[The cardiorenal syndrome and optimal treatment of renal anemia]. / Le syndrome cardio-rénal et le traitement optimal de l'anémie rénale.

The cardiorenal syndrome is a clinical and pathophysiological concept illustrating the relationship between the two organs, and is mainly based on the control of volemia. Heart failure is an example of this entity: when congestive heart failure becomes refractory, ultrafiltration by various modes of dialysis is needed. Ambulatory peritoneal ultrafiltration is a good alternative for the management of treatment-resistant congestive heart failure. Erythropoietin is the main treatment of anaemia of chronic renal failure for dialysed and predialysed patients, or patients with congestive heart failure and renal insufficiency. Correction of anaemia needs to be controlled at a maximal haemoglobin level of 12 g/dl.

Pup circadian rhythm entrainment--effect of maternal ganglionectomy or pinealectomy.

In rodents, during late embryonic and early neonatal development, circadian rhythms develop in synchrony with those of their mothers, which in turn are synchronized with the environmental photoperiod. This paper examines the effect of maternal ganglionectomy (pineal gland sympathetic denervation) or extirpation of the pineal gland on pups' drinking rhythms, a behavior that is continuously monitored in individual animals starting after weaning and studied up to 3 weeks later. Maternal ganglionectomy or pinealectomy performed on the 7th day of gestation significantly disrupts rat pups' drinking behavior, within and among litters. In both treatments, circadian rhythm characteristics of the free-running period (tau), phase, amplitude and alpha were significantly altered compared to those of the control pups born from sham-operated mothers. With the exception of the alpha component, both maternal treatments have similar effects. When melatonin was given to the mothers instead of the endogenous pineal secretory activity for 5 days during the late period of gestation, this treatment reversed the effects of maternal ganglionectomy and pinealectomy. These observations, together with previous studies of our group, indicate that the maternal superior cervical ganglia and pineal gland are necessary components of the mechanism for maternal synchronization, and that maternal melatonin may, directly or indirectly, affect the performance of the pups' central oscillator during early pup rat development.

Effects of continuous light on rat parotid gland structure and reactivity.

The effects of continuous light on ultrastructural organization and sympathetic secretory responses of the rat parotid gland are reported. After 50 days of continuous light exposure, the fine structure of the parotid gland exhibited features of enhanced secretory activity as judged by the striking development of rough endoplasmic reticulum and Golgi complexes, the depletion of secretory granules and the increased turnover of secretory cells. The secretory responses of parotid gland to isoproterenol revealed that continuous light induced a 30% increase in amylase release. This secretory hyperactivity appears to be related to a postsynaptic supersensitivity of sympathetic fibers of the autonomic nervous system.

Effect of simvastatin therapy on cell membrane cholesterol content and membrane function as assessed by polymorphonuclear cell NADPH oxidase activity.

Cell membrane cholesterol is an important determinant of membrane fluidity. Changes in fluidity have important consequences for membrane function. Treatment of hypercholesterolaemia could therefore affect membrane function by reducing cell membrane cholesterol levels. The aim of this study was to determine whether treatment with simvastatin affects membrane cholesterol and the activity of the polymorphonuclear cell membrane enzyme NADPH oxidase. Blood was obtained from 12 hypercholesterolaemic patients before, and 6 weeks after, treatment with simvastatin, and from 20 normolipidaemic subjects. Cell cholesterol was in the unesterified from indicating that it was membrane-associated. Pre-treatment mean cell cholesterol concentration in the hyperlipidaemics was higher (P < 0.05) than in the normolipidaemics [4.19 fmol/cell, 95% confidence interval (CI) 3.38-5.05 versus 3.10 fmol/cell, 95% CI 2.58-3.61]. There was a strong correlation between cell cholesterol content and NADPH oxidase lag phase (R(s) = 0.76, P < 0.01). Cell cholesterol fell to 3.52 fmol/cell (95% CI 2.77-4.28, P < 0.05) following treatment and there was a correlation (R(s) = 0.61, P < 0.05) between the reductions in cell cholesterol and lag phase.

Maternal coordination of the daily rhythm of malate dehydrogenase activity in testes from young rats: effect of maternal sympathetic denervation of the pineal gland and administration of melatonin.

Chronic sympathetic denervation of the pineal gland by bilateral removal of the superior cervical ganglia (SCG) was performed on female rats 30 days before impregnation. The offspring, maintained in the dark from birth, had disruption of the malate dehydrogenase circadian rhythm in the testes at 25 days of age. A daily injection of melatonin (1 mg/kg s.c. at 10:00 or 18:00 h) to denervated mothers from the 14th day of pregnancy up to the 10th day postpartum produced one daily phase in the enzyme activity of tests in the offspring. Entrainment of daily enzyme activity also was obtained when the hormone was administered orally to the pups during the postnatal period or when pups were reared by intact (not denervated) foster mothers. The results indicate the involvement of the maternal pineal gland in the maternal transfer of photoperiodic information necessary for the coordination of the circadian system in young rats.

Modification of the beta-adrenergic sensitivity of rat submandibular gland by constant light.

