Feeding in infancy: Short- and long-term effects on cardiovascular function

Cardiovascular responses of adult organisms to feeding are well characterized and, in general, are understood as acute adaptations required for processing and distributing nutrients. Research over the past several years has shown that infants also have important cardiovascular responses to nutrient intake and that these are regulated by changes in autonomic activity to the heart and vasculature. Recent studies have provided results that suggest these responses in infancy may make an important contribution to the long-term development of cardiovascular function, in particular, adult blood pressure (BP). The purpose of this presentation will be to review the evidence that has led to this conclusion, offer ideas about how this potential early-life shaping of subsequent cardiovascular function may come about, and suggest further studies that will be required in order to characterize the mechanisms responsible for these effects.     

gamma-Aminobutyric acid and cardiovascular function

Evidence supporting the hypothesis that GABA-ergic mechanisms are involved in controlling mammalian cardiovascular function has been reviewed and analyzed. In vivo and in vitro studies with GABA-agonists and GABA-antagonists have revealed that activation of GABA-receptors is involved in the control of blood pressure and heart rate. Further studies conducted with agents that modify central and/or peripheral GABA-ergic systems could lead to the discovery of drugs that might be useful for treating certain cardiovascular disorders in man, such as hypertension and stroke, and should increase our understanding of the pathophysiological bases of such disorders.     

Acute effects of tolamolol on renal function in hypertensive patients.

The renal heamodynamic effects of a single i.v. administration of tolamolol were studied in 9 hypertensive subjects. No change of GFR and ERPF was observed after tolamolol, while urine output decreased and urine creatinine concentration increased. A reduction of the heart rate was confirmed. Blood pressure was unchanged.     

Role of p21-activated kinases in cardiovascular development and function

p21-activated kinases (Paks) are a group of six serine/threonine kinases (Pak1-6) that are involved in a variety of biological processes. Recently, Paks, more specifically Pak1, -2, and -4, have been shown to play important roles in cardiovascular development and function in a range of model organisms including zebrafish and mice. These functions include proper morphogenesis and conductance of the heart, cardiac contractility, and development and integrity of the vasculature. The mechanisms underlying these effects are not fully known, but they likely differ among the various Pak isoforms and include both kinase-dependent and -independent functions. In this review, we discuss aspects of Pak function relevant to cardiovascular biology as well as potential therapeutic implications of small-molecule Pak inhibitors in cardiovascular disease.     

Forecasting stock volatility in the presence of extreme shocks: Short-term and long-term effects

This paper introduces a novel generalized autoregressive conditional heteroskedasticity–mixed data sampling–extreme shocks (GARCH-MIDAS-ES) model for stock volatility to examine whether the importance of extreme shocks changes in different time ranges. Based on different combinations of the short- and long-term effects caused by extreme events, we extend the standard GARCH-MIDAS model to characterize the different responses of the stock market for short- and long-term horizons, separately or in combination. The unique timespan of nearly 100 years of the Dow Jones Industrial Average (DJIA) daily returns allows us to understand the stock market volatility under extreme shocks from a historical perspective. The in-sample empirical results clearly show that the DJIA stock volatility is best fitted to the GARCH-MIDAS-SLES model by including the short- and long-term impacts of extreme shocks for all forecasting horizons. The out-of-sample results and robustness tests emphasize the significance of decomposing the effect of extreme shocks into short- and long-term effects to improve the accuracy of the DJIA volatility forecasts.     

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.     

Acute effects of tolamolol on renal function in hypertensive patients

The renal haemodynamic effects of a single i.v. administration of tolamolol were studied in 9 hypertensive subjects. No change of GFR and ERPF was observed after tolamolol, while urine output decreased and urine creatinine concentration increased. A reduction of the heart rate was confirmed. Blood pressure was unchanged.     

Feeding activity ofMylabris pustulata Thunb. (Coleoptera: Meloidae)

Résumé L'activité nutritive deM. pustulata Thunb. est en général plus intense sur les plantes d'Hibiscus rosasciensis et sur ses fleurs particulier, à la lumière aussi bien que dans l'obscurité. La lumière ne joue donc pas de rôle important dans l'alimentation de cet insecte.

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The authors are indepted to Prof.H. S. Chaudhry for providing necessary facilities during the work.     

Serum cholinesterase: function in lipoprotein metabolism.

Human serum beta-lipoproteins, isolated by percipitation with heparin-calcium mixture, showed cholinesterase activity. The enzyme activity was almost proportional to the lipoprotein concentration. Rats, treated with neostigmine, a cholinesterase inhibitor, showed a significant decrease in serum beta-lipoprotein and in the incorporation of H3-lysine into the lipoprotein compared to untreated controls. The decreased incorporation of H3-lysine into beta-lipoprotein was associated with increased labelling of alpha-lopoprotein. There was no significant difference in the labelling of pre-beta-lipoprotein. We propose that LDL is formed from VLDL in the presence of cholinesterase.     

