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A Gharib

Publications and source records attributed to A Gharib.

At least 19 recordsLinked to original sources
PubMed2005

Potential role of inducible nitric oxide synthase in the sleep-wake states occurrence in old rats.

Extensive evidences now suggest that an association between inducible nitric oxide synthase and oxidative stress takes place during aging. Since the part played by inducible nitric oxide synthase in the sleep impairments associated with aging still remains unexplored, we compared its involvement in old rats (20-24 months) versus adult ones (3-5 months) using polygraphic, biochemical, voltammetric and immunohistochemical techniques. The experiments were conducted either in basal condition or after a systemic injection of selected inducible nitric oxide synthase inhibitors. We found that 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (10 mg/kg, i.p.) or aminoguanidine (400 mg/kg, i.p.) was capable to suppress rapid-eye-movement sleep and induce a delayed enhancement in slow-wave sleep in old rats. These effects did not occur in adult animals. Within the frontal cortex, the laterodorsal tegmentum and dorsal raphe nuclei, the basal inducible nitric oxide synthase activity was 85-200% higher in old rats than in adult ones. In contrast, the neuronal nitric oxide synthase activity did not vary in both groups. 2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine administration significantly reduced inducible nitric oxide synthase activity (70-80% according to the brain areas) independently of age, but significantly decreased the cortical nitric oxide release in old rats. Finally, in frontal cortex and dorsal raphe immunohistochemical analysis showed inducible nitric oxide synthase-positive cells again only in old animals. These data support the idea that nitric oxide produced by inducible nitric oxide synthase plays a role in the triggering and maintenance of rapid-eye-movement sleep during aging.

Age Factors↗
PubMed2003

Changes in the sleep-wake cycle architecture and cortical nitric oxide release during ageing in the rat.

Changes in sleep-wake states and nitric oxide release were examined in aged rats versus young-adult ones. Sleep-wake recordings and nitric oxide measurements were taken from animals chronically equipped with polygraphic and voltametric electrodes. Animals were examined in baseline conditions and in response to a 24-hour paradoxical sleep deprivation. In aged rats, basal amount of paradoxical sleep is decreased during the light phase versus young-adult animals. After paradoxical sleep deprivation, a paradoxical sleep rebound occurs with an amount and intensity that are less marked in aged animals than in young-adult rats. The amplitude of the circadian distribution for wakefulness, slow-wave sleep and paradoxical sleep amounts is reduced with age. Finally, delta-slow-wave sleep and theta-paradoxical sleep power spectra are attenuated either in baseline conditions or after paradoxical sleep deprivation in aged animals. It is also reported that cortical nitric oxide release exhibits a circadian rhythm with higher amplitude in aged rats than in young-adult ones. However, after paradoxical sleep deprivation, a limited overproduction of nitric oxide is obtained compared with young-adult ones. These results, evidencing the dynamics of the nitric oxide changes occurring in relation to the sleep-wake cycle, point out the homeostatic paradoxical sleep regulation as an age-dependent process in which the nitric oxide molecule is possibly involved.

Aging↗
PubMed2003

Nitric oxide voltammetric measurements in the rat brain after gamma irradiation.

The effects of a lethal gamma irradiation were investigated on cerebral NO-ergic system by using a voltammetric method in freely moving rats. It is reported that the cortical NO concentration increases right from the end of the radiation exposure (15 Gy) and reaches a maximal magnitude (+120%) 24 h later. A dose-effect relationship from 2 to 15 Gy for gamma-ray exposure has also been observed. The effects, obtained with either an NO synthase inhibitor nonselective for the different NO synthase isoforms or an NO synthase inhibitor selective for the constitutive isoform, suggest that the radiation-induced increase in NO is likely to be dependent on the inducible NO synthase isoform. Moreover, experiments performed under ex vivo conditions showed that the cortical mRNA level for Ca(++)-independent NO synthase, the brain NOS activity, and urinary nitrites/nitrates increased significantly 24 h after gamma-ray exposure. These results demonstrate that a supralethal whole-body irradiation alters the NO-ergic pathways. The increase in NO obtained under such conditions might constitute a good index of central nervous system radiosensitivity during the acute phase of the radiation syndrome.

