Moringa olifeira Lam. Stimulates Activation of the Insulin-Dependent Akt Pathway. Antidiabetic Effect in a Diet-Induced Obesity (DIO) Mouse Model.

We investigated the antidiabetic effect of Moringa olifeira Lam. in a diet-induced obesity (DIO) mouse model. Six mice were randomly selected as normal controls. Moringa olifeira Lam. leaf extract at a dose of 200, 400 or 600 mg/kg body weight, glibenclamide (Glib) at the dose of 10 mg/kg (positive control) and distilled water at 10 ml/kg (control group) were administered orally by gastric intubation, and each group consisted of six mice. Insulinsensitive tissues (liver, skeletal muscle) were collected to investigate antidiabetic effects and examine the plant's molecular mechanisms. Moringa olifeira Lam. leaf extract prevented weight gain. It also reduced blood glucose in DIO mice. Glib and Moringa olifeira Lam. leaf extract, 400 mg/kg, treatments restored insulin levels towards normal values (P < 0.05 versus diabetic control group). Western immunoblot analysis of different tissues, collected at the end of the study, demonstrated that Moringa olifeira Lam. stimulated activation of the insulin-dependent Akt pathway and increased the protein content of Glut 4 in skeletal muscle. The improvement of hepatic steatosis observed in DIO-treated mice was associated with a decrease in the hepatic content of SREBP-1, a transcription factor involved in de novo lipogenesis. The hepatic PPARα protein content in the plant extract- treated mice remained significantly higher than those of the control group (P < 0.05). In conclusion, this study provides the first evidence for direct action of Moringa olifeira Lam. on pancreatic ß-cells, enhancing glucose-stimulated insulin secretion. This correlated with hypoglycaemic effects in diabetic mice associated with restored levels of plasma insulin.

Moringa oleifera-rich diet and T cell calcium signaling in spontaneously hypertensive rats.

Moringa oleifera is a plant whose fruits, roots and leaves have been advocated for traditional medicinal uses. The physicochemical analysis shows that Moringa oleifera contains more dietary polyunsaturated fatty acids (PUFA) than saturated fatty acids (SFA). The consumption of an experimental diet enriched with Moringa oleifera extracts lowered blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats as compared to rats fed an unsupplemented control diet. Anti-CD3-stimulated T cell proliferation was diminished in both strains of rats fed the Moringa oleifera. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. Studies of platelets from patients with primary hypertension and from SHR support the notion that the concentration of intracellular free calcium [Ca(2+)](i) is modified in both clinical and experimental hypertension. We observed that the basal, [Ca(2+)](i) was lower in T cells of SHR than in those of WKY rats fed the control diet. Feeding the diet with Moringa oleifera extracts to WKY rats did not alter basal [Ca(2+)](i) in T cells but increased basal [Ca(2+)](i) in SHR. Our study clearly demonstrated that Moringa oleifera exerts antihypertensive effects by inhibiting the secretion of IL-2 and modulates T cell calcium signaling in hypertensive rats.

Composition and organization of the SCZ: a large germinal layer containing neural stem cells in the adult mammalian brain.

Two known germinal zones continue to generate new neurons and glia in the adult mammalian brain: the subventricular zone (SVZ), lining the lateral walls of the lateral ventricle, and the subgranular zone of the dentate gyrus. Here we describe a region we will refer to as the subcallosal zone (SCZ). The SCZ is a caudal extension of the SVZ that is no longer associated to an open ventricle. It lies between the hippocampus and the corpus callosum. Cells isolated from the SCZ and cultured as neurospheres behave as neural stem cells in vitro. Using electron and light microscopy, we describe the cell types present in this region and how their organization differs from that of the SVZ. Using retroviral labeling and homotypic-homochronic microtransplantation techniques, we show that the majority of cells born in the SCZ migrate into the corpus callosum to become oligodendrocytes in vivo. This study defines the organization and fate of cells born in a large germinal region of the adult forebrain.

Astrocytes give rise to new neurons in the adult mammalian hippocampus.