Rats exposed for 2, 5, 10, 20, 35 and 50 days to constant light (CL) showed beta-adrenergic desensitization of the submandibular gland as indicated by dose-response curves to 1.5, 2.0, 3.0, 10.0, 30.0 and 50.0 micrograms/kg isoproterenol. The phenomenon, evident with 1.5, 2.0 and 50.0 micrograms/kg after 2 days at CL, was more intense as time of exposure increased to reach values of about 50% those for controls after 20 days. After 35 and 50 days, desensitization showed some reversion, but the secretory responses were still lower than for controls maintained under a typical photoperiod. In the groups of rats exposed to CL for 20 days, gland wet and dry weights were higher (10%) than those of controls. These changes probably indicate an adaptation of the sympathetic control of salivary secretion induced by environmental illumination.

Modification of the beta- and alpha2-adrenergic sensitivity of rat submandibular glands by environmental stimuli and stress.

In man, the rate of resting salivary secretion can be influenced by environmental stimuli related to light dark cycles or by noxious stimuli (stressors) of psychological origin. The sympathetic branch of the autonomic nervous system and the adrenal medulla play an important part in homeostatic responses. Previous observations have shown that chronic exposure of rats to constant light promotes degranulation of parotid acini and desensitization of submandibular beta-adrenergic receptors. Now the submandibular secretory response elicited by beta- and alpha2-adrenergic agonists was studied in rats chronically exposed to environmental conditions that modified the activities of sympathetic efferents to the pineal, salivary and adrenal glands. Adult male rats were exposed to constant light (LL) or constant darkness (DD) for 20 days, or to stress (2 h daily immobilization) for 14 days. Control animals were kept under the usual lighting conditions and without immobilization. Dose response curves to isoproterenol (i.v), before and after administration (i.v.) of a dose (20 microg/kg) of clonidine were obtained. Beta-adrenergic desensitization was observed in all the experimental groups, while alpha2-adrenergic desensitization was only observed in the stress and LL groups. The results suggest that circulating catecholamines could mediate light and stress effects on submandibular beta-adrenergic secretory responses. Extrasynaptic alpha2-adrenoceptors might modulate the submandibular secretory response when predictable environmental stimuli (daily light phase) or unpredictable stressors raise the concentrations of circulating catecholamines.

Alpha-amylase circadian rhythm of young rat parotid gland: an endogenous rhythm with maternal coordination.

The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. alpha-1,4-glucan-4-glucanohydrolase) in the parotid glands of 25-day-old rats were studied under different experimental designs (fasting, reversed photoperiod, constant lighting conditions and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of fasted rats did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod or treated with reserpine or alpha-methyl-p-tyrosine. The rhythm was present, with changes in the acrophase, in parotids of rats kept during their gestation and postnatal life in constant light or dark. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, and with maternal coordination.

Effect of sympathetic denervation of the pineal gland on maternal co-ordination of the circadian rhythm of alpha-amylase in parotid gland from young rats.

Twenty-five-day-old rats maintained in constant darkness since birth and born from mothers kept in the dark since the 14th day of pregnancy showed a circadian rhythm of alpha-amylase content in parotid glands, which may be explained by a mechanism of maternal co-ordination. Rats in the same conditions, except that their mothers had been submitted to bilateral excision of the superior cervical ganglia 30 days before mating, did not show diurnal variations of alpha-amylase activity in the parotid glands. When ganglionectomized mothers were treated with a daily dose of melatonin (1 mg/kg) from the 14th day of gestation up to the 10th day of lactation, their litters showed significant diurnal variations of amylase in the parotid glands, suggesting a role of the maternal pineal gland in the maternal-fetal and/or maternal-neonatal transfer of photoperiodic information.

Effect of photic stimuli on rat salivary glands. Role of sympathetic nervous system.

Saliva secretion during feeding facilitates chewing, swallowing and other oral functions. Between meals, a "resting saliva" is elicited to allow speaking and contribute to maintain soft and hard tissues health. Chewing is the main stimulus for "stimulated saliva" secretion. Mouth dryness and other less well known stimuli control "resting saliva". In humans the stimulus of the light increases the parotid saliva flow rate. Saliva secretion occurs in response to a reflex. Both motor branches of the autonomous nervous system drive efferent outputs to the salivary glands. Cellular bodies of sympathetic motor fibers innervating salivary glands are located in the superior cervical ganglia. A multisynaptic pathway couples the superior cervical ganglia to hypothalamic areas related to the control of autonomous and endocrine functions. Projections from suprachiasmatic nuclei involved in circadian rhythms control reach those areas. Salivary glands postsynaptic beta-adrenoceptors control synthesis and secretion of proteins. Postsynaptic alpha 2-adrenoceptors modulate salivary responses mediated by alpha 1 and beta-adrenoceptors. Parotid alpha-amylase circadian rhythm in suckling rats, suggest that the sympathetic nervous system mediates an effect of light on saliva secretion. Analysis of: 1) parotid fine structure, 2) submandibular secretory response to adrenergic agonists, and 3) submandibular 3H-clonidine binding to alpha 2-adrenoceptors, demonstrated that an increase of sympathetic reflex activity occurs in salivary glands of rats chronically exposed to constant light. Similar effects were observed in rats chronically exposed to immobilization stress. Catecholamine biosynthetic enzyme mRNA levels in adrenal glands and superior cervical ganglia suggest that changes induced by light on salivary sympathetic reflex activity are mediated by plasma catecholamines released by adrenal glands. Post and presynaptic alpha 2 adrenoceptors could play an important role in saliva secretion control when light or stress stimuli modify the sympathoadrenal system.

