Cadmium-induced changes in renal hemodynamics in the domestic fowl

Summary Low i.v. doses of cadmium chloride (15 g Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed.It is suggested that the renal changes following the i. v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

Cadmium-induced changes in renal hemodynamics in the domestic fowl

Low i.v. doses of cadmium chloride (15 micrograms Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed. It is suggested that the renal changes following the i.v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

Influence of sodium balance on atrial natriuretic factor in rats with one-kidney,one-clip renal hypertension

Summary The influence of sodium intake on the gene expression and circulating levels of atrial natriuretic factor (ANF) was investigated in unanesthetized rats with one-kidney, one-clip renal hypertension. After clipping, the rats were maintained for 3 weeks either on a salt-deficient (n=11) or a regular-sodium diet (n=10). Animals which had received the regular-sodium diet exhibited significantly higher ANF mRNA levels in their right and left atria than salt-restricted animals, whereas there was no significant difference in plasma ANF levels.     

High sensitivity of porcine cerebral arteries to endothelin

Summary The threshold concentration of endothelin to induce contractions in porcine cerebral arteries (anterior cerebral, Willis ring and basilar artery) was lower than those for coronary and renal arteries. The median effective concentrations (ED₅₀) of endothelin in cerebral arteries were also significantly lower than those for coronary and renal arteries. There was no significant difference in the sensitivity to endothelin among cerebral arteries, or between coronary and renal arteries. The maximal percentage of contractions induced by endothelin, as compared to that induced by 10^–1 M potassium chloride, was not significantly different between the arteries.     

Modification of theophylline-induced lipolysis in human fat cells after trypsination

Summary Trypsin-treatment of human fat cells results in the potentiation of the lipolytic response and the cAMP accumulation induced by theophylline (5·10^–4 M) but not of those induced by theophylline (5·10^–3 M). The amount of cAMP formed after exposure to theophylline (5·10^–3 M) plus norepinephrine (5·10^–6 M) remains, however, 2.6fold higher in trypsin-treated human fat cells than in the control ones.Acknowledgments. The authors gratefully acknowledge the help of the surgical staff of the C. H. I. of Poissy. This work was supported by grants from the C. H. I. of Poissy and from the Université René Descartes.     

The effect of small doses of antidiuretic hormone on renal excretion of sodium and water in saline loaded acutely hypophysectomized rats

Summary Small doses of vasopressin (200 U min^–1 kg^–1) did not influence the loss of ability of acutely hypophysectomized rats to react by natriuresis to the extracellular fluid volume expansion with saline, inspite of restoring their arterial blood pressure to normal. It is concluded that the level of antidiuretic hormone efficient enough to concentrate urine is not a decisive factor in the homeostatic mechanism promoting the volume natriuresis.Acknowledgment. Skilful technical assistance of Mrs E. Blaková is sincerly appreciated.     

The human α2-plasmin inhibitor: functional characterization of the unique plasmin(ogen)-binding region

The human α₂-plasmin inhibitor (A2PI) possesses unique N- and C-terminal extensions that significantly influence its biological activities. The C-terminal segment, A2PIC (Asn³⁹⁸-Lys⁴⁵²), contains six lysines thought to be involved in the binding to lysine-binding sites in the kringle domains of human plasminogen, of which four (Lys⁴²², Lys⁴²⁹, Lys⁴³⁶, Lys⁴⁵²) are completely and two (Lys⁴⁰⁶, Lys⁴¹⁵) are partially conserved. Multiple Lys to Ala mutants of A2PIC were expressed in Escherichia coli and used in intrinsic fluorescence titrations with kringle domains K1, K4, K4 + 5, and K1 + 2 + 3 of human plasminogen. We were able to identify the C-terminal Lys⁴⁵² as the main binding partner in recombinant A2PIC (rA2PIC) constructs with isolated kringles. We could show a cooperative, zipper-like enhancement of the interaction between C-terminal Lys⁴⁵² and internal Lys⁴³⁶ of rA2PIC and isolated K1 + 2 + 3, whereas the other internal lysine residues contribute only to a minor extent to the binding process. Sulfated Tyr⁴⁴⁵ in the unique C-terminal segment revealed no influence on the binding affinity to kringle domains.     

Hemodynamic studies in a parabiotic model of portal hypertension

Summary Splanchnic and systemic hemodynamic studies were performed in a rat model of parabiosis and portal hypertension. A portal hypertensive and a normal rat were surgically united side to side. A hyperdynamic circulation, characterized by increased cardiac index (413±26 vs 318±23 ml·min^–1·kg^–1; p<0.05) and portal venous inflow (9.61±1.29 vs 6.33±0.36 ml·min^–1·100 g b.wt^–1; p<0.05), was found in all the portal hypertensive rats but not in the normal parabiotic partners. These results do not support the existence of a transferable humoral factor mediating the hyperdynamic circulatory state of chronic portal hypertension.Acknowledgment. The authors express their appreciation to Martha Shea for technical assistance.     

