bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic and Metabolic Studies on Carbohydrate and Amino Acid Metabolism in Rat Liver during Acute Uraemia
Authors: Maier K. P. , Hoppe‐Seyler G. , Talke H. , Frohlich J. , Schollmeyer P. , Gerok W.
Published: March 2008

Abstract. Enzyme activities of the glycolytic, gluconeogenic, and hexose monophosphate pathways were measured in the liver of starved rats 12 and 48 hours after bilateral nephrectomy. Control experiments (sham operated rats) revealed that alterations of enzyme activities were not due to uraemia but to starvation. Alanine‐aminotransferase and aspartate‐ aminotransferase activities, however, were significantly elevated in rat liver 48 hours after nephrectomy when compared with sham operated controls. Concentrations of some of the gluconeogenic intermediates (3‐phosphoglyceric acid, pyruvate, phosphoenolpyruvate and glucose‐6‐phosphate) were significantly higher in the liver of uraemic animals. Amino acid analysis showed an increase in only L‐alanine concentration. It is suggested that the elevated content of pyruvate in the liver during acute uraemia is due to an inhibition of pyruvate degradation. Together with the elevated pyruvate concentration the increase in L‐alanine could be explained as a consequence of the equilibrium of the alanine‐aminotransferase reaction; Kapp. of the reaction is not changed by uraemia. Increased activities of the transaminases and the elevated concentrations of the other metabolites measured might indicate that in the liver of nephrectomized rats there is enhanced gluconeogenesis from substrates other than pyruvate.
Studies on the Metabolic Clearance Rate, Apparent Distribution Space and Plasma Half‐Disappearance Time of Unlabelled Human Growth Hormone in Normal Subjects and in Patients with Liver Disease, Renal Disease, Thyroid Disease and Diabetes Mellitus
Authors: Owens D. , Srivastava M. C. , Tompkins C. V. , Nabarro J. D. N. , Sonksen P. H.
Published: March 2008

Abstract. The metabolic clearance rate (MCR), half‐disappearance time (T½ and apparent distribution space (DS) of unlabelled human growth hormone (HGH) have been studied using the priming dose – constant infusion technique. In 11 normal subjects MCR averaged 2.99 ml/kg/min., T½ 19.0 min. and DS 79.3 ml/kg. There were no differences between males and females and MCR was constant at HGH levels ranging from 5 to 50 ng/ml. In 10 out of 17 patients with chronic liver disease of varying severity MCR/kg was reduced below the lower limit of normal. TV2 was prolonged in 15 of these patients. There was a very close correlation between MCR/kg and DS/kg in liver disease (r = 0.8219). Increased DS/kg accounted for the normal MCR/kg seen in some patients with severe hepatocellular failure. MCR/kg was markedly reduced in three patients'with chronic renal failure. T72 and DS/kg were both significantly increased in this group (48.0 min. and 117.0 ml/kg, respectively). MCR/kg and T72 were normal in one patient with the nephrotic syndrome but normal glomerular filtration rate. MCR/kg was not significantly different from normal in patients with thyrotoxicosis, myxoedema and uncontrolled diabetes mellitus, despite the fact that T½ shorter than normal in thyrotoxicosis and longer than normal in myxoedema. It is suggested that HGH does not normally diffuse freely from the vascular to extravascular extracellular fluid, and that normally a substantial concentration gradient exists between the vascular and extravascular compartments; under these circumstances, the liver and kidneys are the major sites of HGH metabolism. In hepatic and renal failure, this gradient is reduced and extravascular degradation sites may assume more importance in the metabolism of growth hormone. Acute fluctuations in the peripheral blood concentrations of growth hormone indicate alterations in secretion rate and not alterations in metabolism.
The Significance of the Presence of Anti‐IgA Antibodies in Individuals with an IgA Deficiency*
Authors: Nadorp J. H. S. , Voss M. , Buys W. C. , van Minister P. J. J. , van Tongeren J. H. M. , Aalberse R. C. , van Loghem Erna
Published: March 2008

Abstract. Class specific anti‐IgA (anti‐α) antibodies were found in seven out of sixteen patients in whom serum IgA was not demonstrable by the Mancini method (sensitivity down to 0.02 mg/ml). Allotype specific anti‐IgA [anti‐A2m(l)] antibodies were found in an eighth patient. The anti‐IgA antibodies proved to be of the IgG class. In the eight patients with anti‐IgA antibodies, the presence of these antibodies could not be ascribed to immunization by administration of blood products. Isoimmunization in pregnancy and absorption of colostral IgA or animal IgA were other possible causes of anti‐IgA antibodies.–Using a combined IgA/anti‐IgA radioimmunoassay very low IgA levels (0.00013‐0.020 mg/ml) were demonstrable in patients without anti‐IgA antibodies whose serum IgA levels could not be determined by the Mancini method.–IgA metabolism was studied in five IgA‐deficient patients. In two patients the rate of degradation of 132I‐IgA almost equalled that in individuals with a normal serum IgA level. In three patients, however, the rate of degradation was greatly increased. In their sera, in contrast to the first two, class specific anti‐a antibodies were demonstrated.–One of these patients showed an anaphylactic reaction immediately after intravenous injection of mI‐IgA. Only this patient showed complement fixation by the IgA/anti‐IgA complex and IgA stimulation of lymphocytes.–The presence of anti‐IgA antibodies has some important practical implications for those patients who need blood products.
Dynamics of Insulin Release from the Foetal and Neonatal Rat Pancreas
Authors: Asplund Kjell
Published: March 2008

