Antiseizure effects of Anacyclus pyrethrum in socially isolated rats with and without a positive handling strategy.

OBJECTIVE: Aqueous extract of Anacyclus pyrethrum (AEAPR) is used in traditional medicine to treat epilepsy, but whether it has antiseizure properties has not been established. Because extracts of the plant have antioxidant properties, we hypothesized that it may be particularly potent in conditions associated with oxidative stress, in particular social isolation. METHODS: We addressed these objectives in the pilocarpine experimental model of epilepsy using socially isolated rats maintaining contacts with (handled) and without (unhandled) positive handling strategy. Both groups were further divided into treated (AEAPR was added to the drinking water) and untreated groups. Continuous (24/7) electroencephalography (EEG) recordings started in the sixth week after status epilepticus (SE) with a predrug control period of 3 weeks, followed by 3 weeks of daily treatment with AEAPR or water, and finally a postdrug control period of 3 weeks. At the end of the experimental procedure, we measured lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities in the hippocampus to assess oxidative stress. RESULTS: A. pyrethrum treatment significantly reduced seizure frequency by 51% and 57%, duration by 30% and 33%, and severity by 31% and 26% in isolated handled and unhandled rats, respectively. The beneficial effects on seizures were still present 3 weeks after the end of the treatment. The treatment reduced lipid peroxidation as well as SOD, GPx, and catalase activities. SIGNIFICANCE: We conclude that A. pyrethrum has antiseizure and antioxidant properties, even in social isolation conditions.

Anticonvulsive and neuroprotective effects of aqueous and methanolic extracts of Anacyclus pyrethrum root in kainic acid-induced-status epilepticus in mice.

PURPOSE: Epilepsy is a chronic neurological disorder characterized by spontaneous and recurrent seizures. The currently available synthetic antiepileptic drugs have a limited efficacy and are associated with a wide range of side effects. In Ayurveda, Anacyclus pyrethrum root (APR) has been used as a traditional antiepileptic remedy. The aim of the present study is to evaluate the anticonvulsive and neuroprotective effects of aqueous and methanol extracts of Anacyclus pyrethrum root (AEAPR and MEAPR) on experimental model of status epilepticus (SE). METHODS: Twenty four male mice were divided into four groups. The control and KA groups had free access to tap water for 5 days before the intraperitoneal injection of distillated water or kainic acid (KA; 30 mg/kg), respectively. In the treated groups, mice received extracts solutions MEAPR and AEAPR in drinking water at the concentration of 5 g/l for 5 days. At the fifth day, animals received intraperitoneal injection of KA. The behavioral changes latency of seizures, the number of wet dog shakes (WDS) and the mortality were observed over 6 h. Thereafter, the mice were sacrificed for immunohistochemical studies. RESULTS: Pretreatment with MEAPR and AEAPR decreases significantly the frequency of WDS (32.5% and 43.9%, p < 0.01; respectively), and increases considerably the latent period (77.9% and 91.9%, p<0.01; respectively) between the injection of the KA and the appearance of the SE as compared to the KA group. The duration and severity of seizure in the MEAPR or AEAPR-pretreated groups were significantly lower (p < 0.01 and p < 0.05 or p < 0.01; respectively) than those in the KA group. These behavioral results were confirmed by the immunohistochemical study at the level of the hippocampus, in which the c-FOS and GFAP expression of both MEAPR and AEAPR-treated animals largely reduced (p < 0.001) the number of labelled cells with respect to the group, which received the KA alone. CONCLUSION: Our results showed that the MEAPR and AEAPR have anticonvulsive effect and putative neuroprotective effect against seizures induced by KA. Further studies are required to identify its active ingredients responsible for the observed effects.

High-frequency stimulation of the infralimbic cortex, following behavioral suppression of PTSD-like symptoms, prevents symptom relapse in mice.

