Biomedical subjects

M Leshem

Publications and source records attributed to M Leshem.

At least 19 recordsLinked to original sources

PubMed2006

Gender and obesity influence sodium intake and fluid regulation in Zucker rats following repeated sodium depletions.

The Zucker obese rat is an important model for the metabolic syndrome, which includes renal disease and salt-sensitive hypertension, suggesting abnormalities of body fluid regulation. Here, in Zucker rats, lean and obese, and of both sexes, we compared 48 h of sodium intake and fluid regulation responses with repeated depletions with furosemide to repeated control saline injections. Increased urine volume excretion was observed after each furosemide administration for the 4 groups and obese rats excreted more than the leans on the control days. Male obese rats did not excrete sodium nor increase intake of 2% NaCl following the first furosemide administration, whereas the other 3 groups did. Subsequent depletions increased 2% NaCl consumption and urinary sodium excretion in all groups. Males excreted more sodium in their urine than the females on the control days. Females showed an increase in 2% NaCl intake on control days. Water intake increased in the female leans after each depletion, increased in the males after the 2nd and 3rd depletion and increased in the obese females only after the 2nd depletion. These findings show clearly that there are gender- and weight-related differences in the response of Zucker rats to furosemide-induced depletion. However, the main differences occurred with the first depletion. With repeated depletions the rats adjusted sodium and fluid intake and excretion so that differences due to gender and body weight tended to disappear. Our findings caution against drawing conclusions about differences due to gender and body weight based on single treatments.

Adaptation, Physiological↗

PubMed2005

Increased salt appetite in patients with congenital adrenal hyperplasia 21-hydroxylase deficiency.

Salt appetite was investigated in 14 patients with congenital adrenal hyperplasia of the salt-wasting form (SW group), 12 patients with the simple virilized form who are not salt losing, and 18 healthy siblings. Salt appetite was evaluated by questionnaire, preference tests, and dietary analyses. The findings showed that SW who were not therapeutically normalized showed increased salt appetite but no change in sweet preference. Their salt appetite correlated with symptoms of salt wasting, namely, plasma renin activity, plasma K(+), and urine Na(+) and (inversely) with blood pressure. Sensitivity to the taste of NaCl was not altered. Factor analyses of a larger group confirmed the distinction between salt appetite and sweet preference, but intake of dietary Na(+) and sweet carbohydrates and intake of salty and sweet snacks did not reflect distinct salt or sweet preferences. We confirm that putative perinatal dehydration, due to maternal nausea and vomiting during pregnancy, childhood vomiting, and diarrhea with occasional saline infusion, was related to increased salt appetite in adolescence. The findings suggest that salt appetite in humans is determined by interdependent, innate, physiological, and acquired attributes. Salt appetite in SW patients is an adaptive response mediated by the renin-angiotensin system, an innate predisposition to acquire salt preference (in anticipation of both sodium loss and its consequence), and imprinting by perinatal hyponatremic occurrences. Our findings contribute to understanding human salt intake, provide insight into the motivation for salt in patients with congenital adrenal hyperplasia 21-OH deficiency, and may point the way to improvements in therapeutic compliance in these patients.

Adolescent↗

PubMed2004

Enhancement revisited: the effects of multiple depletions on sodium intake in rats vary with strain, substrain, and gender.

