bluuebunny/crossref_metadata_2025 huggingface dataset:
The Inhibitory Effect of Phosphonates on the Formation of Calcium Phosphate Crystals in vitro and on Aortic and Kidney Calcification in vivo
Authors: Fleisch H. A. , Russell R. G. G. , Bisaz S. , Mühlbauer R. C. , Williams D. A.
Published: March 2008

Abstract 1. Various phosphonates, which are compounds containing C‐P bonds, have been studied to see whether they are able to inhibit, in a manner similar to that of pyrophosphate and the condensed phosphates, the crystallization of calcium phosphate in vitro and the pathological calcification of the aorta and the kidneys of rats given large amounts of vitamin D3.

2. Six of the ten compounds studied markedly increased the minimum product, [Ca] × [P], required to induce the precipitation of calcium phosphate in vitro under physiological conditions of pH, ionic strength and temperature. Inhibition was observed at concentrations as low as 10‐7—106M.

3. Most of the diphosphonates, particularly those possessing P‐C‐P bonds, showed some ability to inhibit the calcification of the aortas and kidneys of rats treated with large amounts of vitamin D3. The most effective inhibitors were methylene diphosphonate (MDP), ethane‐1‐hydroxy‐1: I‐diphosphonate (EHDP) and diehloromethylene diphosphonate (Cl2MDP).

4. The phosphonates that possess P‐C‐P bonds thus appear to have effects on the deposition of calcium phosphate in vitro and in vivo similar to those of inorganic pyrophosphate and the condensed phosphates, which possess P‐O‐P bonds. These phosphonates differ from the condensed phosphates in that they inhibit kidney calcification as well as aortic calcification and are active by mouth as well as parenterally. The wider spectrum of activity of the phosphonates in vivo may be due to the fact that they are more resistant to chemical and enzymic breakdown.

5. Phosphonates might be used therapeutically in man against diseases in which calcium salts deposit in soft tissues.
Influence of Energy‐Coupling Inhibitors on the Respiration of Tightly‐Coupled Human Skeletal Muscle Mitochondria*
Authors: Mockel J. , Dumont J. E.
Published: March 2008

Abstract A standardized preparation method for the study by polarographic technique of human skeletal muscle mitochondria is described. The mitochondria thus obtained are tightly coupled, exhibiting high respiratory control ratios with classical responses to energy‐coupling inhibitors; they are also able to accumulate calcium, this uptake being blocked by inhibition of the phosphate carrier system. Arsenate uncoupling and integrity of the electron transport chain are demonstrated polarographically. The properties of human skeletal muscle mitochondria are generally similar to those of rat‐skeletal muscle and‐liver mitochondria; differences are discussed.
Comparative Effects of Exercise and Isocapnic Voluntary Hyperventilation on Pulmonary Haemodynamics in Chronic Bronchitis and Emphysema
Authors: Lockhart A. , Nader F. , Tzareva M. , Schrijen F.
Published: March 2008

Abstract (1) Twelve patients with chronic bronchitis and/or pulmonary emphysema with borderline pulmonary artery Eressure and arterial blood gases have been submitted to aemodynamic studies in order to compare changes in the pulmonary circulation brought about by leg exercise and by voluntary hyperventilation with comparable breathing rate, tidal volume and arterial blood gases during both periods.

(2) Minute ventilation (Exercise: 12.1 ± 1.9 l. min‐l m‐2; hyperventilation: 12.8± 1.8 1 · min‐1· m‐2), breathing rate (E: 22.6 ±3.4, H: 23.5 ±3.8), percentage arterial oxygen saturation (E: 94.7±3.3%, H: 95.9±2.7%) and carbon dioxide tension (E: 45.5 ± 5.1 mm Hg, H: 46.8 ± 5.1 mm Hg) did not differ significantly during exercise and hyperventilation, thus suggesting that both mechanical forces acting upon intrathoracic structures and pulmonary vasomotor tone were comparable.

(3) During exercise pulmonary arterial mean pressure (31.4±5.7mm Hg) and pulmonary wedge pressure (13.2± 4.2 mm Hg) rose significantly (p < 0.001) and consistently. During hyperventilation pulmonary arterial mean pressure rose slightly (22.1 ± 5.5 mm Hg, p < 0.05) and the increase in average pulmonary wedge pressure was insignificant (10.0±5.4 mm Hg), although the latter rose markedly in five cases. Pulmonary vascular resistances were not consistently modified. Pulmonary wedge pressure was not correlated with minute ventilation but was positively correlated with the amplitude of respiratory variations in intrathoracic pressure.

(4) Thus, our data suggested that the rise in pulmonary artery and wedge pressures during exercise was due to the combined effects of large intrathoracic pressure swings and of an increase in the haemodynamic load of the left ventricle.
Serum Thyrotropin Level during Growth in Man*
Authors: Golstein‐Golaire Jacqueline , Delange François
Published: March 2008

Abstract. TSH levels were measured by radioimmunoassay in the sera of 60 Belgian euthyroid subjects, aged from 4 to 32 years. A significantly higher TSH level was found in children aged from 7 to 15 years, when compared to the level obtained in adults. This increased TSH concentration and various indications of increased thyroid function during the growth spurt suggest a hyperstimulation of the thyroid at that period of life.
Alkaline Phosphatase: Diagnostic Value of Isoenzyme Determination
Authors: Ohlen J. , Pause H. , Richter J.
Published: March 2008