Animals↗
PubMed2001

Regulation of expression and enzymatic activities of tyrosine and tryptophan hydroxylases in rat brain after acute electroconvulsive shock.

Acute electroconvulsive shock (ECS) causes a significant increase of protein synthesis in depressive patients and such an increase raises the possibility that the regulation of specific proteins and enzymatic activities in the brain might be one of the mechanisms required for the induction of long-term adaptive neurochemical changes after electroconvulsive therapy. In current studies, we investigated and compared simultaneously the short- and long-term effects of an acute ECS on the expression and enzymatic activities of both tyrosine and tryptophan hydroxylases (TH and TpOH, respectively) in different rat brain areas. Our results demonstrated that an acute ECS produced: (1) a long-lasting decrease in TH and TpOH protein levels in locus ceruleus (LC), ventral tegmental area (VTA) and in TpOH protein level in the raphe centralis (RC), maximal at 72 h, with concomitant changes in mRNA levels and enzymatic activities in the LC only; (2) large increase of TpOH protein levels in the frontal cortex (Cxf) (+145%) and increase of TH protein levels in the hippocampus (Hip) (+207%), maximal at 72 h and 7 days which was not accompanied by corresponding increase of in vivo enzymatic activities. Furthermore, a second ECS increased in vivo TpOH activity in the Cxf (+19%) while decreasing K(m) value (-50%) for tetrahydrobiopterin cofactor. A stability of the observed findings on TpOH activity in the Cxf after repeated ECS might be one of the mechanisms for the antidepressant effects of electroconvulsive therapy.

5-Hydroxytryptophan↗
PubMed2001

Timing and the control of variation.

Two rat experiments shed light on how variation in behavior is regulated. Experiment 1 used the peak procedure. On most trials, the 1st bar press more than 40 s after signal onset ended the signal and produced food. Other trials lasted much longer and ended without food. On those trials, the variability of bar-press duration increased greatly after the 1st response more than 40 s after signal onset. In Experiment 2, which asked whether the increase was due to the omission of expected reward or the decrease in reward expectation, reward expectation had a strong effect on response duration, whereas omission of expected reward had little effect. In both experiments, response rate and response duration changed independently, suggesting that they reflect different parts of the underlying mechanism. In Experiment 1, response durations implied that timing of the signal was more accurate than the rate-vs.-time function might suggest. Experiment 2 suggested that lowering reward expectation increases variation in response form.

Animals↗
PubMed1999

Early and prolonged widespread increase in brain protein synthesis following a single electroconvulsive shock in free-moving rats.

The autoradiographic method with l-[35S] methionine ([35S]Met) was used to determine the effect of a single electroconvulsive shock (ECS) on local rates of protein synthesis in the adult rat brain in free-moving conditions. We have estimated the relative contribution of methionine derived from protein breakdown to the intracellular precursor amino acid pool (tRNA pool) for protein synthesis. In steady-state conditions, we showed a large contribution (around 60%) of Met recycling into the precursor pool (lambda=0.37+/-0.11), after a single ECS. In all the 36 brain regions examined, apparent rates of protein synthesis were greatly increased (21-50%) 3 h after a single ECS indicating a generalized effect in rat brain. This ECS-induced activation of the overall rate of brain protein synthesis persisted for at least 24 h after cessation of ECS. This is consistent with the hypothesis that electroconvulsive therapy is associated with long-term molecular changes in neuronal activity.

Analysis of Variance↗
PubMed1999

Biochemical and autoradiographic measurements of brain serotonin synthesis rate in the freely moving rat: a reexamination of the alpha-methyl-L-tryptophan method.