Repeated sodium depletion enhances spontaneous sodium intake in animals and humans, and may be a significant determinant of lifelong sodium intake. In rats, even a single sodium depletion is reported to enhance both need-induced and spontaneous sodium intakes enduringly. Both types of increases are reported to plateau after two to three depletions, and to be greater in females. Here, in two strains of rats, Wistar (W) and Sprague-Dawley (SD), and in two laboratories using different W substrains, in Israel and France, we studied the influence of repeated sodium depletions on need-induced and spontaneous sodium intake. Need-induced intake in W increased incrementally, but in SD, need-induced intake occurred fully at the first depletion. In both cases, the response was not related to changes in the diuretic efficacy of furosemide. In all strains, depletions enhanced spontaneous sodium intake, but the enhancement dissipated within days following each depletion, and only attained significance over the whole 7-week experiment in male SD. Enhancement was not greater in females, despite their greater spontaneous sodium intakes. Finally, in rats given a choice of NaCl and CaCl2, depletions enhanced only NaCl intake, both need-induced and spontaneous, attesting to the specificity of the appetite in both its forms. Our findings show that enhancement of need-induced and spontaneous sodium intake resulting from repeated sodium depletions depends upon the gender and strain of rats, and it does not result from an altered diuretic response. Persistent enhancement of spontaneous sodium intake is not a ubiquitous phenomenon.

Analysis of Variance↗

PubMed2004

Role of oxytocin and vasopressin in the transitions of weaning in the rat.

Sucklings (18-day-old) and weanlings (35-day-old) were injected icv with oxytocin or its antagonist (both 0.5 microg/1 microl), or vasopressin (1.0 ng/1 microl) or its antagonist (100 ng/1 microl), prior to 4-min observation in a behavioral maze with a sibling in one box and their anesthetized dam in the other. Oxytocin abolished nipple attachment in sucklings, decreased time spent with the dam, and increased self-grooming. The oxytocin antagonist had little influence on behavior. Vasopressin increased self-grooming while its antagonist reduced passive contact with the dam, increased active contact with her, and increased exploration and activity. We conclude that these neuropeptides have diverse roles during weaning, maintaining sucklings' behavior or promoting weaning, and subserving the transition from attachment to the dam to independence from her. We propose that these neurochemicals, and others, mediate the neural, affiliative, and affective changes of weaning, and that the term "weaning" should be understood to encompass these behavioral transitions.

Animals↗

PubMed2003

Salt conditions a flavor preference or aversion after exercise depending on NaCl dose and sweat loss.

Sodium supplementation during or after exertion improves hydration. We hypothesized that it may therefore improve well being after exercise-induced sodium loss. To avoid cognitive-biased interpretations of the taste of salt, we used untasted salt in swallowed capsules to condition preference for the flavor of a drink. In four 90 min exercise sessions, 2-3 days apart, participants drank 100 ml of a novel drink and swallowed a capsule, either empty (placebo), or containing 200, 400 or 600 mg NaCl (n=20 in each group). We found both increases and decreases in flavor preference conditioning, depending on salt dose and level of sweat loss: in groups receiving salt supplementation, high levels of sweat loss induced greater flavor conditioning of preference than low levels of sweating. However, 600 mg NaCl conditioned a flavor aversion relative to placebo, which was greater in exercisers sweating little. We conclude that since untasted salt conditioned flavor preference in direct proportion to the amount of sweat lost, replenishment of the sodium lost in sweat induces a rewarding physiological state. The results provide further evidence for the physiological determinants of human salt appetite, and buttress the evidence that post-ingestive effects condition food preferences. Conditioned flavor preference may also provide a useful measure of the benefits of other nutrient additives in sports drinks.

Adult↗

PubMed2002

Intake and hedonics of calcium and sodium during pregnancy and lactation in the rat.

These experiments sought to distinguish whether increased calcium intake during pregnancy and lactation in the rat is due to arousal of a specific calcium appetite, with altered taste hedonics, as occurs with sodium depletion, to reduced taste sensitivity, or to the hyperdipsia of reproduction. We find that, during pregnancy and lactation, CaCl(2) intake is not increased more (in fact less) than intakes of control tastants, MgCl(2) and quinine HCl, and multiparous dams do not have a greater calcium intake than primaparous dams. Changes in taste reactivity to CaCl(2) and to NaCl do not correlate with changes in intake of these minerals during pregnancy or lactation, suggesting that alterations in hedonics or sensitivity do not explain the increased intake of these minerals. Taken together with the increased intake of all the tastants, it may be that the increased intakes of calcium and sodium during reproduction are not due to respective specific appetites or to a general mineral appetite but rather to the reproduction-increased ingestion that may meet all the dam's increased mineral and nutrient requirements. Differences in the degree of increased intakes of tastes may be due to specific alterations in their transduction during reproduction.