Abstract. The dynamics of glucose‐stimulated insulin release from pieces of foetal and neonatal rat pancreas were studied in an in vitro perifusion system. During an initial 60‐min. equilibration period, the tissue was perifused with a phosphate‐buffered medium containing 0.4 mg/ml glucose. This was followed by a 40‐min. stimulation period, in which the medium glucose concentration was 3.0 mg/ml. Tissue obtained from foetuses of 21.5 days' gestation displayed only a small initial peak of insulin release when exposed to a high glucose concentration. At one day post partum, a low initial response to glucose was followed by a small but significant secondary rise in insulin secretion. At six days of age, a pronounced immediate response and a subsequent constant high level of insulin output were recorded during the stimulation period. At one day of age, the addition of 5 mM arginine to the perifusion medium during the stimulation period caused a marked increase of insulin output during both the early and the late phase, compared with glucose alone. – The present data indicate that the mechanism responsible for the initial phase of glucose‐stimulated insulin release is already present in the rat during late foetal life, although it is probably not completely mature. The development of the second phase of the secretory response seems to be an essentially postnatal event. The dynamics of insulin release in the immature rat appear to be similar to those reported in prediabetic and some diabetic individuals. The intriguing possibility that the predisposition to diabetes may be associated with a lack of normal development of the insulin secreting mechanism seems to deserve further consideration.
A Specialized Membrane Junction between Nerve Endings and B‐Cells in Islets of Langerhans
Authors: Orci L. , Perrelet A. , Ravazzola M. , Malaisse‐Lagae F. , Renold A. E.
Published: March 2008

Abstract. The use of lanthanum as an extracellular tracer in isolated islets of Langerhans reveals zones of narrowing of the extracellular space (synaptic cleft) between nerve endings and B‐cells. These narrowed zones are interpreted as gap junctions and their presence shows that such endings have the morphological characteristics of both electrical and chemical synapses.
Adaptation of the Oxygen Affinity of Haemoglobin in Acute Hypoxia*,**
Authors: Kleeberg U.R. , Rühle K.H. , Schilling M. , Freitag M. , Schlehe H. , Konietzko N. , Matthys H.
Published: March 2008

Summary. When the adaptation of the oxygen affinity of haemoglobin (Hb) to acute hypoxia is tested in healthy volunteers with and without Dipyridamole1 (D), the Bohr‐effect is shown to play the dominant role for the position of the oxygen dissociation curve (ODC). If the Bohr‐effect is eliminated by calculating a pH corrected P50, a shift to the right is observed after only 2 hours of continued hypoxia. This decrease of the O2‐affinity of Hb correlates with an increase in red cell 2, 3‐DiphosphogIycerate (DPG). Under D.‐medication the 2, 3‐DPG levels are significantly higher than the controls. The 2% increase of O2‐availability induced by D. however is fully reversed by the Bohr effect.

To raise the O2 supply at the tissue level in acute hypoxia, the human organism prefers an increase in O2‐binding and ‐transport to a decrease in the O2‐affinity of Hb. The continued respiratory alkalosis raises the 2, 3‐DPG level thus gradually compensating for the primary increase in the oxygen affinity of haemoglobin.
Influence of Perchlorate on the Secretion of Non‐Thyroxine Iodine by the Normal Human Thyroid Gland
Authors: Bürgi H. , Benguerel M. , Knopp J. , Kohler H. , Studer H.
Published: March 2008

Abstract. Several authors have postulated that endogenous iodide produced by the deiodination of iodotyrosines in the thyroid feeds into a different thyroidal iodide compartment than transported iodide which enters the gland from outside. One argument for the existence of two separate iodide compartments is the observation that under certain experimental conditions perchlorate completely discharges transported iodide from the thyroid, while it has no such effect on endogenous iodide. This latter observation however has not been confirmed by all studies and remained controversial. – We therefore reinvestigated the effect of perchlorate on the secretion of endogenous iodide by a new, sensitive method. Five normal volunteers received tracer amounts of iodide‐125I p.o. and 11 days later thyroxine‐131I I.V. Two days later the following serial measurements were started: serum protein‐bound labelled iodine (PB125I, PB131), serum total thyroxine and urinary excretion of 125I, 127I and 131I. – In the control period the non‐thyroxine iodine secretion calculated from the above measurements was 40 μg/day. Under perchlorate 200 mg three times daily this value rose significantly to 66 μg/day. Non‐thyroxine iodine comprises the secreted triiodothyronine plus the secreted endogenous iodide. Assuming that the former value remained constant, our data show that perchlorate indeed discharges part, though not all, of the endogenous iodide. These data do not rule out a second iodide compartment, but they are also compatible with a simple one compartment model.
Effect of Bovine Parathyroid Hormone 1–34 Fragment on Renal Production and Excretion of Adenosine 3‘, 5’ Monophosphate in Man
Authors: Czekalski Stanislas , Loreau Nadine , Paillard Francoise , Ardaillou Raymond , Fillastre Jean‐Pavd , Mallet Eric
Published: March 2008

