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Abnormality in prostacyclin-stimulatory activity in sera from diabetics.

A reduction in prostacyclin (PGI2) production by vascular wall may cause platelet hyperaggregability in diabetics, which is considered to be a possible pathogenesis of diabetic vascular complications. In the present study, the presence of PGI2-stimulatory activity (PSA) in rat and human plasma-derived serum (PDS) was confirmed by cultured bovine aortic endothelial cells. PSA in PDS was significantly decreased in streptozotocin-induced diabetic rats and in patients with non-insulin-dependent diabetes mellitus (NIDDM). PDS from patients with NIDDM showed less PSA prior to the clinical onset of diabetic vascular complications, such as retinopathy and proteinuria. The reduction in PSA was still observed in dialyzed PDS from the patients with NIDDM. The nondialyzable PSA was heat-stable at 56 degrees C for 30 minutes and partially stable at 100 degrees C for five minutes. This activity was not extractable with diethylether and was precipitable with trichloroacetic acid. The study of Sephadex G-50 column chromatography showed that a major part of PSA in dialyzed PDS was found in the area of the molecular weight of 12,000 to 17,000 daltons. In conclusion, the reduction in PSA from diabetics may cause a reduction of PGI2 production by vascular wall, subsequently contributing to the development of diabetic vascular complications.

6-Ketoprostaglandin F1 alpha↗

Accelerated aging of dermal fibroblast-like cells from senescence-accelerated mouse (SAM). 1. Acceleration of population aging in vitro.

Fibroblast-like cells were isolated from the senescence accelerated mouse (SAM) and cultured, after which evidence of accelerated senescence was sought. Fibroblast-like cell lines were established from the dorsal dermis of neonate mice of both the accelerated senescence-prone strain, SAMP11 and the accelerated senescence-resistant strain, SAMR1. All cell lines from both strains showed a crisis in growth and were immortalized. At crisis, all cultures were composed of morphologically characteristic senescent cells. However, in cell lines from SAMP11, this change was more rapid and at earlier population doublings (PDs) than seen in cell lines from SAMR1. Crises (SAMP11; SAMR1) were also operationally taken to be the point of the least change in PDs (11.2 +/- 1.1; 15.4 +/- 0.5 PDs), the least saturation density (11.3 +/- 0.8; 19.1 +/- 2.6 PDs), and the longest population doubling time (10.1 +/- 0.8; 14.2 +/- 0.6 PDs). Crisis occurred significantly earlier (P < 0.05) and the aging process was accelerated in cell lines from SAMP11, compared with lines from SAMR1. This evidence tends to support various observations made in the accelerated senescence-prone strains of SAMP, in vivo.

Aging↗

Comparative study of the precipitation of low density lipoproteins by aortic proteodermatan sulphate and heparin.

The aortic proteoglycans and heparin were shown to form insoluble complexes with human low density lipoproteins (LDL). The effect of temperature, polyethylene glycol and ionic strength on the formation of complexes between porcine aortic proteodermatan sulphate (PDS) and LDL has been studied by laser nephelometry and comparisons made with heparin LDL complexes. Turbidity was a nonlinear function of the quantity of LDL precipitated by PDS. The turbidity of aggregates was constant at temperatures between 2 degrees C and 30 degrees C but increased with temperature above 30 degrees C up to 50 degrees C. The formation of insoluble complexes decreased rapidly with increasing NaCl concentration. Polyethylene glycol enhanced the turbidity at 20 degrees C but not at 37 degrees C. It also increased the resistance of complexes to dissociation by increasing ionic strength. The turbidity of heparin--LDL complexes was linearly correlated with the quantity of precipitated LDL. The heparin-LDL aggregates were less sensitive to modification of temperature and ionic strength than the PDS-LDL aggregates. These results suggest that ionic interactions are weaker in PDS-LDL complexes than in the heparin-LDL complexes. Non-coulombic interactions and/or temperature dependent conformational changes may be involved in the stabilization of supramolecular PDS-LDL aggregates. No such interactions or changes appear to be involved in complex formation between heparin and LDL.

Animals↗

Major depression and personality disorder.