BACKGROUND: We have previously demonstrated, in mice, that antidepressant treatment can prevent relapse of PTSD-like behaviors (avoidance, hyperarousal, and anxiety) through increased activation in the infralimbic cortex (IL) of the medial prefrontal cortex. OBJECTIVE: Here, we examined whether direct high-frequency stimulation (HFS) of the IL, provoking its heightened activation (i.e., long-term potentiation, LTP), would also prevent the return of PTSD-like symptoms. METHODS: A 1.5-mA foot-shock was used to generate PTSD-like symptoms in Swiss mice. In Experiment 1, local field potentials were recorded in the IL to test whether normal IL LTP can be induced after the suppression of PTSD-like symptoms. In Experiment 2, IL HFS was applied after symptom suppression, but prior to the provocation of relapse, to test HFS effect on symptom return. RESULTS: We observed that PTSD-like state was associated with impairment in IL HFS-induced IL LTP. However, IL LTP induction was near normal when PTSD-like symptoms were suppressed. We then found that IL HFS, applied after symptom suppression, prevented symptom return. CONCLUSIONS: Increased activation of the IL may be a key mechanism preventing PTSD relapse. Prefrontal cortex deep brain stimulation may, therefore, be relevant for preventing PTSD symptom return in remitted high-risk patients.

Anti-inflammatory, Antinociceptive, and Antioxidant Activities of Methanol and Aqueous Extracts of Anacyclus pyrethrum Roots.

Anacyclus pyrethrum (L.) is a plant widely used in Moroccan traditional medicine to treat inflammatory and painful diseases. The objective of the present study was to evaluate the antinociceptive, anti-inflammatory and antioxidant activities of aqueous and methanol extracts of Anacyclus pyrethrum roots (AEAPR and MEAPR). The anti-inflammatory effect of AEAPR and MEAPR was determined in xylene-induced ear edema and Complete Freund's Adjuvant (CFA)-induced paw edema. The antinociceptive activity of AEAPR and MEAPR (125, 250, and 500 mg/kg) administered by gavage was examined in mice by using acetic acid-induced writhing, hot plate, and formalin tests, and the mechanical allodynia were assessed in CFA-induced paw edema. In addition, the in vitro antioxidant activities of the extracts were determined by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method, ferric reducing power and ß-carotene-linoleic acid assay systems. AEAPR and MEAPR produced significant reductions in CFA-induced paw edema and xylene-induced ear edema. A single oral administration of these extracts at 250 and 500 mg/kg significantly reduced mechanical hypersensitivity induced by CFA, which had begun 1 h 30 after the treatment, and was maintained till 7 h. Chronic treatment with both extracts significantly reduced mechanical hypersensitivity in persistent pain conditions induced by CFA. Acute pretreatment with AEAPR or MEAPR at high dose caused a significant decrease in the number of abdominal writhes induced by acetic acid injection (52.2 and 56.7%, respectively), a marked increase of the paw withdrawal latency in the hot plate test, and also a significant inhibition of both phases of the formalin test. This antinociceptive effect was partially reversed by naloxone pretreatment in the hot plate and formalin tests. Additionally, a significant scavenging activity in DPPH, reducing power and protection capacity of ß-carotene was observed in testing antioxidant assays. The present study suggests that AEAPR and MEAPR possess potent anti-inflammatory, antinociceptive and antioxidant effects which could be related to the presence of alkaloids and phenols in the plant. In addition, the antinociceptive effect of APR extracts seems to partly involve the opioid system. Taken together, these results suggest that Anacylcus pyrethrum may indeed be useful in the treatment of pain and inflammatory disorders in humans.

[Malignant infantile osteopetrosis revealed by choanal atresia: A case report]. / Ostéopétrose maligne infantile révélée par une atrésie des choanes : à propos d'un cas.

Malignant infantile osteopetrosis is a rare genetic disease characterized by increased bone density due to osteoclastic dysfunction. We report on the case of a 3-month-old girl who was referred to our hospital by the ENT department for severe anemia in the context of bilateral choanal atresia. Clinical examination showed failure to thrive, anemia, respiratory distress, bilateral choanal atresia, and chest deformation. The abdomen was soft with large hepatosplenomegaly. We noted a lack of eye tracking, no optical-visual reflexes, and left nerve facial paralysis. The blood count showed normocytic normochromic anemia with severe thrombocytopenia. The infectious work-up and blood smears were negative. The skeleton X-ray showed diffuse bone densification of the skull, long bones, pelvis, vertebrae, and ribs. The facial bone CT confirmed membranous choanal atresia. The molecular biology search for the TCIRG1 gene mutation was not available. The patient had supportive treatment (transfusion, oral steroid, vitamin D, oxygen, nutrition). Bone marrow transplantation was indicated but not available. She died at 6 months in a context of severe anemia and bleeding. Malignant infantile osteopetrosis is rare and symptoms are nonspecific. Diagnosis should be considered in young infants presenting refractory anemia, particularly in the context of choanal atresia. Bone marrow transplantation remains the only curative treatment.