Abstract. Biologically active bovine parathyroid hormone (b PTH) 1–34 fragment infused over one hour in normal subjects produced an immediate and sharp increase in the excreted fractions of filtered bicarbonate, sodium and potassium, followed by the return to pre‐infusion levels as soon as the administration of b PTH was stopped. There was a gradual but steady increase in the excreted fraction of filtered phosphate but a decrease in the excreted fraction of filtered calcium and magnesium. The excreted fractions of these ions were still abnormal 150 minutes after the completion of PTH infusion. The urinary excretion of 3'5′‐cyclic AMP increased immediately about one hundred‐fold but returned rapidly to pre‐infusion levels. Urinary clearance of cyclic AMP approximated glomerular filtration rate in control periods and was twenty to thirty times greater during b PTH infusion. In subjects overloaded with bicarbonate, b PTH brought about a decrease in bicarbonate Tm and the same effects on the urinary excretion of other electrolytes. 3'5′‐cyclic AMP excretion was clearly higher in control periods and reached higher levels during b PTH infusion When compared to subjects without an alkaline load. 3'5′‐cyclic AMP excretion and fractional clearance were also clearly higher in subjects not given b PTH when control periods were compared to periods with bicarbonate infusion or after acetazolamide administration. During distal blockade obtained by simultaneous administration of chlorothiazide and ethacrynic acid, there was a delay in the rise of 3'5′‐cyclio AMP excretion after b PTH administration. It can be concluded from these studies that the pattern of excretion of 3'5′‐cyclic AMP is similar to that of bicarbonate, sodium and potassium. The increase of 3'5′‐cyclic AMP excretion when urinary pH is above 7 suggests a diffusion trapping mechanism for the secretion into the lumen of this nucleotide. Distal diuretics used in distal blockade did not inhibit 3'5′‐cyclic AMP production but delayed its secretion into urine.
Deposits of IgD in Renal Disease. Immunohistological Study of 180 Renal Biopsies
Authors: Tarantino A. , Imbasciati E. , Limido D. , Pietrogrande M. , Ponticelli C.
Published: March 2008

Abstract. IgD deposits have been investigated by an indirect immunofluorescence technique in 180 renal biopsies carried out on patients with various renal diseases.

IgD was not present in nephrotic syndrome with minimal changes or focal glomerulosclerosis, in mesangial proliferative glomerulonephritis, in chronic advanced glomerulonephritis, in rheumatoid purpura and in other various nephropathies with predominant non‐glomerulor lesions.

Significant deposits of IgD were identified in 12 out of 16 cases of membranoproliferative glomerulonephritis, in 15 out of 23 cases of membranous nephropathy, in 11 out of 21 cases of focal proliferative glomerulonephritis with mesangial IgA deposits, in 2 out of 5 cases of proliferative glomerulonephritis with crescents and in 1 out of 6 cases of proliferative exudative glomerulonephritis.

All cases of lupus nephritis and nephritis associated with mixed cryoglobulinaemia Bhowed IgD deposits.

In diabetic glomerulosclerosis, IgD was found in 1 out of 4 biopsies and only in the exudative lesions.

In 5 out of 8 cases of amyloidosis anti‐IgD serum stained the amyloid substance irregularly. In such cases IgD was found in association with other immunoglobulins and complement with the same localization. These findings suggest that IgD may participate in the immunological processes which lead to the development of glomerular deposits, mainly in cases of chronic glomerular diseases.
Influence of Portacaval Shunt on Bile Formation in the Rat*
Authors: Prandi Danielle , Dumont Micheline , Erlinger Serge
Published: March 2008

Abstract. Bile flow and bile acid secretion were measured in rats 21 to 28 days after a portacaval shunt and in sham‐operated and normal animals. The following results were obtained. (1) Bile flow was significantly lower (6.65±SEM 0.36 μl min‐1‐100 g‐l) in the shunted rats than in the shamoperated animals (8.21 ± SEM 0.21 μl min‐1 100 g‐1; P < 0.01). (2) Bile acid excretion was not significantly different in the shunted rats (0.27±SEM 0.03μmol‐min‐1100g‐1) and the sham‐operated rats (0.26±SEM 0.02 μmol‐min‐1 ‐100 g‐1; NS). (3) During bile acid infusions, there was a linear relationship between bile flow and bile acid excretion in both groups of animals. The slope of the relationship was similar, suggesting that the osmotic activity of the bile acids was not modified in the shunted animals, and the bile acid‐independent flow, estimated by the extrapolation of this relationship to a zero bile acid excretion, was significantly lower in the rats with a portacaval shunt (5.20±SEM 0.40 μ min‐1 100 g‐1) than in the sham ‐operated animals (6.50±SEM 0.30 μl min‐1 100 g‐1; P < 0.02). (4) The liver weight was significantly lower in the rats with a portacaval shunt than in the sham‐operated animals and there was a parallel decrease of liver weight (–17%) and of the bile acid‐independent flow (–22%). No difference was found between the sham‐operated rats and the normal rats. It is concluded that portacaval shunt in the rat results in a decreased bile flow, due to a decrease in the bile acid‐independent flow. Since bile acid secretion rate remained unchanged, it is suggested that the secretion of bile acids on the one hand and the bile acid‐independent flow on the other are regulated by separate mechanisms.
Bile Salt Metabolism and Bile Formation in the Rat with a Portacaval Shunt
Authors: Herz R. , Paumgartner G. , Preisig R.
Published: March 2008

Abstract. Biliary secretion of bile salts and bile flow were studied in Sprague Dawley rats with liver atrophy resulting from an end‐to‐side portacaval shunt and in sham‐operated controls. Three weeks after the shunt operation the liver to body weight ratio was reduced by 41%. This hepatic atrophy was accompanied by a reduced bile flow, which was 4.9 ± 0.3 (SEM) and 5.9 ± 0.2 (SEM) (xl/min per 100 g body wt. in shunted and sham‐operated animals, respectively. By contrast, bile salt pool size and bile salt secretion were not significantly changed by the portacaval shunt. Shunted animals maintained a normal bile salt pool size by increasing bile salt synthesis per unit of liver weight. Thus, cholate synthesis, calculated from cholate pool size and 14C‐cholate turnover rate, was 3.3 ± 0.4 (SEM) and 1.8 ± 0.2 (SEM) μmol/24 h per g liver in shunted and sham‐operated rats, respectively. It is concluded that the atrophic liver in the rat with a portacaval shunt is able to maintain normal bile salt secretion rates and that the observed decrease of bile flow results from a diminution of bile salt independent bile formation.
Dynamics of Insulin Release and Microtubular‐Microfilamentous System
Authors: Somers G. , Obberghen E. Van , Devis G. , Ravazzola M. , Malaisse‐Lagae F. , Malaisse W. J.
Published: March 2008

