Defensin stimulates the binding of lipoprotein (a) to human vascular endothelial and smooth muscle cells

There is evidence to suggest that elevated plasma levels of lipoprotein (a) [Lp(a)] represent a risk factor for the development of atherosclerotic vascular disease, but the mechanism by which this lipoprotein localizes to involved vessels is only partially understood. In view of studies suggesting a link between inflammation and atherosclerosis and our previous finding that leukocyte defensin modulates the interaction of plasminogen and tissue-type plasminogen activator with cultured human endothelial cells, we examined the effect of this peptide on the binding of Lp(a) to cultured vascular endothelium and vascular smooth muscle cells. Defensin increased the binding of Lp(a) to endothelial cells approximately fourfold and to smooth muscle cells approximately sixfold. Defensin caused a comparable increase in the amount of Lp(a) internalized by each cell type, but Lp(a) internalized as a consequence of defensin being present was not degraded, resulting in a marked increase in the total amount of cell-associated lipoprotein. Abundant defensin was found in endothelium and in intimal smooth muscle cells of atherosclerotic human cerebral arteries, regions also invested with Lp(a). These studies suggest that defensin released from activated or senescent neutrophils may contribute to the localization and persistence of Lp(a) in human vessels and thereby predispose to the development of atherosclerosis.     

Ventilation is stimulated by small reductions in arterial pressure in the awake dog

Changes in arterial pressure commonly accompany respiratory adaptations. The purpose of this study was to determine, in awake dogs (n = 6), the degree to which small acute decreases in arterial pressure affect ventilation and acid-base balance. Mean arterial pressure (MAP) was reduced by 6 +/- 2, 10 +/- 3, and 16 +/- 2% by intravenous infusion of sodium nitroprusside for sequential 20-min periods. In another experiment, the ventilatory response to hypercapnia was determined during MAP reduction of 16 +/- 3%. Step reductions in MAP were accompanied by increases in minute ventilation (maximum increase 152 +/- 75%) and step reductions in arterial PCO2 (PaCO2; maximum reduction -4.8 +/- 0.8 Torr). Although eupneic PaCO2 threshold was lowered during MAP reduction, ventilatory sensitivity to CO2 remained unchanged. Despite the lowered PaCO2, arterial [H+] remained constant (acid-base balance was maintained) as a result of a concurrent decrease in strong ion difference. Plasma renin activity increased during MAP reduction (93 +/- 39%) and may have contributed to the increase in minute ventilation, inasmuch as angiotensin II can stimulate respiration by a central mechanism. Evidence is provided that nitroprusside is unlikely to be a primary factor in these hypotensive responses. We conclude that relatively modest decreases in MAP have a consistent stimulatory effect on respiratory control. Therefore it is important to take into account effects of small changes in MAP when interpreting mechanisms for respiratory responses in awake animals.     

Development of 5'-nucleotidase staining in the olfactory bulbs of normal and naris-occluded rats

The distribution of the adenosine-producing ecto-enzyme 5'-nucleotidase was investigated histochemically in the developing rat olfactory bulb. Rat pups underwent either unilateral surgical occlusion of the right external naris or sham surgery on postnatal day 1. At 10, 20, or 30 days postpartum, horizontal sections of the olfactory bulb were reacted histochemically to reveal the locus and intensity of 5'-nucleotidase activity. Relative staining levels were determined by optical densitometry in standardized bulb regions. A marked, age-related increase in staining density was observed. Reaction product was found primarily in neuropil areas. The P10 and P20 control animals did not exhibit right/left differences in bulb staining; however, some laterality was observed in P30 animals. Inter-glomerular and regional variations were observed throughout the developmental period, including (1) differences between neighboring glomeruli; (2) a gradient in the dorsal-ventral axis of the bulb; and (3) a higher staining density in the medial-caudal portion of the bulb. In subjects with occluded nares, asymmetries in right/left bulb 5'-nucleotidase staining patterns were detected throughout development. Bulbs ipsilateral to the blocked nares exhibited increased staining density, suggesting that the procedure enhanced enzymatic activity. Understanding these variations in 5'-nucleotidase staining may be important for a complete understanding of the mechanisms of olfactory bulb maturation and may give insight into the possible role of this enzyme in synaptic malleability during nervous system development and regeneration.     

Avoidant personality disorder and the generalized subtype of social phobia.

