Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey

<p>Abstract</p> <p>Background</p> <p>The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications.</p> <p>Methods</p> <p>A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period.</p> <p>Results</p> <p>Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay.</p> <p>Conclusion</p> <p>Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.</p

Oral bioavalability of Silymarin phytocomplex formulated as self-emulsifying pellets

The objective of this study was to develop new solid self-emulsifying pellets to deliver milk thistle extract (Silymarin). These pellets were prepared via extrusion/spheronisation procedure, using a self-emulsifying system or SES (Akoline MCM\uae, Miglyol\uae, Tween 80\uae, soy lecithin and propylene glycol), microcrystalline cellulose and lactose monohydrate. To select the most suitable formulations for extrusion and spheronisation, an experimental design of experiences was adopted. The screening amongst formulations (13 different blends) was performed preparing pellets and evaluating extrusion profiles and quality of the spheronised extrudates. The pellets were characterized for size and shape, density, force required to crush them. Although more than one type of pellets demonstrated adequate morphological and technological characteristics, pellets prepared from formulation 7 revealed the best properties and were selected for further biopharmaceutical investigations, including in vitro dissolution and in vivo trials on rats to study serum and lymph levels after oral administration of the pellets. These preliminary technological and pharmacokinetic data demonstrated that extrusion/spheronisation is a viable technology to produce self-emulsifying pellets of good quality and able to improve in vivo oral bioavailability of main components of a phytotherapic extract of more than 100 times by enhancing the lymphatic route of absorption

PET and MRI studies applied on characterization of Fisher/F98 rat glioma model

Introduction: Preclinical brain tumor models have provided a wealth of information on the biology, imaging and experimental therapeuticsof brain tumors. The aim of our study is characterized Fisher/F98 rat glioma model using Positron Emission Tomography (PET) and Magnetic Resonance (MR) analysis to set up an experimental model useful to study the efficacy of new colloidal vectors for chemotherapy. Methods: Syngenic rat brain-glioma models (Fisher/F98) was obtained by stereotactic (x=2; y=5; z=3) implantation of different cell concentrations (102, 103, 104 and 105). To monitor tumor growth progression, rats underwent once a week Gadolinium enhanced T1-MRI studies followed by [18F]FDG PET studies, starting from 7 days after surgery. A group of animals performed also [18F]FAZA PET studies to evaluate regional tissue hypoxia. To improve quantification, PET and MRI images were fused using PMOD 2.7 software. Max radiotracers uptake was calculated for tumor,frontal cortex, cerebellum and background using region of interest (ROI) analysis. Radioactivity concentration values expressed in MBq/g were then transformed into percentage of injected dose per gram of tissue (%ID/g). Moreover, histological analysis of proliferation, apoptosis, differentiation, neoangiogenesis and hypoxia markers were performed. Results: Mean survival time of rats injected with 104 and 105 cells was nine days. One week after surgery, MRI revealed a rapid growth that reached 0.11 cm3 mean tumour volume. Animals injected with 103 and 102 cells showed a mean survival time of 18 and 24 days respectively. In rats injected with 103 cells, tumor was revealed 14 days after surgery at MRI and [18F]FDG PET and successively tumors rapidly increased. Disease course in 102 cells injected rats was slower. Tumors were characterized by high [18F]FDG uptake and hypoxic subareas which only partially overlapped. Hypoxic areas were mainly localized in correspondence to Gd-enhanced regions whereas hyper glucose metabolic areas were localized in the outer part of the tumors. At histological analysis tumoral masses showed an infiltrative pattern of growth and moderate neoangiogenesis. Tumors obtained at animals death showed diffused necrotic areas. HIF1 was clearly expressed by glial and neuronal cells in oedematous and hypoxic areas. Conclusions: Our study indicates that Fisher/ F98 rat glioma model reproduces the characteristic of aggressiveness of human glioblastoma. Tumor was characterized by high glucose metabolism and by hypoxic sub-areas. The concentration of 102 cells permits to better monitor disease onset and progression and to plan experiments to test new anti-neoplastic therapies efficacy

A Trans-Specific Polymorphism in ZC3HAV1 Is Maintained by Long-Standing Balancing Selection and May Confer Susceptibility to Multiple Sclerosis

The human ZC3HAV1 gene encodes an antiviral protein. The longest splicing isoform of ZC3HAV1 contains a C-terminal PARP-like domain, which has evolved under positive selection in primates. We analyzed the evolutionary history of this same domain in humans and in Pan troglodytes. We identified two variants that segregate in both humans and chimpanzees; one of them (rs3735007) does not occur at a hypermutable site and accounts for a nonsynonymous substitution (Thr851Ile). The probability that the two trans-specific polymorphisms have occurred independently in the two lineages was estimated to be low (P = 0.0054), suggesting that at least one of them has arisen before speciation and has been maintained by selection. Population genetic analyses in humans indicated that the region surrounding the shared variants displays strong evidences of long-standing balancing selection. Selection signatures were also observed in a chimpanzee population sample. Inspection of 1000 Genomes data confirmed these findings but indicated that search for selection signatures using low-coverage whole-genome data may need masking of repetitive sequences. A case-control study of more than 1,000 individuals from mainland Italy indicated that the Thr851Ile SNP is significantly associated with susceptibility to multiple sclerosis (MS) (odds ratio [OR] = 1.47, 95% confidence intervals [CI]: 1.08-1.99, P = 0.011). This finding was confirmed in a larger sample of 4,416 Sardinians cases/controls (OR = 1.18, 95% CI: 1.037-1.344, P = 0.011), but not in a population from Belgium. We provide one of the first instances of human/chimpanzee trans-specific coding variant located outside the major histocompatibility complex region. The selective pressure is likely to be virus driven; in modern populations, this variant associates with susceptibility to MS, possibly via the interaction with environmental factor