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PubMedDate not supplied

Stimulatory activity on prostacyclin production decreases in sera from streptozotocin-induced diabetic rats.

We recently reported that serum stimulatory activity on prostacyclin (PGI2) production by cultured bovine aortic endothelial cells decreased in noninsulin-dependent diabetic patients. In the present study, this activity was compared in streptozotocin-induced (STZ) diabetic rats and controls. Platelet-poor plasma-derived serum (PDS) from Wistar male rats stimulated 6-keto-PGF1 alpha production (a stable metabolite of PGI2) by cultured bovine aortic endothelial cells, rat lung fibroblasts, and rat aortic rings in a time- and dose-dependent manner. Namely, PDS from rats has a stimulatory activity on PGI2 production (PGI2 stimulatory activity; PSA). Furthermore, PSA in PDS from STZ diabetic rats (n = 12) significantly decreased as compared with that from control rats (n = 10) using three types of in vitro systems. The reduction in PDS-stimulated PGI2 production by the vascular wall may lead to platelet hyperaggregation and thrombus formation in diabetics, which is considered to be involved in the pathogenesis of diabetic macro- or microangiopathy.

6-Ketoprostaglandin F1 alpha↗
PubMed2002

Impact of Alzheimer's disease and rivastigmine treatment on activities of daily living over the course of mild to moderately severe disease.

OBJECTIVES: To investigate the relationship between activities of daily living (ADL) impairment and Alzheimer's disease (AD) severity in mild to moderately severe AD patients receiving the cholinesterase (ChE) inhibitor rivastigmine. METHODS: ADLs were evaluated using the Progressive Deterioration Scale (PDS). Disease severity was assessed with the Global Deterioration Scale (GDS). Patients were participants in one of three double-blind, placebo-controlled trials with rivastigmine. RESULTS: Baseline PDS scores differed significantly (P<.001) by disease severity. At Week 26, PDS declines from baseline for placebo patients were significantly different at all disease stages. Specific ADL affected were disease stage-dependent. Rivastigmine treatment (6-12 mg/day) resulted in total PDS scores being significantly improved compared with placebo at all disease stages, although the effect on individual items differed by severity. CONCLUSIONS: ADL impairment differs across the stages of AD. Greater impairment in total ADL scores is observed with increasing severity of illness. However, the stage of illness determines the type of ADLs lost. Treatment response to rivastigmine occurs with mild, moderate and moderately severe AD, with the largest effect in patients with advancing severity of disease.

Activities of Daily Living↗
PubMed2001

CSF glutamate/GABA concentrations in pyridoxine-dependent seizures: etiology of pyridoxine-dependent seizures and the mechanisms of pyridoxine action in seizure control.

Several lines of evidence suggest that the binding affinity of glutamate decarboxylase (GAD) to the active form of pyridoxine is low in cases of pyridoxine-dependent seizures (PDS) and that a quantitative imbalance between excitatory (i.e. glutamate) and inhibitory (i.e. gamma-aminobutyric acid, GABA) neurotransmitters could cause refractory seizures. However, inconsistent findings with GAD insufficiency have been reported in PDS. We report a case of PDS that is not accompanied by an elevated cerebrospinal fluid (CSF) glutamate concentration. Intravenous pyridoxine phosphate terminated generalized seizures which were otherwise refractory to conventional anti-epileptic medicines. No seizure occurred once oral pyridoxine (13.5 mg/kg per day) was started in combination with phenobarbital sodium (PB, 3.7 mg/kg per day). The electroencephalogram (EEG) normalized approximately 8 months after pyridoxine was started. The patient is gradually acquiring developmental milestones during the 15 months follow-up period. The CSF glutamate and GABA concentrations were determined on three separate occasions: (1) during status epilepticus; (2) during a seizure-free period with administration of pyridoxine and PB; and (3) 6 days after suspension of pyridoxine and PB and immediately before a convulsion. The CSF glutamate level was below the sensitivity of detection (<1.0 microM) on each of the three occasions; the CSF GABA level was within the normal range or moderately elevated. The CSF and serum concentrations of vitamin B6-related substances, before pyridoxine supplementation, were within the normal range. We suggest that (1) PDS is not a discrete disease of single etiology in that insufficient activation of GAD may not account for seizure susceptibility in all cases and (2) mechanism(s) of anti-convulsive effect of pyridoxine, at least in some cases, may be independent of GAD activation.