Abstract. The isoenzyme pattern of the alkaline phosphatases was determined in the sera of 51 normal subjects, 28 patients with hepatobiliary diseases and 17 patients with bone diseases. Two quick and technically simple methods of differentiation were used for a semiquantitative determination: stereospecific sensitivity to L‐phenylalanine, especially of the small intestine phosphatase, and the separation of the bone and liver/biliary tract phosphatases by a combination of heat inactivation and stereo‐specific inhibition. The basic principles of these methods are described. The results, statistically evaluated, are discussed. The alkaline phosphatase activity in the serum of healthy adults stems from isoenzymes of the small intestine (about 20%), of bone and of hepatobiliary origin. In hepatobiliary diseases the proportion of bone to liver/biliary tract phosphatases changes significantly in favour of the latter. In diseases of the skeleton, however, which are accompanied by increased activity of serum alkaline phosphatase, there is a significant increase in the absolute fraction of bone phosphatase in the total activity. In addition to the demonstration of these qualitative and quantitative changes in the isoenzyme distribution patterns, limiting values were determined for a normal group; values outside these can be considered as pathognomonic for diseases of the liver and biliary tract and the skeleton respectively. Of particular importance for early diagnosis is the fact that changes in the isoenzyme distribution pattern are demonstrable not only when the total activity is increased, but at a time when the serum activity lies still within normal limits. The methods used are suitable for a rapid and reproducible semiquantitative determination of the isoenzymes of alkaline phosphatase, and for early differential diagnosis of diseases of the skeleton (especially metastatic tumours), the liver and biliary tract.
Relationship between Faecal Bile Acids, Absorption of Fat and Vitamin B12, and Serum Lipids in Patients with Ileal Resections
Authors: Miettinen T. A.
Published: March 2008

Abstract. Faecal bile salt, neutral steroid and fat excretion, vitamin B12 absorption, and jejunal lipids, bile acids and cholesterol during fat digestion, serum cholesterol and cholesterol synthesis were measured in 3 patients with incomplete (IIR) and 9 patients with complete (CIR) resection of the terminal ileum. These parameters were virtually normal in IIR and in one case with CIR while in other cases they were frequently abnormal, bile salt excretion being increased up to 12‐fold. The finding that faecal bile salts correlated positively with faecal fat and cholesterol synthesis, and negatively with jejunal constituents and serum cholesterol, supports the previously unproved concept that augmented elimination of cholesterol into faeces as bile acids proportionately depletes serum cholesterol despite increased cholesterol synthesis, proportionately decreases jejunal bile salts despite markedly augmented bile acid production and proportionately impairs micellar solubilization of lipids during fat absorption, leading to steatorrhoea. Furthermore, faecal bile salts showed a positive correlation with faecal water and a negative one with the Schilling test values. Faecal bile salts are suggested to be a sensitive indicator of ileal dysfunction.
Absorption and Metabolism of L‐Dopa by the Human Stomach
Authors: Rivera‐Calimlim L. , Dujovne C. A. , Morgan J. P. , Lasagna Louis , Bianchine J. R.
Published: March 2008

Abstract. The absorption and gastric metabolism of L‐dopa (L‐dihydroxyphenylalanine) were studied in 14 Parkinsonian patients. Patients were given p. o. 25 μCi (500 mg) 14C L‐dopa labelled at the β‐carbon mixed with 2 g polyethylene glycol as a dilution marker. Absorption was evaluated by determining the gastric rate of absorption, gastric clearance, serum levels, and urinary excretion of 14C. L‐dopa and its metabolites in the gastric juice and serum were fractionated by column chromatography. Patients with gastric juice pH of 1.2‐2.1 had a gastric rate of absorption of 62.6±4.7 mg/h with a gastric clearance of 31.7.4.1 ml/h. The gastric emptying time was 228±96min. 17.2–26.4% of total radioactivity in the gastric juice were dopa metabolites. Patients with gastric pH of 6.9‐7.2 had a very rapid emptying time (an average of 22 min.) with no gastric absorption. The amount of metabolites in their gastric juice was insignificant. Gastric absorption and emptying time were reduced in patients when the gastric pH was raised to 3.5‐4.5 with antacids. Serum peak concentrations were higher and more rapidly achieved in patients with high gastric pH than in those with low pH.

The most rapidly achieved and highest serum peak levels were observed in patients with partial gastrectomy and in those who were given the drug by duodenal infusion. It appears that direct absorption of L‐dopa by the stomach may be limited by gastric metabolism of the drug, a possibility supported by the study in vitro of human stomach tissue obtained at surgery. The inverse relationship between the gastric emptying time and serum levels suggests that the intestine is the major site of L‐dopa absorption. Thus factors that prolong gastric emptying time may lower serum levels of L‐dopa by delaying access of the drug to the site of absorption and by increasing metabolism before absorption.
Plasma Triglyceride Metabolism in the Adult Nephrotic Syndrome
Authors: Kekki M. , Nikkilä E. A.
Published: March 2008