Biochemical approaches were used in freely moving rats to determine, under steady-state conditions, the brain/arterial plasma partition coefficients of L-tryptophan and alpha-[3H]methyl-L-tryptophan, from which the lumped constant for the alpha-methyl-L-tryptophan method of estimating the rate of brain serotonin synthesis is calculated. The lumped constants were significantly different in the various structures examined: 0.149 +/- 0.003 in the raphe dorsalis, 0.103 +/- 0.002 in the raphe centralis, 0.087 +/- 0.003 in the reticular formation, and 0.62 +/- 0.08 in the pineal gland. From these data we proposed a two-compartment model to calculate the rate of serotonin synthesis by quantitative autoradiography using a three-time point experiment. Rates of synthesis for the raphe dorsalis and the reticular formation (620 +/- 57 and 80 +/- 35 pmol/g of tissue/min, respectively) were similar to those measured simultaneously by biochemical means, but rates were 50% higher for the raphe centralis (568 +/- 90 vs. 381 +/- 31 pmol/g of tissue/min). The lack of dynamic equilibrium of the tracer between plasma and tissue pools may explain the discrepancy between the two methods. Our findings did not confirm previous data, indicating that the application of the autoradiographic method to measure the rate of brain serotonin synthesis using alpha-methyl-L-tryptophan as tracer has limitations.

Animals↗
PubMed1999

Dietary docosahexaenoic acid-enriched phospholipids normalize urinary melatonin excretion in adult (n-3) polyunsaturated fatty acid-deficient rats.

Melatonin (MEL) plays an essential role in physiologic functions associated with darkness. We examined the effects of docosahexaenoic acid (DHA)-enriched phospholipids from pig brains (BPL) or hen eggs (EPL), as sources of DHA, on lipid FA composition of pineal membranes and daytime and nighttime concentrations of 6-sulfatoxymelatonin (aMT6) in adult male control and (n-3)-deficient rats fed BPL and EPL diets for 5 wk. In two experiments, at 3 wk of age, rats were divided into subgroups and fed semipurified diets containing either peanut oil [(n-3)-deficient group] or peanut plus rapeseed oil (control group) and two dietary formulas containing either 3.5 g/100 g diet of BPL (Experiment 1) or 5.0 g/100 g diet of EPL (Experiment 2). BPL and EPL diets provided approximately 200 mg of DHA/100 g diet. During the daytime, aMT6 concentrations were not significantly different among groups. Conversely, the (n-3)-deficient rats had significantly lower nighttime aMT6 concentrations than the control rats. BPL and EPL did not affect urinary nighttime aMT6 concentration in the control group, whereas (n-3)-deficient + BPL or EPL groups exhibited significantly higher nighttime aMT6 concentrations than the (n-3)-deficient group (76 and 110%, respectively). The level of DHA was significantly higher in the pineal glands of control rats than in (n-3)-deficient rats. In rats fed EPL and BPL, the level of DHA reached a plateau, between 10 and 11 mg/100 mg total fatty acids in control + BPL or EPL and (n-3)-deficient + BPL or EPL groups. These findings suggest that new DHA-enriched formulas may be used as an efficient alternative source of (n-3) polyunsaturated fatty acids to normalize MEL secretion.

Animals↗
PubMed1998

Counteraction of spaceflight-induced changes in the rat central serotonergic system by adrenalectomy and corticosteroid replacement.

The effects of a 17-day spaceflight duration on serotonergic measures in various parts of rat brain have been studied (flight-SHAM group). The contribution of the activation of the hypothalamo-pituitary-adrenal axis (HPA) related to the response of the central serotonin system was evaluated in adrenalectomized with chronic corticosterone replacement rats (flight-ADX+CORT group). These two groups of rats were compared to their respective ground-based controls. Physiological parameters (body, adrenal and thymus weights) and corticosterone levels were measured. In flight-SHAM group as compared to controls, adrenal hypertrophy and elevation in plasma corticosterone levels (174%) were observed, without change in thymus mass. In most brain areas studied, significant decreases in TRP, 5-HTP and 5-HIAA were found associated with lower levels of 5-HT in cortex, thalamus and striatum. Conversely, there were elevations in TRP, 5-HTP levels in striatum and increases in 5-HIAA/5-HT ratios, an index of 5-HT turnover, in cortex, striatum and olfactory bulb while the hypothalamus was the sole region where a fall was observed. In ADX rats with chronic corticosterone replacement these effects were not observed in the majority of brain areas. It is concluded that a 17-day spaceflight exerted an inhibitory effect on serotonin metabolism, probably by activation of the HPA axis. The results could not distinguish between the effects of microgravity and the stress associated with landing.

Adrenal Glands↗
PubMed1996

Modulation of norepinephrine-stimulated cyclic AMP accumulation in rat pinealocytes by n-3 fatty acids.