Glutamate Decarboxylase↗
PubMed2002

Oxidative DNA damage as a marker of aging in WI-38 human fibroblasts.

Cause-effect relationships between oxidative stress, DNA damage and aging were investigated in WI-38 human diploid fibroblasts at 21, 41 or 58 population doublings (PDs), corresponding to young, middle age or old fibroblasts, respectively. Oxidative DNA damage was evaluated by immunohistochemical detection of 8-hydroxy-2'deoxyguanosine (8-OHdG) adducts or by single cell microgel electrophoresis (COMET assay). Aging was evaluated by growth rate, senescence-associated-beta-galactosidase (SA-beta galactosidase) activity, cell cycle distribution, and expression of p21. Our results demonstrate that (i) oxidative DNA damage is proportional to the age of cells (ii) DNA damage in old/58 PDs cells reflects both an increased susceptibility to oxidative stress, induced by acute exposure to sub-lethal concentrations of hydrogen peroxide (H(2)O(2)), and a reduced efficiency of repair mechanisms. We also show that mild chronic oxidative stress, induced by prolonged exposure to 5 microM H(2)O(2), accelerates aging in fibroblasts. In fact, this treatment increased 8-OHdG levels, SA-beta-galactosidase activity, and G0/G1 cell cycle arrest in middle age/41 PDs, making them similar to H(2)O(2)-untreated old/58 PDs cells. Although other mechanisms may concur in mediating the effects of H(2)O(2), these results lend support to the concept that oxidative stress may be a key determinant of aging. Measurements of oxidative DNA damage might therefore be exploited as reliable marker of cellular aging.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Deception in prison assessment of substance abuse.

The relationship of The Paulhus Deception Scales (PDS; ) to the Texas Christian University Drug Screen I was investigated in participants screened for a voluntary in-prison substance abuse treatment program. Mean PDS scores for 35 female and 277 male prison inmates were significantly higher than the inmate norms in the test manual. All three PDS scale scores were negatively related to symptom endorsement and to the diagnosis of drug dependence. Almost 37% of participants produced protocols of questionable validity, with 22% faking-good and 14.7% faking-bad. However, over 90% of participants obtained scores that were not covered by the manual's profile typology. These findings underline the importance of deception to correctional assessment and the need for more information on the psychometrics and operating characteristics of the PDS in correctional settings.

Adult↗
PubMed2000

Premorbid personality disorders in schizophrenia.

Premorbid personality disorders (PD) were studied retrospectively in 40 schizophrenic patients by interviewing the parents and patients who were reliable with the SCID-II. 85% of the patients had premorbid PDs. The most frequent premorbid PDs were: avoidant PD (32. 5%), schizoid PD (27.5%), paranoid PD (20%), dependent PD (20%) and schizotypal PD (12.5%). In most of the patients, two or more PDs could be diagnosed simultaneously (47.5%), comorbilidity of the premorbid PDs in schizophrenia being the most common one. The most frequent combination was avoidant-schizoid-schizotypal PD.

Adult↗
PubMed2001

Associations of past conduct disorder with personality disorders in 'non-psychotic' psychiatric inpatients.

The aim was to investigate associations of a history of features of DSM-III-R conduct disorder (CD) with features of DSM-III-R personality disorders (PDs) and psychopathy, in inpatient psychiatric practice. Fifty-six psychiatric inpatients, without a history of specified 'psychoses', were assessed by the SCID structured interview for DSM-III-R PDs and the 'Psychopathy Checklist Revised' (PCL-R). In a sample in which 59% had borderline PD, significant associations between a history of CD criteria and the adult features of antisocial PD (APD) were relatively specific compared with other PDs, but were weaker in women. However, significant correlations between the number of positive CD criteria and PCL-R scores were similar in both genders. The relatively specific associations between CD and adult features of APD are likely to be relevant to psychiatric patients who show various presentations of PD, if these include some adult features of APD. The findings inform the understanding of the development and classification of PDs.

Adolescent↗
PubMed2002

A study of release mechanisms of different ophthalmic drugs from erodible ocular inserts based on poly(ethylene oxide).

