Comparison of the in vivo pharmacokinetics and in vitro dissolution of raltegravir in HIV patients receiving the drug by swallowing or by chewing.

The pharmacokinetics of raltegravir (RAL) in HIV patients is characterized by high interpatient/intrapatient variability. We investigated the potential contribution of the drug pharmaceutical formulation to RAL pharmacokinetics. We first compared in vivo the pharmacokinetics of RAL for 67 patients to whom the drug was administered by swallowing the intact tablet with those obtained from 13 HIV-infected patients who chewed the RAL tablet due to swallowing difficulties.

Robot training of upper limb in multiple sclerosis: comparing protocols with or without manipulative task components.

In this pilot study, we compared two protocols for robot-based rehabilitation of upper limb in multiple sclerosis (MS): a protocol involving reaching tasks (RT) requiring arm transport only and a protocol requiring both objects' reaching and manipulation (RMT). Twenty-two MS subjects were assigned to RT or RMT group. Both protocols consisted of eight sessions.

Identification of new hematopoietic cell subsets with a polyclonal antibody library specific for neglected proteins.

The identification of new markers, the expression of which defines new phenotipically and functionally distinct cell subsets, is a main objective in cell biology. We have addressed the issue of identifying new cell specific markers with a reverse proteomic approach whereby approximately 1700 human open reading frames encoding proteins predicted to be transmembrane or secreted have been selected in silico for being poorly known, cloned and expressed in bacteria. These proteins have been purified and used to immunize mice with the aim of obtaining polyclonal antisera mostly specific for linear epitopes.

Inflammation and neurological adverse drugs reactions: a case of long lasting impaired consciousness after oxatomide administration in a patient with gastroenteritis.

Oxatomide at therapeutic doses generates occasionally drowsiness in children. When administered at toxic doses, however oxatomide may induce long lasting impaired consciousness. We now report a case of severe long lasting impaired consciousness induced by therapeutic doses of oxatomide occurring in a child affected by acute gastroenteritis.

Nitric oxide donor and non steroidal anti inflammatory drugs as a therapy for muscular dystrophies: evidence from a safety study with pilot efficacy measures in adult dystrophic patients.

This open-label, single centre pilot study was designed to evaluate safety and tolerability of the combination of the drugs isosorbide dinitrate, a nitric oxide donor, and ibuprofen, a non steroid anti-inflammatory drug, in a cohort of adult dystrophic patients (Duchenne, Becker and Limb-Girdle Muscular Dystrophy). Seventy-one patients were recruited: 35, treated with the drug combination for 12 months, and 36 untreated. Safety and adverse events were assessed by reported signs and symptoms, physical examinations, blood tests, cardiac and respiratory function tests.

A tailored exercise of manipulation of virtual tools to treat upper limb impairment in Multiple Sclerosis.

We developed a robot-assisted rehabilitation protocol, specifically designed to treat cerebellar and motor symptoms in subjects with Multiple Sclerosis. The task consists of controlling a `virtual' tool (a mass-spring system), under the effect of a resistive force. The exercise is designed in such a way that task difficulty and the degree of resistance are automatically adjusted to the individual patients' impairment.

Perceptions and patterns of use of generic drugs among Italian family pediatricians: first round results of a web survey.

Prescription of generic medicines represents an efficacious healthcare cost containment strategy. In some European countries and in the US, generic medicines are largely prescribed. In Italy, generic drugs prescription rate is lower.

Inter- and intra-patient variability of raltegravir pharmacokinetics in HIV-1-infected subjects.

Objectives: Limited studies in healthy volunteers and in HIV-1-infected patients have shown that raltegravir pharmacokinetics are characterized by high inter-patient variability. Only scanty data are, however, available on intra-patient raltegravir variability. The present study was designed to evaluate in parallel the inter- and intra-patient variability of raltegravir pharmacokinetics in HIV-1-infected patients during routine therapeutic drug monitoring (TDM).

Limited sampling strategies for the estimation of atazanavir daily exposure in HIV-infected patients.

Stepwise multiple regression analyses were applied to 44 atazanavir pharmacokinetic profiles from 44 HIV-1 infected patients concomitantly treated with raltegravir with the goal of identifying limited sampling strategies for the prediction of drug AUC(0-12) . Atazanavir trough-based equations failed to reliably predict daily drug exposure in patients with low drug bioavailability. Conversely, different algorithms based on few samples and associated with good correlation, acceptable bias and imprecision with the measured atazanavir AUC(0-12) were identified.

Optimizing immunosuppressive drug dosing in pediatric renal transplantation. Part of a special series on Paediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni.

Kidney transplantation in pediatric patients has become a successful and routine procedure, with overall 1-year patient and graft survival rates exceeding 95%. These success rates, however, are not maintained in the long-term, as reported 10-year graft survival rates are in the 50-60% range. Further improvement of long-term allograft survival in pediatric transplantation requires specific focus on long term complications such as increased cardiovascular risk and over-immunosuppression, two linked conditions.

The virtual time to contact in the evaluation of balance disorders and prediction of falls in people with multiple sclerosis.

Purpose: The purpose of the study was to compute Virtual Time to Contact (VTC) from stabilometric assessment to study balance impairments in people with multiple sclerosis (PwMS). To this purpose we assessed the ability of VTC to discriminate between balance skills of PwMS and healthy subjects (HS), among sensory conditions and between fallers and non fallers.

