Acute and chronic antiparkinsonian effects of the novel nociceptin/orphanin FQ receptor antagonist NiK-21273 in comparison with SB-612111.

BACKGROUND AND PURPOSE: Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonists have been proposed as a novel therapeutic approach to Parkinson's disease. Main limitations of previous studies were the use of structurally similar compounds and the evaluation of their acute effects only. We report here on the acute and long-term antiparkinsonian effects of the novel compound 2-[3-[4-(2-chloro-6-fluoro-phenyl)-piperidin-1-ylmethyl]-2-(morpholine-4-carbonyl)-indol-1-yl]-acetamide (NiK-21273) in comparison with the potent and selective NOP receptor antagonist SB-612111. EXPERIMENTAL APPROACH: Basic pharmacological properties of NiK-21273 were studied in cell lines and isolated tissues (mouse and rat vas deferens). Antiparkinsonian effects were studied in reserpinized mice and 6-hydroxydopamine hemilesioned rats under both acute and chronic administration protocols. KEY RESULTS: In vitro, NiK-21273 behaved as a potent (pA(2) 7.7) and selective NOP receptor antagonist. In vivo, it reduced hypokinesia in reserpinized mice at 0.1 and 1 but not 10 mg·kg(-1), whereas SB-612111 (0.01-1 mg·kg(-1)) provided a dose-dependent antiparkinsonian effect. NiK-21273 ameliorated motor performance in 6-hydroxydopamine hemilesioned rats at 0.5 and 5 but not 15 mg·kg(-1). SB-612111 replicated these effects in the 0.01-1 mg·kg(-1) range without loss of efficacy. Both antagonists synergized with L-DOPA at subthreshold doses. Chronic administration of NiK-21273 provided delayed improvement in baseline activity at 0.5 and 1.5 mg·kg(-1), although tolerance to the higher dose was observed. Conversely, SB-612111 (1 mg·kg(-1)) maintained its effects over time without modifying baseline activity. CONCLUSIONS AND IMPLICATIONS: NOP receptor antagonists provide motor benefit in parkinsonism models although the 'therapeutic' window and long-term effects may vary between compounds.

Comparative genomics of bacteria from the genus Collimonas: linking (dis)similarities in gene content to phenotypic variation and conservation.

Collimonas is a genus of soil bacteria comprising three recognized species: C. fungivorans, C. pratensis and C. arenae. Collimonads share the ability to degrade chitin (chitinolysis), feed on living fungal hyphae (mycophagy), and dissolve minerals (weathering), but vary in their inhibition of fungi (fungistasis). To better understand this phenotypic variability, we analysed the genomic content of four strains representing three Collimonas species (Ter14, Ter6, Ter91 and Ter10) by hybridization to a microarray based on reference strain C. fungivorans Ter331. The analysis revealed genes unique to strain Ter331 (e.g. those on the extrachromosomal element pTer331) and genes present in some but not all of the tested strains. Among the latter were several candidates that may contribute to fungistasis, including genes for the production and secretion of antifungals. We hypothesize that differential possession of these genes underlies the specialization of Collimonas strains towards different fungal hosts. We identified a set of 136 genes that were common in all tested Collimonas strains, but absent from the genomes of three other members of the family Oxalobacteraceae. Predicted products of these 'Collimonas core' genes include lytic, secreted enzymes such as chitinases, peptidases, nucleases and phosphatases with a putative role in mycophagy and weathering.

Third molar extraction. Current trends.

Extraction of third molars is the operation most frequently performed by oral and maxillofacial surgeons. The American National Institute of Health (1979) and the American Association of Oral and Maxillofacial Surgeons (1993) have organised consensus conferences to systematically analyse the scientific evidence and provide official guidelines for the management of third molars. However, some clinical aspects are still controversial: indications for preventive extraction, early extraction, prognosis of impacted teeth, continuous follow-up, relationship with anterior crowding and temporo-mandibular disorders. This article reviews the conclusions from the consensus conferences and integrates them with more recent data. The actual trend seems to justify a more conservative clinical approach rather than an aggressive extraction policy.

[The chin hole. Position and correlation with other mandibular parameters]. / Foro mentoniero. Posizione e correlazione con altri parametri mandibolari.

BACKGROUND: The present study analyzes the position of mental foramen, in order to research possible correlations with other mandibular parameters. METHODS: The study has been conducted on 76 dry mandibles, for each mandible we have measured the exact position of the mental forum respect the other mandibular parameters. Both linear and angular relations and misurations have been made. RESULTS AND CONCLUSIONS: The results obtained confirm that the mental foramen maintains its position by increasing GoGn. The results did not show particularly significant aspects in comparison with the literature on the subject, thus confirming other authors' opinion.

The computed tomographic appearances of cherubism.

The computed tomographic (CT) aspects of six cases of cherubism are described. Through its optimal representation of the lesions, CT enabled certain characteristics of this disease to be substantiated, namely, limitation of the process to the bones of the jaw and primarily superficial development of the mandibular lesions, coupled with an unusual mandibular condylar impairment. Moreover, the composition of this series permitted investigation of the condition in its several stages of progression.

[Evaluation of the nutritional state of patients with maxillo-facial pathology]. / Valutazione dell'andamento nutrizionale in pazienti con patologia maxillo-facciale.

We have studied 19 patients with maxillo-facial trauma from the nutritional point at view. We observed that subjects with serious multiple fractures need a high caloric intake (a positive nitrogen balance is achieved by 100% of patients only when their intake is greater than or equal to 46 cal./kg/day) while patients with less serious fractures need lower caloric intake. The A. underline the importance of nutritional therapy in the patients with "intramaxillar fixation" both for the practical and psychological problems connected with their feeding and for the relationship between nutritional conditions and "metabolic response".