ABSTRACT
Hyaluronan (HA) is central in joint and cartilage functions and to restore synovial fluid viscosity. In patients with osteoarthritis (OA), molecular weight (MW) and concentration of hyaluronic acid (HA) are reduced, diminishing joint lubrication. IL-1ß treatment was used to mimic osteoarthritis in a chondrocytes based in vitro model. The aim of our research, using this model and human chondrocytes was to assess the anti-inflammatory effect of H/L-HA hybrid complexes (SINOVIAL-HL®) in comparison with HA at high (H-HA) and low molecular weight (L-HA) separately used, through the evaluation of specific biomarkers involved in cartilage degradation and correlated to osteoarthritis. Specifically, TNF-α and IL-6 mRNA were evaluated by qRT-PCR. Cytokines levels were measured using Bio-plex assays and COMP-2 through immunofluorescence staining and western blot. H/L-HA significantly reduced inflammation biomarkers respect to both L-HA or H-HA separately considered at transcriptional and protein level.
Subject(s)
Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , In Vitro Techniques , Osteoarthritis/metabolism , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Cartilage/pathology , Chondrocytes/drug effects , Chondrocytes/pathology , Humans , Hyaluronic Acid/therapeutic use , Inflammation/drug therapy , Inflammation/genetics , Inflammation/metabolism , Interleukin-1beta/adverse effects , Interleukin-6/genetics , Models, Biological , Molecular Weight , Osteoarthritis/chemically induced , Osteoarthritis/drug therapy , Osteoarthritis/pathology , Tumor Necrosis Factor-alpha/geneticsABSTRACT
1. Clinical activity, extrapyramidal side-effects were evaluated in 22 schizophrenic out patients diagnosed according to DSM III and treated with haloperidol decanoate (50-300 mg i.m. monthly dose) for 12 months. 2. BPRS total scores did not show significant fluctuations showing a clinical stability of the patient population. 3. Patients with a duration of illness greater than 10 yrs (Group 2) showed significant (p less than 0.01) higher EPSE total scores compared to those with a duration of illness less than 10 yrs (Group 1). 4. A positive correlation was found between the administered dose and haloperidol plasma levels. 5. Patients from Group 2 reached the steady-state more slowly and showed a lower total L/D ratio compared to those from Group 1. 6. The pharmacokinetic approach seems desirable in order to adjust the dose and avoid schizophrenic relapses.
Subject(s)
Antipsychotic Agents/pharmacokinetics , Haloperidol/analogs & derivatives , Schizophrenia/drug therapy , Adult , Dose-Response Relationship, Drug , Female , Haloperidol/blood , Haloperidol/pharmacokinetics , Haloperidol/therapeutic use , Humans , Male , Middle Aged , Recurrence , Schizophrenia/bloodABSTRACT
A naturalistic study was performed on 44 schizophrenic outpatients diagnosed according to DSM III-R and presenting neuroleptic-induced extrapyramidal side-effects. All patients had been treated continuously for the previous 10-12 weeks with haloperidol (HL) combined with orphenadrine (ORD). The dosages of HL and ORD remained unchanged for at least four weeks before the evaluations. All patients were assessed for depressive features (HRS-D), extrapyramidal (EPSE) and anticholinergic (ACS check list) side-effects. The plasma levels of ORD and its metabolite tofenacine (TOF) were determined by gas chromatography. There was a positive relationship between HRS-D and EPSE total scores, while there was a negative relationship between age and EPSE total scores. No relationship between the administered dose and plasma levels of ORD was found. The HL daily dose (mg/kg), ORD plasma levels and the TOF/ORD plasma level ratio seem to influence significantly the severity of residual extrapyramidal side-effects.
Subject(s)
Orphenadrine/therapeutic use , Parkinson Disease, Secondary/drug therapy , Schizophrenia/complications , Adult , Aged , Female , Haloperidol/adverse effects , Humans , Male , Middle Aged , Orphenadrine/analogs & derivatives , Orphenadrine/blood , Parkinson Disease, Secondary/physiopathology , Psychiatric Status Rating Scales , Schizophrenic PsychologyABSTRACT
Twenty-eight elderly inpatients suffering from major depressive episodes (diagnosed according to DSM III) received randomly, on a double-blind basis, amitriptyline (75 mg/die) or fluoxetine (20 mg/die) for five weeks. There were four drop-outs in the amitriptyline group and two drop-outs in the fluoxetine group. Both groups showed a significant amelioration at the end point for Hamilton Rating Scale of Depression scores compared to the baseline value. Anticholinergic side-effects were significantly more severe in the amitriptyline group. Weight gain was detected only in patients receiving amitriptyline.
Subject(s)
Amitriptyline/therapeutic use , Depressive Disorder/drug therapy , Fluoxetine/therapeutic use , Aged , Amitriptyline/adverse effects , Appetite/drug effects , Body Weight , Depressive Disorder/psychology , Double-Blind Method , Female , Fluoxetine/adverse effects , Humans , Male , Psychiatric Status Rating Scales , Randomized Controlled Trials as TopicABSTRACT
Pharmacokinetics parameters describing the time course of concentrations of mianserin (MIA) in plasma and brain and the relationship between plasma and brain concentrations were studied after acute and chronic administration of increasing doses of MIA in adult mice. There was a linear relationship between the area under the curve (AUC), the maximum concentration (Cmax) and doses, in plasma and brain, both during acute and chronic experiments (p less than 0.05). A five-fold variation in plasma and brain terminal half-life (t 1/2) after chronic administration of the drug was observed, possibly due to a reduction in plasma drug clearance (CL). The values of Cmax and AUC in plasma and brain showed an increase of respectively about three and twelve times after chronic treatment. A very good correlation was observed between plasma and brain Cmax in both acute and chronic experiments; brain Cmax was 10.2 (+/- 0.16) times higher than plasma Cmax after acute administration and 12.08 (+/- 1.33) times higher after chronic administration.
