Pharmacokinetics of voriconazole after a single intramuscular injection in large falcons (Falco spp.).

Voriconazole is one of the main azoles used to treat invasive aspergillosis in falconry raptors and birds. Despite the fact that there are studies for oral and intravenous use of voriconazole in birds, there are none for its effect after intramuscular use. Empirical use of intramuscular voriconazole in falcons, indicated quicker therapy response than the oral one. Aim of this study is to evaluate the in vivo pharmacokinetic disposition of injectable voriconazole after a single intramuscular injection in large falcons (i.e., Gyrfalcons, Saker falcons, Peregrine falcons). No clinical side effects were observed in the falcons. Absorption of voriconazole was rapid (0.5-2 hours) and reached a plasma level (>1 µg/ml) which is above the minimal inhibitory concentration (MIC) for all known Aspergillus strains. This level was maintained for 16 to 20 hours, thus indicating that a single injection of 12.5 mg/kg is not enough if T > MIC is taken into consideration. On a newer aspect, according to the AUC24 unbound: MIC parameter would be indicated that this dose would be rather sufficient for most Aspergillus strains.

3D X-ray microscopic analysys on a prosthetically loaded implant with platform-switching and conical connection: a case report.

The histological and histomorphometrical examination were the gold standard in the qualitative and quantitative analyses of the peri-implant tissue around the implant. In recent years, the field of microscopy has witnessed a considerable enhancement of the performance of microscopes that have very high resolution performance and allowing very sophisticated analysis even larger than traditional preparations. The possibility to have an affordable analyses of whole implant with the surrounding different tissues (soft and hard tissues) without the traditional pre-treatment necessary for the histological analysis may represent a goal to describe material properties and behaviors or simply to visualize structural details. The aim of the present study were to evaluate a 3D X-ray microscopic analysis of peri-implant tissue compared to a traditional histological and histomorphometrical analysis of the peri-implant tissues around an implant with a conical connection associated with platform-switching in order to assess the validity of the new analysis technique.

Validation of the Italian version of the WHO-Well-Being Questionnaire (WHO-WBQ) and the WHO-Diabetes Treatment Satisfaction Questionnaire (WHO-DTSQ).

AIM: To validate the Italian version of the World Health Organization (WHO)-Well-Being Questionnaire (WBQ) and the WHO-Diabetes Treatment Satisfaction Questionnaire (DTSQ) in Type 1 and Type 2 diabetic patients. METHODS: The cultural adaptation of the questionnaires was performed by using standard forward/backward techniques. Internal consistency reliability was estimated by Cronbach's alpha coefficient. Construct validity was evaluated using the Short Form-36 (SF-36) Health Status Questionnaire. Finally, the discriminative properties of the questionnaires were evaluated relative to the patients' characteristics. The questionnaires were administered to a random sample of patients identified in twelve outpatient diabetes clinics. RESULTS: Overall, 412 subjects were recruited, of whom 96 (23%) with Type 1 diabetes. Item-scale correlations were >0.40 for all the items. Cronbach's alpha coefficient was 0.86 for the WHO-DTSQ and ranged between 0.79 and 0.91 for the WHO-WBQ. High correlations were found between WHO-WBQ scales and the mental dimensions of the Short Form-36 (SF-36) questionnaire, but not between WHO-DTSQ and SF-36 scores. Women, obese subjects, those with longer diabetes duration and multiple complications showed a worse quality of life in all of the four areas of the WHO-WBQ. In Type 2 diabetic subjects, SF-36 scores, but not WHO-WBQ scores, were able to discriminate the population according to the treatment modalities. Lower levels of treatment satisfaction were related to female gender, longer diabetes duration, insulin treatment, presence of diabetes complications and HbA1c levels >7.0%. The flexibility of the treatement was perceived as a major problem even among patients treated with oral agents. CONCLUSIONS: The WHO-DTSQ can be considered as a valuable instrument to be used internationally for the description of diabetes treatment satisfaction. The WHO-WBQ also shows adequate psychometric properties, but additional data are needed to clarify whether it is more sensitive than SF-36, the most widely used generic instrument.

Diastereoselective synthesis of non-proteinogenic alpha-amino acids.

The synthesis of enantiomerically pure azatyrosine, tribromophenylalanine and trichlorophenylalanine is described, using two methods, diastereoselective alkylation and (or) diastereoselective protonation of chiral enolates.

Quality of care-risk adjustment outcomes model: testing the effects of a community-based educational self-management program for children with asthma.

This article describes the design of an outcomes model incorporating adjustment for patients' risks for various outcomes of care. A community-based educational self-management program for children with asthma is proposed for testing the model. Measures of model components: clinical factors; nonclinical factors; psychological, cognitive, and psychosocial functioning; and patient and client satisfaction are described. Testing this model has implications for guiding the development of individualized culturally sensitive nursing interventions for children with asthma and their parents.

Three-dimensional folding of an RNA hairpin required for packaging HIV-1.

An NMR-based structure is presented for a 20 mer hairpin model of the SL3 stem-loop from the HIV-1 packaging signal. The stem has an A-family structure. However, the GGAG tetraloop appears to be flexible with the second (G10) and fourth (G12) bases extruded from the normal stacking arrangement. The A-base (A11) occupies a cavity large enough for it to jump rapidly between stacking upon G9 (in the loop) and G13 (from the base-pair adjacent to the loop). The H-bonding loci of G10, A11, and G12 are unoccupied in the free RNA structure. The loop should be easily adaptable to binding by the HIV-1 nucleocapsid protein or loop receptors.

Structure of the HIV-1 nucleocapsid protein bound to the SL3 psi-RNA recognition element.

The three-dimensional structure of the human immunodeficiency virus-type 1 (HIV-1) nucleocapsid protein (NC) bound to the SL3 stem-loop recognition element of the genomic Psi RNA packaging signal has been determined by heteronuclear magnetic resonance spectroscopy. Tight binding (dissociation constant, approximately 100 nM) is mediated by specific interactions between the amino- and carboxyl-terminal CCHC-type zinc knuckles of the NC protein and the G7 and G9 nucleotide bases, respectively, of the G6-G7-A8-G9 RNA tetraloop. A8 packs against the amino-terminal knuckle and forms a hydrogen bond with conserved Arg32, and residues Lys3 to Arg10 of NC form a 310 helix that binds to the major groove of the RNA stem and also packs against the amino-terminal zinc knuckle. The structure provides insights into the mechanism of viral genome recognition, explains extensive amino acid conservation within NC, and serves as a basis for the development of inhibitors designed to interfere with genome encapsidation.

Sulfenylation of chiral Schiff bases.

The purpose of this study was to examine the conditions of sulfenylation reactions of chiralα-amino esters Schiff bases to protect the chirality in theα-position.

Neuroexcitatory amino acids: phosphonic analogue of kainic acid.

The enantioselective synthesis of phosphonic analogue of kainic acid is described.