When topical controlled delivery of ophthalmic drugs is realised via erodible inserts, drug bioavailability is maximised, if release is controlled exclusively by insert erosion, since parallel mechanisms which increase the release rate, also increases the dose fraction cleared from the precorneal area by tear fluid draining. The respective contributions of diffusion and erosion to the release mechanism of different drugs, namely, prednisolone (PDS), oxytetracycline hydrochloride (OTH) and gentamicin sulfate (GTS), from erodible ocular inserts based on poly(ethylene oxide) (PEO) of molecular weight 400 or 900kDa was determined by an in vitro technique adequate to predict the release mechanism in vivo. PDS and OTH were released with erosion-controlled kinetics. With therapeutic doses of these drugs in the inserts (0.3mg, 1.5%), the possibility of a purely erosive mechanism was shown to rely upon drug-PEO molecular interactions, which limit drug diffusion in the swollen matrix. This was the case with OTH, for which strong interactions with PEO were measured, whereas some contribution from the parallel diffusive mechanism was evidenced for PDS, which showed weaker interactions with polymer. Such a contribution disappeared when the PDS concentration in the insert was increased to 6%, which suggested that the erosive mechanism is favoured by a drug concentration in the hydrated insert substantially higher than solubility. On the other hand, the release of about 50% GTS dose was controlled by diffusion, due to the high water solubility of this drug, accompanied by weak drug-PEO interactions. In this case the residence time of drug in the precorneal area is expected to be significantly shorter than that of the PEO carrier.

Benzocaine↗
PubMed1998

Polydiaxonon prevents adhesions in the rabbit model: a pilot report.

PURPOSE: Restrictive strabismus is a common and difficult problem confronted by strabismologists. Several materials have been used to minimize the formation of adhesions after strabismus surgery with varying degrees of success. Polydiaxonon (PDS, Ethicon) is an absorbable, nontoxic, nonporous material. We used it as 25 and 50 microm thick sleeves to study its effectiveness in the prevention of adhesions. METHOD: Eight eyes of four adult New Zealand White rabbits were used. To simulate the adhesions, a raw scleral bed was created under the superior rectus insertion in study animals and the muscle capsule facing the sclera was opened. Four study eyes had PDS sleeves inserted around the superior rectus; the other four served as controls. After 4 months the animals were killed. The surgical sites were inspected for adhesions. Light microscopy was also performed. RESULTS: Virtually no adhesion formation was noted in the study eyes. In the control group, however, dense adhesions were seen. Light microscopy confirmed these results. No significant amount of foreign material was found. There was no toxicity resulting from PDS. CONCLUSIONS: This demonstrated nearly complete prevention of adhesions in the rabbit model. PDS sleeves appear to have potential in surgery for restrictive strabismus.

Absorbable Implants↗
PubMed2002

Personality disorders and depression.

BACKGROUND: Personality disorders (PDs) were assessed among depressed out-patients by clinical interview before and after antidepressant treatment with fluoxetine to assess the degree of stability of PD diagnoses and determine whether changes in PD diagnoses across treatment are related to the degree of improvement in depressive symptoms. METHOD: Three hundred and eighty-four out-patients (55% women; mean age = 39.9 +/- 10.5) with major depressive disorder (MDD) diagnosed with the SCID-P were enrolled into an 8 week trial of open treatment with fluoxetine 20 mg/day. The SCID-II was administered to diagnose PDs at baseline and endpoint. RESULTS: A significant proportion (64%) of our depressed out-patients met criteria for at least one co-morbid personality disorder. Following 8 weeks of fluoxetine treatment, there was a significant reduction in the proportion of patients meeting criteria for avoidant, dependent, passive-aggressive, paranoid and narcissistic PDs. From baseline to endpoint, there was also a significant reduction in the mean number of criteria met for paranoid, schizotypal, narcissistic, borderline, avoidant, dependent, obsessive-compulsive, passive aggressive and self-defeating personality disorders. While changes in cluster diagnoses were not significantly related to improvement in depressive symptoms, there were significant relationships between degree of reduction in depressive symptoms (percentage change in HAM-D-17 scores) and degree of change in the number of criteria met for paranoid, narcissistic, borderline and dependent personality disorders. CONCLUSIONS: Personality disorder diagnoses were found to be common among untreated out-patients with major depressive disorder. A significant proportion of these patients no longer met criteria for personality disorders following antidepressant treatment, and changes in personality disorder traits were significantly related to degree of improvement in depressive symptoms in some but not all personality disorders. These findings suggest that the lack of stability of PD diagnoses among patients with current MDD may be attributable in part to a direct effect of antidepressant treatment on behaviours and attitudes that comprise PDs.

Adolescent↗
PubMed2006

Dimensional representations of DSM-IV cluster A personality disorders in a population-based sample of Norwegian twins: a multivariate study.