Abstract.The kinetic parameters of plasma triglyceride metabolism were determined in 14 adult subjects with the nephrotic syndrome by endogenous labelling of circulating triglyceride with tritiated glycerol. The triglyceride production (turnover) rate and theapparentKmof removal were calculated from the slope of the radioactivity disappearance curve and compared to a normal control material studied previously. Plotting of the individual data in a log scale of triglyceride concentration versus turnover with the normal area and saturation curves in the background allowed a detailed characterization of the nature of kinetic alterations occurring in disease. It was found that in the majority of cases with the nephrotic syndrome the plasma triglyceride concentration and rate of influx are slightly above normal. However, theapparentKmof removal was significantly increased suggesting that efflux may also be somewhat impaired. In four cases the plasma triglyceride was produced at a rate which exceeded the value predicted by the normal saturation curves and it is believed that an uncontrolled overproduction of plasma triglyceride was present in these cases.—Complete remission of disease in one case brought both triglyceride concentration and turnover rate rapidly to normal values. An eight‐hour infusion of human serum albumin in another patient promptly caused a return of high triglyceride turnover to normal.— The primary change behind the nephrotic hypertriglyceridaemia seems to be a controlled increase of plasma triglyceride synthesis. In some cases, however, this overproduction occurs in an uncontrolled fashion and in a number of patients decrease of removal efficiency contributes to the development of hyperglyceridaemia. All of these changes can be explained on the basis of an increased FFA/albumin molar ratio in plasma giving rise to the elevation of unbound FFA fraction.
Plasma Lecithin: Cholesterol Acyltransferase Activity in Liver Disease*
Authors: Calandra S. , Martin M. J. , McIntyre N.
Published: March 2008

Abstract. In liver disease the proportion of plasma cholesterol present in the form of ester is lower than that found in normal subjects. Recent work has suggested that a plasma enzyme, lecithin: cholesterol acyltransferase (LCAT), may be a major f actorin the physiological regulation of plasma cholesterol ester levels. In patients with a variety of hepatobiliary disorders LCAT activity was found to be reduced and a study of the effects of interaction between normal and jaundiced plasmas supported the hypothesis that the low LCAT activity was due mainly to a reduction in the plasma concentration of the enzyme.

When bile salts were added to an in vitro system clear evidence of inhibition of LCAT was produced only with concentrations higher than those normally found in the plasma of patients with liver disease. This casts doubt on the suggested role of bile salts as in vivo inhibitors of the enzyme.

The cholesterol ester concentration of plasma showed good correlation with its LCAT activity when this was measured in a standard substrate. Our results suggest that reduction in LCAT activity may be an important factor in the production of the low ester: free ratio found in almost all hepatic disorders.
Plasma Concentrations of the Urate‐Binding Alpha1–2‐Globulin in Patients with Different Types of Primary Gout as Compared to Healthy Control Subjects
Authors: Alvsaker J. O. , Seegmiller J. E.
Published: March 2008

Abstract. The relationship between the plasma concentrations of the urate‐binding alpha1–2, globulin in patients with different types of primary gout and in healthy control subjects has been studied by an immuno‐assay method based on diffusion in antibody‐agar plates. Plasma from 33 different individuals was investigated including healthy control subjects, asymptomatic, normouraemic subjects from a gouty kindred previously shown to have reduced plasma urate‐binding capacities, patients with and without an incomplete hypoxanthine‐guanine‐phosphoribosyl‐transferase (PRT) deficiency associated with gout, as well as one case of LeschNyhan syndrome and one case of xanthinuria. In gouty subjects previously demonstrated to have a reduced urate‐binding capacity and in their asymptomatic relatives with this defect the plasma concentrations of the urate‐binding alpha1–2 globulin were reduced to 25% of the values found in healthy control subjects. This protein deficiency could hardly result from hyperuricaemia as protein concentrations within normal limits were found in three subjects with gout associated with an incomplete PRT‐deficiency as well as in the case of LeschNyhan syndrome. The finding of a normal protein concentration in these last cases further indicates that the urate‐binding alpha1–2 globulin deficiency may represent an additional modality in which the pathogenetic heterogeneity in primary gout can be expressed.
The Composition and Metabolism in Vitro of Adipose Tissue Fat Cells of Different Sizes
Authors: Björntorp P. , Sjöström L.
Published: March 2008

Abstract. Fat cells of different sizes were isolated from the same sample of adipose tissue by collagenase treatment and fractionation by flotation in an isoosmolar medium. Protein, phospholipid and cholesterol increased with increasing fat cell size. Cholesterol correlated most closely with fat cell volume but phospholipid apparently with surface. Most of fat cell cholesterol was found in the triglyceride droplet, and only a smaller part in a particulate fraction from fat cells. Incorporation of labelled glucose into triglyceride increased with fat cell size, apparently in proportion to fat cell surface rather than diameter or volume. This was the case also with incorporation into fatty acids. The association between fat cell size and metabolism was present also in alloxan diabetic rats. Short term insulin deficiency thus does not abolish the increase of metabolic activity with fat cell size. Analyses of activities of selected glycolytic enzymes and of fatty acid synthesis from acetate in cell‐free systems showed a similar dependence on fat cell size, demonstrating that isotope dilution phenomena in large and small fat cells are probably not responsible. — Lipolytic activity in the basal state and after epinephrine stimulation was increased in large fat cells, which also reesterified more fatty acids than small fat cells when calculated according to the balance method. — It was concluded that larger fat cells are metabolically more active than smaller fat cells. The increase of glyceride‐glycerol labelling and of glycerol release from larger fat cells suggests an increased triglyceride turn‐over in these fat cells. Large fat cells might thus be considered as an active metabolic sub‐compartment of adipose tissue.
The Stimulus‐Secretion Coupling of Glucose‐Induced Insulin Release VIII. Combined Effects of Glucose and Sulfonylureas*
Authors: Malaisse W. J. , Mahy M. , Brisson G. R. , Malaisse‐Lagae F.
Published: March 2008