Abstract. The effect of colchicine upon glucose‐induced insulin release by the isolated perfused rat pancreas was examined in order to characterize the participation of the β‐cell microtubular apparatus in the biphasic insulin secretory response to glucose. After a short pretreatment (25 min.) with a low colchicine concentration (2.10‐5M), both the early and late phases of glucose‐induced insulin secretion were markedly enhanced. As either the concentration of colchicine or the length of the pretreatment period with this mitotic spindle‐inhibitor were increased, the facilitating effect faded out and partial inhibition of insulin release was observed. However, colchicine, even at high concentration, markedly enhanced the residual early release of insulin evoked by glucose in the presence of diazoxide (0.05 mg/ml). These findings suggest that (i) a fraction of the early phase of insulin secretion completely escapes from the inhibitory effect of colchicine and may correspond, therefore, to a modality of hormonal release which does not involve the oriented intracellular translocation of secretory granules; and (ii) extensive disruption of the micro‐tubular apparatus is associated with inhibition of insulin release, especially during the late phase of the secretory response to glucose.
Incorporation Rate of Leucine into Proteins in Human Liver Slices
Authors: Stakeberg H. , Gustafson A. , Scherstén T.
Published: March 2008

Abstract. The rate of incorporation of leucine into hepatic proteins in liver slices from 42 patients was studied. Zero order kinetics for the incorporation of leucine in relation to the incubation time and to the amount of incubated proteins were obtained, provided that the medium contained a complete amino acid mixture with a concentration 4 times that of normal human serum. – Inulin space and water content of the preparation were of the same magnitude as reported for rat liver. The presence of fructose (5.5 mM) in the medium caused an inhibition of the rate of incorporation of leucine into pro teins. Insulin in the medium, however, stimulated tho incorporation rate. – Assuming that the rate of incorporation of leucine into hepatic proteins is representative of protein synthesis, the half‐life of liver proteins can be calculated to be 35 days for subjects below 60 years of age. For those who were older than 60 years, the protein turnover rate was approximately 30% higher.
Light Chain Type Ratio of IgA‐Producing Cells in Human Jejunal Biopsies
Authors: Mul N. A. J. , de Boer L. E. M. , Taminiau J. A. , Ballieux R. E.
Published: March 2008

Abstract. As part of an investigation on a possible relationship between the serum IgA and the immunoglobulins synthesized by the plasma cells in the intestinal mucosa, immunoglobulin‐producing cells in human jejunal biopsies were characterized by class and type of intracellular immunoglobulins. In biopsy Specimens from 22 patients, with various diagnoses except multiple myeloma, the average percentage of IgA‐producing cells was 83 %, that of IgG‐producing cells 5 % and that of IgM‐producing cells 12 %, with a wide range for individual patients. For the IgA‐producing cells the k/Λ ratio was determined and the average ratio was found to be 63: 37, within a very limited range for individual patients. There was no correlation between the relative number of IgA‐producing cells in the biopsy specimens and the IgA concentration in the serum. Additionally biopsy specimens from 3 patients with a monoclonal immunoglobulin‐A component in their serum were studied. In one of those there was a remarkable shift in the k/Λ ratio, indicating that the light chain distribution of the intestinal IgA plasma cells was affected by the lympho‐proliferative process.
The Effect of Pregnancy on the Control of Lipolysis in Fat Cells Isolated from Human Adipose Tissue
Authors: Elliott J. A.
Published: March 2008

Abstract. 1. Lipolysis has been estimated by measuring the release of glycerol in isolated adipose tissue cells obtained from women in early prognancy, late pregnancy and 1–3 days post partum and from non‐pregnant women. 2. Adipocytes of women at the end of pregnancy exhibited higher rates of lipolysis in response to adrenaline (1. 5–15 μM) plus phentolamine (13 μM) than those of non‐pregnant women or those in early pregnancy. 3. Lipolysis in response to adrenaline plus phentolamine in fat cells from women 1–3 days post partum was reduced compared to that at the end of gestation but was enhanced relative to that in the non‐pregnant or early pregnant state. 4. Basal lipolysis also tended to be greatest at term. 5. Under conditions where the production of cyclic AMP was not rate limiting for the stimulation of lipolysis, that is in the presence of dibutyryl cyclic AMP (1 mM) or adrenaline (15 yM) plus phentolamine (13 μM) plus caffeine (1 mM), the release of glycerol in cells from women at term and in the puerperium was greater than that in women in the non‐pregnant or early pregnant state. 6. Cell levels of cyclic AMP rose after incubation with adrenaline (6 μM) plus phentolamine or adrenaline (15 μM) plus phentolamine plus caffeine (1 mM) but were similar in all four groups of women. 7. It is concluded that the observed enhancement of lipolysis demonstrated in fat cells from women at the end of pregnancy reflects an increase in hormone‐sensitive lipase activity rather than a modification of hormone receptor site sensitivity or of the rates of synthesis or breakdown of cyclic AMP. 8. This increase in adipose tissue lipolysis at the end of gestation could contribute to the reported rise in plasma nonesterified fatty acids in the final weeks of pregnancy.
Differences among Hyperlipoproteinaemic Subjects in the Response of Lipoprotein Lipids to Resin Therapy
Authors: Miller N. E. , Nestel P. J.
Published: March 2008

Abstract. It has been reported that cholesterol turnover is raised when hypercholesterolaemia occurs in association with elevated levels of very low density lipoprotein, but normal when hypercholesterolaemia reflects an increase in the concentration of low density lipoprotein alone. The relationship of plasma lipoprotein levels to cholesterol metabolism has been further investigated in the present experiments, in which the acute effects on lipoprotein lipids of stimulating cholesterol turnover with a bile acid‐sequestering resin, colestipol, have been compared in normal subjects and in patients with four types of hyperlipoproteinaemia.

