From cerebral palsy to developmental coordination disorder: Development of preclinical rat models corresponding to recent epidemiological changes.

Cerebral palsy (CP) is a complex syndrome of various sensory, motor and cognitive deficits. Its prevalence has recently decreased in some developed countries and its symptoms have also shifted since the 1960s. From the 1990s, CP has been associated with prematurity, but recent epidemiologic studies show reduced or absent brain damage, which recapitulates developmental coordination disorder (DCD). In previous studies, we developed a rat model based on mild intrauterine hypoperfusion (MIUH) that recapitulated the diversity of symptoms observed in preterm survivors. Briefly, MIUH led to early inflammatory processes, diffuse brain damage, minor locomotor deficits, musculoskeletal pathologies, neuroanatomical and functional disorganization of the primary somatosensory (S1) cortex but not in the motor cortex (M1), delayed sensorimotor reflexes, spontaneous hyperactivity, deficits in sensory information processing, and memory and learning impairments in adult rats. Adult MIUH rats also exhibited changes in muscle contractile properties and phenotype, enduring hyperreflexia and spasticity, as well as hyperexcitability in the sensorimotor cortex. We recently developed a rat model of DCD based on postnatal sensorimotor restriction (SMR) without brain damage. Briefly, SMR led to digitigrade locomotion (i.e., "toe walking") related to ankle-knee overextension, degraded musculoskeletal tissues (e.g., gastrocnemius atrophy), and lumbar hyperreflexia. The postnatal SMR then led to secondary degradation of the hind-limb maps in S1 and M1 cortices, altered cortical response properties and cortical hyperexcitability, but no brain damage. Thus, our 2 rat models appear to recapitulate the diversity of symptoms ranging from CP to DCD and contribute to understanding the emergence and mechanisms underlying the corresponding neurodevelopmental disorders. These preclinical models seem promising for testing strategies of rehabilitation based on both physical and cognitive training to promote adaptive brain plasticity and to improve physical body conditions.

[Seroprevalence of HBsAg in pregnant women in central Morocco]. / Séroprévalence de l'AgHBs chez la femme enceinte dans le centre du Maroc.

Maternal-fetal transmission of hepatitis B virus (HBV) is a global public health problem leading to the implementation of strengthened prevention measures. Viral replication in HIV-positive mother, assessed based on HBeAg positivity and the rate of viral load, determines the contamination risk which is very important during perinatal period. Mothers with chronic HBV are a real reservoir of vertical transmission of this infection. This is a prospective investigation of 1120 pregnant Moroccan women aiming to study the seroprevalence of HBsAg which was 2.35%, in order to supply the national evidence on this topic. Among these HIV-positive women who were HBsAg positive, 79.1% were HBeAg negative and underwent molecular research that was positive in 89.4% of cases. Immunization of women of childbearing age is one of the major pillars of prevention of HBV vertical transmission. Only 2.4% of our patients were vaccinated. This highlights the role of screening during pregnancy, which should focus on raising awareness about the importance of immunization in HIV-negative women and of monitoring using molecular biology tools in HIV-positive mothers in order to establish an appropriate prophylactic treatment.

[Visceral leishmaniasis in adults: about twelve cases]. / La leishmaniose viscérale chez l'adulte à propos de douze cas.

Visceral leishmaniasis is a vector-borne disease essentially associated with Leishmania infantum infection in the Mediterranean basin. Although rare in adults, its prevalence has recently increased even among immunocompetent individuals. The aim of our study is to reveal the epidemiological features of visceral leishmaniasis in adults and the importance of biological diagnostic in the identification of this disease. Our study spanned six years from January 2009 to January 2014 and data were collected from twelve patients hospitalized at University Hospital Hassan II, Fez. Alteration of general state and splenomegaly dominated the clinical picture. Biologically, anemia was almost constant. Diagnosis was confirmed by parasite identification at the level of bone marrow. The response to treatment was favorable for all our patients. Thus, visceral leishmaniasis recrudescence in adults and its nonspecific clinical picture must lead the clinicians to suspect it when fever accompanying splenomegaly occurs, thus enabling early diagnosis and therapeutic management.

