Effects of acute ethanol exposure on the early inflammatory response after excisional injury.

Background: Alcohol consumption is involved in over half of all trauma-related injuries. These patients are known to exhibit a higher incidence of mortality and morbidity following injury compared with patients not exposed to ethanol. As studies from our laboratory demonstrated that ethanol exposure impairs re-epithelialization and angiogenesis after dermal wounding and because the earlier inflammatory phase of wound healing is likely to influence later responses, we chose to examine neutrophil infiltration and chemokine and proinflammatory cytokine levels in the skin following administration of a dermal excisional wound.

Motions or muscles? Some behavioral factors underlying robotic assistance of motor recovery.

Robotics and related technologies have begun to realize their promise to improve the delivery of rehabilitation therapy. However, the mechanism by which they enhance recovery remains unclear. Ultimately, recovery depends on biology, yet the details of the recovery process remain largely unknown; a deeper understanding is important to accelerate refinements of robotic therapy or suggest new approaches.

Lessons learned from psoriatic plaques concerning mechanisms of tissue repair, remodeling, and inflammation.

Following injury, skin establishes a balance between too little inflammation increasing risk of infection, and excessive inflammation contributing to delayed wound healing and scarring. Mounting evidence indicates both initiation and termination of inflammation involve active mechanisms. Not only does inflammation itself seem to be a paradox because inflammatory responses are both essential and potentially detrimental, but one chronic inflammatory skin disease (e.

Exogenous pro-angiogenic stimuli cannot prevent physiologic vessel regression.

Background: In healing wounds, rising levels of vascular endothelial growth factor (VEGF) induce a period of robust angiogenesis. The levels of pro-angiogenic factors in the wound begin to decline just before a period of vascular regression, suggesting that these mediators are necessary to sustain vessel density. The purpose of this study was to determine if the maintenance of pro-angiogenic stimuli in the wound would prevent physiological vessel regression.

Diminished induction of skin fibrosis in mice with MCP-1 deficiency.

Scar and fibrosis are often the end result of mechanical injury and inflammatory diseases. One chemokine that is repeatedly linked to fibrotic responses is monocyte chemoattractant protein-1 (MCP-1). We utilized a murine fibrosis model that produces dermal lesions similar to scleroderma to evaluate collagen fibrillogenesis in the absence of MCP-1.

Norepinephrine modulates the inflammatory and proliferative phases of wound healing.

Background: Injury results in the massive release of norepinephrine (NE) into the peripheral circulation. Recent investigations have demonstrated functional adrenoreceptors on the cellular mediators of cutaneous wound healing and NE-induced phenotypic alterations in immune cells have been demonstrated in vitro. Despite this, there is little description of how NE might alter the phases of wound healing in vivo.

Short-duration robotic therapy in stroke patients with severe upper-limb motor impairment.

Chronic motor deficits in the upper limb (UL) are a major contributor to disability following stroke. This study investigated the effect of short-duration robot-assisted therapy on motor impairment, as measured by clinical scales and robot-derived performance measures in patients with chronic, severe UL impairments after stroke. As part of a larger study, 15 individuals with chronic, severe UL paresis (Fugl-Meyer < 15) after stroke (minimum 6 mo postonset) performed 18 sessions of robot-assisted UL rehabilitation that consisted of goal-directed planar reaching tasks over a period of 3 weeks.

Novel function for vascular endothelial growth factor receptor-1 on epidermal keratinocytes.

Vascular endothelial growth factor (VEGF-A), a potent stimulus for angiogenesis, is up-regulated in the skin after wounding. Although studies have shown that VEGF is important for wound repair, it is unclear whether this is based solely on its ability to promote angiogenesis or if VEGF can also promote healing by acting directly on non-endothelial cell types. By immunohistochemistry and reverse transcriptase-polymerase chain reaction, expression of VEGF receptor-1 (VEGFR-1), but not VEGFR-2, was detected in murine keratinocytes during wound repair and in normal human epidermal keratinocytes (NHEKs).

Customized interactive robotic treatment for stroke: EMG-triggered therapy.

A system for electromyographic (EMG) triggering of robot-assisted therapy (dubbed the EMG game) for stroke patients is presented. The onset of a patient's attempt to move is detected by monitoring EMG in selected muscles, whereupon the robot assists her or him to perform point-to-point movements in a horizontal plane. Besides delivering customized robot-assisted therapy, the system can record signals that may be useful to better understand the process of recovery from stroke.