Neurogenesis in the dentate gyrus of the hippocampus persists throughout life in many vertebrates, including humans. The progenitors of these new neurons reside in the subgranular layer (SGL) of the dentate gyrus. Although stem cells that can self-renew and generate new neurons and glia have been cultured from the adult mammalian hippocampus, the in vivo primary precursors for the formation of new neurons have not been identified. Here we show that SGL cells, which express glial fibrillary acidic protein and have the characteristics of astrocytes, divide and generate new neurons under normal conditions or after the chemical removal of actively dividing cells. We also describe a population of small electron-dense SGL cells, which we call type D cells and are derived from the astrocytes and probably function as a transient precursor in the formation of new neurons. These results reveal the origins of new neurons in the adult hippocampus.

Carateristiques des affections opportunistes sous traitement antiretroviral chez les patients VIH positifs suivis dans le service des maladies infectieuses d'Abidjan

Objectif ecrire les caracteristiques des infections opportunistes chez es sujets VIH positifs sous traitement ARV et suivis dans le service des Maladies Infectieuses et Tropicales d'Abidjan. Methodes : L'etude a porte sur les patients ayant beneficie du traitement ARV entre octobre 1998 et janvier 2000. Ont ete analysees les donnees sociodemographiques; (sexe; age; lieu de residence; statut matrimonial; revenu mensuel; nationalite) donnees cliniques (poids; score de karnofsky; infections opportunistes) et les donnees immuno-virologiques (taux de Cb4; la charge virale) a chaque visite: M0; M1; M4; M7; Mb; M13; M16. Resultat: Sur 410 patients ayant un bilan pretherapeutique : 38 patients ont ete traites par ARV. Parmi ces 188 patients (115 hommes; 73 femmes); 60 patients ont ete pretraites (32pour cent) et 128 patients naifs (68pour cent); 106 patients etaient sous tritherapie et 82 patients sous bitherapie. Au debut du traitement; 76 patients etaient porteurs d'infections opportunistes (40pour cent) dominees par les lesions dermatologiques (31;6pour cent) et la candidose buccale (27;6pour cent). Au cours du traitement; 46 patients ont developpe de nouvelles IOs (24pour cent) dominees par la candidose (17pour cent) et la tuberculose (11pour cent). Elles etaient plus frequentes dans la bitherapie (37pour cent); parmi les sujets sans prophylaxie (37pour cent); les patients inobservants (29pour cent); les patients avec Cb4 200mm3 (40pour cent); au cours des 4 premiers mois de traitement (65pour cent) et avec les tritherapies sans antiprotease (33pour cent). L'incidence de ces infections opportunistes a progressivement diminue et beaucoup plus marquee sous la tritherapie. Conclusion : Cette etude vient encore une fois de plus; d'identifier les facteurs -susceptibles de favoriser la survenue des IOs sous traitement ARV. Cela souligne l'interet de la tritherapie; de l'observance au traitement et de la chimioprophylaxie pour eviter ces complications infectieuses; cause des deces precoces des personnes vivant avec le VIH/SIDA

Comparative effects of developmental thiamine deficiencies and ethanol exposure on the morphometry of the CA3 pyramidal cells.

Maternal alcoholism and thiamine deficiency are frequently considered to be the causal agents of the central nervous system (CNS) damage associated with mental retardation in the offspring. For further understanding of pathological mechanisms underlying CNS damage in both disorders, histological studies were undertaken in developing rats to compare the hippocampus CA3 pyramidal cells measurements and density between three patterns of thiamine deficiency and chronic alcohol exposure. Female rats were given thiamine-deficient diet during different periods of gestation and lactation to obtain pre-, peri-, and postnatal thiamine-deficient pups. Twelve percent ethanol/water drinking fluid was given to mothers throughout gestation and lactation to obtain ethanol-exposed pups. Thiamine was administered during developmental ethanol exposure to assess the extent of interference between ethanol and thiamine metabolism. Nondrug-treated dams were allowed ad lib access to food and water during gestation and lactation to yield control pups. Hippocampus histology was performed in 45-day-old rats, and the CA3 pyramidal cells measurements and density assessed and compared between all treatment groups. It appears that the mean nuclear size of pyramidal cells in the field CA3 was significantly reduced in all the treatments compared to the control. While the mean nuclear size decreased more severely in development ethanol exposure than in the three patterns of thiamine deficiency, no significant difference was noted when pre-, peri-, and postnatal thiamine-deficient rats were compared. However, thiamine administration during developmental ethanol exposure partially restored the mean nuclear size. In contrast, comparisons between ethanol-exposed pups and the three patterns of thiamine-deficient pups, exhibited similar intensity in the deficit of CA3 pyramidal cells. Cell loss generated by ethanol treatment was not suppressed by thiamine administration. Common and separate mechanisms underlying the effects of alcohol intoxication and thiamine deficiency on cell death and cell atrophy were suggested.