Animals↗

PubMed2000

Prevalence of celiac antibodies in children with neurologic disorders.

Neurologic complications are a recognized but unusual manifestation of celiac disease (CD) in adults and children. The use of antigliadin and antiendomysial antibodies in screening has revealed the frequency of CD among symptom-free individuals to be high. Recently, a high frequency (57%) of antigliadin antibodies was demonstrated in adult patients with neurologic dysfunctions of unknown cause. We investigated the yield of screening for CD in children with common neurologic disorders. One hundred sixty-seven children, 1-16 years of age, were included in the study: 41 with migraine headaches, 39 with attention-deficit disorder with or without hyperactivity, 36 with epileptic disorders, and 51 with hypotonia and motor abnormalities. Positive IgG antigliadin antibodies were evident in 22 children (13%) in the study group compared with three children (9%) in the control group. However, in all children, negative IgA and endomysial antibodies were observed; thus duodenal biopsies were not performed. Contrary to studies performed in adults, these results did not demonstrate any relationship between common neurologic disorders without a specific diagnosis during childhood and CD. Thus screening for CD does not need to be routinely included in the diagnostic evaluation of children with these disorders.

Adolescent↗

PubMed1999

Exercise increases the preference for salt in humans.

Salt preference was evaluated in 21 male students before and after 1 h routine exercise by measuring their preferred concentration of NaCl in tomato soup. Before exercise, baseline measures of preference were similar to those of 21 matched student controls that did not exercise. Immediately after exercise, the amount of NaCl added to flavour the soup increased by approximately 50% in comparison to pre-exercise baselines and to non-exercising controls. Concentration of sugar flavouring tea was unaltered. Twelve hours after exercise, preferred concentrations of both salt in soup and of sugar in tea were elevated. There were no changes, at any of these time intervals, in the preferences of the control students that did not exercise. These delayed and non-specific changes in preferences are attributed to hunger. However, we speculate that the immediate and specific increase in NaCl preference after exercise is due to sodium loss (in perspiration) and/or sympathetic arousal that activates the hormones, aldosterone and angiotensin II in humans, and that in animals increases salt preference. Our findings provide further evidence for the physiological regulation of salt preference in humans.

Adult↗

PubMed1999

Calcium hunger in the parathyroidectomized rat is specific.

Calcium ingestion consequent on a challenge to calcium homeostasis such as parathyroidectomy or calcium deficient diet often appears to be nonspecific: rats rendered calcium deficient by a calcium-deficient diet increase ingestion of many tastants besides calcium, including MgCl2 and in particular, NaCl. Rats rendered calcium deficient by parathyroidectomy (PTX) have also been reported to increase ingestion of magnesium. Thus, magnesium, a chemically related molecule, and NaCl, a preferred mineral, pose challenges to the notion of a specific calcium hunger in calcium-deficient rats. Here, we reexamine the specificity of calcium preference of rats rendered calcium hungry by PTX by allowing them to choose between CaCl2 and MgCl2, and between CaCl2 and NaCl. We find that PTX rats clearly prefer calcium to either tastant. A review of the literature on tastant selection by calcium-hungry rats suggests that, given the choice between calcium and other tastants, they prefer calcium. Our findings lend credence to the notion of a calcium specific appetite in calcium-deficient rats.

Animals↗

PubMed1999

The ontogeny of salt hunger in the rat.