[Cutaneous larva migrans syndrome on a malformed foot (a case report)]. / Syndrome de larva migrans cutanée sur pied malformé (à propos d'un cas).

Cutaneous larva migrans syndrome is a subcutaneous dermatitis caused by hookworms' larvae, originating from animals in parasitic impasse in humans. Transcutaneous infestation is favored by contact with contaminated soil. We report the case of a 15-month-old child, native of Guinea - Bissau, suffering from cutaneous larva migrans syndrome on a malformed foot. This malformation in the form of a syndactyly, associated with a tumefaction of the foot cause a delay in the standing position. Besides, the fact that the child never wears shoes because of the sick foot is another factor contributing to the patient's infestation by the larvae of the nematode.

Noradrenergic terminals regulate L-DOPA-derived dopamine extracellular levels in a region-dependent manner in Parkinsonian rats.

AIMS: Serotonin (5-HT) neurons mediate the ectopic release of dopamine (DA) induced by L-DOPA in the Parkinsonian brain. We hypothesized that the participation of noradrenalin transporters (NET) in the clearance of DA may account for the lower effect of L-DOPA in extrastriatal regions compared with the striatum. METHODS: Using a multisite intracerebral microdialysis approach, we tested the influence of the pharmacological blockade of NET and/or the destruction of noradrenalin (NE) fibers on DA and 5-HT release in the striatum, hippocampus (HIPP), substantia nigra pars reticulata (SNr) and prefrontal cortex (PFC) of 6-hydroxydopamine-lesioned rats. RESULTS: L-DOPA (12 mg/kg, i.p.) increased DA extracellular levels to a lesser extent in the SNr, PFC and HIPP compared with the striatum. The NET blockers desipramine (10 mg/kg, i.p.) and reboxetine (3 mg/kg, i.p.) potentiated L-DOPA effect in the PFC, SNr and HIPP but not in the striatum. The NE neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg, i.p. 1 week before dialysis experiment) potentiated L-DOPA effect in the SNr and HIPP. 5-HT extracellular levels were enhanced only when L-DOPA was combined to NET blockers. CONCLUSION: Noradrenalin neurons are indirectly involved in the mechanism of action of L-DOPA in part through the heterologous reuptake of DA in extrastriatal regions.

A tobacco extract containing alkaloids induces distinct effects compared to pure nicotine on dopamine release in the rat.

It has been suggested that minor alkaloids in plants play a role in the biological and neuronal actions of nicotine. We hypothesized that these molecules modulate the effect of nicotine on the activity of central dopamine (DA) neurons, one of the main cellular targets in addiction to drugs. In this study the effect of a single intraperitoneal injection of either nicotine or an alkaloid extract of the tobacco plant (0.5 mg/kg) on the efflux of DA were investigated. DA was measured in vivo by intracerebral microdialysis in the nucleus accumbens and the striatum of freely-moving rats. Results show that nicotine enhanced accumbal and striatal DA extracellular levels (+47 and 20% above baseline, respectively). The extract also evoked a significant increase in DA extracellular levels in both regions (+33 and +38% above baseline). However, this effect was significantly higher compared to nicotine in the striatum only. In conclusion, the tobacco extract enhanced the neurochemical effect of nicotine alone in the striatum, a response that could underlie the higher propensity of developing addictive-like behavior using nicotine with tobacco alkaloids.

Physiological and pharmacological properties of 5-methoxytryptophol.