Thiamine administration during chronic alcohol intake in pregnant and lactating rats: effects on the offspring neurobehavioural development.

A number of mechanisms may be involved in the pathogenesis of thiamine deficiency in the alcoholic. Among these mechanisms are inadequate dietary intake of thiamine, impaired intestinal transport of the vitamin and decreased conversion of thiamine to the active coenzyme. The present study was undertaken to further investigate the mechanism by which alcohol can interfere with thiamine deficiency in the brain. Thus, the neurobehavioural development of rat pups (E) nursed by 12% ethanol/water-drinking mothers, or pups (E-T) nursed by mothers drinking 12% ethanol/water + thiamine hydrochloride mixture, was monitored from the 1st to 45th postnatal days. Appropriate pair-fed saccharose (S) and ad libitum controls (C) were assessed. Histological studies were performed at the age of 45 days on the hippocampal CA3 pyramidal neurons of the offspring from each treatment. Exposing rat pups to ethanol during pregnancy and lactation showed a significant impairment of neurobehavioural development, more cornered pyramidal cells in the hippocampal field CA3, reduced cell number and cell size. The results point out long-lasting effects of maternal alcohol exposure in the offspring. Both functional and structural studies showed that neurotoxic effects of developmental alcohol exposure were not reversed by thiamine administration. However, adverse effects of undernutrition following developmental alcohol exposure were suppressed by thiamine administration. From this work, we suggest that inadequate dietary intake of thiamine and impaired intestinal transport of the vitamin are not critical mechanisms leading to thiamine deficiency in chronic alcoholism. The most prevalent mechanism contributing to ethanol-induced thiamine deficiency in chronic alcoholics would be the alteration of thiamine metabolism, and particularly the reduction of the vitamin conversion to its metabolically active form TPP (thiamine pyrophosphate).

Psychomotor functions in developing rats: ontogenetic approach to structure-function relationships.

The functional development of the central nervous system (CNS) in the rat was studied from the 10th to the 45th postnatal day, through the ontogeny of psychomotor and sensory functions, by a battery of behavioral tests. The ontogenetic development of 10 different functions was described. The results showed that novelty-induced functions matured progressively in an adult-like pattern of functioning in the 3rd postnatal week. Indeed, exploratory activity was low at the 10th day, increased significantly to reach highest values from 20th to 30th postnatal day, then declined at the 45th postnatal day. No habituation was exhibited by 10- and 15-day-old rats; it appeared at the age of 20 days. Emotional reactivity induced by the novelty of surroundings clearly appeared from the 20th postnatal day, when the features of adult animal were reached. It appeared also that reflex and automatic motor functions came to maturity by the age of 3 wk, while voluntary motor functions continued to improve until the 30th day. Thus, the latency of the hind paw lifting reflex occurrence significantly decreased from the 10th to the 20th postnatal day, when the most improved values were reached. The wire-grasping times increased from the 10th to the 25th postnatal day in an exponential fashion. Locomotor activity developed significantly from the 10th to the 15th day, when the mature locomotion pattern was exhibited. The coordination of complex movements and motor initiative appeared only after the 20th postnatal day. The latencies of execution of crawling along the wire and of leap onto the ground decreased significantly from the 20th to the 45th day. These studies reveal the presence of the caudal to rostral sequence of CNS development, predicting a spatio-temporal functional maturation of nuclei and centers in the rat's CNS. The building of the time-sequence of regional maturation of the brain integrated activities was attempted.

Functional development of central nervous system in the rat: ontogeny of nociceptive thresholds.

The functional development of central nervous system (CNS) in the rat has been studied from the 10th to the 45th postnatal day, through a sensory function: nociception. Baseline pain responsiveness has been assessed with the tail-flick procedure. The mean tail-flick latency clearly decreases from the 10th to the 25th day, and remains stationary from this age to 45 days. The maturational processes underlying these reductions of tail-flick latencies in developing rats are discussed.

Effects of Mel B arsobal and alpha-difluoromethylornithine on the awakening electroencephalogram of humans with gambiense trypanosomiasis disease: preliminary report.