Effect of chronic constant light on sensitivity of rat submandibular gland.

A consistent difference in the secretory response between submandibular (SM) glands of rats maintained under constant light (CL) during 50 days and those of rats under a photoperiod (14 h light: 10 h dark) was found. We have used alpha 1-adrenergic, muscarinic, peptidergic and beta-adrenergic secretagogue agents to study the secretory response of rat SM glands "in vivo". The response to phenylephrine, methacholine and substance P, was increased by exposure CL, while that to isoproterenol was diminished. The changes in the sensitivity of the secretory response from SM gland of rats under CL might be related to changes in the normal interplay of various receptors as well as to possible alteration in the intracellular signal transduction. It may represent and adaptive process of the nervous control of saliva secretion by environmental light and be of physiological and clinical interest.

Circadian rhythm of alpha-amylase in rat parotid gland.

The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. (alpha-1,4-glucan-4-glucanohydrolase) in parotid gland of 25 day old rats was studied under different experimental conditions (fast, reversed photoperiod, constant light or darkness and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of rats fasted or exposed for 7 days to constant darkness did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod and it disappeared in animals submitted to constant light or darkness for 15 days or treated with reserpine or alpha-methyl-p-tyrosine. The rhythm persisted, with minor changes in the acrophase, in parotids of rats kept during their gestation and post-natal life in constant light or darkness. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, under autonomous nervous system control and maternal coordination. This model appears to be useful in the study of sympathetic nervous system control of target organs and circadian rhythms in general.

The Brookhaven National Laboratory electron beam ion source for RHIC.

As part of a new heavy ion preinjector that will supply beams for the Relativistic Heavy Ion Collider and the National Aeronautics and Space Administration Space Radiation Laboratory, construction of a new electron beam ion source (EBIS) is now being completed. This source, based on the successful prototype Brookhaven National Laboratory Test EBIS, is designed to produce milliampere level currents of all ion species, with q/m=(1/6)-(1/2). Among the major components of this source are a 5 T, 2-m-long, 204 mm diameter warm bore superconducting solenoid, an electron gun designed to operate at a nominal current of 10 A, and an electron collector designed to dissipate approximately 300 kW of peak power. Careful attention has been paid to the design of the vacuum system, since a pressure of 10(-10) Torr is required in the trap region. The source includes several differential pumping stages, the trap can be baked to 400 C, and there are non-evaporable getter strips in the trap region. Power supplies include a 15 A, 15 kV electron collector power supply, and fast switchable power supplies for most of the 16 electrodes used for varying the trap potential distribution for ion injection, confinement, and extraction. The EBIS source and all EBIS power supplies sit on an isolated platform, which is pulsed up to a maximum of 100 kV during ion extraction. The EBIS is now fully assembled, and operation will be beginning following final vacuum and power supply tests. Details of the EBIS components are presented.

Optical beam profile monitor and residual gas fluorescence at the relativistic heavy ion collider polarized hydrogen jet.

A gas fluorescence beam profile monitor has been implemented at the relativistic heavy ion collider (RHIC) using the polarized atomic hydrogen gas jet, which is part of the polarized proton polarimeter. RHIC proton beam profiles in the vertical plane of the accelerator are obtained as well as measurements of the width of the gas jet in the beam direction. For gold ion beams, the fluorescence cross section is sufficiently large so that profiles can be obtained from the residual gas alone, albeit with long light integration times. We estimate the fluorescence cross sections that were not known in this ultrarelativistic regime and calculate the beam emittance to provide an independent measurement of the RHIC beam. This optical beam diagnostic technique, utilizing the beam induced fluorescence from injected or residual gas, offers a noninvasive particle beam characterization and provides visual observation of proton and heavy ion beams.

Ontogeny of alpha-amylase circadian rhythms in rat parotid gland.

The content of alpha-amylase (alpha-1,4-glucan-4-glucanohydrolase, EC 3.2.1.1.) and total soluble proteins of parotid glands (from rats exposed to a photoperiod of 14 hr light: 10 hr dark), have been determined every 2 or 3 hr over 24 hr periods in 15, 25 and 90-day-old rats. In 35-, 45- and 72-day-old rats, determinations were performed only at 0100 and 1400 hr. The alpha-amylase and total soluble protein contents from 90-day-old rats show a circadian variation, with a maximum value at 2200 hr and a minimum at 1400 hr. Parotids from 15- and 25-day-old rats also show a circadian rhythm. The minimum value is recorded at 0100 hr and the maximum at 1400 hr. At day 35 and after, there is an inversion of the amylase rhythm. In immature rats, it appears that alpha-amylase and soluble protein are under the influence of another synchronizer, whose timing is independent of that imposed by mastication of solid food.