Salt hunger is the behaviour of an animal suffering sodium deficiency. It is characterised by an increased motivation to seek and ingest sodium, and the ability to distinguish between sodium and other salts. Here I review the development of salt hunger in the rat. Salt hunger develops rapidly between birth and weaning. It can first be demonstrated 72 h postnatally when an intracerebroventricular injection of renin elicits greater swallowing of NaCl solution than water and greater mouthing of solid fragments of NaCl than of an artificial sweetener. However, sodium deficit per se cannot arouse the hunger at this age, and first elicits increased intake of NaCl only at 12 days-of-age. The next landmark is at 17 days-of-age when the hormonal synergy of aldosterone and central angiotensin II first elicits salt hunger, as it does in the adult. The specificity of the hunger for the sodium ion also develops postnatally: the 72 h-old sodium-hungry neonate does not distinguish between NaCl and other mono- and di-valent chloride salts but, increasingly during development, the sodium hungry pup distinguishes salts and by weaning age NaCl is clearly preferred to other salts almost as it is in adults. Early development may also be a sensitive period for determining lifelong preferences, and indeed, acute perinatal sodium depletion induces a lifelong enhancement of salt intake. Taken together, these findings demonstrate how a behaviour develops precociously and how, when the behaviour becomes important at weaning, the rat pup is competent to meet its sodium requirements, and may be adapted to anticipate sodium deficit.

Aging↗

PubMed1999

Ontogeny of calcium preference in the parathyroidectomized rat.

The ontogeny of calcium ingestion and preference was examined in parathyroidectomized (PTX) rats. Sucklings were tested by means of oral infusion. Four-day-old neonatal rats increased ingestion of CaCl2 after PTX but the effect was not specific to calcium because intake of MgCl2 was also increased. After 6 days of age the increase was more specific to calcium. The response increased in potency until 20 days of age. Weanlings were tested by measuring intakes from two burets, one with CaCl2 and one with MgCl2. Twenty-six-day-old weanlings showed a mild preference for CaCl2, but by 30 days of age the preference for calcium was similar to that reported for adult rats.

Age Factors↗

PubMed1998

Salt preference in adolescence is predicted by common prenatal and infantile mineralofluid loss.

We investigated early determinants of salt preference in humans. In animals, physiological events, among them perinatal mineralofluid loss, contribute to long-term salt intake. Recent findings suggest that in humans prenatal mineralofluid loss (high levels of maternal vomiting) may increase the lifelong avidity for salt in offspring. Here we report that commonly occurring events that cause mild fluid loss and electrolyte imbalance in infancy, as well as prenatally, predict the avidity for salt in adolescents. Using questionnaires, 50 mothers recalled incidence and severity of infantile diarrhea and vomiting in their adolescent offspring. The adolescents' avidity for salt was determined by testing the preferred concentration of salt in soup, voluntary consumption of salty snack items, and by self report of salt use habits, and a dietary questionnaire. A reported history of mineralofluid loss including maternal vomiting and infantile vomiting and diarrhea increases the avidity for salt but not for sweet. Thus, commonly occurring early mineralofluid loss may contribute to lifelong salt intake. The findings raise the possibility that other causes of mineralofluid loss such as hemorrhage, exercise-induced dehydration, or neonatal diuretic therapy may also increase the avidity for salt, and its attendant health risks.

Adolescent↗

PubMed1998

Neonatal diuretic therapy may not alter Children's preference for salt taste.

Human neonates are occasionally treated with diuretics, and we investigated whether this causes a long-term enhancement of salt preference. Salt preference was examined in children aged 4-11 years. Twenty one of the children had received furosemide therapy as preterm neonates, and 24 were preterm neonates from the same ward that had no furosemide therapy. No differences were found between the two groups in preferred concentration of NaCl in soup, in consumption of salty items, and in blood and urine sodium and creatinine. However, in a tested subsample, fractional excretion of sodium (FENa) was higher in the neonatally treated children, suggesting increased salt intake. Reported severity of morning sickness in the mother when pregnant with the child, the child's history of diarrhoea and vomiting and degree of dietary salt exposure were obtained by questionnaire. These variables also did not influence salt preference, or blood and urine sodium and creatinine, except for a correlation between dietary salt exposure and blood sodium concentration. We conclude that while the physiological evidence suggests increased salt intake in children treated neonatally with furosemide, more sensitive tests of salt preference at this age are required to reveal any influence early mineralofluid loss may have on salt preference in childhood.