The authors examined an interview and paper-and-pencil assessment of the DSM-III personality disorders (PDs) in depressed inpatients, and depressed relatives of psychiatric patients and never-ill controls who had a lifetime history of major depression. The rates of PDs according to the Structured Interview for DSM-III Personality Disorders (SIDP) were similar in the two groups, except for borderline PD which was more frequent in the inpatients. Of the individuals with a PD, the patients were more likely than the relatives to have two or more PDs, and the borderline and histrionic patients were more prototypic of these disorders than were the borderline and histrionic relatives. In contrast to the SIDP results, the rates of PDs according to the Personality Disorders Questionnaire (PDQ) were higher in the patient sample. These results thus extend the previously described high rates of PDs in depressed patients to a sample of individuals with a lifetime history of treated or untreated depression, and they suggest that interview assessments of personality may be less sensitive to the state effects of depression than are questionnaires.

Adult↗

Mechanical implications of paired motor unit discharges in pathological and voluntary tremor.

Paired motor unit discharges (PDs), i.e., two discharges of the same motor unit (MU) with short interval, and their relation to tremor amplitude were studied in the first dorsal interosseous muscle (FDI) of patients with parkinsonian or essential tremor and in normal subjects mimicking tremor. In both pathological and voluntary tremor, interdischarge intervals of PDs were inversely correlated with the amplitude of the subsequent tremor beat, i.e., PDs with shorter intervals were followed by higher tremor beats. To further assess their mechanical impact, PDs were simulated by applying paired stimuli to MUs of the FDI in normal subjects using intramuscular microstimulation. Following paired stimuli, summation of twitch responses was more than linear. This was also the case with the paired stimuli applied at a tremor-like repetition rate (5 Hz). These findings stress the importance of PDs for tremor expression.

Adult↗

Paroxysmal depolarization shifts induced by bicuculline in CA3 neurons of hippocampal slices: suppression by the organic calcium antagonist verapamil.

Organic calcium antagonists have been reported to abolish epileptic neuronal discharges elicited by pentylenetetrazol and penicillin. It was tested whether the organic calcium antagonist verapamil is able to suppress also paroxysmal depolarization shifts (PDS) induced by bicuculline. This is of special interest, since bicuculline is assumed to produce PDS by blocking GABAergic synaptic inhibition. The experiments were performed on CA3 neurons of hippocampal slices (guinea pig). Verapamil (40, 60, and 80 microM) reduced amplitude, duration and frequency of appearance of PDS until the generation of PDS failed. The results indicate that calcium currents are also involved in bicuculline PDS, and that bicuculline exerts its epileptogenic action, at least in part, on extrasynaptic sites.

Animals↗

Effect of APV and ketamine on epileptiform activity in the CA1 and CA3 regions of the hippocampus.

Intracellular recordings were obtained from hippocampal CA1 and CA3 pyramidal neurons maintained in vitro. The ability of the NMDA receptor antagonists ketamine and APV to suppress picrotoxin-induced epileptiform burst activity was examined. Activity was recorded either after a single orthodromic stimulation, which gave rise to paroxysmal depolarization shift (PDS), or during a 500 msec train of 50 Hz stimulation, which produced a sustained depolarization. In the CA1 and CA3 areas, both the PDS and sustained depolarization were reduced by APV (20 microM) and ketamine (100 microM). APV reduced the area under the PDS by 24 +/- 3% and 32 +/- 4% in CA1 and CA3 neurons, respectively. The corresponding reductions in the sustained depolarization were 10 +/- 2% and 22 +/- 4%. Ketamine reduced the PDS by 43 +/- 4% and 31 +/- 4% in CA1 and CA3 and decreased the sustained depolarization by 21 +/- 3% and 12 +/- 3%. In all cases, NMDA receptor antagonists had a significantly greater effect on the PDS than the sustained depolarization. These results indicate that, although not essential for generation of paroxysmal activity, NMDA receptors make significant contributions to epileptiform activity in both CA1 and CA3 regions of the hippocampus.

2-Amino-5-phosphonovalerate↗

Electrospinning polydioxanone for biomedical applications.

Polydioxanone (PDS) is a colorless, crystalline, bioabsorbable polymer that was first developed specifically for wound closure sutures. The compatibility, degradation rate, and mechanical properties (including shape memory) of PDS are of interest when considering the design of tissue engineering scaffolds. This research presents the electrospinning of PDS to fabricate unique nanofibrous structures for a variety of biomedical applications. Electrospinning is a polymer processing technique that utilizes an electric field to form fibers from a polymer solution or melt and allows the fabrication of nanofibrous non-woven structures. Results demonstrate the ability to control the fiber diameter of PDS as a function of solution concentrations and the fiber orientation with our prototype electrospinning apparatus. The results also show dependence between the fiber orientation and the elastic modulus, peak stress, and strain to failure of PDS in a uniaxial model.