This work showed that docosahexaenoic (22:6n-3) and eicosapentaenoic (20:5n-3) acid supplementation for 48 h have opposite effects on the norepinephrine-stimulated cyclic AMP accumulation in rat pinealocytes. We found that 22:6n-3 supplementation of pineal cells, done by increasing specifically 22:6n-3 in phospholipid and triacylglycerol pools, led to inhibition of norepinephrine-stimulated cyclic AMP production whereas 20:5n-3 supplementation, by increasing 20:5n-3, and 22:5n-3 and 22:6n-3 in the same pools, stimulated it. In contrast, direct treatment of pinealocytes with each fatty acid (50 microM) did not affect cyclic AMP production in the presence of (0.1-10 microM) norepinephrine. The results indicate that, using pharmacological agents such as forskolin or prazosin: (a) neither basal nor forskolin-stimulated cyclic AMP levels were modified in fatty acid-supplemented cells compared to control cells; (b) in the presence of 1 microM prazosin, the activation by 20:5n-3 was still effective whereas no additional inhibition of norepinephrine stimulation was observed in 22:6n-3-supplemented cells. Taken together our results suggest that 22:6n-3 or 20:5n-3 supplementation modulates specifically the alpha 1- or beta-adrenoceptors in the rat pineal gland.

Adrenergic alpha-Antagonists↗
PubMed1996

Stimulation of human sperm during capacitation in vitro by an adenosine agonist with specificity for A2 receptors.

The effects of an adenosine agonist with specificity for A2 receptors, on human sperm prepared for in vitro fertilization (IVF), were examined to verify physiological effects and possible pharmacological use. 5' -N-ethyl-carboxamidoadenosine (NECA), when added at 100 microM over 30 min in B2 medium, did not induce a spontaneous acrosome reaction after 0, 3, and 6 h capacitation in B2, nor did it modify sperm motility. However, NECA increased the number of capacitated spermatozoa able to respond (p < 0.05) to A23187 (10 microM) after 6 h preincubation in B2 medium. This effect was associated with an increase in cAMP production, which was measured by RIA after 10 and 20 min incubation with NECA in uncapacitated sperm, and with changes in the kinetics of protein tyrosine phosphorylation as revealed by Western blot. Phosphorylation of a 95-kDa protein was enhanced by NECA in uncapacitated sperm and inhibited in capacitating sperm (incubated 1 h in B2), whereas phosphorylation of a 50-kDa protein was systematically enhanced whatever the preincubation time. NECA can stimulate uncapacitated human sperm via cAMP production and protein phosphorylation/dephosphorylation without inducing an acrosome reaction or influencing motility. Cyclic AMP-dependent protein kinase A seems to positively control protein phosphorylation involved in human capacitation. Adenosine present in the tubal fluid or produced by the spermatozoon itself may influence capacitation in vivo through sperm A2 receptors. In cases of male infertility, use of NECA in sperm handling for IVF should be evaluated as a means to improve capacitation without increasing the possibility of a premature spontaneous acrosome reaction.

Acrosome↗
PubMed1996

[Myocardial infarction with normal coronary angiography. Apropos of 9 cases. A retrospective and comparative study].