Very low density lipoprotein (VLDL) lipids increased in every subject. The increase was greatest in patients with type IV or type V hyperlipoproteinaemia, least in normal subjects and in those with type Ha hyperlipoproteinaemia, and intermediate in patients with type lib hyperlipoproteinaemia. The induced increments in VLDL cholesterol and triglyceride mass were accordingly positively correlated with the pre‐treatment concentrations. Low density lipoprotein (LDL) lipids decreased during resin therapy in all subjects, except those with type IV or type V hyperlipoproteinaemia in whom there was a transient rise. The reductions in LDL cholesterol were significantly greater in patients with type II hyperlipoproteinaemia than in the normal volunteers, and in both groups of subjects were proportionately greater than those in LDL triglyceride.

These findings demonstrate clear differences among the hyperlipoproteinaemias in the response of lipoprotein lipids to resin therapy, and provide further evidence for the heterogeneity of cholesterol metabolism in these conditions. The colestipol‐induced changes in type IV and type V patients could be partially reproduced in normal subjects during the consumption of high carbohydrate diets, which might be expected to increase VLDL synthesis. It is suggested, therefore, that the synthesis of VLDL cholesterol may be enhanced in such patients, and that any rise in LDL cholesterol observed during resin therapy reflected subsequent metabolism of VLDL to LDL rather than diminished LDL cholesterol clearance.
Force Velocity Characteristics of Oesophageal Muscle: Interaction of Isoproterenol and Calcium
Authors: Cohen Sidney
Published: March 2008

Abstract. The purpose of this study was to evaluate the interaction of isoproterenol and calcium upon the force velocity characteristics of opossum oesophageal circular muscle, in vitro. Isotonic and isometric recordings were used to determine the velocity of shortening and force, respectively. All muscle was studied at its length of optimal tension development (Lo). To determine the effect of isoproterenol upon muscle contractility, studies were performed at 2. 5 mM and 5. 0 mM calcium Kreb's solution. The maximal velocity of shortening (V max) and the peak force (Po) of oesophageal muscle were 6. 2 ± 0.3 mm/s and 16. 8 ± 1. 0 gm, respectively, at 2. 5 mM calcium. Isoproterenol (10‐5 M) decreased the V max to 4. 9 ± 0.6 mm/s and the Po to 9. 8 ± 1. 3 gm (P < . 01). Increased calcium (5. 0 mM), alone, did not alter either V max or Po. However, at 5. 0 mM calcium, 10‐5 isoproterenol reduced the V max to 6. 0 ± 0.6 mm/s (P > . 05) and the Po to 13. 9 ± 0.8 gm (P < . 05). These studies indicate that isoproterenol significantly reduces the V max and Po of oesophageal smooth muscle during the neural mediated “off response”. This effect of isoproterenol is reversed, in part, by an increase in calcium concentration.
Transport ATPases of Cardiac Sarcolemma in 20, 25‐Diazacholesterol Induced Myopathy
Authors: Fiehn W. , Seiler D. , Kuhn E. , Bartels D.
Published: March 2008

Abstract. 20, 25‐Diazacholesterol, known to induce myotonia in skeletal muscle, also affects cardiac muscle as can be concluded from the development of cardiomegaly. At the same time (Na+, K+) ATPase of cardiac sarcolemmal membranes of the 20, 25‐diazacholesterol treated rats showed an increased activity as compared with control animals (91 % and 46 % stimulation respectively). The Ca++ stimulated ATPase showed the same tendency (96 % and 64 % stimulation).

In the plasma of the treated rats creatine phosphokinase activity was found to be elevated whereas the amount of protein‐bound iodine was decreased, a finding that is common in myotonic dystrophy.
Synthesis of Immunoglobulins and 15 Other Proteins by Diseased Human Kidneys
Authors: Poortmans J. , Bienenstock J.
Published: March 2008

Summary. In an effort to determine the synthetic capacity of human kidneys for serum proteins, pieces of both kidneys removed at operation prior to transplantation were placed in organ culture. Incubation with 14C labelled amino acids and subsequent radioimmunoelectrophoresis with antisera to all five classes of immunoglobulins showed synthesis of IgG by all 5 pairs of kidneys of IgA and IgE by 4, and of IgM by 2. None synthesized IgD. Radioimmunoelectrophoresis with specific antisera to 15 non‐immunoglobulin proteins revealed synthesis of lactoferrin and uromucoid while several other serum proteins, such as al antitrypsin and α2 macroglobulin, known for their binding properties, showed apparent synthesis. No evidence for secretory component synthesis was seen despite positive immunofluorescent localization in the tubular cells. Further, Zn α2 and β2GP I also showed positive immunofluorescence but negative synthesis. It seems possible that these latter proteins may not be synthesized by the tubular cells but rather may be actively excreted or reabsorbed by them.
Contrasting Effects on Plasma Lipoproteins of Intravenous Versus Oral Administration of a Triglyceride‐Phospholipid Emulsion
Authors: Thompson G. R. , Segura R. , Hoff H. , Gotto A. M.
Published: March 2008