Biocompatible Materials↗

Parental vaccine safety concerns. The experiences of pediatricians and family physicians.

OBJECTIVES: Recently several concerns regarding vaccine safety have received significant media attention. Primary care physicians are the most common interface for parents with the immunization delivery system and are likely to have the greatest opportunity for exposure and experience with parental vaccine safety concerns. METHODS: Mail survey study of a national random sample of 750 pediatricians (PDs) and 750 family physicians (FPs) was conducted in 2000. Outcome variables of primary interest included the number of parental vaccine refusals in the past year, frequency of specific parent vaccine safety concerns, and actions taken by physicians when parents refused a vaccine. Chi-square analysis was used to determine the significance of the association of each outcome variable of interest with physician specialty, frequency of vaccine refusal, and the demographic variables. Multivariate analysis explored the potential for independent predictors of physicians who experienced increases in vaccine refusal. RESULTS: The response rate was 70%. Overall, 93% of PDs and 60% of FPs reported at least one parental vaccine refusal in their practice in the past year. PDs also were more likely than FPs to report an increase in the number of vaccine refusals over the past year (18% v 8%, p =0.01), while FPs were more likely to report a decrease in vaccine refusals over the same time period (18% v 11%; p <0.5). PDs were more likely than FPs to provide additional information regarding vaccines to parents who refused vaccines and/or to discuss the issue at later visits. The most common concerns of parents were related to short-term reactions and pain from multiple injections. CONCLUSIONS: While almost all PDs and most FPs experienced at least one vaccine refusal from parents in the past year, far fewer physicians of both specialties observed an increase in their occurrence. Physicians must work to be consistently well informed of both the benefits of immunization as well as the issues of parental concern regarding vaccine safety.

Child, Preschool↗

Same causes, same cures.

Thanks to the continuing bio-medicinal efforts, similar causes underlying the pathogenesis of Alzheimer's disease (AD) and prion diseases (PDs) have been revealed, which include oxidative stress, excessive transition metal ions, and misfolded/aggregated proteins. Therefore, the therapeutic strategy for one disease may be effective for the other. More interestingly, accumulating evidence indicates that not just the strategies but also the prescriptions may be shared by AD and PD treatments. In this review, we first summarize the known dual fighters against AD and PDs (which include antioxidants, metal chelators, and protein aggregation inhibitors), and then indicate that some super-dual-fighters may hit multiple targets implicated in AD and PDs, whose structural features highlight the importance of aromatic moiety and phenolic groups. These findings not only provide important clues to accelerating the screening of anti-AD and anti-PDs drugs but also help to understand the etiology of AD and PDs.

Alzheimer Disease↗

Mood patterns and variations associated with personality disorder pathology.

This study examined mood and mood variation in relation to varying forms and degrees of personality disorder (PD) pathology. Mood experiences of 98 psychotropic medication-free individuals were repeatedly assessed over a 4-day period. Persons with PDs (n = 57) generally displayed neutral to moderately positive moods; however, overall mood valence was less positive when compared to those without PDs (n = 41). Mood ratings demonstrated moderate covariations with anxious-fearful (A-F) PD traits but little or no association with erratic-emotional-dramatic (E-D) and odd-eccentric (O-E) PD traits once common variance among PD dimensions was removed. For PD diagnostic categories, the presence of avoidant and/or depressive PDs was most strongly associated with negative mood. When dimensional scores based on specific PD trait features were considered, avoidant, depressive, borderline, passive-aggressive, obsessive-compulsive, dependent, paranoid, and schizoid PD traits demonstrated the most reliable associations with negative mood. Apart from borderline PD features, traits associated with other E-D cluster PDs displayed little or no associations with mood quality. Consistent with previous research, mood variability emerged as an internally consistent and stable individual difference variable. Mood variability, however, was not generally associated with PD diagnostic categories or traits. Implications of this study's findings are considered in relation to the conceptual modeling of PDs.

Adult↗

Results of interval debulking surgery compared with primary debulking surgery in advanced stage ovarian cancer.