This retrospective study was designed to determine the characteristics of myocardial infarction with normal coronary arteries. The files of consecutive patients admitted to hospital for a first infarction in 1992 and 1993 were analysed. Patients younger than 70 years of age, who had undergone coronary angiography during their admission to hospital were selected. A total of 109 infarctions complied with these criteria and 9 of them were associated with angiographically normal coronary arteries. In this series, patients with angiographically normal coronaries tended to be younger than those with at least one stenotic coronary artery (47 +/- 13 years vs 55 +/- 11 years, p = 0.07). The sex ratio did not differ between the two groups. The body mass index of patients with normal coronary arteries was significantly lower (22.9 +/- 3.9 kg/m2 vs 26.3 +/- 3 kg/m2; p = 0.02). These patients more frequently reported a history of phlebitis (3/9 kg/cm2 vs 26.3 +/- 3 kg/cm2; p = 0.02). These patients more frequently reported a history of phlebitis (3/9 vs 2/100). The frequency of anterior and posterior infarctions was virtually the same. Myocardial infarction with normal coronary arteries appears to be less severe, as reflected by the creatine phosphokinase peak (867 +/- 268 IU/l vs 1921 +/- 1389 IU/l), the maximal sum of ST elevation (5 mm vs 16 +/- 12 mm; p = 0.05), the percentage of left ventricular akinesia on angiography (25.5 +/- 4 vs 38.7 +/- 11.8; p = 0.01), and the lower ventricular end-diastolic pressure (11.5 +/- 3.5 mmHg vs 38.7 +/- 11.8 mmHg; p = 0.02). Fewer complications were observed during the acute phase, with no deaths. During the subsequent follow-up, with a median of 2 years, no recurrent infarctions, no cardiac decompensation and no deaths were observed in the group with normal coronary arteries. Two patients presented an episode of angina and one developed a recurrent episode of phlebitis. In the other group of 100 patients, 12 deaths were observed during the acute period, followed subsequently by 2 other deaths, 10 episodes of recurrent angina, 2 recurrent infarctions and 12% of patients developed heart failure. In this series, infarction with normal coronary arteries therefore appears to have a good prognosis, possibly because of more limited myocardial necrosis. No abnormalities of haemostasis or coagulation were observed in these patients.

Adult↗
PubMed1995

Distribution and metabolism of arachidonic and docosahexaenoic acids in rat pineal cells. Effect of norepinephrine.

The time-course incorporation of 10 microM [14C]arachidonic (AA) and docosahexaenoic (DHA) acids into glycerolipids was studied in rat pineal cells. The incorporation of both labeled fatty acids into total lipids was approximately equal, but their distribution profiles among the various cell lipids showed marked differences. The esterification of [14C]DHA in the neutral lipids, triacylglycerols (TAG) and cholesterol esters (CE), was 2-fold higher than that of [14C]AA whereas the opposite could be observed in total phospholipids (PL). The order of incorporation into PL was phosphatidylcholine (PC) > phosphatidylinositol (PI) = phosphatidylethanolamine (PE) for [14C]AA and PC = PE for [14C]DHA, the incorporation of both fatty acids being not detected in phosphatidylserine (PS) and that of DHA not in PI. When using 0.5 microM [3H] fatty acids, the respective distribution patterns resembled that of fatty acids at 10 microM, except for a lower proportion in TAG. The stimulation of 3H-labeled cells by 100 microM norepinephrine induced a 170% increase of basal release of [3H]AA into the medium, while [3H]DHA was virtually not released. However, the analysis of cell labeling revealed that both [3H] fatty acid levels were decreased in PL and increased in TAG. These findings suggest different involvement for AA and DHA in the pineal function. The preferential incorporation of DHA in TAG suggests that TAG might play an important role in the pineal enrichment with DHA. The absence of DHA release after NE stimulation, which however cannot be ascertained, may raise the question of the role of DHA in NE transduction.

Animals↗
PubMed1995

Decrease of brain phospholipid synthesis in free-moving n-3 fatty acid deficient rats.

The autoradiographic method with [14C]-docosahexaenoic acid ([14C]22:6 n-3) was used to determine whether a diet deficient in n-3 fatty acids, inducing a decrease in 22:6 n-3 circulating level, was associated with changes in local rates of phospholipid synthesis in the rat brain. As compared with rats fed a normal diet (peanut plus rapeseed oil), a n-3 fatty acid deficiency [peanut oil group (P group)] induced a generalized decrease (-35 to -76%) of 22:6 n-3 incorporation rates into phospholipids in all the regions examined. This effect was confirmed by using [3H]22:6 n-3 infusion by biochemical analysis and quantifications corrected for the contribution of docosahexaenoate derived from lipid store recycling to the unesterified pool, taken as the precursor pool for phospholipid synthesis in the whole brain. In normal or n-3 fatty acid-deficient rats, the values of the brain-to-plasma 22:6 n-3 specific activity ratio (psi) were similar (0.03), indicating that a considerable endogenous source of 22:6 n-3 (97%), likely derived from phospholipid degradation, dilutes the specific activity of the tracer coming from plasma. Using the specific activity of 22:6 n-3 in plasma instead of brain would thus lead to a gross underestimation of the rate of phospholipid synthesis. The results also demonstrate that the pattern of 14C or 3H distribution in brain lipids was not modified by the n-3 fatty acid-deficient diet. The major lipids labeled were phospholipids, particularly phosphatidylethanolamine. Nevertheless, the unesterified 22:6 n-3 concentrations in plasma and brain were significantly reduced (eight-and threefold, respectively) in the P group. In addition, the proportion of 22:6 n-3 in the brain total lipid fraction, total phospholipids, and phosphatidylcholine, -ethanolamine, and -serine was significantly decreased in n-3 fatty acid-deficient rats. This was partially compensated for by an increase in the 22:5 n-6 level. These results are discussed in relation to the limitation of 22:6 n-3 use to quantify, by the quantitative autoradiographic method, changes in local rates of phospholipid synthesis in rat brain.

