Polymorphic CYP2D6 is the enzyme that activates the opioid analgesic tramadol by O-demethylation to its active metabolite O-demethyltramadol (M1). Our objective was to determine the opioid effects measured by pupillary response to tramadol of CYP2D6 genotyped volunteers in relation to the disposition of tramadol and M1 in plasma. Tramadol displayed phenotypic pharmacokinetics and it was possible to identify poor metabolizers (PM) with >99 % confidence from the metabolic ratio (MR) in a single blood sample taken between 2.5 and 24 h post-dose. Homozygous extensive metabolizers (EM) differed from PM subjects by an almost threefold greater (P=0.0014) maximal pupillary constriction (Emax). Significant correlations between the AUC and Cmax values of M1 versus pupillary constriction were found. The corresponding correlations of pharmacokinetic parameters for tramadol itself were weaker and negative. The strongest correlations were for the single-point metabolic ratios at all sampling intervals versus the effects, with rs ranging from 0.85 to 0.89 (p‹0.01). It is concluded that the concept of dual opioid/non-opioid action of the drug, though considerably stronger in EMs, is valid for both EM and PM subjects. This is the theoretical basis for the frequent use and satisfactory efficacy of tramadol in clinical practice when given to genetically non-selected population., O. Slanař, M. Nobilis, J. Květina, R. Mikoviny, T. Zima, J. R. Idle, F. Perlík., and Obsahuje biblografii a bibliografické odkazy
Brachiola algerae (Vavra et Undeen, 1970), a parasite of Anopheles mosquitoes, has also been isolated from a human cornea, a cutaneous nodule and deep muscle tissue. All three human isolates of B. algerae are morphologically, serologically, and genetically similar to the mosquito-derived isolates including the original isolate of Vavra and Undeen. All of these isolates grew well in mammalian cell cultures at 37°C and produced spores. Transmission electron microscopy revealed that all developmental stages including meronts, sporoblasts and spores were diplokaryotic and developed in direct contact with the host cell cytoplasm, a feature characteristic of the genus Brachiola. Spores of all isolates reacted well, in the immunofluorescence assay, with the rabbit anti-B. algerae serum. In the immunoblot assay, although the overall banding patterns of the human and mosquito isolates were similar, minor differences could be discerned. Sequencing of the PCR products of the amplified SSU rRNA gene revealed the existence of two distinct genotypes; the original mosquito (Undeen) isolate belonged to genotype 1 and the isolate from cornea and that from the deep muscle biopsy to genotype 2, whereas the isolates from a mosquito and one of the other two human isolates (one from skin abscess) had both genotypes, 1 and 2. It is known that spores of mosquito-derived B. algerae can not only proliferate in mammalian cell cultures at 37°C but also can infect mice when injected into footpads or deposited on the corneal surface. These observations indicate that the spores have potential to be a risk factor for humans, especially those with immunodeficiency.
In the field, supplemental application of N fertilizer to rice (Oryza sativa) shortly before the beginning of heading stage increases leaf N content and enhances photosynthesis during the grain-filling period. In search of varietal differences in leaf gas exchange in response to supplemental N application, we examined 13 rice varieties grown in the field during two successive years. The varieties included japonica and indica varieties, both of which are widely grown in Japan. The response to supplemental N application could not be separated clearly between variety groups; some of the japonica varieties, but none of the indica varieties, exhibited significant increase in stomatal conductance (gs) after supplemental N application. Supplemental N was more effective to increase stomatal aperture in the varieties with inherently lower gs. Varieties that showed greater response of g s to supplemental N application might be able to adjust their stomatal aperture with appropriate N control. Although the internal-to-ambient CO2 mole fraction ratio and the leaf carbon isotopic composition (δ13C) differed among varieties as a result of variations in stomatal aperture and the CO2 requirement of mesophyll, supplemental N application barely influenced these parameters, because it only moderately affected stomatal aperture. Since δ13C tended to increase with increasing number of days from transplantation to heading stage in japonica varieties, δ13C values were more sensitive to differences in growth rate between years than to N application., S. Shimoda, A. Maruyama., and Obsahuje bibliografii