Behavioral and cognitive changes after early postnatal lesions of the rat mediodorsal thalamus.

Early insults to the thalamus result in functional and/or structural abnormalities in the cerebral cortex. However, differences in behavioral and cognitive changes after early insult are not well characterized. The present study assessed whether early postnatal damage to mediodorsal nucleus of the thalamus (MD), reciprocally interconnected with the prefrontal cortex, causes behavioral and cognitive alterations in young adult rats. Rat pups at postnatal day 4 received bilateral electrolytic lesion of MD, or a MD Sham lesion or were anesthetized controls; on recovery they were returned to their mothers until weaning. Seven weeks later, all rats were tested with the following behavioral and cognitive paradigms: T-maze test, open field test, actimetry, elevated plus maze test, social interactions test and passive avoidance test. Rats with bilateral MD damage presented with disrupted recognition memory, deficits in shifting response rules, significant hypoactivity, increased anxiety-like behavior, deficits in learning associations as well as decreased locomotor activity, and reduced social interactions compared to MD Sham lesion and anesthetized Control rats. The lesion also caused significant decreases in pyramidal cell density in three frontal cortex regions: medial infralimbic cortex, dorsolateral anterior cortex, and cingulate Cg1 cortex. The present findings suggest a functional role for MD in the postnatal maturation of affective behavior. Further some of the behavioral and cognitive alterations observed in these young adult rats after early MD lesion are reminiscent of those present in major psycho-affective disorders, such as schizophrenia in humans.

[Treatment of child hydrocephalus by endoscopic third ventriculostomy in Senegal]. / Traitement de l'hydrocéphalie de l'enfant par ventriculocisternostomie endoscopique au Sénégal.

INTRODUCTION: Since its advent, endoscopic third ventriculostomy (ETV) has been an effective alternative to shunt placement for the treatment of hydrocephalus. The aim of this study was to report the results of our experience with this technique in children in Senegal. MATERIALS AND METHODS: This was a retrospective study of 70 cases of children aged between 5 months to 15 years who were treated by ETV in the Neurosurgery Department of Fann Hospital in Dakar, between January 2010 to December 2012. The results were evaluated based on the clinical criteria of Drake and the Canadian Pediatric Neurosurgery Study Group. The mean follow-up duration was 24 months (9-32 months). RESULTS: The mean age at diagnosis was 29 months. A male predominance (sex-ratio 1/3) was observed. We also noted a macrocephaly in 64.4 % of cases, psychomotor retardation in 40 % and decreased vision in 31.4 %. Headache and vomiting were found in 42.8 % and 61.4 % respectively. The main etiology was a stenosis of the mesencephalon aqueduct (30 %), followed by a Dandy-Walker malformation (25.7 %). Significant intraoperative bleeding was found in 2.8 % of patients. The most common postoperative complication was CSF leakage (18.6 %), followed by infections (14.2 %). The success rate according to the clinical criteria of Drake was 71.4 %. This success rate was influenced by the age of patients and the hydrocephalus etiology. No deaths occurred. CONCLUSION: The endoscopic third ventriculostomy is a simple, safe and effective technique. Its advantages in terms of quality of life and morbidity compared with bypass valves makes it the technique of choice, particularly in developing countries.

Insecticidal properties and chemical composition of essential oils of some aromatic herbs from Morocco.