5-methoxytryptophol (5-ML) is a pineal indoleamine derived from serotonin shown to be biologically active in a number of species. This indolamine exhibits a circadian pattern synchronized with the day-night cycle with significant increases during daylight, already recognized in vertebrates. The multiplicity of physiological and endocrine functions of 5-ML is remarkable; it is involved in circadian rhythms, reproduction and sexual processes. Furthermore, a number of pharmacological benefits of 5-ML have been reported, including immunomodulatory, antitumor and antioxidative activities. However, the molecular mechanisms of these pharmacological effects remain unclear. The purpose of this article is to provide an overview on the general properties and physiological functions of 5-ML. An attempt has been made to fully document all studies performed using 5-ML. In addition, this article aims to gain insight into the current state of knowledge regarding pharmacological and therapeutic effects of this indoleamine.

Comparative study of the anti-inflammatory and antinociceptive effects of two varieties of Punica granatum.

CONTEXT: Studies have shown that pomegranate, Punica granatum Linn. (Lythraceae), has remarkable biological and medicinal properties. OBJECTIVE: This work aimed to explore and compare the analgesic and anti-inflammatory activities of the methanol extract (MoE) obtained from fruit peels of two varieties of pomegranate: Amrouz (MoEA) and Sefri (MoES). MATERIALS AND METHODS: Antinociceptive activity of MoEA and MoES was examined using four models of pain. The extracts were administered by the intraperitoneal route (i.p.) in writhing (50, 100 and 150 mg/kg) and formalin tests (25, 50 and 100 mg/kg) and by intra-cerebroventricular injection (i.c.v.) in hotplate and tail-immersion tests (10, 25 and 50 µg/3 µl/rat). anti-inflammatory activity was studied using the hind paw egg albumin test (50, 100 and 150 mg/kg, i.p.). RESULTS: In the writhing test, the index of pain inhibition (IPI) was 52% for MoEA (150 mg/kg, i.p.) and 29% for MoES (150 mg/kg, i.p.). In the formalin test, the IPI of early and late phase were, respectively, 75% and 82% for MoEA (100 mg/kg, i.p.) and 8% and 63% for MoES (100 mg/kg, i.p.). In the hotplate and tail-immersion test, MoEA and MoES increased in a dosedependent manner the reaction latency to the thermal stimuli. MoEA seems to be more potent than MoES. Only the analgesic effect of MoEA was partially inhibited by pretreatment with naloxone. Both extracts exerted a significant anti-inflammatory effect. DISCUSSION AND CONCLUSIONS: The results demonstrated that P. granatum contains active constituents, which possess antinociceptive and anti-inflammatory activity, justifying its popular uses.

Prenatal exposure to tobacco extract containing nicotinic alkaloids produces morphological and behavioral changes in newborn rats.

Tobacco exposure is not only a health concern for adults but has also been shown to exert deleterious effects on the health of the fetus, newborn, child, and adolescent. Decreased cognitive function, lower Intellectual Quotient (IQ) and deficits in learning and memory in children have been associated with maternal smoking during pregnancy. In this study, we have studied the effect of a tobacco plant extract on the growth and development in the rat. The extract contained relative proportions of alkaloids, including nicotine, purified by chemical separation. Pregnant rats received oral doses of either control (NaCl) or tobacco extract during the entire gestational period. Offspring length and body weight were measured. Each day, the offspring were observed for the following physical parameters: hair growth, incisor eruption and eye opening. The day of appearance of these developments was recorded. Before weaning, the offspring were examined to test their cliff avoidance response (6 postnatal day (PN)), surface righting reflex (05, 07, 13 postnatal day), swimming development (10, 12 postnatal day), negative geotaxis response (7,9,13 and 17 postnatal day) and jumping down choice cage (15, 17 postnatal day). Administration of tobacco extract to dams during the entire gestation period affects behavior and development in pups. The observed effects were a delay in opening eyes, incisor eruption and hair appearance, behavioral developments and an alteration in the rate of success behavior. However, in the jumping down choice cage test there was no difference compared to control animals. The results suggest that tobacco extract has a significant effect on the development of behavioral patterns, orientation and motor coordination and function. They also suggest significant growth retardation and teratogenic effects.