Abstract. Sulfonylureas such as BS4231 and HB419 stimulate insulin secretion in pieces of rat pancreatic tissue. Their insulinotropic effect requires the presence of a sufficient amount of calcium in the incubation medium. Both sulfonylureas markedly stimulate calcium uptake by isolated islets of Langerhans, their stimulant action being more marked in the absence of glucose or at low glucose concentration than at higher glucose levels. Theophylline alone does not stimulate insulin secretion, but it significantly enhances insulin release in the presence of BS4231. This finding is interpreted as another indication that sulfonylureas, like glucose or leucine, favour calcium accumulation in the beta cell by modifying the balance between calcium influx and efflux across the plasma membrane. Heavy water, a microtubules‐stabilizer, inhibits the insulinotropic action of sulfonylureas, but does not affect BS4231‐induced calcium uptake. These data suggest that the insulinotropic action of sulfonylureas results from the accumulation of calcium in the beta cell, and the subsquent activation of the microtubular‐microfilamentous system involved in the emiocytosis of insulin secretory granules.
Enzyme Response to Thyrotoxicosis and Hypothyroidism in Human Liver and Muscle: Comparative Aspects*
Authors: Nolte J. , Pette D. , Bachmaier B. , Kiefhaber P. , Schneider H. , Scriba P. C.
Published: March 2008

Abstract. 1. Activities of phosphoglucomutase, hexokinase, glucose‐6‐phosphate dehydrogenase, triosephosphate dehydrogenase, mitochondrial glycerophosphate dehydrogenase, hexosediphosphatase and phosphoenolpyruvate‐carboxykinase, of enzymes involved in the citric acid cycle and connected pathways, of hydroxyacyl‐CoA dehydrogenase and carnitine acetyltransferase were determined in biopsy specimens of liver and of tibialis anterior muscle from thyrotoxic and hypothyroid patients and from controls. The results are compared with data obtained from liver and red and white muscle of thyrotoxic rats and guinea pigs. 2. Concomitant with diminished glucose tolerance, the glucokinase activity is decreased in thyrotoxic human liver. The decrease of rat liver glucokinase activity as a response to administered thyroid hormones is found to be dose‐dependent. A relationship between the diminished glucose tolerance in thyrotoxicosis and the decrease of glucokinase activity is discussed. The increase of hexokinase activity (isozyme II) is the most interesting finding in thyrotoxic human muscle because of its possible significance with respect to the elevated metabolic rate. The activity of triosephosphate dehydrogenase, (NADP) malate dehydrogenase, phosphoenolpyruvate carboxykinase and carnitine acetyltransferase is markedly enhanced in human thyrotoxic liver, whereas that of phosphoglucomutase is diminished. 3. Mitochondrial glycerophosphate dehydrogenase, which is known to be markedly increased in the liver and red muscle of thyrotoxic rats, is not increased in the liver and tibialis anterior muscle of thyrotoxic patients, nor in the liver and white muscle of thyrotoxic guinea pigs. The enzyme responses to thyrotoxicosis in human liver and muscle are more similar to those of the guinea pig than of the rat.
Effects of Cholecystokinin and Metoclopramide on Jejunal Movements of Water and Electrolytes and on Transit Time of Luminal Fluid in Man
Authors: Matuchansky C. , Huet P. M. , Mary J. Y. , Rambaud J. C. , Bernier J. J.
Published: March 2008

Abstract. The effects of cholecystokinin and metoclopramide upon jejunal transit time of luminal fluid, net movements of water and electrolytes and unidirectional fluxes of sodium were studied in 11 normal subjects, each one being his own control. An intestinal perfusion technique with a four‐lumen tube was used. This allowed a simultaneous determination of mean transit time and absorption rate of water and electrolytes through a 35 cm segment of jejunum, (a) Cholecystokinin induced a significant decrease in mean transit time of fluid along the test segment. This effect was primarily due to a striking reduction (40% or more) in the mean diameter of the intestinal lumen, (b) Simultaneously there was a significant increase in net water, sodium and chloride secretion into the lumen, whereas net transport of potassium and bicarbonate was not affected. The lumen‐to‐blood unidirectional flux of sodium was obviously reduced but the opposite flux did not significantly change, (c) Similar changes in water and electrolyte movements were observed in subjects in whom transit time was primarily decreased by metoclopramide. (d) A close correlation was found between changes in transit time and net water and sodium transport into the lumen, in both cholecystokinin and metoclopramide studies.

These results suggest that intestinal hypermotility may result, per se, in an increased secretion rate of water and electrolytes across the proximal small bowel. The implication of these findings in clinical conditions associating watery diarrhoea with intestinal hypermotility is discussed.
Peripheral Glucose Uptake in Relation to Physiological Levels of Plasma and Lymph Insulin
Authors: Camu Fréderic , Rasio Eugenio
Published: March 2008

Abstract. The effects of physiological increments of plasma immunoreactive insulin upon tissue glucose uptake, tissue insulin uptake and lymph insulin levels were studied in the hind‐limb (65% muscle, 27% skin and subcutaneous fat) of 38 anaesthetized dogs.

During intravenous glucose tolerance tests, the tissue glucose uptake remained within baseline values, whereas the net rates of glucose utilization and the concentrations of arterial plasma insulin increased as the load of glucose injected was raised. Significant amounts of endogenous insulin were cleared from plasma but were not recovered in lymph.