Five males and three females, at the encephalic stage of sleeping sickness, were submitted to trypanocide therapies. Three of the patients were treated with the Mel B Arsobal drug, the five others with difluoromethylornithine, using different protocols. Awakening electroencephalographic data were obtained prior to treatment and, at regular intervals, during and after treatment. Prior to treatment the awakening tracings showed important abnormalities (slow delta waves were superimposed on theta background rhythms). During treatment (except in one patient treated with Arsobal) recordings returned gradually to fast rhythms and several days after therapy, tracings returned to the normal awakening patterns. The use of the awakening electroencephalogram as a tool to test effects of curative drugs in the sleeping sickness syndrome is discussed.

Auditory event-related potentials and reaction times during simple sensorymotor tasks in subjects with sickle cell disease and related hemoglobinopathies.

40 subjects of both sexes assigned to five groups of 8: healthy students, homozygous sicklemics, hemoglobin SC sicklemics, sickle cell Bo thalassemics, and sickle cell B+ thalassemics were subjected to 1/simple auditory stimuli; 2/paired auditory stimuli. The subjects were asked to respond quickly, by pressing a push button on detection of the simple stimulus or the unconditional stimulus of paired stimuli. A subsequent increase in reaction times and a reduction in event-related potential component amplitudes were obvious in major (SS and SC) sicklemics compared to controls and sickle cell B thalassemics. Between simple and paired auditory conditions, reaction times were more increased in sicklemics than in controls. These findings suggest that impairment of attentiveness, performance and cognitive capability in sicklemics is a function of sickle cell anemia severity.

[Cortical reactivity during reaction time tests in sprinters]. / Réactivité corticale au cours d'épreuves de temps de réaction chez les sprinters.

Thirty-two male subjects divided into 4 groups (of 8--controls, witnesses, students in physical and athletic education (PAE) and sprinters--were submitted to 1) simple auditory stimuli, 2) paired auditory stimuli, and 3) simple and paired auditory stimuli. The subjects, except the control group, have been assigned the task of quickly responding by pressing a button, accordingly the detection of the simple stimulus, of the imperative stimulus when the stimuli are paired, or the simple and imperative stimuli when they are randomly matched. The results show that the amplitude of the event-related potential components and of the CNV is significantly more important in sprinters and PEA students than in other groups. The differences indicate a greater adaptative reactivity of attentional mechanisms in athletes. In all the groups, the variations in the event-related potentials and of the CNV, as well as the variations of RT between conditions 1 and 2, indicate that the effects of activation and preparation differ depending on whether or not the signal for execution of the motor response is preceded by a preparatory signal. The decrease in event-related potentials and CNV amplitude and the elongation of RT in divided attention condition suggest that when subjects have to distinguish, at the same time, simple and paired auditory stimuli, interferences are induced. The attention is disturbed performance are impaired. Sprinters are less susceptible to interferences than control persons, their performances remaining significantly better.

Motor skill acquisition influences brain responsiveness in sprinters.

Contingent negative variation (CNV) and reaction time were examined in four groups of eight young adult men: controls, witnesses, students in physical and athletic education, and sprinters. Subjects, except the control group, were asked to detect and respond quickly by pressing a button in the following experimental conditions: 1) simple auditory stimuli, 2) paired auditory stimuli, 3) mixed simple and paired auditory stimuli.- A higher CNV voltage and lower reaction time and reaction time variability were obvious in students in physical and athletic education and sprinters, compared to controls and witnesses. In all the groups CNV amplitude declined in the third condition, reaction time and reaction time variability augmented from condition 1 to condition 3. These results show that relationships couple attentiveness and motor activation processes. The motor activation differed for simple starter and presignalled starter conditions (conditions 1 and 2). An increase of discrimination difficulty diminished the performance.

Relation between warning stimuli and contingent negative variation in man.

Seven right handed male students were submitted to standard and target paired auditory stimuli to determine the relationship between contingent negative variation (CNV) and the slow negative waves following non paired stimuli. The warning stimuli informed subjects whether or not the impending unconditional stimulus implied a motor response. Subjects were instructed to execute the motor task at less than one second after unconditional stimulus. They were informed that the standard warning stimulus would be followed by an additional stimulus which confirmed its detection. Recordings of standard warning stimulus condition showed a subsequent increase in CNV amplitude. This significant increase appeared to be related to an enhancement in the subject's expectation towards the additional stimulus. The lowered CNV voltage in target condition seemed to be linked to the instructions, which involved a motor preparation after the imperative stimuli occurrence. It is suggested that the CNV may represent not only a general anticipatory but also an orienting process related to the signal value of the warning stimulus.