The essential oils (EOs) of Artemisia herba alba, Rutachalepensis and Satureja calamintha aerial parts were analysed by GC/MS and the EOs were tested for their toxicity against two flour beetles, Tribolium castaneum and Tribolium confusum. EO composition showed that the major compounds were pulegone, menthone and menthol for S. calamintha, camphor and ß-thujone for A. herba alba and 2-undecanone for R. chalepensis. Contact bioassay showed that all EOs were toxic to adults of T. castaneum and T. confusum. Higher toxicity was found with the EOs from S. calamintha and R. chalepensis (LD50 of 0.09-0.13 µL/cm(2) and LD90 of 0.17-0.29 µL/cm(2)). In fumigant toxicity test, A. herba alba and S. calamintha EOs produced insecticidal activity with S. calamintha EO being more toxic with LD50 and LD90 values of 10.5 and 19.1 µL/L air, respectively, for T. confusum against 7.8 and 17.4 µL/L air, respectively, for T. castaneum.

Prenatal exposure to fenugreek impairs sensorimotor development and the operation of spinal cord networks in mice.

Fenugreek is a medicinal plant whose seeds are widely used in traditional medicine, mainly for its laxative, galactagogue and antidiabetic effects. However, consumption of fenugreek seeds during pregnancy has been associated with a range of congenital malformations, including hydrocephalus, anencephaly and spina bifida in humans. The present study was conducted to evaluate the effects of prenatal treatment of fenugreek seeds on the development of sensorimotor functions from birth to young adults. Pregnant mice were treated by gavage with 1 g/kg/day of lyophilized fenugreek seeds aqueous extract (FSAE) or distilled water during the gestational period. Behavioral tests revealed in prenatally treated mice a significant delay in righting, cliff avoidance, negative geotaxis responses and the swimming development. In addition, extracellular recording of motor output in spinal cord isolated from neonatal mice showed that the frequency of spontaneous activity and fictive locomotion was reduced in FSAE-exposed mice. On the other hand, the cross-correlation coefficient in control mice was significantly more negative than in treated animals indicating that alternating patterns are deteriorated in FSAE-treated animals. At advanced age, prenatally treated mice displayed altered locomotor coordination in the rotarod test and also changes in static and dynamic parameters assessed by the CatWalk automated gait analysis system. We conclude that FSAE impairs sensorimotor and coordination functions not only in neonates but also in adult mice. Moreover, spinal neuronal networks are less excitable in prenatally FSAE-exposed mice suggesting that modifications within the central nervous system are responsible, at least in part, for the motor impairments.

The developmental neurobehavioral effects of fenugreek seeds on prenatally exposed mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Fenugreek (Trigonella foenum graecum (L.)), is a medicinal plant whose seeds and leaves are widely used in Moroccan traditional medicine. Consumption of fenugreek seeds during pregnancy has been associated with a range of congenital malformations, including hydrocephalus, anencephaly and spina bifida. In previous work we have shown that exposure of pregnant mice to aqueous extract of fenugreek seeds (AEFS) leads to reduced litter size, intrauterine growth retardation, and malformations. However, there have been no studies to date of its longer-term neurobehavioral effects. We investigated these effects in prenatally exposed mice. MATERIALS AND METHODS: Pregnant females were exposed to 0, 500 or 1000 mg/kg/day AEFS, by gavage, for the whole period of gestation. Pups body weight was measured at 1, 7, 14, 21 and 28 day of age. Behavior of progeny was evaluated three weeks after birth using the open field, the rotarod test and the continuous alternation task by the T-maze. At 28 postnatal day age, brain of progeny was removed and cut for histological evaluation. RESULTS: The progeny of exposed mice displayed reduced body weight at birth (1000 mg/kg group: 27%; 500 mg/kg group: 32%) and reduced brain weight (10% in both treated groups). Both males and females mice prenatally exposed to AEFS displayed a significant decrease in the locomotor activity, in the boli deposits during the open field test and in motor coordination. These results seem to show that exposure to AEFS induces a depressive effect in the offspring. Assessment on a continuous alternation T-maze test showed a significant reduction in successful spontaneous alternations in males and females but only in the 1000 mg/kg group. CONCLUSION: These results suggest that prenatal exposure of mice to high dose of fenugreek seeds causes growth retardation and altered neurobehavioral performance in the post-weaning period in both male and female.

Prospective, randomized trial comparing 5-FU/LV with or without oxaliplatin as adjuvant treatment following curative resection of gastric adenocarcinoma.

