In people trying to lose weight, there are often repeated cycles of weight loss and regain. Weight cycling is, however, not limited to obese adults but affects people of normal weight, particularly young women, who are unhappy with their appearance. Furthermore, the onset of a pattern of weight cycling is shifting towards younger ages, owing to the increasing prevalence of overweight and obesity in children and adolescents, and the pressure from the media and society for a slim image even for normal weight children. Although there is still controversy whether weight cycling promotes body fat accumulation and obesity, there is mounting evidence from large population studies for increased cardiovascular risks in response to a behavior of weight cycling. Potential mechanisms by which weight cycling contributes to cardiovascular morbidity include hypertension, visceral fat accumulation, changes in adipose tissue fatty acid composition, insulin resistance and dyslipidemia. Moreover, fluctuations in blood pressure, heart rate, sympathetic activity, glomerular filtration rate, blood glucose and lipids that may occur during weight cycling -with overshoots above normal values during weight regain periods -put an additional load on the cardiovascular system, and may be easily overlooked if humans or animals are studied during a state of relatively stable weight. Overshoot of those risks factors, when repeated over time, will stress the cardiovascular system and probably contribute to the overall cardiovascular morbidity of weight cycling.

Chronic cyclosporine A (CsA) nephrotoxicity has been widely assessed but only few studies have described acute nephrotoxicity. As CsA is now used for short periods, we developed an experimental model of acute CsA-induced nephrotoxicity. Renal clearances of inulin and para-aminohippurate were assessed in 35 New Zealand rabbits. Group 1: control, no treatment; group 2: CsA 25 mg/kg per day in 0.5 ml/kg per day for 5 days; group 3: vehicle Cremophor-EL, 0.5 ml/kg per day for 5 days; group 4: follow-up, the same as group 2, then CsA discontinuation for 31 days. Compared with group 1, CsA significantly decreased glomerular filtration rate (GFR), renal blood flow (RBF), and diuresis, with a significant increase in renal vascular resistance (RVR). The proportional fall in GFR (-32.3%) and RBF (-33.1%) suggests both pre- and postglomerular vasoconstriction. Discontinuation of CsA in group 4 led to normalization of RVR with improvement of other renal function parameters. Compared with group 1, Cremophor-EL induced no significant changes but an increased RBF. Microvacuolization of proximal tubule epithelial cells was the sole histological abnormality observed only in group 2. The overall results suggest that CsA induced a vasomotor acute renal failure which was not due to Cremophor-EL. This effect was partly reversible after discontinuation of treatment.

The number of pregnant women receiving immunosuppressants for anti-rejection therapy or autoimmune diseases is increasing. All immunosuppressive drugs cross the placenta, raising questions about the long-term outcome of the children exposed in utero. There is no higher risk of congenital anomalies. However, an increased incidence of prematurity, intrauterine growth retardation (IUGR) and generally low birth weight has been reported, as well as maternal hypertension and preeclampsia. The most frequent neonatal complications are those associated with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids, immunological disturbances with azathioprine and cyclosporine, and hyperkalemia with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in utero is still limited and experimental studies raise the question whether there could be an increased incidence at adult age of some pathologies including renal insufficiency, hypertension and diabetes.

We suggest that the difference found in the FRN amplitude is associated with difficulties of patients in interpreting another's behavior. Although schizophrenic patients correctly activate neuronal bases in the proposer condition, they were not able to activate the same networks in the responder condition, thereby exposing their difficulties in social interaction.

In cerebral arteries, alterations of vascular reactivity have been observed but not well molecularly characterized. Therefore, we have hypothesized that cerebrovascular reactivity could be modified by aging via a modification of Ca These results show that aging induces a decrease of contractility correlated with modifications of the expression of genes encoding Ca 2+ signaling toolkit. Globally, the amplitude of Ca 2+ signals was decreased, whereas their duration was increased by a defection of Ca 2+ store refilling.

Working memory (WM) deficits constitute a core symptom of schizophrenia. Inadequacy of WM maintenance in schizo-phrenia has been reported to reflect abnormalities in the excitation/inhibition (E/I) balance between pyramidal neurons and parvalbumin basket cells, which may explain alterations of the dynamics of gamma and delta oscillations. To address this issue, we assessed event-related gamma (35-45 Hz) and delta (0.5-4 Hz) oscillatory responses in a visual n-back WM task in patients with first-episode psychosis (FEP) and healthy controls (HC). Periodicity analyses of oscillations were computed to explore the relationship between the psychiatric status and the WM load-related processes reflected by each frequency range. The correspondence between nested delta-gamma oscillations was estimated to assess the strength of the frontal E/I balance. In HC, gamma oscillations were synchronized by the stimulus in a 50-150 ms time range for all tasks, and periodicity of the delta cycle was comparable between the tasks. In addition, synchronization of gamma oscillations in HC occurred at the maximal descending phase of the delta cycle half-period, supporting the coexistence of delta-nested gamma oscillations. Compared with controls, FEP patients showed a lack of gamma synchronization independently of the nature of the task, and the period of delta oscillation increased significantly with the difficulty of the WM task. We thus demonstrated in FEP an inability to encode multiple items in short-term memory associated with abnormalities in the relationship between oscillations related to the difficulty of the WM task. These results argue in favor of a dysfunction of the E/I balance in psychosis.