BACKGROUND: Results of IDS (after three to four courses of induction chemotherapy) were compared with PDS followed by chemotherapy in patients treated for advanced stage ovarian cancer (stage IIIC or IV). STUDY DESIGN: A retrospective study was done on a group of 57 patients who underwent IDS (because of an unresectable tumor) compared with a group of 28 patients treated with PDS (for resectable disease) followed by chemotherapy. All patients were treated between 1996 and 2001 by the same team of surgeons and received the same regimen of chemotherapy (platinum based plus paclitaxel). RESULTS: Optimal cytoreductive surgery (residual disease < or = 2 cm) was achieved in IDS and PDS groups in 84% (48 of 57) and 100% (28 of 28) of patients, respectively. Complete resection was observed in 51% (29 of 57) of patients in the IDS group and 54% (15 of 28) of patients in the PDS group. The rates of bowel resection, large peritoneal resection, and postoperative morbidity were significantly reduced in the IDS group. After adjusting for the size of residual disease (< or /= 2 cm and absence of residual tumor), overall and event-free survival were not different in the two groups. CONCLUSIONS: Survival rates were similar in patients with advanced stage ovarian cancer who underwent IDS or PDS. The rates of surgical resection and morbidity were reduced after IDS. IDS can be safely used in unresectable advanced stage ovarian cancer.

Adult↗

Impulsivity, aggressiveness, and DSM-IV personality disorders.

The aim of this study is to assess whether impulsive and aggressive traits can be placed on a continuum with DSM-IV Cluster B Personality Disorders (PDs) and to determine if different aspects of these personality traits are specifically associated with individual Cluster B PDs. The study group comprised 461 outpatients admitted consecutively to a clinic that specializes in the diagnosis and treatment of PDs. Principal component analyses clearly suggested a five-factor structure of both normal and psychopathological personality traits. Importantly, measures of impulsivity, aggressiveness and novelty seeking formed a part of the principal component that clustered all Cluster B PDs. Regression analyses indicated that impulsive traits were selectively associated with Borderline PD whereas different aspects of aggressiveness were useful in discriminating Narcissistic PD from Antisocial PD. Sensation seeking traits formed a part of Histrionic PD. These results indicate that impulsive/aggressive traits may be useful in explaining both why Cluster B PDs tend to covary, and why they frequently differ in clinical pictures and courses.

Adult↗

Which factors may play a pivotal role on determining the type of psychiatric disorder in children and adolescents with epilepsy?

Physicians have become aware of the high prevalence of psychiatric disorders (PDs) in children and adolescents with epilepsy; however, there are many controversies as to which factors may have an important role in the different types of PD. This study was designed to assess the main PD; verify the age of onset compared with the age of diagnosis of the PD; and determine which factors may be correlated with the type of PD described. For this purpose, a multidisciplinary team evaluated children and adolescents (4-18 years) with epilepsy and analyzed patient-related factors such as age (grouped according to Piaget's cognitive scale: <6 years, 7-13 years, >13 years), sex, family history of PDs, and cognitive status. With respect to epilepsy features, we considered age of onset, duration, seizure control at the time of psychiatric evaluation, refractoriness, antiepileptic drugs (mono- vs polytherapy), seizure type (generalized vs focal), and epilepsy type (idiopathic vs symptomatic/probably symptomatic). Depression occurred in 36.4% and attention-deficit hyperactivity disorder (ADHD) in 29.1%, these being the most frequent PDs in this series. Focal epilepsy was significantly more frequent in children and adolescents with PDs. As to the type of PD, age was an important factor, with a predominance of ADHD in children and depression in adolescents (P<0.0001). Family history was contributory for depression, but not for others PDs (P<0.0001). Depression remained underdiagnosed and untreated for a longer period. Impact of early diagnosis and treatment remains unknown.

Adolescent↗

Do personality disorders exist? On the validity of the concept and its cognitive-behavioral formulation and treatment.

Since the introduction of personality disorders as important diagnostic categories in the DSM-III [APA (1980). Diagnostic and statistical manual of mental disorders (3rd ed.). Washington, DC: American Psychiatric Association] the concept of personality disorder (PD) has met both skepticism and enthusiasm. This paper addresses criticisms, reviews theoretical and empirical evidence for the concept of personality disorders (PD), critically discusses widespread clinical ideas about PDs, and reviews cognitive-behavioral models and treatments of PDs. It is concluded that there is enough evidence for the usefulness of PDs as diagnostic categories. A confirmatory factor analysis for instance yielded very reasonable evidence for the categories hypothesized by the DSM. Contradicting widespread ideas, research indicates that PDs are not a contraindication for cognitive-behavioral treatments of axis-I problems, and that there are even indications that PD pathology itself can be successfully treated using modified CBT methods. In stark contrast to the generally rich empirical history of CBT, research on cognitive models and treatment of PDs is virtually absent. However, the sparse attempts indicate that cognitive models may be fruitful in this area. Future research should be directed at further developing and testing cognitive conceptualizations and treatment models.

