Introduction. Maxillary bone losses often require additional regenerative procedures: as a supplement to the procedures of tissue regeneration, a platelet concentrate called PRF (Platelet Rich Fibrin) was tested for the first time in France by Dr. Choukroun.Aim of the present study is to investigate, clinically and histologically, the potential use of PRF, associated with deproteinized bovine bone (Bio-Oss), as grafting materials in pre-implantology sinus grafting of severe maxillary atrophy, in comparison with a control group, in which only deproteinized bovine bone (Bio-Oss) was used as reconstructive material.Materials and Methods. 60 patients were recruited using the cluster-sampling method; inclusion criteria were maxillary atrophy with residual ridge < 5mm. The major atrophies in selected patients involved sinus-lift, with a second-look reopening for the implant insertion phase. The used grafting materials were: a) Bio-Oss and b) amorphous and membranous PRF together with Bio-Oss. We performed all operations by means of piezosurgery in order to reduce trauma and to optimize the design of the operculum on the cortical bone. The reopening of the surgical area was scheduled at 3 different times.Results. 72 sinus lifts were performed with subsequent implants insertions.We want to underline how the histological results proved that the samples collected after 106 days (Early protocol) with the adding of PRF were constituted by lamellar bone tissue with an interposed stroma that appeared relaxed and richly vascularized.Conclusions. The use of PRF and piezosurgery reduced the healing time, compared to the 150 days described in literature, favoring optimal bone regeneration. At 106 days, it is already possible to achieve good primary stability of endosseous implants, though lacking of functional loading.

The lower radiation dose and reduced costs of CBCT make this a useful substitute for CT; however, this study has shown that, in order to more accurately define the bone density with CBCT, a conversion ratio needs to be applied to the VV.

Recently we reported the pharmacological characterization of the 9,10-dihydropyrrolo[1,3]benzothiazepine derivative (S)-(+)-8 as a novel atypical antipsychotic agent. This compound had an optimum pK(i) 5-HT(2A)/D(2) ratio of 1.21 (pK(i) 5-HT(2A) = 8.83; pK(i) D(2) = 7.79). The lower D(2) receptor affinity of (S)-(+)-8 compared to its enantiomer was explained by the difficulty in reaching the conformation required to optimally fulfill the D(2) pharmacophore. With the aim of finding novel atypical antipsychotics we further investigated the core structure of (S)-(+)-8, synthesizing analogues with specific substituents; the structure-activity relationship (SAR) study was also expanded with the design and synthesis of other analogues characterized by a pyrrolo[2,1-b][1,3]benzothiazepine skeleton, substituted on the benzo-fused ring or on the pyrrole system. On the 9,10-dihydro analogues the substituents introduced on the pyrrole ring were detrimental to affinity for dopamine and for 5-HT(2A) receptors, but the introduction of a double bond at C-9/10 on the structure of (S)-(+)-8 led to a potent D(2)/5-HT(2A) receptor ligand with a typical binding profile (9f, pK(i) 5-HT(2A)/D(2) ratio of 1.01, log Y = 8.43). Then, to reduce D(2) receptor affinity and restore atypicality on unsaturated analogues, we exploited the effect of specific substitutions on the tricyclic system of 9f. Through a molecular modeling approach we generated a novel series of potential atypical antipsychotic agents, with optimized 5HT(2A)/D(2) receptor affinity ratios and that were easier to synthesize and purify than the reference compound (S)-(+)-8. A number of SAR trends were identified, and among the analogues synthesized and tested in binding assays, 9d and 9m were identified as the most interesting, giving atypical log Y scores respectively 4.98 and 3.18 (pK(i) 5-HT(2A)/D(2) ratios of 1.20 and 1.30, respectively). They had a multireceptor affinity profile and could be promising atypical agents. Compound 9d, whose synthesis is easier and whose binding profile is atypical (log Y score similar to that of olanzapine, 3.89), was selected for further biological investigation. Pharmacological and biochemical studies confirmed an atypical antipsychotic profile in vivo. The compound was active on conditioned avoidance response at 1.1 mg/kg, a dose 100-times lower than that required to cause catalepsy (ED(50) >90 mg/kg), it induced a negligible increase of prolactin serum levels after single and multiple doses, and antagonized the cognitive impairment induced by phencyclidine. In conclusion, the pharmacological profile of 9d proved better than clozapine and olanzapine, making this compound a potential clinical candidate.