Case-Control Studies↗

PubMed1998

Pseudotumour cerebri complicating varicella in a child.

Pseudotumour cerebri is a clinical syndrome characterized by increased intracranial pressure in the absence of intracranial pathology. The possible association between this condition and infections has already been mention in a few case series. This paper describes a 6-y-old girl with a classical picture of pseudotumour cerebri: which developed 1 week following varicella. To the authors' knowledge, this is the first description suggesting this association. Additional reports are required to support the possible relationship between the two conditions.

Chickenpox↗

PubMed1997

Hemodialysis increases the preference for salt in soup.

Eighteen hemodialysis patients rated 7 concentrations of salt in soup immediately before dialysis and 24 h later. Preference ratings were higher after dialysis. Patients over 65 years old did not increase their ratings. Hypertensive patients increased their preference for salt after dialysis like normotensives, but rated lower concentrations of salt as more intense and were less able to discriminate the intensity of salt taste. The findings suggest that humans may respond to reductions in bodily sodium with a delayed increase in preference for salt.

Adult↗

PubMed1996

Sodium depletion and maternal separation in the suckling rat increase its salt intake when adult.

To establish whether neonatal sodium depletion increases the adult's avidity for NaCl, 12-day-old suckling pups were injected with the natriuretic-diuretic furosemide (1 mg) while with their dams. The injections surged plasma aldosterone, and when the rats were adult (70 days), their spontaneous intake of 3% NaCl was increased. Additional experiments investigated whether maternal separation has a similar effect and could thus be a source of individual variation in salt intake of the adult. Fifteen-day-old pups were separated from their dams for 24 h in an incubator. When adult, their intake of 3% NaCl was increased. Availability of saline during maternal separation obviated the effect. The increase in adult intake of 3% NaCl was specific insofar as drinking of water was not increased similarly. The results show that the adult rat's avidity for sodium can be increased by postnatal natriuresis and possibly stress. The implications of the findings are discussed.

Aldosterone↗

PubMed1994

Intracerebroventricular injection of renin in the neonatal rat reveals a precocious sodium appetite that is dissociated from renin-aroused thirst.

Previous research on the ontogeny of sodium appetite in the rat has shown that sodium deficit first engenders sodium intake at 12 days of age, whereas direct stimulation of the brain renin--angiotensin system by intracranial injection of renin increases intake of NaCl solution as early as 3 days postnatally. Similar activation of brain angiotensin also increases thirst, so that the specificity of the precocious sodium intake remains undetermined. In this article we report experiments that dissociate neonatal renin-evoked sodium appetite and thirst, and establish the specificity of the appetite. Our findings confirm that sodium appetite can first be discerned at 3 days of age, and show that it rapidly develops until 12 days of age. During this developmental window, renin-evoked sodium appetite is dissociated from thirst because (a) NaCl is preferred to water, (b) the appetite develops faster than thirst, and (c) 3-day-old renin-stimulated pups will avidly lick dry NaCl. These results show that activation of brain angiotensin in the 3-day-old rat pup evokes a precocious and specific sodium appetite.

Age Factors↗

PubMed1994

Ontogeny of the ionic specificity of sodium appetite in the rat pup.

Sodium-deficient adult rats prefer NaCl to other monochloride salts (e.g., Denton, 1991; Schulkin, 1991). However, it is not known when or how this specificity develops. Our experiments charted the development of the ionic specificity of sodium appetite aroused by sodium depletion or intracerebroventricular injection of renin. We compared intake of 3% NaCl to three other monochlorides, potassium (K), ammonium (NH4), and lithium (Li), and calcium chloride (CaCl2) at various ages between 72 hr postnatal and weaning. This revealed a biphasic developmental scheme: The adult pattern of discrimination between the salts emerges between 3 and 18 days of age. Subsequently, the preference for Na over the other salts increases into adulthood.

Aging↗