No glucose response was observed in the hind‐limb tissues during intra‐arterial infusions of exogenous insulin in conditions of strict normoglycaemia and constant blood flow. The infusions of insulin were designed to simulate the levels of endogenous hormone achieved in plasma during the glucose tolerance tests. Again, a high percentage of the injected insulin was fixed to the hind‐limb tissues with no detectable rise of leg‐lymph levels. At higher plasma insulin concentrations, both tissue glucose uptake and lymph insulin levels were increased.

The results show that the effect of plasma insulin on glucose uptake by muscle and fat in vivo is a threshold phenomenon. From the present knowledge of the physiology of lymph formation, the threshold phenomenon could largely be accounted for by insulin adsorption to the blood capillary walls.
The Role of Insulin in the Regulation of α‐Amylase Synthesis in the Rat Pancreas
Authors: Söling H. D. , Unger K. O.
Published: March 2008

Abstract. Changes in pancreatic exocrine enzyme activities were studied in different forms of experimental diabetes in rats. The effects of adrenalectomy on these changes were measured. The early actions of insulin on pancreatic enzyme activities and on incorporation of (4,5‐3H)‐leucine into amylase were also determined. The main results are:

Alloxan‐diabetes leads to a decrease in amylase activity, a decreased rate of amylase synthesis and an increase in the activities of trypsinogen and chymotrypsinogen as described by Palla et al. [9]. Only the decrease in amylase activity correlates with the increase in blood glucose concentration.

Adrenalectomy does not reverse the changes in the activities of exocrine pancreatic enzymes induced by diabetes.

Diazoxide‐diabetes is accompanied by an increase in all pancreatic enzyme activities, most probably due to the inhibition of enzyme secretion.

After treatment with streptozotozin a significant decrease in pancreatic amylase activity appears after 36 h. Amylase activity continues to fall during the following days, in contrast the increase in the activities of proteolytic enzymes is not significant until the 4th day.

Insulin treatment of severely diabetic, non‐ketotic rats leads, as early as 90 min. after injection, to a significant increase in pancreatic amylase activity with no change in the other exocrine enzyme activities. A decrease in all enzyme activities, seen 6 h after insulin, is due to enhanced enzyme secretion.

As soon as 2 h after injection insulin leads to a significant increase in the incorporation of (4,5‐3H)‐leucine into pancreatic amylase but not into total pancreatic protein. This increase is completely abolished by actinomycin D.

Short‐term effects of adrenalectomy (20 h) and effects of substitution with 6‐α‐fluoro‐16α‐methyl‐prednisolon on the incorporation of (4,5‐3H)‐leucine into pancreatic amylase and total pancreatic protein result mainly from changes in the size of the cold leucine pool.

According to these results insulin regulates pancreatic amylase synthesis mainly at the level of transcription. Insulin plays a permissive role in pancreatic amylase synthesis and is not involved in short‐term regulation of amylase synthesis in the non‐diabetic state. Clinical findings in juvenile diabetics indicate a similar type of regulation for amylase synthesis.
Thyrotropin Response to Synthetic Thyrotropin‐Releasing Hormone in Normal Subjects and in Patients with Nontoxic Goiter
Authors: Beckers C. , Maskens A. , Comette C.
Published: March 2008

Abstract. 400 μg TRH given intravenously to normal subjects produced a peak serum TSH within 20 or 30 min. TSH levels were significantly increased as early as 10 min. after the injection. An oral dose of 10 mg of TRH gave a slower and more sustained response in normal subjects. The magnitude of the TSH response was directly related to the basal serum TSH level and inversely proportional to the basal concentration of blood thyroxine. No alteration in the normal pattern of TSH response was observed in patients with euthyroid nontoxic goiters. The data obtained from the normal subjects indicate that the magnitude of the pituitary response to TRH is closely related to the level of the circulating thyroid hormones. Thus, in patients with thyroid pathology the significance of the TSH response curve to TRH must be interpreted after taking into account the level of circulating thyroid hormones. This is particulary important before drawing conclusions concerning any primary defect of the hypothalamo‐pituitary system in thyroid pathology.
Plasma Endogenous Triglyceride Transport in Hypertriglyceridaemia and Effect of a Hypolipidaemic Drug (SU‐13437)
Authors: Nikkilä Esko A. , Kekki Matti
Published: March 2008

Abstract. The kinetics of plasma endogenous triglyceride transport were assessed in nine hyperglyceridaemic patients before and after treatment with an effective hypolipidaemic compound of the clofibrate group, phenolic ether Su‐13437. The triglyceride turnover was measured by endogenous 3H‐glycerol labelling technique and the results were compared to those obtained earlier in selected normal subjects. In the untreated stage the plasma triglyceride transport (production) rate was above the normal range in seven of the nine patients but it did not correlate with the triglyceride concentration. On the other hand, the logarithm of the concentration showed a significant inverse correlation with the fractional transport rate. During administration of the drug both the plasma triglyceride concentration and production rate fell in all subjects, the mean decreases being 52 and 35%, respectively. The response of the fractional transport rate to treatment was very variable and although the mean increase of 26% was significant the change did not correspond to the decrease in the triglyceride concentration. On the basis of these observations it is suggested that the primary defect in most cases of type IV endogenous hyperglyceridaemia is an increased inflow transport of plasma triglycerides but the actual plasma triglyceride level is ultimately determined by the inherent type of transport kinetics. The compound Su‐13437 is an effective triglyceride‐concentration‐lowering agent which acts mainly by decreasing the production of plasma triglycerides.
Folate Deficiency in Malnutrition, Malabsorption, and During Phenytoin Treatment Diagnosed by Determination of Serine Synthesis in Lymphocytes
Authors: Ellegaard Jørgen , Esmann Viggo
Published: March 2008

Abstract A new method for the detection of folate deficiency by measuring the rate of incorporation of 14C‐formate into serine in isolated lymphocytes has been applied to a group of 24 control subjects and 23 patients. 5 of the patients suffered from malnutrition, 14 had malabsorption and 4 were under treatment with phenytoin.