Maternal influences on cardiovascular pathophysiology

Elevated blood pressure (BP) is of special clinical significance because of its association with pathophysiologies such as heart disease, renal failure, and stroke. We described the development of a protocol for use with hypertensive rats in which prepubertal exposure to a high salt (8% NaCl) diet results in a pathophysiological syndrome including rapid increase in BP, failure to maintain normal weight gain, renal damage, cerebrovascular lesions, and early mortality. These phenomena are described for the inbred spontaneously hypertensive rat (SHR), and for reciprocal F₁ hybrids of a cross between SHR and the Dahl salt-sensitive (SS/Jr) inbred strain. The study with reciprocal F₁s revealed striking effects of maternal environment on pathophysiological response to a high salt diet. F₁s nurtured by SHR mothers weighed less at 35 days of age, and after exposure to the high salt diet suffered more rapid BP increases, greater incidence of stroke, body weight loss, and mortality, than F₁s nurtured by SS/Jr dams. These results suggest that maternal mediation of the nutritional status of the animal may play an important role in determining susceptibility to elevated BP and subsequent pathophysiology associated with exposure to a high salt diet. The implication of these findings for human hypertension is briefly discussed.     

The role of glycine in the biosynthesis of steroids

Zusammenfassung Während der Biosynthese von Cholesterol mit homogenisierter Rattenleber wird [2-¹⁴C] des Glycins viel besser eingebaut als [1-¹⁴C].Saccharomyces cerevisiae produziert radioaktives Squelen (ausser Ergosterol mit Radioaktivität des Ringsystems) mit [2-¹⁴C] Glycin und mit [3-¹⁴C] Serin, aber nicht mit [1-¹⁴C] Glycin.

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Studies on Biosynthesis. Part VI. For Part V, seeA. K. Bose, K. S. Khanchandani andB. L. Hungund, Experientia,27, 1403 (1971). b) Presented at the 164th National Meeting of the American Chemical Society, New York, August, 1972.

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The support of this research by Stevens Institute of Technology and Sandoz Foundation is gratefully acknowledged. We wish to thank Drs.P. T. Funke, M. S. Manhas, P. K. Bhattacharyya, M. Anchel andH. Levey for valuable discussions and help with some of the experiments.     

Influence of sodium balance on atrial natriuretic factor in rats with one-kidney, one-clip renal hypertension

The influence of sodium intake on the gene expression and circulating levels of atrial natriuretic factor (ANF) was investigated in unanesthetized rats with one-kidney, one-clip renal hypertension. After clipping, the rats were maintained for 3 weeks either on a salt-deficient (n = 11) or a regular-sodium diet (n = 10). Animals which had received the regular-sodium diet exhibited significantly higher ANF mRNA levels in their right and left atria than salt-restricted animals, whereas there was no significant difference in plasma ANF levels.     

The effect of insulin on the glycogen metabolism of isolated fat cells

Résumé (1) Des adipocytes isolés à partir du tissu adipeux épididymaire du rat ont été incubés dans des milieux contenant du glucose (1¹⁴C) et des concentrations variables d'insuline. La quantité de glucose (1¹⁴C) transformée en glycogène (¹⁴C), (¹⁴C)O₂ et triglycerides (¹⁴C) a été déterminée. (2) On démontre que la quantité de glucose (1¹⁴C) transformée en glycogène par des adipocytes peut être évaluée et qu'elle est fonction de la concentration d'insuline. (3) La comparaison entre les effets d'insuline sur les transformations du glucose (1¹⁴C) en glycogène (¹⁴C), en triglycerides (¹⁴C) ou (¹⁴C)O₂ révèle que l'insuline a une action apparemment directe sur l'incorporation du glucose au glycogène. (4) Ce fait serait donc dû à un effet direct de l'insuline sur une réaction dans la synthèse du glycogène par les adipocytes ou à une grande affinité des enzymes participant à la synthèse du glycogène pour le glucose-1-phosphate et à leur faible capacité pour la synthèse du glycogène.     

Maternal influences on cardiovascular pathophysiology.