BACKGROUND: The 'odd' or 'Cluster A' personality disorders (PDs) - paranoid, schizoid and schizotypal PDs - were created in DSM-III with little empirical foundation. We have examined the relationship between the genetic and environmental risk factors for dimensional representations of these three personality disorders. METHOD: These personality disorders were assessed using the Structured Interview for DSM-IV Personality (SIDP-IV) in 1386 young adult twin pairs from the Norwegian Institute of Public Health Twin Panel. Using Mx, a single-factor independent pathway twin model was fitted to the number of endorsed criteria for the three disorders. RESULTS: The best-fit model included genetic and unique environmental common factors and genetic and unique environmental effects specific to each personality disorder. Total heritability was modest for these personality disorders and ranged from 21% to 28%. Loadings on the common genetic and unique environmental factors were substantially higher for schizotypal than for paranoid or schizoid PD. The proportion of genetic liability shared with all Cluster A disorders was estimated at 100, 43 and 26% respectively for schizotypal, paranoid and schizoid PDs. CONCLUSION: In support of the validity of the Cluster A construct, dimensional representations of schizotypal, paranoid and schizoid PD are all modestly heritable and share a portion of their genetic and environmental risk factors. No evidence was found for shared environmental or sex effects for these PDs. Schizotypal PD most closely reflects the genetic and environmental liability common to all three Cluster A disorders. These results should be interpreted in the context of the limited power of this sample.

Adult↗
PubMed2006

Genetic and environmental influences on dimensional representations of DSM-IV cluster C personality disorders: a population-based multivariate twin study.

BACKGROUND: The DSM-IV cluster C Axis II disorders include avoidant (AVPD), dependent (DEPD) and obsessive-compulsive (OCPD) personality disorders. We aimed to estimate the genetic and environmental influences on dimensional representations of these disorders and examine the validity of the cluster C construct by determining to what extent common familial factors influence the individual PDs. METHOD: PDs were assessed using the Structured Interview for DSM-IV Personality (SIDP-IV) in a sample of 1386 young adult twin pairs from the Norwegian Institute of Public Health Twin Panel (NIPHTP). A single-factor independent pathway multivariate model was applied to the number of endorsed criteria for the three cluster C disorders, using the statistical modeling program Mx. RESULTS: The best-fitting model included genetic and unique environmental factors only, and equated parameters for males and females. Heritability ranged from 27% to 35%. The proportion of genetic variance explained by a common factor was 83, 48 and 15% respectively for AVPD, DEPD and OCPD. Common genetic and environmental factors accounted for 54% and 64% respectively of the variance in AVPD and DEPD but only 11% of the variance in OCPD. CONCLUSION: Cluster C PDs are moderately heritable. No evidence was found for shared environmental or sex effects. Common genetic and individual environmental factors account for a substantial proportion of the variance in AVPD and DEPD. However, OCPD appears to be largely etiologically distinct from the other two PDs. The results do not support the validity of the DSM-IV cluster C construct in its present form.

Adult↗
PubMedDate not supplied

Prenatal determinants of schizophrenia: what we have learned thus far?

The Prenatal Determinants of Schizophrenia (PDS) study was designed to examine early antecedents to schizophrenia. Based in the Child Health and Development Study cohort assembled in 1959-1967, over 12,000 cohort members were followed in the PDS study for psychiatric disorders. Using the extensive data and biological samples prospectively collected beginning during pregnancy, PDS investigators have examined the influence of prenatal exposures on risk of schizophrenia in adulthood. Here we describe a few key findings from the PDS with respect to prenatal infection, nutrition, and toxic exposures.

Biomarkers↗
PubMed2005

Isolation and characterization of phytoene desaturase cDNA involved in the beta-carotene biosynthetic pathway in Dunaliella salina.

The green alga Dunaliella salina is one of the best and most important biological sources of beta-carotene; however, to date the molecular basis of the beta-carotene biosynthesis process in D. salina is still unresolved. The dehydrogenation of phytoene is the second step in the carotenoids biosynthetic pathway, and the phytoene-related desaturases are the key enzymes in the beta-carotene biosynthetic pathway. A phytoene desaturase (Pds) cDNA with a 1752 bp open reading frame was cloned by RT-PCR and RACE-PCR methods on the basis of a modified switching mechanism at 5' end of the RNA transcript (SMART) technology from D. salina. The predicted protein sequence displays a high identity (up to 65%) with phytoene desaturases of higher plants and cyanobacteria. The highest amino acid sequence identity (91%) is shared with the phytoene desaturase sequence of Dunaliella bardawil, and a dinucleotide-binding motif lies in the N-terminal. The phylogenetic analysis shows that D. salina Pds is closer to higher plants and cyanobacteria than bacterial and fungi. These results together demonstrated the cloned Pds cDNA of D. salina is a Pds-type gene, and it is postulated that in D. salina the first two dehydrogenations, by which phytoene is converted into zeta-carotene, are carried out by this putative phytoene desaturase.