In 17 of these patients, functional folate deficiency was diagnosed by a decreased rate of serine synthesis in the lymphocytes. 11 cases of folate deficiency were found by measuring the folate concentration of erythrocytes by the L. casei method. The lymphocyte method failed in only one case out of 18.

In the 24 control subjects the average incorporation of 14C‐formate into serine per 109 lymphocytes per 4 h was 9.2 ± 0.4% (range 6.3–14.3 %) of added activity. For 16 patients with functional folate deficiency, the corresponding value was 4.1 ± 0.3% (range 1.0–5.9%). The folate activities of lymphocytes from 12 patients before and after 4 weeks of oral treatment with 15 mg folic acid daily were 3.4±0.3 and 7.5±1.0% respectively. The lymphocytes responded within 4 weeks to deprivation of or treatment with folic acid.

The 14C‐formate incorporation into methionine, RNA sad protein showed the same pattern as the incorporation into serine.
A Second Enzyme Defect in Acquired Lactase Deficiency: Lack of Small‐Intestinal Phlorizin‐Hydrolase
Authors: Lorenz‐Meyer H. , Blum A. L. , Haemmerli H. P. , Semenza G.
Published: March 2008

Abstract Adult acquired lactase deficiency is accompanied by the lack of small‐intestinal phlorizin‐hydrolase activity, an enzyme which had not been previously investigated in man. The two activities correlate closely in the human biopsy specimens examined. These observations, together with others previously made on the rat lactase‐phlorizin‐hydrolase complex, point to related biological regulation mechanism(s) for the two enzymes (or active sites).

Phlorizin‐hydrolase activity in the human small intestine is due to more than one catalytic site. Lactase itself is responsible for only one quarter of the total phlorizin‐hydrolase activity.
Hypo‐β‐Lipoproteinaemia Associated with Auto‐Antibodies Against β‐Lipoproteins
Authors: Noseda Giorgio , Riesen Walter , Schlumpf Eva , Morell Andreas
Published: March 2008

Abstract In a 19 year old patient, presenting a severe hypo‐β‐lipoproteinaemia and a polyclonal IgG gammopathy, all known causes of hypo‐β‐lipoproteinaemia could be excluded. The patient's IgG reacted with homologous and autologous low density lipoproteins like an antibody, the binding activity being localized in the Fab fragment of the IgG molecule. The reactive part of LDL appeared to be the protein moiety (apoprotein LDL). Turnover studies with radioiodinated LDL showed that the reduction of the LDL concentration in the patient's serum was due to a decreased synthesis of LDL and also possibly to an immunelimination of LDL.
The Effect of Obesity and Cushing's Disease on the Incorporation of Glucose into Lipid and Esterification of Palmitate by Human Adipose Tissue
Authors: Wilson J.P.D. , Galton D.J.
Published: March 2008

Abstract 1. Rates of lipogenesis from glucose and palmitate have been measured in adipose tissue obtained from patients with obesity, diabetes, Cushing's disease and surgical controls.

2. Conversion of glucose into neutral lipid when expressed on the basis of tissue protein decreased in the following order: Cushing's patients, controls, obese patients.

3. A similar pattern of incorporation of T‐palmitate into neutral lipid was observed for the three groups of patients, except the differences were less marked.

4. Maximal activities of phosphofructokinase in adipose tissue are reduced in obesity (p< 0.05) and diabetics (p< 0.1) compared to surgical controls.

5. Five of the patients with Cushing's disease had an abnormal glucose tolerance test and showed a reduction in maximal activities of hexokinase (p< 0.05) in adipose tissue compared to the other four patients with Cushing's disease when expressed on a wet weight basis.
Insulin Responses to Glucose and Secretin in Uraemic and Normal Subjects
Authors: Isaac R. , Nivez M. P. , Ardaillou R. , Meyrier A.
Published: March 2008

Abstract. Insulin secretion was studied in two groups of subjects: controls and uraemic patients on maintenance haemodialysis. Two procedures were used: 1) four rapid glucose injections before, during and after an infusion of glucose 2) five injections of secretin at varying time intervals. The system of two functional insulin pools, as first described in normal man by Porte and Bagdade [1] is also observed in uraemic subjects. Basal insulin level is increased and glucose tolerance impaired in this group. Insulin secretion from the two pools is higher when insulin plasma levels are expressed as absolute values but becomes lower when relative values calculated as per cent of the base line are considered. Thus uraemia may be considered as associating insulin antagonism and resistance to relatively defective insulin secretion.
Fibroblasts as an Experimental Tool in Metabolic and Hormone Studies
Authors: Morell B. , Froesch E. R.
Published: March 2008

Abstract. .Before cell cultures can be used as a tool for metabolic and endocrine research, standardized conditions for stationary and growing cells must be established. Our results with chicken embryo fibroblasts and with WI‐38 human fibroblasts demonstrate that the metabolic behaviour of these cells differs depending on whether they are in a stationary phase (without serum) or in a growing phase (with serum). Energy during growth is derived almost exclusively from glycolysis. Two additional factors determine the rate of glucose consumption and lactate production: The glucose concentration in the medium and the density of the cells, i.e. the number of cells per surface area. Using a pulse of labelled thymidine it can be shown that after a delay fibroblasts simultaneously go through the first S‐phase under the stimulatory influence of serum. Stationary cells behave metabolically as contact‐inhibited cells with regard to glucose consumption and lactate production.

