Etanercept decreases tumor necrosis factor-α activity in chronic wound fluid

High levels of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, are present in the wound fluid of chronic nonhealing wounds. This leads to increased inflammation, cytokine expression, and ultimately results in impaired wound healing and tissue destruction. Etanercept is a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1. It is an effective inhibitor of TNF-alpha and has been shown to provide rapid and sustained improvement in rheumatoid arthritis by acting as a soluble receptor binding TNF-alpha and preventing its proinflammatory activities. Therefore, the aim of this study was to determine whether Etanercept could inhibit TNF-alpha activity in chronic wound fluid. Wound fluid was collected from the venous leg ulcers of 16 different patients. The effect of Etanercept on TNF-alpha activity was evaluated using both a TNF-alpha bioassay and an enzyme-linked immunoassay. Etanercept was found to reduce the cytotoxic effect of chronic wound fluid on L929 fibroblasts by approximately 30% and neutralized TNF-alpha binding in the enzyme-linked immunoassay by up to 80%. Direct application of Etanercept to chronic wounds may therefore reduce the inflammatory activity of TNF-alpha, which could reduce the chronicity of venous leg ulcers and thus aid in the healing of these wounds.     

Medical and financial implications of discontinuing a statewide free insulin program involving 3,720 people

In 1981 a statewide program supplying free insulin to 3,720 patients of state health clinics was discontinued. We attempted to assess whether this action had an adverse effect medically and financially on those concerned. A computer randomized sample of 351 patients (9%) was studied by personal interview and questionnaire. Information obtained focused on certain events that occurred 18 months before and after the program ceased. Measurements used to determine medical impact were number of hospitalizations, emergency room and physician visits, changes in weight and glucose levels, and episodes of ketoacidosis. Financial impact was measured by cost of hospitalization and physician visits. Our results revealed no significant changes in any of the medical parameters studied except for fasting serum glucose levels above 300 mg/dl, which occurred less frequently after the free insulin program was discontinued. There were fewer hospitalizations, more visits to physicians, and no change in number of emergency room visits after discontinuance of the free program. The overall cost saving was estimated to be +883,558 for the 18-month study period, in addition to the +550,000 the plan had been costing the state.     

Antidepressant and other centrally acting drugs regulate glucocorticoid receptor messenger RNA levels in rat brain

The effect of imipramine, desipramine, ketanserin and lithium on Type II glucocorticoid receptor (GR) mRNA levels was studied in rat brain regions involved in the control of the hypothalamo-pituitary-adrenal (HPA) axis, the dysregulation of which has been implicated in the pathophysiology of major depression. Northern blot analysis of Type II GR mRNA showed that treatment of male rats with either desipramine or imipramine increased hypothalamic and hippocampal GR mRNA levels. Upregulation of GR mRNA following administration of imipramine was found in brain regions of female rats, while desipramine had no effect. Ketanserin increased levels of GR mRNA in hippocampus of male, but not female, rats. Lithium also was able to induce important increases rat brain GR mRNA; this effect was particularly marked in females.

We conclude that desipramine, imipramine, ketanserin and lithium can modulate GR mRNA in regions of rat brain involved in the control of the HPA axis and may have a common mechanism of action at the level of the GR gene. Sexual dimorphism for drug regulation of brain GR mRNA content was shown and may be related to sex differences in the prevalence of certain affective disorders.     

A comparison of placement methods using a two-in-one dentin pin

Experiments were performed to determine the effect of pin channel preparation with standard and reduction speed handpieces, and pin seating by hand and with motor drive. The greatest retention was achieved by preparation with a standard handpiece at 6000 rpm, and manual pin placement with a hand driver. The most consistent retention values were achieved using the reduction handpiece. All preparation and placement combinations examined produced a clinically acceptable result.     

The association of circulating endotoxin with the development of the adult respiratory distress syndrome

Despite extensive investigation, the pathogenesis of the adult respiratory distress syndrome (ARDS) remains uncertain. As yet, there is no clear explanation of why some patients at risk for ARDS develop the syndrome, whereas others do not. Neutrophils and complement fragments have been implicated in the acute lung injury, but it is clear from published data that evidence of complement activation alone predicts neither the development nor the severity of ARDS. We investigated whether the combination of endotoxin, a leukocyte-priming agent, and complement fragments, leukocyte-stimulating agents, was associated with the development of ARDS. Ninety-eight patients were identified as being either at risk for the development of ARDS or having ARDS, and serial blood samples were obtained. There was no correlation between C5 fragments and the development of ARDS. C3 fragment levels were increased in 89% of the patients with ARDS, but they were also increased in 62% of patients at risk. Endotoxin was detected in 74% of the plasma samples obtained from patients at risk who subsequent developed ARDS and in 64% of the plasma samples obtained from the patients with ARDS. In contrast, only 22% of the plasma samples obtained from the patients at risk who did not develop ARDS had measurable endotoxin. We suggest that the combination of endotoxin and complement fragments may be one mechanism involved in the development of ARDS.     

Human gammaherpesvirus cytokines and chemokine receptors.

Most herpesviruses of the beta and gamma subfamilies encode homologues of cytokines and chemokine receptor- related G protein-coupled receptors (GPCRs). The roles of these proteins during normal virus replication in the infected host have not been defined in most cases, but the available data and extrapolation from what is known about the properties and functions of their cellular counterparts indicate that they play primary roles in immune evasion or in activating cellular signaling cascades that enhance virus productive replication. Cytokines and chemokine receptors specified by the two human gammaherpesviruses, human herpesvirus 8 (HHV-8) and Epstein-Barr virus (EBV), are the subject of this review. HHV-8 encodes three chemokines, a homologue of interleukin-6, and a CXCR2-related chemokine receptor, while EBV encodes a distinct GPCR and a homologue of interleukin-10. While these viral cytokines and chemokine receptors no doubt contribute to virus biology, their properties indicate that they may also be involved in virus-induced neoplasia. This review discusses the properties, functions, and likely roles of HHV-8 and EBV cytokines and chemokine receptors in relation to both virus biology and virus-associated disease.     

The structure and correlates of perfectionism in African American children.

This study examined the structure and symptom correlates of perfectionism in a sample of 6th-grade, urban, African American children using the Child and Adolescent Perfectionism Scale (CAPS; Flett, Hewitt, Boucher, Davidson, & Munro, 2000). Confirmatory factor analysis showed inadequate fit of the original subscales. Exploratory factor analysis suggested 3 dimensions of perfectionism: A Socially Prescribed and a Self-Oriented-Critical factor were described as maladaptive, whereas a Self-Oriented-Striving factor was proposed as adaptive. Cross-sectional correlations among the perfectionism dimensions and symptoms of psychopathology fit well with the adaptive versus maladaptive model. In addition, Socially Prescribed Perfectionism showed a robust predictive relation to 7th-grade internalizing symptoms, especially depression, in boys. Results are discussed in the context of the cultural and socioeconomic characteristics of this African American sample and suggestions for future research are provided.