Adult↗

Effect of trabecular aspiration on intraocular pressure in pigment dispersion syndrome and pigmentary glaucoma.

OBJECTIVE: Recently, we described a new form of nonfiltering glaucoma surgery-trabecular aspiration-designed to increase trabecular outflow in pseudoexfoliation glaucoma. This study was carried out to investigate whether trabecular aspiration is equally safe and effective in the treatment of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). STUDY DESIGN: Prospective, nonrandomized comparative trial with historical control. PARTICIPANTS: Twenty eyes of 20 patients with medically uncontrolled intraocular pressure (IOP) caused by PDS or PG were treated by trabecular aspiration. INTERVENTION: Trabecular pigment particles were cleared with a pressure of 100 to 200 mmHg using a specially designed aspiration probe. MAIN OUTCOME MEASURES: The IOP and number of medications before and after surgery were measured. Intraoperative and postoperative complications were analyzed. Surgical success was defined as IOP < or = 21 mmHg with no more than one topical medication. Results were compared with those previously reported with similar treatment of pseudoexfoliative glaucoma. RESULTS: Mean pretreatment IOP averaged 27.0 (standard deviation [SD], 3.3) mmHg and was significantly reduced to 23.7 (SD, 3.9) mmHg at last follow-up (20.1 +/- 8.6 months). However, the cumulative life-table success rates were only 42% and 15% at 3 and 12 months, respectively. Considering both groups separately, the success rates in the PDS group were 63% and 18% at 3 and 12 months compared with a success rate of 12% in the PG group as early as 1 month after surgery. CONCLUSIONS: Eyes with PDS responded better to trabecular aspiration than do those with PG, indicating that PDS and PG are two successive stages of the same disease process. Altogether, trabecular aspiration failed to achieve long-term pressure control in either of the two groups.

Adult↗

A comparison of the adenosine-mediated synaptic inhibition in the CA3 area of immature and adult rat hippocampus.

We compared the effects of the adenosine A1 receptor activation on the postsynaptic potentials (psps) recorded from the CA3 area of immature (postnatal days 10-20) and adult rat hippocampal neurons in vitro. The adenosine A1 receptor agonist 2-phenyl-isopropyl-adenosine (PIA, 1 microM) depressed the stimulus-induced psps less in immature and more in adult neurons. In the presence of the GABAA receptor antagonist bicuculline methiodide (BMI, 10 microM), PIA reduced the duration and number of action potentials of the stimulus-induced paroxysmal depolarizations (PDs) in immature neurons, while it blocked PDs in adult neurons. Spontaneous BMI-induced PDs, were blocked by PIA in less than half (5/12) immature and all (6/6) adult neurons. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 microM) enhanced the stimulus-induced psps in immature and adult neurons alike; this effect did not lead to stimulus-induced bursting in immature neurons. DPCPX induced spontaneous bursts (proconvulsant effect) in only 2/16 immature but in all adult (12/12) neurons. In BMI, DPCPX increased the duration and number of action potentials of the stimulus-induced PDs in immature and adult neurons alike (by about 30%), but it increased the rates of occurrence of spontaneous PDs in significantly more adult neurons. In conclusion, our results suggest that adenosine, acting via A1 receptors, is a more effective endogenous anti-epileptic in adult than in immature hippocampus, a fact which may contribute to the susceptibility of the latter to epileptogenesis.

Adenosine↗

Psychomotor desadaptation syndrome.

This article constitutes a description of a clinical entity that has been observed and that we have described in French literature for over 10 years. This syndrome has been named 'la Régression Psychomotrice' in the french language and is termed here 'psychomotor desadaptation syndrome' (PDS). Postural impairments, neurological signs and psychological features have been found to be associated with PDS. Postural and neurological disorders were characterized by retropulsion, muscle tone modification, and the loss of reactive and protective postural reactions. Psychological features consisted of slowness of cognitive processing, often associated with anxiety and a fear of falling. PDS may be considered as a functional disorder, and clinicians must identify not only predisposing factors, but also etiological ones. The medical treatment of these factors and specific readaptation approaches must be associated with the management of PDS. PDS appears to be a reversible syndrome if a multidisciplinary approach and early management are undertaken.

Journal Article↗