It appeals that serum triggers off a sequence of metabolic events including increased glycolysis, thymidine incorporation into DNA and growth.
Acute Renal Failure after Folate: NaKATPase in Isolated Rat Renal Tubule
Authors: Schmidt U. , Torhorst J. , Huguenin M. , Dubach U. C. , Bieder I. , Funk B.
Published: March 2008

Abstract. Using refinements of quantitative histochemistry, i.e. oil‐well technique, enzymatic Pi analysis and NADP/ NADPH cycling, the activity of NaKATPase (E.C. 3.6.1.3), an enzyme involved in transmembrane ion transport, was measured in single dissected segments of the proximal and distal tubule of male rats 10 min., 30 min., 60 h and 14 days after folate administration (250 mg/kg body weight). 10 min. after injection the onset of acute renal failure was already apparent by an increase in blood urea of 45 per cent and cessation of urine flow. 60 h after folate the rats became polyuric. The kidney wet weight rose by 40 per cent in a few minutes after the injection due to universal tubular dilatation. During the first hours numerous folate casts were localized, mainly in the thick ascending iimb of Henle's loops. In addition precipitates were found intracellularly in the distal part of the proximal convoluted tubules. The straight portion of the proximal tubules was free of precipitates. 10 min. after the injection tubular segments containing folate material did not show Na K ATPase activity, whereas the folate free tubular segments revealed a residual activity of 30 per cent. Only 15 per cent of the tubules within one lyophilized section had collapsed proximal portions with control activity values. However, the less collapsed segments of the distal tubules revealed a loss of Na K ATPase activity of 55 per cent. Thus folate seems to affect the distal tubule first of all. 60 h after folate administration, when kidney growth reached its maximum, the whole nephron lost its Na K ATPase activity. No tubular cell degeneration or necrosis could be detected during the development stage or the sustained phase of renal failure. After addition of folate to renal homogenate, Na K ATPase exhibited activation (+ 35 per cent) and inhibition (–42 per cent and more) of activity plotted against folate concentration. A careful evaluation of the available evidence led to the conclusion that the acute renal failure induced by folate differs markedly from other models by a directly altered tubular cell metabolism in the development stage of oliguria. Acute tubular obstruction may initiate oliguria. However it seems unlikely that tubular obstruction will be the unique pathogenic factor for this syndrome, especially for the development of the tremendous kidney growth. The inhibition of tubular Na K ATPase activity after folate may indicate an impaired tubular active reabsorption capacity which would be involved in the acute renal failure. The most important finding is that glomerular filtration does not seem to be a primary factor in the development of oliguria after folate administration.
Does Chronic Hypercapnia Entail an Adaptive Improvement of Extra‐Cellular Space Buffering against Acute PCO2 Changes?*
Authors: Leuenberger Ph. , Karmann U. , Held R.
Published: March 2008

Abstract. Schwartz and coworkers have shown recently that chronic hypercapnia entails a marked decrease of the d(H+)/dPCO2 ratio in plasma, in response to acute PCO2 changes in vivo. They have interpreted this finding as an indication of improved CO2 buffering performance by the extracellular space, mediated by an unidentified mechanism. This hypothesis is reviewed in the light of a theoretical treatment of CO2‐titration regarding extracellular space as an isolated buffered solution.– It is concluded here that renal compensation during chronic hypercapnia without changes in the buffering properties can account for much if not all of the observed effect through the quantitative relationships governing CO2 equilibrium. Reasons for the use of Van Slyke's “buffer value” rather than the d(H+)/dPCO2 ratio as an analytical parameter of extracellular CO2‐buffering performance are presented by reference to the general theory of titration.
The Effect of Clofibrate on the Elimination of Cholesterol as Bile Acids in Patients with Hyperlipoproteinaemia Type II and IV
Authors: Einarsson Kurt , Hellström Kjell , Kallner Mora
Published: March 2008

Abstract. The turnover of 14C‐cholic acid and 3H‐chenode‐oxycholic acid was studied in hyperlipaemic patients before and during treatment with clofibrate. ‐ Before therapy the total formation of bile acids recorded for 6 patients with hyperlipoproteinnemia type Il (387± 70 mg/day, mean ± S.E.) was considerably less than that encountered for 6 patients with hyperlipoproteinaemia type IV (1 379 ± 221 mg/day). This difference was mainly due to a high synthesis of cholic acid in the latter patients. ‐ The administration of clofibrate had no consistent effect on the half‐life, pool size and turnover of the bile acids in the patients with type II lipoprotein pattern. The combined synthesis of cholic acid and chenodeoxycholic acid decreased in all patients with hyperlipoproteinaemia type IV and amounted on average to 549± 97 mg/day. The effect on the formation of chenodeoxycholic acid was insignificant but the turnover of cholic acid decreased from 1076± 243 to 333 ± 85 mg/day.
The Relation between Plasma Cholesterol and Cholesterol Synthesis in Rats with Experimental Biliary Obstruction
Authors: Calandra S.
Published: March 2008

Summary. The relationship between serum cholesterol and the rate of cholesterol synthesis in liver and intestine was studied in rats with experimental ligation of the bile duct. In the acute stages of biliary obstruction the level of plasma cholesterol increased several fold above the control level and was accompanied by a similar rise in the rate of hepatic and intestinal cholesterogenesis.