Methods: VTC was calculated to characterize balance performance in 47 PwMS and 13 HS in four different sensory conditions during quiet standing.

Co-administration of raltegravir reduces daily darunavir exposure in HIV-1 infected patients.

The potential drug-to-drug interaction between darunavir and raltegravir in the setting of HIV infection is a highly debated issue still unresolved. In the present study we have evaluated the pharmacokinetics of darunavir and ritonavir in 53 HIV-1 infected patients with or without concomitant raltegravir administration. The assessment of trough plasma drug concentrations was carried out in all subjects and the potential influence of raltegravir on darunavir and ritonavir disposition, assessed by specific pharmacokinetic evaluations in a subgroup of 25 patients.

A novel polyclonal antibody library for expression profiling of poorly characterized, membrane and secreted human proteins.

The YOMICS™ antibody library (http://www.yomics.com/) presented in this article is a new collection of 1559 murine polyclonal antibodies specific for 1287 distinct human proteins.

Effect of kinesio taping on standing balance in subjects with multiple sclerosis: A pilot study\m{1}.

Objective: The aim of this study was to assess the effect of Kinesio Taping on body stability in subjects with MS.

Study Design: Non controlled intervention study in a Rehabilitation Unit.

Intervention: A consecutive convenience sample of 15 individuals with multiple sclerosis was assessed.

An experimental paradigm to assess postural stabilization: no more movement and not yet posture.

A ground reaction based method is proposed to evaluate the hypothesis that a stabilization phase occurs in transitions towards erect posture, following the macroscopic movement and preceding the quiet final erect posture, whose aim is to control and dissipate the residual inertial unbalancing forces occurring at the transition end. The experimental protocol considers three tasks leading to the final erect posture: taking a step forward (F), sit-to-stand (S), and bending the trunk forward (B), The method mainly consists of the fitting of a negative exponential function on the instability time profile following the end of the transition movement. The model parameters Y(0), T, and Y(inf), respectively, quantify the initial instability rate, a time duration related to the stabilization, and the final asymptotic instability rate.

A dual acting compound releasing nitric oxide (NO) and ibuprofen, NCX 320, shows significant therapeutic effects in a mouse model of muscular dystrophy.

A resolutive therapy for muscular dystrophies, a heterogeneous group of genetic diseases leading to muscular degeneration and in the severe forms to death, is still lacking. Since inflammation and defects in nitric oxide generation are recognized key pathogenic events in muscular dystrophy, we have analysed the effects of a derivative of ibuprofen, NCX 320, belonging to the class of cyclooxygenase inhibiting nitric oxide donator (CINOD), in the α-sarcoglycan null mice, a severe mouse model of dystrophy. NCX 320 was administered daily in the diet for 8months starting 1month from weaning.

Reliability and validity of an instrument to measure quality of life in the dysarthric speaker.

Objective: To develop a tool to measure quality of life (QOL) in the dysarthric speaker (QOL-DyS).

Patients And Method: The study consisted of two phases: scale development and item reduction (phase 1), and reliability and validity analysis (phase 2). The 100-item 'Dysarthria from the Point of View of the Dysarthric Patient' questionnaire was used for item development; the data from 50 dysarthric patients were measured for internal consistency and the 40-item QOL-DyS was developed.

Limited sampling strategies for the estimation of raltegravir daily exposure in HIV-infected patients.

Stepwise multiple regression analyses were applied to 50 raltegravir pharmacokinetic profiles from 50 HIV patients with the goal to identify limited sampling strategies for the prediction of drug area under the time-concentration curve (AUC(0-12)). Raltegravir single sampling point-based equations failed to reliably predict daily drug exposure. Conversely, different algorithms based on few samples and associated with good correlation, acceptable bias, and imprecision with the measured raltegravir AUC(0-12) were identified.

Expression of DNA repair genes in ovarian cancer samples: biological and clinical considerations.

The purpose of this study was to investigate retrospectively the mRNA expression of genes involved in different DNA repair pathways implicated in processing platinum-induced damage in 171 chemotherapy-naïve ovarian tumours and correlate the expression of the different genes with clinical parameters. The expression of genes involved in DNA repair pathways (PARP1, ERCC1, XPA, XPF, XPG, BRCA1, FANCA, FANCC, FANCD2, FANCF and PolEta), and in DNA damage transduction (Chk1 and Claspin) was measured by RT-PCR in 13 stage I borderline and 77 stage I and 88 III ovarian carcinomas. ERCC1, XPA, XPF and XPG genes were significantly less expressed in stage III than in stage I carcinoma; BRCA1, FANCA, FANCC, FANCD2 gene expressions were low in borderline tumours, higher in stage I carcinomas and lower in stage III samples.

Atypical pharmacokinetics of atazanavir in an HIV-1-infected patient.

An HIV-infected patient with very low atazanavir (ATV) plasma trough concentrations despite clinical signs of poor drug tolerability was described. By therapeutic drug monitoring (TDM), the authors found that the patient had an atypical ATV pharmacokinetics characterized by rapid drug absorption followed by very fast drug clearance probably attributable to his genetic background. This case underlines the importance of traditional and pharmacogenetic-based TDM for the individualization of ATV therapy in HIV-1 patients.