increased values for (β-and γ-globulin; serum albumen levels fell during the course of the experimental disease. Of the 5 liver function tests examined, the strong-iodine flocculation test and the thymol and zinc-sulphate turbidity tests were found to indicate liver injury in the second phase of the disease. Liver excretory function was determined by measuring bromsulphthalein clearance rate throughout the disease in 4 sheep dosed with sporidesmin at 1.0 mg./kg. Impairment of excretory function was observed to occur during 2 well-defined phases of the induced disease and its likely implications are examined.

Some functional manifestations of the protein depletion of sheep tissues

In order to elucidate the alterations in tissue function of Merino sheep feeding on a low protein, low energy diet, the sequential measurement of a number of clinical parameters has been performed. Emphasis has been directed to the protein storage tissues, and the following indices were measured: bromsulphthalein clearance; serum levels of glutamic oxalacetic transaminase, glutamic pyruvic transaminase, total cholesterol, cholesterol esters, total proteins, electrophoretic protein fractions, and urea; urinary volume, and urine creatine, creatinine, and urea. Alterations in these indices were consistent with a marked degree of liver dysfunction occurring after several weeks on the experimental diet. No significant changes were apparent in the functional ability of kidney or muscle.

Some effects of carbon tetrachloride intoxication on liver and kidney function in sheep.

Observations have been made of the effect of toxic doses of carbon tetrachloride per os on bromsulphthalein clearance, p-aminohippurate synthesis from p-aminobenzoate, plasma concentrations of bilirubin, glutamate oxalacetate and glutamate pyruvate transaminase, protein fractions, creatinine, urea, creatine, "guanidine", phenols, potassium, sodium, calcium, lipid fractions and amino acids, prothrombin time, blood ammonia concentrations, urine volume, specific gravity, osmolarity, protein concentration, and p-aminohippurate and creahine clearances. It was found that a marked degree of both kidney and liver dysfunction followed administration of carbon tetrachloride. There was a similar degree of liver dysfunction in those sheep that died and in those that survived. Kidney dysfunction was much more severe in those animals that died. The kidney dysfunction preceded the symptoms in all cases.

EFFECTS OF GROWTH HORMONE ON METABOLIC AND ENDOCRINE FACTORS IN HYPOPHYSECTOMIZED DOGS

Hypophysectomy in dogs caused reductions in: the level of sugar in the blood; the volume % of packed red blood corpuscles; the rate of clearance of bromsulphthalein; the weight of the pancreas; the amount of insulin extractable from the pancreas; and the weights of the kidneys, heart, and adrenal glands. The glucose tolerance of hypophysectomized dogs was significantly less than that of normal dogs.The administration of growth hormone during 5 days to hypophysectomized dogs caused: increase of blood sugar but not to diabetic levels; elevation and prolongation of the glucose tolerance curve; increased erythrocyte sedimentation rate; reduced volume % of red blood corpuscles; restoration of bromsulphthalein clearance to normal; reduction of the insulin extractable from the pancreas to 60% of the pretreatment level; increases in the weight, total lipid, dry fat-free residue, and water of the liver; and restoration of the kidney weight and lipid content to normal. Little or no glycosuria or ketonuria and no anorexia occurred under these conditions.The same treatment of normal dogs with growth hormone caused: increase of blood sugar to diabetic levels; elevation and prolongation of the glucose tolerance curve; increased erythrocyte sedimentation rate; decreased volume % of packed red blood corpuscles, glycosuria, ketonuria, albuminuria, and anorexia; great decrease in the amount of insulin extractable from the pancreas to 6% normal; increase in the total lipid, dry fat-free residue, and water of the liver, increase in the weight and lipid of the kidney; and increase in the weight of the ventricles of the heart. The bromsulphthalein clearance was not altered. The physiological significance of these findings is discussed, particularly the production by growth hormone of more pronounced diabetes and greater reduction of insulin extractable from the pancreas in normal than in hypophysectomized dogs.

EFFECTS OF GROWTH HORMONE ON METABOLIC AND ENDOCRINE FACTORS IN HYPOPHYSECTOMIZED DOGS

Hypophysectomy in dogs caused reductions in: the level of sugar in the blood; the volume % of packed red blood corpuscles; the rate of clearance of bromsulphthalein; the weight of the pancreas; the amount of insulin extractable from the pancreas; and the weights of the kidneys, heart, and adrenal glands. The glucose tolerance of hypophysectomized dogs was significantly less than that of normal dogs.The administration of growth hormone during 5 days to hypophysectomized dogs caused: increase of blood sugar but not to diabetic levels; elevation and prolongation of the glucose tolerance curve; increased erythrocyte sedimentation rate; reduced volume % of red blood corpuscles; restoration of bromsulphthalein clearance to normal; reduction of the insulin extractable from the pancreas to 60% of the pretreatment level; increases in the weight, total lipid, dry fat-free residue, and water of the liver; and restoration of the kidney weight and lipid content to normal. Little or no glycosuria or ketonuria and no anorexia occurred under these conditions.The same treatment of normal dogs with growth hormone caused: increase of blood sugar to diabetic levels; elevation and prolongation of the glucose tolerance curve; increased erythrocyte sedimentation rate; decreased volume % of packed red blood corpuscles, glycosuria, ketonuria, albuminuria, and anorexia; great decrease in the amount of insulin extractable from the pancreas to 6% normal; increase in the total lipid, dry fat-free residue, and water of the liver, increase in the weight and lipid of the kidney; and increase in the weight of the ventricles of the heart. The bromsulphthalein clearance was not altered. The physiological significance of these findings is discussed, particularly the production by growth hormone of more pronounced diabetes and greater reduction of insulin extractable from the pancreas in normal than in hypophysectomized dogs.