BACKGROUND: To investigate the efficacy and toxicity of FOLFOX4 regimen and LV5Fu2 regimen in patients with advanced gastric adenocarcinoma after curative gastrectomy. METHODS: Eighty patients with gastric adenocarcinoma after curative gastrectomy were randomized to receive a 2-h infusion of leucovorin (LV; 200mg/m(2)/d) followed by a 5-fluorouracil (5-FU) bolus (400mg/m(2)/d) and 22-h infusion (600 mg/m(2)/d) for 2 consecutive days every 2 weeks, either alone or together with oxaliplatin 85 mg/m(2) as a 2-h infusion on day 1 (FOLFOX4 regimen or LV5Fu2 regimen). The observation points were recurrence free survival, overall survival and toxicity of the two groups. RESULTS: All patients had received curative gastrectomy (R0 resection) before received either of the two regimens. The 3-year recurrence free survival rate and the 3-year overall survival rate in FOLFOX4 group were all significantly better than those in the control group (median, 30.0 months vs. 16.0 months, P<0.05; 36.0 months vs. 28.0 months, P<0.05). COX multivariant analysis was used to evaluate the prognostic factors and oxaliplatin was found to be the independent prognostic factor and could improve the survival rate in FOLFOX4 group. Grade 3/4 peripheral neuropathy occurred in 19% in FOLFOX4 group. There was no significant difference between the two groups in neutropenia, leukopenia, anemia, gastrointestinal reaction and so on. Three patients in each group were lost to follow up during treatment. CONCLUSION: FOLFOX4 regimen showed good efficacy and an acceptable safety profile for patients with advanced gastric adenocarcinoma after curative gastrectomy compared with the control group. It may prove to be a suitable alterative regimen in this indication.

[Evaluation of integrated management of childhood illness three years after implementation in a health care district in Senegal]. / Evaluation de la Prise en Charge Intégrée des Maladies de l'Enfant dans un district du Sénégal après 3 ans de mise en place.

The strategy of Integrated Management of Childhood Illness (IMCI) has been recommended by both WHO and UNICEF for first-level health facilities to control the main childhood diseases in developing countries. In Senegal, IMCI was adopted in 1996 and had been implemented in several pilot health districts by the year 2000. This study was conducted three years after implementation of IMCI in the Darou Mousty health district. The purpose was to evaluate determinant factors for implementation as well as the required skills of personnel. Evaluation was based on a review of IMCI records at health care facilities in the District and a survey to collect the opinion of healthcare workers involved in the program. All qualified personal, i.e. two doctors, eleven nurses and one midwife at the time of the survey, had received training in the IMCI approach. Although they all stated that this training improved their skills in managing paediatric patients, only 16 % used the approach on a regular basis. The most frequently reported reason for non-use was unwieldiness of IMCI procedures. According to IMCI guidelines, proper procedures were used in only 53 of the 1465 children (3.6%) who consulted during the study period. This low compliance rate was due to the inability of healthcare personnel to apply therapeutic protocols, plan appointments or identify emergency cases. These findings suggest that basic training and in-service courses must place greater emphasis on IMCI procedures and that regular supervision is needed to optimize this strategy in Senegal.

[Etiologic factors of prematurity in Ziguinchor maternity hospital center (Senegal)]. / Facteurs étiologiques de la prématurité au centre hospitalier régional de Ziguinchor, Sénégal.

A case-control study was conducted between September 2003 and January 2004. Fifty four newborn babies born before 37 weeks of gestation resulting from 47 pregnancies including 7 multiple pregnancies were compared to 105 newborn babies born between 37 and the 42 weeks of gestation. Parturient geographical origin, marital status, age, alcohol or tea consumption and height were not significantly associated to premature birth (p > 0.05). On the other hand, a higher parity or equal to 3, a number of antenatal care lower than 3 were significantly associated with the risk of premature birth (p < 0.05). But a gestity and a parity lower than 3 and a number of antenatal consultations higher or equal to 3 had a protective effect (OR < 1; p < 0.05). We recommend a reinforcement of malarial prevention during pregnancy according to WHO recommendations and the improvement of the quality of the antenatal care in the Ziguinchor medical district.

The distribution of NPY-like immunoreactivity in the chameleon brain.