Social phobia and avoidant personality disorder (APD) may be given as comorbid diagnoses. However, it is not known if the labels provide independent, useful diagnostic information. The authors classified social phobics by social phobia subtype and presence of APD. Generalized social phobics with and without APD (ns?=?10 and 10) and nongeneralized social phobics without APD (n?=?10) were distinguished on measures of phobic severity. The generalized groups also showed earlier age at onset and higher scores on measures of depression, fear of negative evaluation, and social anxiety and avoidance than did the nongeneralized group. APD criteria of general timidity and risk aversion were more frequently endorsed by social phobics with AD. The data suggest that both the generalized subtype of social phobia and the presence of APD do provide useful diagnostic information, but the additional diagnosis of APD may simply identify a severe subgroup of social phobics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The value of indium-111-labelled leucocyte imaging and ultrasonography in the investigation of pyrexia of unknown origin

The aim of this study was to assess indium-111 leucocyte imaging and ultrasound in the investigation of pyrexia of unknown origin (PUO), as well as the predictive value of available clinical information on the radiological outcome. 256 111In leucocyte scans performed over a 5 year period were reviewed. There were 59 scans in 58 patients who fulfilled recognized criteria for true PUO; 47 of these patients had ultrasound. In 15 patients the fever settled and no diagnosis was made; the source of PUO was infective in 20 and non-infective in 24. In the group as a whole, the sensitivities of leucocyte scan and ultrasound were 25% and 23% with specificities of 100% and 83%, respectively. In infective cases of PUO, the sensitivities were 20% for both modalities. There was no correlation between leucocyte count or differential, C reactive protein or the presence or absence of antibiotics. In the cases where the leucocyte scan led to the diagnosis of infection, the scan was performed within 4 weeks of the onset of symptoms. The results show that an infective cause for PUO is established in less than 50% of cases. The leucocyte scan is specific and although not very sensitive can often be a guide to subsequent cross-sectional imaging. If an infective cause for the PUO is strongly suspected, 111In leucocyte scanning may be more sensitive if performed in the first few weeks of fever.     

Brief coping skills treatment for cocaine abuse: substance use outcomes at three months

AIMS: Coping skills training, a promising treatment approach for alcoholics, was adapted for use with cocaine abusers and effects on outcome were investigated. DESIGN: A cocaine-specific coping skills training (CST) package was compared to an attention placebo control when both were added to a comprehensive treatment program. SETTING: The sites were two private substance abuse treatment facilities, one residential and rural, and one an urban partial hospital. PARTICIPANTS: Substance abusers in treatment with cocaine abuse or dependence were selected. INTERVENTION: The CST intervention was conducted in individual sessions. It involved functional analysis of high risk situations and coping skills training based on the functional analysis. FINDINGS: Clients who received CST had significantly fewer cocaine use days and the length of their longest binge was significantly shorter during the 3-month follow-up period compared to clients in the control condition. CST did not affect relapse rates or use of other substances. CONCLUSIONS: Results support the notion that cocaine-specific CST is a promising adjunct to treatment for cocaine abusers.     

Traumas and other adverse life events in adolescents with alcohol abuse and dependence

OBJECTIVE: Clinical observation suggests that adolescents with alcohol use disorders often have complex histories that include childhood maltreatment and other traumas. The aim of this study was to determine the relationships among adolescent alcohol use disorders and a broad range of traumas and adverse life events. METHOD: The subjects were 132 adolescents with alcohol dependence, 51 adolescents with alcohol abuse, and 73 adolescents recruited from the community as a control group. Trauma history was assessed by a semistructured interview and other adverse life events by questionnaire. RESULTS: Traumatic events reflecting interpersonal violence had occurred in many of the adolescents with alcohol dependence and abuse and few of the control adolescents. Adolescents with alcohol abuse or dependence, compared with control subjects, were 6 to 12 times more likely to have a physical abuse history and 18 to 21 times more likely to have a sexual abuse history. Sexual abuse was more common in females, and victimization by other violent acts was more common in males. Many other adverse life events were also significantly more common in the alcohol use disorder groups than in the control group, including having a close friend die, arguments within the family, and legal difficulties. CONCLUSIONS: These results demonstrate that trauma and other adverse life events are strongly associated with alcohol use disorders in adolescents. Clinical screening of adolescents with alcohol use disorders for a range of traumatic events is recommended.