Antisense knockdown of the Shaker-like Kv1.1 gene abolishes the central stimulatory effects of amphetamines in mice and rats.

Amphetamine (AMPH) is an indirect sympathomimetic compound classified as a substrate-type releaser that distinguishes it from other stimulants that act as uptake 1 blockers, such as cocaine (COC). In mammals, AMPH elicits central stimulation, hypermotility, anorexia, analgesia and analeptic activity, mainly through the increase of extracellular brain dopamine (DA). The inversion of vesicular transporters and/or intravesicular alkalinization is assumed to have a role in AMPH-induced exocytosis. However, the action mechanism of this compound has not yet been completely clarified. Recent evidence on the action of AMPHs indicates potassium channel-blocking properties in peripheral tissues. We investigated the possible involvement of a Shaker-like Kv1.1 channel subtype in the central effects of AMPH, using an antisense oligodeoxyribonucleotide (aODN) that specifically and reversibly inhibits the expression of these channels in the brain. The effect of aODN pretreatments was studied by evaluating the modification of behavioral effects induced in mice through the intracerebroventricular administration of AMPH, COC, or other compounds. The aODN in mice almost completely blocked the stimulatory effects of AMPH and other releasers but was ineffective in reducing the central activity of COC. In aODN-pretreated rats a strong reduction of the AMPH, but not of the COC-stimulated DA efflux from nucleus accumbens was observed. Our results suggest that the stimulant effects of AMPH and chemically related compounds, but not COC, require the presence of functionally active Kv1.1 channels in the brain.     

Freeze-drying polymeric colloidal suspensions: nanocapsules, nanospheres and nanodispersion. A comparative study.

Different polymeric nanoparticles were freeze-dried and the powders compared to determine the influence of the lipophilic core (Miglyol 810) or benzyl benzoate) and polymeric material (poly(epsilon-caprolactone) or Eudragit S90) on their drug content and morphology. Diclofenac, a non-steroidal anti-inflammatory drug, was used as a model. To characterize the products, a biological experiment based on the evaluation of the mucosal toxicity of diclofenac was conducted. Nanocapsule and nanosphere suspensions were prepared by nanoprecipitation and freeze-dried after the addition of colloidal silicon dioxide. The powders were examined under scanning electron microscopy (SEM) and gastrointestinal tolerance of products was evaluated in rats. Powders presented drug contents between 90.2+/-5.5 and 101.1+/-1.9% (HPLC). SEM analyzes showed non-spherical microparticles and, at higher magnifications, the micro-powder surface presented a homogeneous nanocovering. Regarding the gastrointestinal tolerance, with the exception of benzyl benzoate-loaded formulations, powders presented lesional indexes lower than the diclofenac salt solution. In contrast to the literature, nanocapsules can be dried by freeze-drying without leakage of drug or breaking the capsule wall.     

Meiosis of Wheat × Lymegrass Hybrids

Meiosis was examined in pollen mother cells of F1 hybrids made from crosses between wheat (Triticum aestivum) and lymegrass (Leymus arenarius and L. mollis). Fluorescence genomic in situ hybridization detected pairing between wheat and lymegrass chromosomes during prophase I and metaphase I. Such pairing, when resulting in bivalent formation, was likely to yield correct disjunction, and hence intergenomic recombination could be incorporated into the gametes. Bivalents in these hybrids, however, were more frequently formed between chromosomes of the same parental origin. Univalents were common, whereas multivalents were not clearly detected. Meiotic behaviour in some cells was not totally aberrant, and this may have accounted for the presence of normal pollen. The results are discussed in relation to intergenomic pairing, meiotic behaviour in wide-hybrids and genome relationships, including the Leymus genome origin.     

Histological evaluation of a tooth with hyperplastic pulpitis and periapical osteosclerosis

Histological examination was carried out in a case of hyperplastic pulpitis associated with periapical osteosclerosis.     

Assessment of vector microfilarial uptake as a comparatively non-invasive technique for monitoring onchocerciasis treatment campaigns in the Americas

Summary Since 1992, efforts have been made to combat onchocerciasis in Guatemala through mass distribution of ivermectin. The impact of the campaign is assessed by taking skin-snips from sentinel groups within selected communities. This method gives an estimate of the prevalence and intensity of infection, and thus the efficacy of the treatment. In some communities people are becoming reluctant to volunteer for skin-snipping, and so there is a need for an alternative technique that will give quantitative results. In most hyperendemic communities in Guatemala, biting blackflies are so ubiquitous that few people object to allowing 10 to 20 flies to engorge upon them. We examined data on the quantitative uptake of microfilariae by Simulium ochraceum before and after ivermectin distribution to see whether results similar to skin-snip data could be obtained. Counts of microfilariae ingested by S. ochraceum are compared to the numbers found in skin-snips from the same volunteers. In a group of 31 untreated infected persons, a skin-snip survey detected 64.5% positive, while feeding flies (vector microfilarial uptake, VmfU) detected 96.8%. Post-treatment, in a sample of 58 of whom 52 (89.7%) had a history of infection, both skin-snips and VmfU detected 54.2%. Vector blood meals contained more microfilariae than a mg of skin before treatment, but both recorded about equal numbers after treatment. When the data set was subdivided to compare samples taken at 2–3, 6–8 and 14–17 months post-treatment, the effect of ivermectin was still apparent at 6–8 months, but had virtually disappeared by 14 months post-treatment. A surprising observation was that the flies ingested fewer microfilariae from treated persons than was expected from the skin densities as estimated by skin-snip. This effect lasted for over 8 months, and could indicate that ivermectin has a greater effect on transmission than previously suspected. We conclude that VmfU could be used as an alternative to skin-snipping, and discuss the ethical implications.     

Cerebrospinal fluid purine metabolites after complex febrile convulsions

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and uric acid were determined in cerebrospinal fluid (CSF) of 15 children after complex febrile seizures (CFS) and in 27 after simple febrile seizures (SFS), and compared with those in a control group of 63 children. There was no statistically significant difference between the groups for any of these metabolites, suggesting that CFS and SFS neither significantly disturb the metabolism of nucleotides, nucleosides or bases nor significantly deplete neuron adenosine triphosphate levels.     

Elimination and minimization of the spherical aberration of intraocular lenses in high myopia

By applying Seidel aberration theory we have studied the spherical aberration of intraocular lenses in place ( S _IL), and the total spherical aberration of pseudophakic eyes ( S _IT). The optimum lens shapes for zero S _IL and S _IT or for minimum S _IL and S _IT of 12 schematic, highly myopic eyes were investigated. When the power required for emmetropization is positive, the total Seidel spherical aberration of the whole eye cannot be zero but can only be minimized. If the power of the intraocular lens is negative, the total Seidel spherical aberration of the whole eye can be made zero, and one of the optimum lens shapes would be meniscus with the convex surface towards the retina. In addition to improving the quality of the image, the lens has advantages from the physiological point of view, since it helps to maintain the structure of the eye.