Neuroprotective Effects of a Variety of Pomegranate Juice Extracts (PJE) Against the Excitotoxin Quinolinic Acid in Human Primary Neurons.

BACKGROUND: Quinolinic acid (QUIN) excitotoxicity is mediated by elevated intracellular Ca2+ levels, and nitric oxide (NO•) mediated oxidative stress leading to DNA damage, and cell death due to energy restriction. METHODS: We evaluated the effect of a series of pomegranate juice extracts (PJE), Helow, Malasi, Qusum, and Hamedh, with antioxidant properties on QUIN induced excitotoxicity on primary cultures of human neurons. RESULTS: We showed that Helow and Malasi can attenuate QUIN-induced excitotoxicity to a greater extent than Qusum and Hamedh from Oman. Similarly, both Helow and Malasi were able to attenuate QUIN-induced Ca2+ influx and nNOS activity to a greater extent compared to Qusum, and Hamedh. All extracts reduced the oxidative effects of increased NO• production, and hence preventing NAD+ depletion and cell death. CONCLUSION: In addition to the well-known antioxidant properties of these natural phytochemicals, the inhibitory effect of some of these compounds on specific excitotoxic processes such as calcium influx provides additional evidence for the beneficial health effects of PJE in excitable tissue, particularly within the CNS.

Excitotoxicity in the pathogenesis of autism.

Autism is a debilitating neurodevelopment disorder characterised by stereotyped interests and behaviours, and abnormalities in verbal and non-verbal communication. It is a multifactorial disorder resulting from interactions between genetic, environmental and immunological factors. Excitotoxicity and oxidative stress are potential mechanisms, which are likely to serve as a converging point to these risk factors. Substantial evidence suggests that excitotoxicity, oxidative stress and impaired mitochondrial function are the leading cause of neuronal dysfunction in autistic patients. Glutamate is the primary excitatory neurotransmitter produced in the CNS, and overactivity of glutamate and its receptors leads to excitotoxicity. The over excitatory action of glutamate, and the glutamatergic receptors NMDA and AMPA, leads to activation of enzymes that damage cellular structure, membrane permeability and electrochemical gradients. The role of excitotoxicity and the mechanism behind its action in autistic subjects is delineated in this review.

Effect of ivermectin on combined intestinal protozoal infection (giardiasis and cryptosporidiosis).

Ivermectin, a broad spectrum antiparasitic agent has become a promising drug for treating parasitic infection and infestation. This study was carried out to investigate its activity against two common protozoal infection, giardiasis and cryptsporidiosis in a rat model. The results of this study showed that ivermectin therapy is effective against both parasites at a dose of 200 micrograms/kg.

Rett syndrome: a mitochondrial disease?

Six girls between 2 years 9 months and 15 years of age with Rett syndrome were thoroughly investigated. Blood ammonia levels varied between 42 and 123 mumol/L, and serum lactate concentration was slightly elevated in two girls. Electroencephalograms showed a dysrhythmic pattern during wakefulness; during drowsiness and light sleep, bilateral bursts of spike or multispike-and-wave activity were seen in all but the oldest girl. In one of the younger girls, slight cortical atrophy was found on computed tomographic scan. Muscle biopsy was performed on all girls, and electron microscopy revealed abnormal mitochondria. Physical signs such as somatic hypotrophy with extremely small muscle mass, and unsatisfactory weight gain in spite of good appetite are found in Rett syndrome. These attributes, as well as reports of ornithine carbamoyltransferase deficiency, may support a mitochondrial dysfunction. The mitochondrial changes indicate either a mitochondrial mutation or more probably an X-borne modulator gene mutation. Another genetic possibility discussed is the "metabolic interference" of an X-borne allele. Further delineation of such mitochondrial changes may clarify the causal metabolic defect in Rett syndrome.

Intervertebral discitis in childhood.

Many paediatricians are unaware of the disease entity of discitis, which must be included in the differential diagnosis of several acute and subacute diseases of infancy and childhood. In order to draw attention to this disorder, three Swedish and two Arabic children, aged from 9 months to 3 years, are jointly presented. The onset of symptoms was 2-4 weeks prior to admission. The clinical diagnosis was verified by plain X-ray of the spine and bone scanning. Two of the children had low grade fevers. The erythrocyte sedimentation rates were moderately elevated, while white blood cell counts were normal or slightly increased. Blood cultures were negative. The children were treated with immobilization, and three of them received antibiotics. Full recovery was achieved in all children after 1-2 months. The diagnostic procedure and the rationale of using or not using antibiotic treatment is discussed.

Abnormal mitochondria in the Rett syndrome.

Two girls with Rett syndrome were investigated including muscle biopsy. The electron microscopy study revealed abnormally swollen and dumb-bell shaped mitochondria. Based on the findings of mitochondrial changes it can be assumed that such changes are due to a mitochondrial mutation steered by an X-borne gene mutation. As a result and because the mitochondrial DNA is maternally inherited, the male zygote may not be implanted or it will proceed to an early embryonal death. The mitochondrial changes with the ensuing effects may be the basic cause of the syndrome.