Abstract. The effect of fat on plasma lipoproteins was compared when administered by the oral and intravenous routes to healthy control subjects on a low fat diet for 5–6 weeks. During this time each subject underwent two 5 day periods of fat supplementation with a soya bean triglyceride‐egg yolk phospholipid emulsion (Intralipid), once via intragastric tube, once intravenously. Changes in plasma lipoproteins were assessed by measurement of their lipid and protein content. Intragastric fat administration significantly decreased the level of very low density lipoprotein (VLDL), whereas intravenous fat administration caused a significant rise in low density lipoprotein (LDL). Morphological evidence of persistence of exogenous phospholipid in plasma following intravenous fat administration was confirmed by alterations in the fatty acid composition of lecithin in the d 1. 006–1. 063 fraction of plasma. In vitro studies showed that ex change readily occurred between Intralipid and LDL lecithin, causing the latter to assume a more saturated pattern. It is concluded that the occurrence of similar changes in vivo could explain the rise in low density lipoprotein following intravenous fat, possibly by influencing the catabolic rate of the apoprotein. Hydrolysis of ingested phospholipids during absorption presumably explains why none of these changes occurred after oral fat supplementation, and would seem to be an important regulatory function of the small intestine in relation to plasma lipoprotein metabolism.
Changes in Potassium Content of Erythrocytes during Exercise in Man
Authors: Kawakami Y. , Kishiy F. , Uchiyama K. , Irie T. , Murao M.
Published: March 2008

Abstract. Factors affecting erythrocyte K+ content and plasma electrolytes during light exercise were examined in 8 normal subjects and 27 patients with chronic obstructive lung disease. The patients were classified into bronchitis, emphysema and intermediate groups. Arterial blood was obtained during rest, after 2, 5, and 7 min. of exercise on a bicycle ergometer (30 km/h without mechanical brake), and at 10 and 20 min. during recovery for analysis of PO2, PCO2, plasma H, Na+, K, and Cl‐, erythrocyte K+ content and whole blood lactate. Plasma H increased significantly in all subjects after 2 min. of exercise and PCO2 rose in normal, bronchitis, and emphysema groups during exercise, whereas PO2 did not change significantly. Plasma K rose promptly after the beginning of exercise and remained at high values during exercise. The rapid rise in PCO2 was associated with a significant decrease of calculated erythrocyte K in patients with chronic bronchitis. Although changes in plasma H were dependent on both PCO2 and lactate, erythrocyte K+ changes were significantly related only to changes in PCO2. These results indicate that the decrease in erythrocyte K+ is mainly controlled by changes in arterial PCO2 during light exercise in patients with chronic bronchitis.
Decreased Haem Synthetase Activity in Blood Cells of Patients with Erythropoietic Protoporphyria
Authors: de Goeij A. F. P. M. , Christianse K. , van Steveninck J.
Published: March 2008

Abstract. A constant finding in erythropoietic protoporphyria (E. P. P.) is a raised protoporphyrin content of the erythrocytes. It has been shown before that the biosynthesis of this protoporphyrin takes place in the erythroid cell. In circulating blood cells of patients with E. P. P. the haem synthetase activity is significantly decreased. This observation and the increased protoporphyrin concentration in the cells can be explained by assuming a decreased stability of haem synthetase in the red blood cells of E. P. P. patients.
Insulin Metabolism, Insulin Sensitivity and Hormonal Responses to Insulin Infusion in Patients Taking Oral Contraceptive Steroids
Authors: Srivastava M. C. , Oakley N. W. , Tompkins C. V. , Sönksen P. H. , Wynn V.
Published: March 2008

Abstract. The metabolism of unlabelled human monocomponent insulin was studied in a group of six patients being treated with combined oestrogen‐progestogen oral contraceptives (OC) and conroared with a group of ten normal subjects. The parameters of insulin metabolism ware determined by a priming dose ‐ continuous infusion technique which enabled measurements of metabolic clearance rate (MCR) of insulin to be made at four separate steady state hormone concentrations spanning the physiological range. In normal subjects MCR was greatest at low insulin concentrations, falling from 24. 7 ml/kg/min. at 16 μU/ml to 11. 4 ml/kg/min. at a mean concentration of 280 μU/ml. In the OC group, MCR averaged 20.5 ml/kg/min. and did not change with increasing plasma insulin concentration. The plasma half‐disappearance time (T 1/2) was longer than normal in the OC group (5. 6 vs. 4. 4 min., p < 0. 05) despite a higher MCR. The prolonged T 1/2 indicated that the apparent distribution space was increased in those on OC (166. 6 vs. 82. 7 ml/kg., p < 0. 0025). The results are interpreted as indicating increased capillary permeability to insulin and increased peripheral degradation. The fact that MCR did not fall in the OC group with increasing plasma insulin concentrations whereas it did in normal subjects, suggested that OC leads to the loss of saturable component of insulin degradation that is present in normal subjects. Insulin sensitivity (as judged by induced hypoglycaemia) was reduced in the OC group while growth hormone responses were within the normal range. Plasma Cortisol was increased in those taking OC but the response to insulin induced hyperglycaemia was less marked than normal. The results indicate a significant alteration in insulin metabolism in these subjects, which may contribute to the impairment of carbohydrate tolerance seen in some women taking combined OC.
(Pro‐)Insulin Biosynthesis and Release of Newly Synthesized (Pro‐)Insulin from Isolated Islets of Rat Pancreas in the Presence of Amino Acids and Sulphonylureas+,++
Authors: Schatz H. , Nierle C. , Pfeiffer E. F.
Published: March 2008