Feeding a high cholesterol diet before the ligation of the bile duct resulted in a marked reduction in the absolute rate of cholesterol synthesis in both liver and intestine of obstructed rats, but it had no effect on the plasma cholesterol level.

The administration of cycloheximide completely prevented the increase in hepatic and intestinal cholesterogenesis in obstructed rats but did not cause a fall in the level of total plasma cholesterol.

These results would suggest that the accumulation of cholesterol in the plasma of rats with acute biliary stasis is not dependent upon the increased rate of cholesterol synthesis in liver and intestine.
Rapid and Simple Microtest for the Diagnosis of Chronic Granulomatous Disease (NBT‐Test with Candida Albicans)
Authors: Heyne K. , Preisig E. , Hitzig W. H.
Published: March 2008

Abstract. A slide test is described for the cytochemical determination of NBT‐reduction in leucocytes stimulated by phagocytosis of Candida albicans spores. Reliable results were obtained in 198 healthy controls, 12 carriers of and 18 patients with chronic granulomatous disease, with one questionable result in each group.
Morphometry of Dog Liver: Comparison of Wedge and Needle Biopsies*
Authors: Hess Felix A. , Gnägi Hans Rudolf , Weibel Ewald R. , Preisig Rudolf
Published: March 2008

Abstract. Needle biopsies of liver provide a very small sample of tissue for electron microscopy; the question therefore arises whether such material can be used for morphometric studies. To elucidate this problem, needle biopsies from normal dog livers were compared with matched block biopsies, the standard procedure for electron microscopy. With the help of stereological methods various morphometric parameters characterising liver parenchyma and hepatocyte organelles were assessed. Satisfactory correlations could be established for the volume of hepatocytes and sinusoids, whereas the volume and surface of the bile canaliculi were systematically larger in needle biopsies; this could be due to the procedure of biopsy removal by the needle. The size and composition of hepatocyte cytoplasm were found to be unaffected by needle biopsy. Occasional statistically significant differences were found for microbodies and endoplasmic reticulum; these differences showed no consistent trend and could be eliminated by increasing the sample size.—It is concluded that needle biopsies can be used for morphometric studies in the electron microscope, but that at least two biopsies should be used for some parameters in order to assure representative sample size.
Binding of Human FSH and Its Subunits to Rat Testis
Authors: Schwartz S. , Bell J. , Rechnitz S. , Rabinowitz D.
Published: March 2008

Abstract. Specific binding of 125I‐human follicle stimulating hormone (hFSH) to rat testicular tissue has been demonstrated. Labelled FSH for binding studies was prepared by iodinating very lightly to achieve a low specific activity of 1–12 μCi/μg and then purifying the iodinated hormone on a long G‐100 Sephadex column. Selected fractions from the gel filtration were suitable for binding. Aggregates of FSH molecules appeared to bind better to the testicular tissue fraction than did single molecules of iodinated FSH. No significant binding of iodinated FSH occurred in other tissues tested, i.e. spleen, liver, kidney and heart. Three dissimilar hFSH‐containing preparations—one from pituitary, LER‐1366, and two urinary preparations—displaced labelled hFSH from testicular tissue fractions in a relationship proportional to the biological activity of the preparation. Competition was shown by isolated ß chain of hFSH but only at a concentration fifty times that of intact hFSH; α subunit of hFSH was even less potent. These data indicate that specific binding of hFSH to target organs is a property of the whole molecule, and not of its subunits. Human chorionie gonadotrophin competed with tracer FSH for binding to rat testis, but at a concentration 100 times that of FSH; a lesser degree of competition was shown by human luteinizing hormone and insulin, again only at very high concentrations of these hormones; albumin was inactive in the system.
Sex Difference in the Kinetics of Triglyceride Metabolism in Normal and Hypertriglyceridaemic Human Subjects
Authors: Olefsky Jerrold , Farquhar Jolin W. , Reaven Gerald M.
Published: March 2008

Abstract. Several years ago we demonstrated in man that increasing plasma very low density lipoprotein (VLDL) triglyceride (TG) concentrations were associated with increasing VLDL‐TG production rates, and that this relationship described a rectangular hyperbola which could be characterized in terms of enzyme kinetics. Utilizing this approach Nikkila and Kekki confirmed these observations in a large group of normal subjects. Moreover, after analyzing the Km and Vmax values of their subjects they noted a striking and important sex difference: females were found to have significantly lower Km values than men, whereas the Vmax values for the two groups were the same. This indicates that for a given VLDL‐TG production rate, females will have lower plasma TG concentrations. We have now studied 53 subjects with widely varying plasma TG concentrations, and have been able to detect a similar sex difference in subjects with hypertriglyceridaemia. Furthermore, we have noted a highly significant direct relationship between TG concentration and production in both sexes, and have found no relationship between an individual's Km value and his coexisting plasma TG level. These results allow us to conclude that: 1) the sex difference in TG kinetics which Nikkila and Kekki originally note in normals can now be extended to include hypertriglyceridaemic subjects, and 2) in general, overproduction, and not underutilization, is the initiating event in most cases of hypertrigiyceridaemia.