The effect of sodium-n-dipropyl acetate on gamma-aminobutyric acid-dependent inhibition in the rat cortex and substantia nigra in relation to its anticonvulsant activity.

1. We have examined the time course of the anticonvulsant property of valproate sodium on electroshock-induced convulsions in rats and a comparison of this has been made with the action of the drug on single unit activity in the rat brain. 2. Intraperitoneal valproate sodium (100 to 400 mg/kg) protected rats from electroshock-induced convulsion. This effect was dose-dependent, the latency of the effect decreasing as a function of dose from 5 to 2 min. 3. The time course of this anticonvulsant property was paralleled by a pronounced inhibition of the spontaneous firing rate of cortical and nigral neurones, following intraperitoneal administration of valproate sodium (100 to 400 mg/kg). 4. The inhibitory action of microiontophoretically applied gamma-aminobutyric acid (GABA) and muscimol on the firing rate of cortical neurones was potentiated within 1 to 3 min of microiontophoretic application of valproate sodium. In contrast, the inhibitory action of glycine on cortical neurones was unaffected during the microiontophoretic application of valproate sodium. 5. Microiontophoretically applied valproate sodium also potentiated inhibitory responses to GABA in rats which had received 100 mg/kg of a GABA-transaminase inhibitor, gabaculine, i.p. 16 h previously. 6. The duration of trans-synaptic inhibitory responses in the substantia nigra and cortex following submaximal electrical stimulation of the striatum and cortex respectively was, in general, unaffected by either intraperitoneal or local application of valproate sodium. 7. These observations are discussed in terms of the mechanisms underlying the rapid onset of the anticonvulsant properties of valproate sodium.     

Unilateral partial tibia defect with preaxial polydactyly,general micromelia,and trigonomacrocephaly with a note on “developmental resistance”

We report a boy with predominantly unilateral severe tibia defect with a high grade of preaxial polydactyly. Family history suggests the possibility of autosomal dominant inheritance with reduced penetrance and quite variable expressivity. The boy's phenotype and other previously reported examples of predominantly unilateral involvement in autosomal dominant and autosomal recessive limb mutations strongly suggest a hypothesis of developmental resistance in the uninvolved parts.     

Contamination by Selected Organochlorine Pesticides (OCPs) in Surface Soils in Hanoi, Vietnam

An evaluation of selected organochlorine pesticide residues [p,p′- dichlorodiphenyltrichloroethane (DDT), p,p′- dichlorodiphenyldichloroethylene (DDE), p,p′- dichlorodiphenyldichloroethane (DDD), α, β, γ and δ- hexachlorocyclohexane (HCH)] in the surface soils of Hanoi, Vietnam was carried out. Sixty representative soil samples were collected from the centre of Hanoi and five surrounding districts. In agricultural areas, ΣDDT concentrations ranged from < 0.02 to 171.83 ng g⁻¹ (mean 89.86 ng g⁻¹) dry weight, whereas ΣHCH concentrations ranged from < 0.05 to 20.57 ng g⁻¹ (mean 8.03 ng g⁻¹) dry weight. Investigation of the ratio of different isomers in the soil samples indicates that there has been no recent input of DDT and HCH in the study area.     

Neural and metabolic regulation of macronutrient intake and selection

There is considerable disagreement regarding what constitutes a healthy diet. Ever since the influential work of Cannon and Richter, it was debated whether the 'wisdom of the body' will automatically direct us to the foods we need for healthy lives or whether we must carefully learn to eat the right foods, particularly in an environment of plenty. Although it is clear that strong mechanisms have evolved to prevent consumption of foods that have previously made us sick, it is less clear whether reciprocal mechanisms exist that reinforce the consumption of healthy diets. Here, we review recent progress in providing behavioural evidence for the regulation of intake and selection of proteins, carbohydrates and fats. We examine new developments in sensory physiology enabling recognition of macronutrients both pre- and post-ingestively. Finally, we propose a general model for central neural processing of nutrient-specific appetites. We suggest that the same basic neural circuitry responsible for the homoeostatic regulation of total energy intake is also used to control consumption of specific macro- and micronutrients. Similar to salt appetite, specific appetites for other micro- and macronutrients may be encoded by unique molecular changes in the hypothalamus. Gratification of such specific appetites is then accomplished by engaging the brain motivational system to assign the highest reward prediction to exteroceptive cues previously associated with consuming the missing ingredient. A better understanding of these nutrient-specific neural processes could help design drugs and behavioural strategies that promote healthier eating.     

Incidence of fusarium species and mycotoxins in silage maize

Maize is frequently infected by the Fusarium species producing mycotoxins. Numerous investigations have focused on grain maize, but little is known about the Fusarium species in the entire plant used for silage. Furthermore, mycotoxins persist during the ensiling process and thus endanger feed safety. In the current study, we analyzed 20 Swiss silage maize samples from growers' fields for the incidence of Fusarium species and mycotoxins. The species spectrum was analyzed morphologically and mycotoxins were measured by LC-MS/MS. A pre-harvest visual disease rating showed few disease symptoms. In contrast, the infection rate of two-thirds of the harvest samples ranged from 25 to 75% and twelve different Fusarium species were isolated. The prevailing species were F. sporotrichioides, F. verticillioides and F. graminearum. No infection specificity for certain plant parts was observed. The trichothecene deoxynivalenol (DON) was found in each sample (ranging from 780 to 2990 μg kg(-1)). Other toxins detected in descending order were zearalenone, further trichothecenes (nivalenol, HT-2 and T-2 toxin, acetylated DON) and fumonisins. A generalized linear regression model containing the three cropping factors harvest date, pre-precrop and seed treatment was established, to explain DON contamination of silage maize. Based on these findings, we suggest a European-wide survey on silage maize.     

Genotyping of CYP2B6 and therapeutic drug monitoring in an HIV-infected patient with high efavirenz plasma concentrations and severe CNS side-effects

We present a case with important pharmacogenetic and pharmacokinetic aspects of antiretroviral therapy in a patient with high efavirenz concentrations, severe CNS side-effects and low lopinavir concentrations. Despite therapeutic drug monitoring and subsequent efavirenz dosage reductions, side-effects did not resolve completely and lopinavir concentrations remained relatively low.