[Effects of optic nerve section in baboons on the geniculate and cortical spike activity during various states of vigilance]. / Effets de la section des nerfs optiques chez le babouin sur l'activité à type de pointes genouillées et corticales au cours des divers états de vigilance.

Eye movement potentials during wakefulness (EMPs) and so-called spike (PGO) activities were studied in 4 adult baboons before and after optic nerve (ON) section. The latter was performed either in two stages at a 23-day interval or simultaneously. During wakefulness in the intact animal, triphasic EMPs were observed in darkness with smaller amplitude and longer duration than in the light. After section of one ON, the 3 EMP components persisted, but with a smaller amplitude of the first wave. After section of the second ON morphological changes appeared: the amplitude and duration of the potentials were intermediate between those noted in darkness and light but with an intermingled sharp spike. Geniculate EMPs reappeared 11 days after simultaneous ON section, with the same evolution as previously described. During slow wave and REM sleep, intact animals presented lateral geniculate (LG) monophasic and biphasic spikes, called spikes I and II. At the cortex, they occurred either generalized or limited to one area (anterior or posterior) and were called pontogeniculocortical spikes (PGC). After section of one ON, the pattern of occurrence of phasic activities remained identical in LG. Sharp spikes (spike III) appeared; then their occurrence increased. At the end of the second month after the second section, only spikes II and III remained, spike I disappearing, while PGC amplitude diminished. When both ONs were cut simultaneously, spike III was observed from the first day and PGC activity tended to disappear partially for 11 days. Their later evolution was similar to that noted previously. However, changes were seen earlier (the highest rate of spike III occurring at day 35). In both cases, PGC spikes at the cortex increased in amplitude and frequency of occurrence.

[Effects of optic nerve section in baboons on the EEG activity and sleep-waking cycles]. / Effets de la section des nerfs optiques chez le babouin sur l'activité EEG et les cycles veille--sommeil.

EEG rhythms recorded during the various states of alertness and sleep--waking cycles were studied in 4 baboons before and after optic nerve section. Visual deafferentation induced a general increase in amplitude of all the cortical rhythms, with general accentuation of pre-existing activities such as occipital eye movement potentials (EMPs), the fronto-rolandic rhythm and the alpha rhythm, spindles, REM ponto-geniculo-cortical (PGC) spikes; an increase in amplitude of the geniculate rhythmic activity, its frequency and occurrence was also noticed. When the blind baboons were placed in a monotonous environment, sleep--waking cycles occurred at any time of the 24 h. Total sleep time and total REM duration were not changed; however, deep sleep (stages 3 and 4) duration decreased (by around 50%) whereas stages 1 and 2 increased. The light factor thus plays a role in the sleep--waking cycle organization. However, its influence does to seem to be essential since its loss can be compensated by auditory stimulation. Finally, light possibly influences the systems involved in slow wave sleep regulation.

Nonhuman primates: laboratory animals of choice for neurophysiologic studies of sleep.

A systematic study was made of several nonhuman primates to learn more about their relative usefulness for studies of sleep. Species studied included the Guinea baboon (Papio papio), Kenya or yellow baboon (P cynocephalus), olive baboon (P anubis), sacred baboon (P hamadryas), vervet monkey (Cercopithecus aethiops), rhesus monkey (Macaca mulatta), bonnet monkey (M radiata), crab-eating monkey (M fascicularis), patas monkey (Erythrocebus patas), chimpanzee (Pan troglodytes), mongoose lemur (Lemur mongoz), black lemur (Lemur macaco fulvus), and bushbaby (Galago senegalensis). Comparisons were made of electroencephalographic activity, states of vigilance, and responses to sleep-waking drugs. The results showed that there were major similarities among the genera studied as well as individual intrageneric and intraspecies differences. It was concluded that the chimpanzee, olive baboon, and rhesus monkey were the best species for comparative studies, and that the rhesus monkey was the best single model because of its well defined sleep organization and ease of handling and housing.