The distribution of neuropeptide Y (NPY) immunoreactivity was studied in the brain of the chameleon. Cell bodies and fibers displaying NPY-like immunoreactivity were widely dispersed throughout the brain and at the highest density in the telencephalon and diencephalon. Immunolabeled cell bodies were numerous in the medial and dorsomedial cortex and in the dorsal ventricular ridge, while the striatum and basal telencephalon only contained sparsely scattered NPY-positive somata. Immunopositive neurons were densely distributed in the dorsal thalamus (particularly in the perirotundal belt), the area triangularis, the nucleus geniculatus lateralis pars dorsalis, the periventricular hypothalamus and the medial eminence. In the pretectum, NPY-immunoreactive cell bodies were limited to the nucleus posterodorsalis, while in the mesencephalon immunolabeled somata were found in the stratum album centrale of the optic tectum and in the substantia nigra. Immunopositive fibers and terminals were particularly dense in the dorsomedial cortex, the periventricular hypothalamus, the nuclei accumbens, suprachiasmaticus and griseus tectalis, in the substantia nigra and in the torus semicircularis. These findings show that the NPY system in the chameleon has the same basic organization as in other vertebrate species, and indicate that this peptide could be also implicated in the regulation of several aspects of cerebral functions. In addition, and of particular interest, is the observation of numerous NPY-immunoreactive neurons and fibers in several visual nuclei, suggesting an important involvement of this substance in the visual function.

Immunocytochemical detection of fos protein combined with anterograde tract-tracing using biotinylated dextran.

The present report deals with an axonal tract-tracing procedure in rat enabling visualization of anterogradely transported biotinylated dextran amine (BDA) combined with immnunocytochemical detection of Fos protein following electrical stimulation of the brain. This method allows us to evaluate whether a given structure, receiving both injection of BDA and electrical stimulation, elicits neuronal activation in another part of the brain via direct or indirect projections. We have used the method at the light microscopic level to determine the connectivity of the sensorimotor cortex in the rat. In various parts of the forebrain and brainstem, BDA-labeled fibers originating from the cortex were observed in close apposition to Fos-like immunoreactive cells (FLI) activated by stimulation. This result suggests a direct (probably monosynaptic) projection. On the contrary, FLI neurons were observed in areas devoid of direct afferents, indicating a cascade of activations. The method described in this protocol is applicable for functional anatomy purposes elsewhere within the central nervous system. It constitutes a preliminary step in identifying the validity of a pathway before examination of the reality of the monosynaptic relationship at the electron microscopic level.

Distribution of cortical fibers and fos immunoreactive neurons in ventrolateral medulla and in nucleus tractus solitarius following the motor cortex stimulation in the rat.

The present study demonstrates that the motor cortex (MC) stimulation induces expression of Fos-like immunoreactivity (FLI) in the rostro-caudal parts of ventrolateral medulla (VLM) and nucleus tractus solitarius (NTS). The coupling of biotinylated dextran (BD) injections with the MC stimulation also permits to identify cortical labeled fibers in the vicinity of FLI neurons in the VLM. Results suggest that the MC is involved in a direct and an indirect modulation of bulbar cardiovascular nuclei.

Fronto-parietal control of electrodermal activity in the cat.

The aim of this work was to investigate the direct involvement of the fronto-parietal cortex in the control of spinal autonomic centers eliciting electrodermal activity (EDA). This autonomic response, linked with the activity of sweat glands, was recorded as skin potential responses (SPRs) from forepaws in the cat. Animals were paralyzed by gallamine and SPRs were obtained under halothane anaesthesia. For each animal, a transection of the medulla sparing only pyramidal tracts was carried out. SPRs were elicited by direct electrical stimulation of pericruciate and posterior parietal cortical areas before and after such a transection. Results showed that in intact preparations, stimulation of the pericruciate cortex evoked SPRs at lower thresholds than the posterior parietal cortex. After the bulbar transection, only the stimulation of pericruciate areas still elicited SPRs at low intensities. Results are interpreted as indicating that fronto-parietal control of EDA is probably mediated by a double descending system: one involving corticoreticulospinal pathways and a direct corticospinal one. We hypothesized that the somatic motor cortex initiates descending programs to autonomic centers at bulbar and spinal levels, and that these centers are involved in autonomic adjustments to somatomotor movements.