Abstract. The influence of arginine, lysine, tolbutamide and glibenclamide on (pro‐)insulin biosynthesis and release of newly synthesized (pro‐)insulin was studied in isolated islets of rat pancreas. Islets were incubated with 3H‐leucine and glucose in the presence and absence of the test agents. Proinsulin and insulin of islets and incubation media were separated by gel filtration on Sephadex G 50. Estimations were carried out for radioactivity and immunoreactivity for insulin. All four test substances were able to enhance insulin release whereas no stimulation of leucine incorporation into (pro‐)insulin was found. Arginine and tolbutamide even markedly reduced (pro‐)insulin synthesis. Conversion of proinsulin to insulin was not affected by any of the test agents. For studying the influence of the 4 substances on secretion of newly synthesized (pro‐)insulin two experimental models were used: 1) Labelling of the islets in the presence of the test agents, followed by uniform stimulation with glucose alone in the presence or absence of Ca++. 2) Addition of the 4 test substances after uniform prelabelling of the islets. 1) Presence of arginine and sulfonylureas during labelling resulted in a significantly enhanced relative fractional release of newly synthesized (pro‐)insulin, although the bulk of secreted hormone appeared to stem from the storage pool also under these conditions. The enhanced fractional release was persistent also during the postlabelling period when the islets had been labelled in the presence of arginine or glibenclamide. On the other hand, a decreased release of newly synthesized (pro‐)insulin was observed during the postlabelling period in islets labelled in the presence of tolbutamide. Lysine was without significant effects in both periods. Omission of calcium ions during the postlabelling period inhibited the release of both immunoreactive and radioactive hormone. 2) When amino acids or sulphonylureas were added after prelabelling no signifcant changes were found in the specific radioactivity of released (pro‐)insulin or in the fractional release of newly synthesized hormone. Enhanced release of fresh granules from the beta cell might explain the increased fractional release of newly synthesized (pro‐) insulin when labelling is carried out in the presence of arginine and sulphonylureas, especially glibenclamide.
Changes of EEG and Pulmonary Venous Admixture During a Protein Load in Patients With Cirrhosis
Authors: Schomerus H. , Buchta I. , Arndt H.
Published: March 2008

Abstract. 21 patients with cirrhosis of the liver and 24 control patients were studied before and after a protein load (120 g protein per day during one week). An EEG was recorded and a visual assessment of frequency pattern was performed. Venous admixture was estimated during hyperoxia. According to the EEG frequency pattern the patient group with cirrhosis was subdivided into those with EEG slowing after the protein load (n = 7) and those without (n = 14). The following results were obtained: 1) Resting arterial blood gases did not change in either group. 2) There was a significant increase of the AaDO2 (difference between alveolar pO2 and peripheral arterial pO2) in cirrhotics and controls. 3) The increase in AaDO2 was significantly larger in those cirrhotics showing EEG slowing compared to those without EEG ‐ slowing or to the controls. 4) Fractional venous admixture increased significantly in those cirrhotics showing EEG slowing. There was no significant change in those patients who did not show EEG changes or in the controls.
On the Mechanism of Action of Triamterene: Effects on Transport of Na+, K+, and HVHCO‐3 ‐ions.
Authors: Knauf H. , Wais U. , Lübcke R. , Albiez G.
Published: March 2008

Abstract. The rat salivary duct epithelium, which actively transports Na+., K+., and H /HCO‐3 in a manner similar to renal distal tubules, was used as a model tissue to study the mechanism of action of triamterene on electrolyte transport. 10‐4 M triamterene completely blocked Na+ resorption and lowered net K+ secretion to half that of controls, whereas HCO3‐ accumulated in the lumen, probably due to a decrease in H+ secretion. The rates of K+ and H+/HCO‐3 transport in the presence of triamterene did not differ from those determined after omission of Na+ from the luminal fluid. This was considered to be evidence against a direct action of triamterene on transport of K+ and HVHCO‐3. Triamterene rapidly and reversibly reduced the transepithelial electrical potential difference. This was due to almost complete abolition of Na+ conductance of the luminal membrane at 10‐4 M triamterene, whereas K+ conductance was not altered. Triamterene, administered in vitro from the interstitial side of the isolated duct epithelium, was ineffective even at the highest concentrati ons. The activities of the Na–K–ATPase, the Mg‐ATPase and the microsomal HCC^‐ATPase were influenced by 10‐4 M triamterene in a similar fashion. These effects were clearly demonstrated only in the homogenate of the duct tissue and not in intact cells in the isolated duct preparation. Therefore they were considered unspecific. The transport studies demonstrate a grimary effect of triamterene on Na+ entry from lumen to cell. Influences on net K+ and H+/HCO‐3 transport are secondary consequences of functional coupling between movement of Na+ and movement of K+ and H+ across the luminal cell membrane.
Effect on Plasma Aldosterone, Renin Activity and Cortisol of Acute Volume Depletion Induced by Ethacrynic Acid under Constant Infusion of Angiotensin II and Dexamethasone in Man
Authors: Gaillard R.C. , Merkelbach U. , Riondel A.M. , Vallotton M.B. , Muller A.F.
Published: March 2008