Amino Acid Sequence↗
PubMed2006

Ten-year stability of personality disorders among outpatients with mood disorders.

One of the core propositions in most clinical and descriptive models of personality disorders (PDs) is that these conditions are stable over time. However, the available empirical literature suggests that PDs are far less stable than these models imply. The present study examines the 10-year stability of PDs in a sample of depressed outpatients who were assessed for the full range of Axis II conditions across 5 assessments. Three primary issues are addressed: (a) the stability of categorical PD diagnoses, (b) the relative stability of dimensional PD traits, and (c) the absolute stability of PD traits. The stability of PD diagnoses was poor to fair, and the stability of dimensional PD traits was fair to moderate. Growth curve analyses revealed complex patterns of change in absolute scores for PD traits across the 10-year interval. Stability of PDs was generally comparable to that of anxiety disorder diagnoses and normal personality traits.

Adolescent↗
PubMed2005

Influences of beliefs and personality disorders on treatment outcome in anxiety patients.

The present study investigated the effects of personality disorders (PDs) and specific PD-related beliefs on the results of (cognitive-)behavioral therapy for anxiety disorders in a sample of 398 outpatients. The authors used a prospective design in which relationships between PD variables before treatment and outcome measures at posttest and follow-up were evaluated with multilevel analyses. People with PDs and PD-related beliefs reported higher symptom levels at outcome. However, these effects were not as strong as might be expected on the basis of prevailing clinical thought in this area. Dropout rates were not influenced by the presence of 1 or more PDs or PD-related beliefs. Results indicate that treatment of anxiety disorders in patients with concomitant one or more PDs is appropriate.

Adult↗
PubMed2003

The representation of four personality disorders by the schedule for nonadaptive and adaptive personality dimensional model of personality.

This study examined the relationships of the Schedule for Nonadaptive and Adaptive Personality (SNAP) model of personality to 4 targeted personality disorders (PDs) in a large multisite sample of patients. Data were examined from 529 patients, who were assigned 1 of 5 primary diagnoses: borderline, schizotypal, avoidant, and obsessive-compulsive PDs and major depression without PD. Patients were administered the SNAP questionnaire and results were compared among diagnostic groups and between patient groups and nonclinical norms. Results indicated that the dimensions of the model appear to have considerable promise in differentiating normal from abnormal personality, particularly in the propensity of individuals with PDs to manifest negative affects and interpersonal detachment. Furthermore, the model appeared to successfully distinguish specific PDs, a property that represents a particular challenge for dimensional models of personality.

Adaptation, Psychological↗
PubMed1999

The Pendred syndrome gene encodes a chloride-iodide transport protein.

Pendred syndrome is the most common form of syndromic deafness and characterized by congenital sensorineural hearing loss and goitre. This disorder was mapped to chromosome 7 and the gene causing Pendred syndrome (PDS) was subsequently identified by positional cloning. PDS encodes a putative transmembrane protein designated pendrin. Pendrin is closely related to a family of sulfate transport proteins that includes the rat sulfate-anion transporter (encoded by Sat-1; 29% amino acid sequence identity), the human diastrophic dysplasia sulfate transporter (encoded by DTD; 32%) and the human sulfate transporter 'downregulated in adenoma' (encoded by DRA; 45%). On the basis of this homology and the presence of a slightly modified sulfate-transporter signature sequence comprising its putative second transmembrane domain, pendrin has been proposed to function as a sulfate transporter. We were unable to detect evidence of sulfate transport following the expression of pendrin in Xenopus laevis oocytes by microinjection of PDS cRNA or in Sf9 cells following infection with PDS-recombinant baculovirus. The rates of transport for iodide and chloride were significantly increased following the expression of pendrin in both cell systems. Our results demonstrate that pendrin functions as a transporter of chloride and iodide, but not sulfate, and may provide insight into thyroid physiology and the pathophysiology of Pendred syndrome.

Animals↗