ABSTRACT
BACKGROUND: There is a lack of consistent evidence regarding associations of neurological soft signs (NSS) with illness-related variables in schizophrenia. This study examined NSS in first-episode psychotic patients with respect to their factor structure and associations with risk factors, pre-morbid characteristics, psychopathology and spontaneous extrapyramidal syndromes. METHOD: First-episode, drug-naive patients with schizophrenia-spectrum disorders (n=177) were assessed for NSS using the Neurological Evaluation Scale, and its 26 constituting items were factor analysed. The identified neurological dimensions were then entered into hierarchical regression models as outcome dependent variables of a set of predictors including risk factors (familial loading for schizophrenia, obstetric complications), pre-morbid characteristics (neurodevelopmental delay, symptoms of attention deficit-hyperactivity disorder, pre-morbid functioning), psychopathological domains (reality distortion, disorganization, negative symptoms, mania, depression, catatonia) and spontaneous extrapyramidal syndromes (parkinsonism, dyskinesia, akathisia). RESULTS: Five neurological domains were identified: sequencing, release signs, sensory integration, abnormal movements and coordination. Multivariate analyses showed independent associations (p<0.01) of sequencing with familial liability to schizophrenia, deterioration of pre-morbid adjustment and parkinsonism; release signs with obstetric complications, catatonic symptoms and parkinsonism; sensory integration with familial liability to schizophrenia; abnormal movements with familial liability to schizophrenia, obstetric complications, parkinsonism and dyskinesia; and coordination with neurodevelopmental delay. The empirically derived factors explained additional variance over and above that explained by subscale scores across the examined variables. CONCLUSIONS: Familial liability to schizophrenia, obstetric complications, neurodevelopmental delay, deterioration in pre-morbid functioning and observable motor disorders appear to contribute independently to domains of neurological dysfunction. The findings support a neurodevelopmental model of NSS in schizophrenia.
Subject(s)
Basal Ganglia Diseases/diagnosis , Delusions/diagnosis , Psychotic Disorders/diagnosis , Schizophrenia/diagnosis , Schizophrenic Psychology , Social Adjustment , Adolescent , Adult , Basal Ganglia Diseases/psychology , Comorbidity , Delusions/psychology , Female , Humans , Male , Middle Aged , Neurologic Examination/statistics & numerical data , Neuropsychological Tests/statistics & numerical data , Parkinsonian Disorders/diagnosis , Parkinsonian Disorders/psychology , Psychometrics , Psychotic Disorders/psychology , Risk Factors , Statistics as Topic , Young AdultABSTRACT
The aim of this study was to develop a direct, simple and rapid high performance liquid chromatographic method for the determination of cidofovir in both skin layers and percutaneous penetration experiments. Samples were chromatographed on a reversed phase encapped column 250 x 4 mm C(8) LiChrospher Select B. The phase mobile consisted on 3% of acetonitrile and 97% of 1.5 mM of tetrabutylammonium dihydrogen phosphate (TADP) and 3.5 mM of disodium hydrogenphosphate adjusted to pH 6. Detection was at 274 nm and the run time was 14 min. The limit of detection was 0.06 microg/ml. The detector response was found to be linear in the concentration range 0.1-10 microg/ml. This assay is a selective, sensitive and reproducible method for the quantification of cidofovir in skin layers and in the receptor compartment of Franz-type diffusion cells after percutaneous studies.
Subject(s)
Antiviral Agents/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Cytosine/pharmacokinetics , Organophosphonates , Organophosphorus Compounds/pharmacokinetics , Skin/metabolism , Calibration , Cidofovir , Cytosine/analogs & derivatives , Humans , Hydrogen-Ion Concentration , Permeability , Reproducibility of Results , Sensitivity and Specificity , Skin Absorption , Spectrophotometry, UltravioletABSTRACT
Distribution of PLGA-microparticles in porcine skin, after its topical application, was studied in vitro using microparticles containing rhodamine as a fluorescent probe. PLGA-microparticles loaded with rhodamine were prepared using a solvent evaporation technique. Skin distribution of fluorescent microparticles was performed, by horizontal and vertical slicing of frozen skin. Fluorescence photomicrographs revealed that PLGA-microparticles could penetrate through the stratum corneum and reach the epidermis. However, permeation experiments showed that these microparticles were not able to reach the receptor compartment of the diffusion cells, even in a period of 24 h. The carriers described in this work could be used as vehicles for topical drug delivery, in order to obtain a sustained drug release into the skin, improving therapy by reduction of time intervals between doses.
Subject(s)
Biocompatible Materials/administration & dosage , Drug Delivery Systems , Lactic Acid/administration & dosage , Polyglycolic Acid/administration & dosage , Polymers/administration & dosage , Skin/metabolism , Administration, Topical , Animals , Fluorescent Dyes/pharmacology , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , Rhodamines/pharmacology , Skin/drug effects , SwineABSTRACT
The goal of this work was to increase the amount of acyclovir (ACV) in the basal epidermis, site of Herpes virus simplex infections, using microparticles as carriers. Poly(D,L-lactic-co-glycolic acid) microparticles loaded with ACV were prepared using a solvent evaporation technique. ACV distribution into porcine skin after topical application of microparticles for 6, 24 and 88 h, was determined by horizontal slicing of the skin. An ACV suspension served for comparison. The results showed that, at 6 and 24 h, the quantity of the drug in the basal epidermis with the microparticles, is similar to that obtained with the ACV suspension. However, after 88 h, the ACV reservoir in the basal epidermis was higher with the microparticles compared with the control suspension. This could be explained by the controlled drug release produced by the vector in the basal epidermis. Besides, at 88 h the amount of ACV detected in the receptor chamber of the diffusion cells was much lower with the microparticles than with the suspension. This type of carrier can improve acyclovir topical therapy since it increases drug retention in the basal epidermis and consequently increases the time intervals between doses.
Subject(s)
Acyclovir/administration & dosage , Antiviral Agents/administration & dosage , Skin Absorption , Acyclovir/pharmacokinetics , Administration, Topical , Animals , Antiviral Agents/pharmacokinetics , Drug Carriers , In Vitro Techniques , Lactic Acid , Microscopy, Electron, Scanning , Microspheres , Particle Size , Polyglycolic Acid , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers , Solubility , Suspensions , SwineABSTRACT
A direct, simple and rapid high-performance liquid chromatographic method has been developed for the determination of ketoprofen with ibuprofen as internal standard. Samples were chromatographed on a 5 microm Kromasil 100 C18 column. The mobile phase was a mixture of acetonitrile-0.01 M KH2PO4 adjusted to pH 1.5 with orthophosphoric acid 85% (60:40, v/v). Detection was at 260 nm and the run time was 10 min. The detector response was found to be linear in the concentration range 0.02 to 40 microg/ml. This HPLC assay has been applied to measure the "in vitro" percutaneous penetration of ketoprofen through rat skin.