Abstract. The influence on plasma aldosterone of acute volume depletion induced by ethacrynic acid was studied in man. The experiments were performed during the morning in supine healthy males receiving a control infusion of 5 % glucose or an infusion of angiotensin II (All) to suppress endogenous renin production or an infusion of dexamethasone to suppress endogenous ACTH. Ethacrynic acid induced in all circumstances a similar diuresis and volume depletion. The rise of plasma renin activity (PRA) was effectively suppressed by All and the rise of plasma Cortisol by dexamethasone. Plasma aldosterone (PA) rose markedly even when the elevation of PRA or Cortisol were suppressed. Yet when both endogenous renin and ACTH secretion were blocked, PA rose much less after ethacrynic acid. This residual increase could be attributed mainly to a decrease of the metabolic clearance rate (MCR) of aldosterone which had been measured before and after ethacrynic acid administration. The data presented indicate that multiple factors influencing PA after acute volume depletion could be dissected out and that renin, ACTH and a decrease of the MCR each contribute to the elevation of PA.
Total and Free Triiodothyronine and Thyroid‐Binding Globulin Concentration in Elderly Human Persons
Authors: Hesch R.‐D. , Gatz J. , Pape J. , Schmidt E. , van zur Mühlen A.
Published: March 2008

Total thyroxine (TT4) and triiodothyronine (TT3) were found to be low in healthy elderly subjects with a preferential decrease of triiodothyronine. In order to determine the importance of these findings 22 healthy elderly subjects were examined.

Free triiodothyronine (FT3), thyroid binding globulin (TBG) concentration and basal thyroid stimulating hormone (TSH) were measured by radioimmunoassay. Liver enzymes, cholesterol and total protein concentration were also assayed. TBG was significantly increased compared to a middle‐aged group and did not correlate with TT4, TT3 and TSH. Basal TSH values were in the normal range and could be detected in all the elderly subjects in contrast to undetectable values in 40 % of the younger subjects. PT3 determined directly did not correlate with the values calculated according to the law of mass action. According to the FT3 values the elderly subjects could be subdivided into three groups independent of their TT4, TT3, TBG and TSH values. FT3 was undetectable in one group, in the low normal to normal range in another and elevated in the third group. Our results suggest that 1) there is no correlation between TT4, TT3, elevated TBG and FT3 determined directly or by calculation, 2) basal TSH values seem to indicate possible hypothyroidism in elderly persons which is correlated with elevated cholesterol levels and 3) FT3 measured directly subdivides this metabolic state into three groups possibly depending on the intracellular concentration of T4.
Oral Versus Intravenous Administration of Butylbiguanide: Effect on Oral Glucose Tolerance in Normal Humans
Authors: Berger E. G. , Moehr P.
Published: March 2008

1. The effect of oral and intravenous administration of butylbiguanide on the oral glucose tolerance test was investigated in 12 normal human volunteers. Orally administered butylbiguanide lowered the oral glucose tolerance curve and the corresponding serum insulin values, whereas intravenously injected butylbiguanide had no effect.

2. The lactate/pyruvate ratio determined 180 min. after glucose ingestion increased after oral butylbiguanide administration. No effect was observed after intravenous administration.

3. The decrease in serum phosphate levels observed after oral glucose loading was not influenced by butylbiguanide administered by either route. In addition, no effect of this drug was observed on fasting levels of glucose, insulin, phosphate, bicarbonate, lactate and pyruvate.

4. These results are compatible with recent observations that biguanides inhibit active transport mechanisms in the intestine. In addition, the effect of biguanides on blood levels of glucose metabolites is discussed with respect to their known action on oxidative phosphorylation.
Motility‐ and blood flow‐dependent absorption of amino acids in canine small intestine*
Authors: PYTKOWSKI BOHDAN , MICHALOWSKI JACEK
Published: March 2008

Abstract. A relationship between L‐phenylalanine and L‐serine absorption, intestinal motility and blood flow has been studied with a canine in situ isolated jejunal loop in acute experiments and in chronic preparations in conscious dogs. During spontaneous rhythmic contractions, as well as after mechanical and pharmacological stimuli, rhythmic changes in blood flow, related to intestinal contractions, were observed. They had no bearing on mean blood flow or absorption as long as they did not occur together with tonic contractions.

The tonic contractions resulted in a prolonged decrease in jejunal blood flow and diminished amino acid absorption rate. Absorption and motility index, as well as blood flow and motility were negatively correlated. There was a positive rectilinear correlation between intestinal blood flow and absorption, regardless of whether changes in blood flow resulted from the increase in motility or were induced by intestinal artery occlusion. These correlations suggest that changes in amino acid absorption during increased motility depend on changes in blood flow. This relationship may be important in clinical syndromes with hypermotility.
Effects of parathyroid hormone on total protein, calcium, magnesium, phosphorus, sodium and potassium concentrations of normal human parotid saliva*
Authors: SCHNEIDER P. , PAUNIER L. , SIZONENKO P. C. , WYSS M.
Published: March 2008

Abstract. The effects of parathyroid hormone (PTH) administered to six young normal adult subjects on protein, calcium, magnesium, phosphorus, sodium and potassium concentrations in parotid saliva have been studied in relation to the salivary flow rate. Stensen's duct was cannulated and excretion patterns of the constituents determined before and after stimulation of saliva production by lemon juice. After a control period (period 1), 50 U of PTH were given i.v. followed by an infusion of 2 U/min for 60–90 min (period 2). In the absence of any detectable changes in plasma, PTH induced a significant rise of salivary protein, calcium and phosphorus concentrations at rest and following lemon juice stimulation, and of sodium concentration, but only at high flow rates for the latter. PTH did not change magnesium and potassium excretions significantly. Control experiments without PTH were performed on five other subjects. Protein, phosphorus and potassium concentrations did not change significantly between period 1 and period 2. Calcium and sodium excretions were reduced and magnesium excretion increased during period 2. These results provide evidence that PTH acts on the parotid gland by affecting protein secretion and electrolyte transport. Possible mechanisms of these changes are discussed.