Animals↗
PubMed1994

Evidence for brain docosahexaenoate recycling in the free-moving adult rat: implications for measurement of phospholipid synthesis.

The specific activity (SA) of unesterified docosahexaenoic acid (22:6 n-3) in the brain and arterial plasma was measured after constant intravenous infusion of [3H] 22:6 n-3 in the free-moving rat. Within 40-105 min, an apparent steady state of labeled unesterified 22:6 n-3 in plasma and in brain was reached. However, the values of the brain to plasma 22:6 n-3 SA ratios ranged from 0.03 to 0.05, indicating that an isotopic equilibrium between brain and plasma was not attained. This suggests that a considerable endogenous source of unesterified 22:6 n-3 (95-97%) (likely derived from lipid metabolism) dilutes the SA of the tracer coming from plasma. Using the SA of 22:6 in plasma instead of brain would thus lead to a gross underestimation of the rate of phospholipid synthesis.

Animals↗
PubMed1994

Formation, metabolism, and action of hepoxilin A3 in the rat pineal gland.

The present study was undertaken to investigate the possible formation of hepoxilin A3 in the rat pineal gland and to study the potential physiological role for this compound in this tissue. Incubation of homogenates of rat pineal glands with arachidonic acid (66 microM) led to the appearance of hepoxilin A3 (HxA3) analyzed as its stable trihydroxy derivative, trioxilin A3 by gas chromatography in both the electron impact and negative ion chemical ionization modes. Endogenous formation of HxA3 is estimated to be 1.43 +/- 0.66 ng/micrograms of protein. This amount is not modified when the tissue is boiled (2.07 +/- 0.66 ng/micrograms of protein). However, the formation of this compound was stimulated to 21.26 +/- 5.82 ng/micrograms of protein when exogenous arachidonic acid was added to the homogenate. Addition of the dual cyclooxygenase/lipoxygenase inhibitor BW 755C (10 micrograms) resulted in a partial blockade of hepoxilin formation. Using [1-14C]HxA3, we demonstrated that the pineal gland contained hepoxilin epoxide hydrolase, which hydrolyzed HxA3 into trioxilin A3. This hydrolysis was inhibited by 1 mumol/L of 3,3,3-trichloropropene-1,2-oxide. In a separate study, HxA3 in the presence of 3,3,3-trichloropropene-1,2-oxide to block the hydrolysis of HxA3 decreased the production of cyclic AMP in cultured organ rat pineals after stimulation with 5'-N-ethylcarboxamidoadenosine, an A1/A2 adenosine receptor agonist. This effect is stereospecific because the (8S)-enantiomer is more active in decreasing cyclic AMP production (-88.7%) than the (8R)-enantiomer. This is the first demonstration of the presence, metabolism, and action of HxA3 in the rat pineal gland.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1994

n-3 fatty acid deficiency increases brain protein synthesis in the free-moving adult rat.

The autoradiographic method with L-[35S]methionine was used to determine the effects of an n-3 fatty acid deficiency on brain protein synthesis. Brain protein synthesis was significantly increased (from 50 to 150%) in 45 of the 52 brain structures studied in n-3 fatty acid-deficient rats as compared with control animals. Biochemical analysis confirmed the increase in overall rate of protein synthesis in brain as a whole.

Animals↗