The key role of intrarenal adenosine in mediating the hypoxemic acute renal insufficiency in newborn rabbits has been well demonstrated using the nonspecific adenosine antagonist theophylline. The present study was designed to define the role of adenosine A 1 receptors during systemic hypoxemia by using the specific A 1 -receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Renal function parameters were assessed in 31 anesthetized and mechanically ventilated newborn rabbits. In normoxia, DPCPX infusion induced a significant increase in diuresis (ϩ44%) and GFR (ϩ19%), despite a significant decrease in renal blood flow (RBF) (Ϫ22%) and an increase in renal vascular resistance (RVR) (ϩ37%). In hypoxemic conditions, diuresis (Ϫ19%), GFR (Ϫ26%), and RBF (Ϫ35%) were decreased, whereas RVR increased (ϩ33%). DPCPX administration hindered the hypoxemia-induced decrease in GFR and diuresis. However, RBF was still significantly decreased (Ϫ27%), whereas RVR increased (ϩ22%). In all groups, the filtration fraction increased significantly. The overall results support the hypothesis that, in physiologic conditions, intrarenal adenosine plays a key role in regulating glomerular filtration in the neonatal period through preferential A 1 -mediated afferent vasoconstriction. During a hypoxemic stress, the A 1 -specific antagonist DPCPX only partially prevented the hypoxemiainduced changes, as illustrated by the elevated RVR and drop in RBF. These findings imply that the contribution of intrarenal adenosine to the acute adverse effects of hypoxemia might not be solely mediated via the A 1 receptor. Adenosine is ubiquitous in the kidney. Intrarenal adenosine vasoconstricts the preglomerular vessels via the A 1 receptors, while dilating the efferent arterioles via the A 2 receptors. It thus affects GFR as well as RBF and its distribution within the kidney. In addition to its vascular actions, intrarenal adenosine modulates renal mechanisms, including TGF, renin release, and the tubular handling of electrolytes and water. Intrarenal adenosine also appears to be an important hemodynamic mediator in some models of vasomotor nephropathy, such as those induced by intramuscular glycerol injection (1), contrast media (2), cisplatin (3), or hypoxemia (4).In animal models as in humans, hypoxemia can lead to functional renal insufficiency (5-7). In the newborn rabbit, acute normocapnic hypoxemia induces renal hypoperfusion with decreased GFR and RBF (4, 7-9). The underlying mechanism of this hypoxemia-induced vasomotor nephropathy still remains controversial. The chemoreceptor-mediated reflex and/or the activation of vasoactive factors such as angiotensin II (AII) (9), endothelin (10), nitric oxide (8), or bradykinin (11) have been suggested to play a role.We previously demonstrated that the administration of theophylline, a nonspecific antagonist to adenosine receptors, ameliorates the hypoxemia-induced renal hemodynamic changes seen in the newborn rabbit model (4). Moreover, in neonates with respiratory distress syndrome (12)

Tocolysis with nonsteroidal anti-inflammatory drugs (NSAIDs) has been widely accepted for several years. Recently, the use of the cyclooxygenase-2 (COX2) preferential NSAID nimesulide has been proposed. However, data reporting neonatal acute renal failure or irreversible end-stage renal failure after maternal ingestion of nimesulide question the safety of this drug for the fetus and the neonate. Therefore, this study was designed to define the renal effects of nimesulide in newborn rabbits. Experiments were performed in 28 newborn rabbits. Renal function and hemodynamic parameters were measured using inulin and para-aminohippuric acid clearances as markers of GFR and renal blood flow, respectively. After a control period, nimesulide 2, 20, or 200 g/kg was given as an i.v. bolus, followed by a 0.05, 0.5, or 5 g · kg Ϫ1 · min Ϫ1 infusion. Nimesulide administration induced a significant dose-dependent increase in renal vascular resistance (29, 37, and 92%, respectively), with a concomitant decrease in diuresis (Ϫ5, Ϫ23, and Ϫ44%), GFR (Ϫ12, Ϫ23, and Ϫ47%), and renal blood flow (Ϫ23, Ϫ23, and Ϫ48%). These results are in contrast with recent reports claiming that selective COX2 inhibition could be safer for the kidney than nonselective NSAIDs. These experiments confirm that prostaglandins, by maintaining renal vasodilation, play a key role in the delicate balance regulating neonatal GFR. We conclude that COX2-selective/preferential inhibitors thus should be prescribed with the same caution as nonselective NSAIDs during pregnancy and in the neonatal period. Because of the role of prostaglandins (PGs) in the genesis of labor (term or preterm), nonselective nonsteroidal antiinflammatory drugs (NSAIDs) have been used as tocolytic drugs for several decades. Meanwhile, the use of NSAIDs during pregnancy to treat toxemia, polyhydramnios, or preterm labor and in the immediate postnatal period to induce closure of a symptomatic patent ductus arteriosus is increasing (1-4). However, side effects that affect mainly the cerebral, mesenteric, and renal microcirculations have been reported in fetuses and neonates (5-10), and NSAID-associated pulmonary hypoperfusion and persistence of fetal circulation may also compromise the newborn renal function (4, 11).It has been claimed that selective cyclooxygenase-2 (COX2) inhibitors could have the same curative effects as nonselective NSAIDs without the deleterious side effects attributed to COX1 inhibition. Therefore, the use of the COX2-preferential NSAID nimesulide (12, 13) has been proposed for tocolysis in humans (14). In a case report, Sawdy et al. (14) found no effect of nimesulide administered from the 16th to the 34th week of gestation on the renal and ductal functions of the fetus. Doppler flow indices for the ductus arteriosus and amniotic fluid index remained normal, and the infant was born with no congenital abnormalities and an uncomplicated neonatal course (14). However, recent data reporting severe oligohydramnios (15)