Elevated blood pressure (BP) is of special clinical significance because of its association with pathophysiologies such as heart disease, renal failure, and stroke. We described the development of a protocol for use with hypertensive rats in which prepubertal exposure to a high salt (8% NaCl) diet results in a pathophysiological syndrome including rapid increase in BP, failure to maintain normal weight gain, renal damage, cerebrovascular lesions, and early mortality. These phenomena are described for the inbred spontaneously hypertensive rat (SHR), and for reciprocal F1 hybrids of a cross between SHR and the Dahl salt-sensitive (SS/Jr) inbred strain. The study with reciprocal F1s revealed striking effects of maternal environment on pathophysiological response to a high salt diet. F1s nurtured by SHR mothers weighed less at 35 days of age, and after exposure to the high salt diet suffered more rapid BP increases, greater incidence of stroke, body weight loss, and mortality, than F1s nurtured by SS/Jr dams. These results suggest that maternal mediation of the nutritional status of the animal may play an important role in determining susceptibility to elevated BP and subsequent pathophysiology associated with exposure to a high salt diet. The implication of these findings for human hypertension is briefly discussed.     

Transport,verteilung und Metabolismus von3H-und14C-markiertem DDT in graviden mäusen unter hungerbelastung

Summary After i.p. application of 1, 0,5 and 0,1 mg p,p' DDT, labelled with³H or¹⁴C, to pregnant mice in different stages of pregnancy, the same level of radioactivity was found in the fetal and maternal blood. Starvation for 2 days caused a significant increase of residues, especially in the liver. Residue levels of DDT and its metabolities DDE, DDD, DCB and (DDOH+DDA) are found in fetal and maternal blood, brain liver and fat.     

Acute toxicity of folic acid in mice

Summary The toxicity of folic acid (PGA) was studied in different inbred strains of mice. LD₅₀ values of PGA by the i.p. route showed a unique toxicity pattern. In some strains, convulsions, ataxia and weakness were observed. Histopathological study in strains S/RVCri, BDF₁, DBA/2 and DBA/2fNCri showed acute renal tubular necrosis.Acknowledgment. The authors thank Ms N. Hasgekar for her technical assistance     

Lack of effect of antioxidant therapy during renal ischemia and reperfusion in dogs

Acute ischemic renal failure is of great clinical importance because of its frequent occurrence and the high mortality it causes. Recent observations indicate that reperfusion has its own dangers because of oxygenderived free radicals. To study this problem, ischemia was evoked in dogs in one kidney, by clamping the left renal artery for 45 min. This was followed by a 90-min period of reperfusion when diuresis, GFR, PAH clearance and sodium and potassium excretion were studied. Besides a control group (n=6), the following treatment groups were investigated. Allopurinol (n=7): 50 mg/kg for two days p.o. and 50 mg/kg in physiological saline infusion during the experiment; a small dose of SOD (n=6): 0.5 mg/kg in infusion, started 1 min before reperfusion and given continuously for 10 min; and a high dose of SOD (n=7): 5 mg/kg as above. In the first 15 min following reperfusion, the renal functions significantly worsened in all groups. Later on, the renal functions gradually improved and in the last period after reperfusion, GFR in the ischemic kidney was 64%, cPAH 59%, diuresis 60% and sodium and potassium excretion were 65% and 76%, respectively, of the basal values in the control group.Treatment with free radical scavengers did not cause any considerable changes in the renal functions. In some respects, the worst results were observed with low-level SOD treatment (cPAH, diuresis, as well as sodium and potassium excretion).At the end of reperfusion, there was a significant drop in sodium excretion by the right (intact circulation) kidney of the treated animals.     

Renal response to acute saline loading in Sabra hypertension-prone and-resistant rats

Summary The renal handling of an oral isotonic saline load was studied in hypertension-prone (SBH), hypertension-resistant (SBN) and the parental Sabra (SB) rats. The diuretic and natriuretic response of SBH rats was unequivocally diminished, thus lending further support to the concept of impaired salt handling in hypertension.This work was supported in part by a grant from Bayer AG, FRG.     

Announcement of the Editor-in-Chief

Announcement.  As decided in July 2005 we continue to publish once a year (in July) the names of the authors and the titles of the two most read (by Internet) Research Papers and Reviews published in Cell. Mol. Life Sci. the previous year. Thus we have the pleasure to provide you with the results of 2005. Research Articles  

Establishment of serum based medium essentially free of proteolytic activity for the culture of mouse pancreatic islets

Summary The present study demonstrates that a) serum based culture medium degrades¹²⁵I insulin; b) heat in-activation of serum (1 h, 56°C) inhibits its proteolytic activity leading to the recovery of more insulin secreted by islets cultured in the presence of high glucose concentration alone or with glucagon; c) aprotinin also favoured the accumulation of secreted insulin by protecting the hormone from a residual degradative capacity of the heat treated serum.This work was supported by a grant (No. 71 5 426-2) from the INSERM and by the CNRS.These results have been presented at the V International Congress of Endocrinology. Hamburg, July 18–24, 1976.Acknowledgments. We should like to thank Mrs E. Gammelgard and K. Christensen for their technical assistance.