PubMed Health⌕ Search

Biomedical subjects

Joseph Vamecq

Publications and source records attributed to Joseph Vamecq.

8 recordsLinked to original sources
PubMed2005

Antiepileptic popular ketogenic diet: emerging twists in an ancient story.

The antiepileptic activity associated with ketogenic diets (KD) have been known for some time. First reports date back to the Middle Ages and even Biblical times where KD was achieved by fasting (i.e. "water diet") [see Swink, T.D., Vining, E.P.G., Freeman, J.M., 1997. The ketogenic diet: 1997. Adv. Pediatr. 44, 297-329, and references therein]. In the early 20th century, changes in the design of the KD were introduced, shifting the so-called "water diet" to a high-fat diet. Initial clinical evaluations undertaken between the 1920s and 1940s were enthusiastic, but the popularity of the KD was retrograded upon clinical introduction of phenytoin and subsequently other antiepileptic drugs. Today, despite a pharmacological arsenal targeting cerebral receptors and specific events in seizure initiation and development, about 30-40% patients are still refractory to available medications. Thus, the KD has been re-introduced in recent years as an alternative therapy, averring to be efficacious against some instances of resistant or intractable epilepsy. Despite a long historical background and enlarged clinical use, identification of the underlying anticonvulsant mechanisms associated with this nonpharmacological approach is still in stagnation. The present review is an attempt to encourage current research orientation through well-based and directed proposals for putative emerging candidates mediating KD anticonvulsant mechanisms. The reader is provided with a special emphasis on ATP-sensitive and recently cloned two-pore (or tandem) domain potassium channels, as well as several emerging conceptual views and advances such as nuclear receptors, uncoupling proteins and gap junctions that the authors speculate may contribute to understanding the basic mechanisms linked to the KD.

Brain Chemistry↗
PubMed2004

[The auto-addictive hypothesis of pathological eating disorders].

The pathogenic role of self-addiction. Addiction to an endogenous chemical is a new paradigm termed 'self-addiction'. It may contribute to the development of certain habits, the pathological nature of which may set-in on the basis of this "self-addictive"dimension. Pathological eating habits could be inscribed in this perspective. Two extreme situations. In well-fed populations, the ingestion of food does not represent a limiting phase in the global feeding process. Its pathological management may, however, lead to two extreme situations: the absence of ingestion (anorexia) and excessive ingestion (bulimia). In favour of the self-addictive hypothesis. Eating disorders are associated with abnormal levels of endorphins and share clinical similarities with psychoactive drug abuse. The key role of endorphins has recently been demonstrated in animals with regard to certain aspects of normal, pathological and experimental eating habits (food restriction combined with stress, locomotor hyperactivity). The factors leading to pathological eating habits. Neurobiological bases for eating disorders and their durability have recently come to light in the recent implication of abnormalities in the recompense system in the onset of addiction. The endorphin self-addictive model in fact appears the most pertinent with regard to the clinical profile of eating habits and integrates the role of stress.

Behavior, Addictive↗
PubMed2004

The neuroprotective effect of the antioxidant flavonoid derivate di-tert-butylhydroxyphenyl is parallel to the preventive effect on post-ischemic Kir2.x impairment but not to post-ischemic endothelial dysfunction.

In the rat model of transient cerebral ischemia induced by intraluminal occlusion of the middle cerebral artery, we investigated the respective roles of ischemia and reperfusion in endothelium-dependent relaxation and smooth muscle relaxation related to the inward rectifier potassium current (Kir2.x), using the Halpern arteriography technique and/or patch-clamp technique. We first demonstrated that reperfusion is necessary to induce a significant impairment of smooth muscle Kir2.x, since ischemia alone has no effect on Kir2.x current density and function. In addition, we demonstrated that both ischemia and reperfusion are necessary for the occurrence of maximal post-ischemic endothelial dysfunction. The crucial role of reperfusion in post-ischemic vascular impairment prompted us to characterize the effect of a new antioxidant synthetic flavonoid derivate, 3'5'di- tert-butylhydroxyphenyl (dt-BC), on both neuronal and vascular injuries. Dt-BC (10 mg/kg) induced a neuroprotective effect as demonstrated by a significant decrease in infarct size, while there was no protective effect with the doses of 3 mg/kg and 30 mg/kg. Parallel to neuroprotection, dt-BC at a dose of 10 mg/kg, but not with doses of 3 mg/kg and 30 mg/kg, prevented post-ischemic impairment of smooth muscle Kir2.x current density and function, while dt-BC had no effect on the post-ischemic alteration of endothelial function whatever doses are used. These data demonstrate the potential of a new synthetic flavonoid derivate to induce neurovascular protection and support a possible relationship between vascular and neuronal protection via pharmacological modulation of oxidative stress.