The effects of X-irradiation,applied in infancy to the head region,on the reproductive system of female rats

Résumé Les rats femelles de 8 jours, dont la tête a été irradiée à une dose atteignant 800 R croissent et se reproduisent normalement. L'ouverture du vagin s'affectue au même moment que chez des témoins. Quelques'un des corporea lutea des femelles gravides irradiées dépassent la taille et le poids maximum.     

Reduced tuberoinfundibular dopaminergic neuronal function in rats after long-term withdrawal of estrogen treatment

Summary Hypothalamic fragments from female rats treated repeatedly with estradiol valerate (EV) and bearing prolactin (PRL)-secreting tumors contained, seven months after the last EV injection, lower concentrations of dopamine (DA) than age-matched controls. Depolarizing concentrations of K⁺ (35 mM) and amphetamine (50 M) evoked in PRL-secreting tumor bearing rats an endogenous DA release significantly lower than in controls.     

Vitamin D receptors in heart: effects on atrial natriuretic factor.

We report that receptors for vitamin D exist in distinct regions of the heart in female and male mice, predominantly in the right atrium where most of the cardial atrial natriuretic peptide (ANF) is produced. Tritiated 1,25-dihydroxyvitamin D3 (1,25-D3, vitamin D, soltriol) and ANF are colocalized in nuclei and cytoplasm respectively in identical cardiomyocytes. Changes of ANF tissue and blood levels under dietary deficiency and treatment with 1,25-D3 suggest direct genomic actions of vitamin D on myoendocrine cells of the atrium for the regulation of ANF manufacture and secretion. These results were obtained by combining thaw-mount autoradiography with immunocytochemistry using tritiated 1,25-D3 and an antibody against rat ANF. This antibody was also used in a radioimmunoassay to determine atrial natriuretic factor in plasma, atria and ventricles of normal or vitamin D-deficient mice.     

Activated protein C binds directly to Tie2: possible beneficial effects on endothelial barrier function

Activated protein C (APC) is a natural anticoagulant with strong anti-inflammatory, anti-apoptotic, and barrier stabilizing properties. These cytoprotective properties of APC are thought to be exerted through its pathway involving the binding of APC to endothelial protein C receptor and cleavage of protease-activated receptors. In this study, we found that APC enhanced endothelial barrier integrity via a novel pathway, by binding directly to and activating Tie2, a transmembrane endothelial tyrosine kinase receptor. Binding assays demonstrated that APC competed with the only known ligands of Tie2, the angiopoietins (Angs). APC bound directly to Tie2 (Kd ~3 nM), with markedly stronger binding affinity than Ang2. After binding, APC rapidly activated Tie2 to enhance endothelial barrier function as shown by Evan’s blue dye transfer across confluent cell monolayers and in vivo studies. Blocking Tie2 restricted endothelial barrier integrity. This study highlights a novel mechanism by which APC binds directly to Tie2 to enhance endothelial barrier integrity, which helps to explain APC’s protective effects in vascular leakage-related pathologies.     

Comparison of the in vitro effects of colchicine and its derivative colchiceine on chondrocyte morphology and function

Summary Colchiceine is a colchicine-metabolite which has been reported to inhibit axonal transport although not binding to brain tubulin. In the present study, colchiceine was shown not to depolymerize cytoplasmic microtubules, nor to mimic other effects of colchicine on the ultrastructure of cultured chondrocytes. In addition, the synthesis of proteoglycans was inhibited by colchicine but slightly stimulated by colchiceine. These results support the idea that the disturbances in cultured chondrocytes caused by colchicine are specifically related to a loss of cytoplasmic microtubules.This work was supported by grants from the Swedish Medical Research Council (proj. No. 12X-03355), the King Gustaf V 80th Birthday Fund, the Swedish Society of Medical Sciences, and from the funds of Karolinska Institutet.     

Comparison of the in vitro effects of colchicine and its derivative colchiceine on chondrocyte morphology and function

Colchiceine is a colchicine-metabolite which has been reported to inhibit axonal transport although not binding to brain tubulin. In the present study, colchiceine was shown not to depolymerize cytoplasmic microtubules, nor to mimic other effects of colchicine on the ultrastructure of cultured chondrocytes. In addition, the synthesis of proteoglycans was inhibited by colchicine but slightly stimulated by colchiceine. These results support the idea that the disturbances in cultured chondrocytes caused by colchicine are specifically related to a loss of cytoplasmic microtubules.