Animals↗
PubMed2003

Potent mammalian cerebroprotection and neuronal cell death inhibition are afforded by a synthetic antioxidant analogue of marine invertebrate cell protectant ovothiols.

Implicit strategies for neuroprotection in the adult brain include GABAA receptor activation, N-methyl-d-aspartate receptor and sodium voltage-gated channel inhibition. Ironically, these same targets may be harmful to the immature or developing brain. Protection has been demonstrated for both immature and mature brain with the use of a synthetic ovothiol analogue. The following beneficial effects have been demonstrated in mice: protection against audiogenic seizures, brain structures with clear-cut delineation of ibotenate-challenged white and grey matter lesions along with exceptional early and delayed protections, and potent cerebral cell death inhibition. The compound lacks both GABAergic activity and sodium channel blocker properties, which may help explain the lack of toxicity normally expressed in an immature brain utilizing these agents [J.W. Olney (2002) Neurotoxicology, 93, 1-10]. The oxidized form of the compound is virtually devoid of antioxidant activity. In vivo it exhibits cerebroprotective properties similar to those of reduced compounds endowed with antioxidant properties. This unexpected finding has prompted an extensive in vitro exploration of underlying molecular mechanisms that have led to the identification of several recycling mechanisms consistent with non rate-limiting conversion of oxidized to reduced compound forms. Taken as a whole, this work offers an unique combined in vitro and in vivo support that: (i). antioxidant therapy, here engineered from marine invertebrate egg protectants, may be a valuable strategy in protecting both mammalian adult and developing brain; and (ii). recycling (thiol-disulphide exchange) properties of the oxidized form of an antioxidant compound are as important as the antioxidant potential exhibited by a bioactive reduced antioxidant in certain neuroprotective processes.

Animals↗
PubMed2002

Melatoninergic neuroprotection of the murine periventricular white matter against neonatal excitotoxic challenge.

Periventricular leukomalacia is one of the main causes of cerebral palsy. Perinatal white matter lesions associated with cerebral palsy appears to involve glutamate excitotoxicity and excess free radical production. When injected intracerebrally into newborn mice, the glutamatergic analog ibotenate induces white matter cysts mimicking human periventricular leukomalacia. Melatonin acts on specific receptors. It also exhibits intrinsic free radical scavenging properties. The goal of the present study is to determine whether melatonin can protect against excitotoxic lesions induced by ibotenate in newborn mice. Mice that received intraperitoneal melatonin had an 82% reduction in size of ibotenate-induced white matter cysts when compared with controls. Although melatonin did not prevent the initial appearance of white matter lesions, it did promote secondary lesion repair. Axonal markers supported the hypothesis that melatonin induced axonal regrowth or sprouting. The protective effects of melatonin were suppressed by coadministration of luzindole, a melatonin receptor antagonist. Forskolin, an adenylate cyclase activator, prevented the protective effects of melatonin; inhibitors of protein kinase C and mitogen-associated protein kinase had no detectable effect. Melatonin and derivatives that block cAMP production through activation of melatonin receptors could represent new avenues for treating human periventricular leukomalacia.

Animals↗
PubMed2002

THC aggravates rat muricide behavior induced by two levels of magnesium deficiency.

A severe magnesium deprivation induces an interspecific aggressive behavior (muricidal behavior, MB) in different strains of rats. Delta9-tetrahydrocannabinol (THC) is also known to induce MB even after a single injection (11 mg/kg) in starving, isolated rats. In the present work, we investigated the MB behavior, for six successive assays 1 h delayed, of two groups of male Long-Evans rats fed 50- or 150-ppm Mg(2+)-deficient diets, for 42 days after a single injection of THC at doses (2, 4 or 8 mg/kg) that did not induce aggressiveness in control rats. This treatment led to Mg(2+) plasma levels of 5+/-0.3 and 12.3+/-0.9 mg/ml vs. 21+/-1.5 mg/ml initially. In the 50-ppm Mg-deficient rat group, all the rats were muricidal but the MB pattern was severely aggravated by THC. In the 150-ppm Mg-deficient rat group, no rat was muricidal but all doses of THC induced a 100% MB. In addition, by quantifying the three phases of MB, we showed through six consecutive hourly muricidal assays, that the two first phases (attack latency and attack on the living mouse) decreased progressively, whereas the third phase (attack on the dead mouse) increased dramatically. This indicates firstly that Mg-deprivation decreases the responsiveness threshold of rats to THC. Secondly, these very low doses of THC induced an aggravation of MB and an acquired hyper-aggressiveness in both 50- and 150-ppm Mg-deficient rats, probably involving different neurotransmitters, mainly serotonin, which is decreased by both treatments.

Aggression↗