Hydrogen peroxide disrupts scarless fetal wound repair.

Cutaneous wound healing is a complex process that leads to the formation of a permanent scar in adult skin. In contrast, early gestation fetal skin undergoes scarless repair. Normally, the repair process in the skin begins with an acute inflammatory response.

Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training.

Few studies have compared the relative benefits of moderate- vs. higher intensity exercise training on improving insulin sensitivity in older people while holding exercise volume constant. Healthy older (73 +/- 10 yr) women (N = 25) who were inactive, but not obese, were randomized into one of three training programs (9-mo duration): 1) high-intensity [80% peak aerobic capacity (V(O2)peak); T(H)] aerobic training; 2) moderate-intensity (65% V(O2)peak; T(M)) aerobic training; or 3) low-intensity (stretching) placebo control (50% V(O2)peak); C(TB)).

Acute ethanol exposure impairs angiogenesis and the proliferative phase of wound healing.

Acute ethanol exposure represents an increased risk factor for morbidity and mortality associated with surgical or traumatic injury. Despite clinical observations suggesting that ethanol exposure before injury alters tissue repair processes, little direct evidence about the mechanism by which ethanol affects the wound healing process is available. In this study, excisional wounds from female BALB/c mice with or without circulating ethanol levels of 100 mg/dl were used to assess wound closure, angiogenesis, and collagen content.

The effect of MCP-1 depletion on chemokine and chemokine-related gene expression: evidence for a complex network in acute inflammation.

The expression of chemokines has been suggested to involve an interdependent network, with the absence of a single chemokine affecting the expression of multiple other chemokines. Monocyte chemoattractant protein (MCP-1), a member of C-C chemokine superfamily, plays a critical role in the recruitment and activation of leukocytes during acute inflammation. To examine the effect of the loss of MCP-1 on expression of the chemokine network, we compared the mRNA expression profiles of MCP-1(-/-) and wild type mice during the acute inflammatory phase of excisional wounds.

Distinct patterns of angiogenesis in oral and skin wounds.

Clinical observation suggests that oral mucosal wounds heal faster than skin; however, little is known about the site-specific differences. Since fetal skin wounds heal rapidly, but are less vascular than adult wounds, we hypothesized that less robust wound angiogenesis might be observed in healing oral mucosa. This study investigated angiogenesis in equivalent-size oral and skin murine wounds.

Best practices for physical activity programs and behavior counseling in older adult populations.

Physical activity offers one of the greatest opportunities for people to extend years of active independent life and reduce functional limitations. The article identifies key practices for promoting physical activity in older adults, with a focus on those with chronic disease or low fitness and those with low levels of physical activity. Key practices identified: (a) A multidimensional activity program that includes endurance, strength, balance, and flexibility training is optimal for health and functional benefits; (b) principles of behavior change including social support, self-efficacy, active choices, health contracts, assurances of safety, and positive reinforcement enhance adherence; (c) manage risk by beginning at low intensity but gradually increasing to moderate physical activity, which has a better risk:benefit ratio and should be the goal for older adults; (d) an emergency procedure plan is prudent for community-based programs; and (e) monitoring aerobic intensity is important for progression and motivation.

Activation of Latent TGF-β1 by Thrombospondin-1 is a Major Component of Wound Repair.

PURPOSE: Thrombospondin 1 (TSP1) is a matrix glycoprotein that regulates cell adhesion, migration, and proliferation, and is a natural inhibitor of angiogenesis. Recent evidence suggests that TSP1 is a major physiologic activator of latent transforming growth factor-β1 (TGF-β1), and that TGF-β1 is important for wound healing. The purpose of this study was to examine whether excisional wound healing in TSP1-deficient mice is compromised as a result of deficient TGF-β1 activation.

Structurally simplified macrolactone analogues of halichondrin B.

A structurally simplified macrolactone analogue of halichondrin B was identified that retains the potent cell growth inhibitory activity of the natural product in vitro.

Neutrophil function in the healing wound: adding insult to injury?

Cells of the innate immune system, including neutrophils and macrophages, are a highly visible component of normal wound healing in adult mammals. The role of inflammatory cells in the healing wound has been widely investigated, and evidence for both positive and negative influences exists. Several recent investigations support the emerging paradigm that robust inflammation is detrimental to wound closure.

Targeted disruption of TGF-beta/Smad3 signaling modulates skin fibrosis in a mouse model of scleroderma.

Transforming growth factor-beta (TGF-beta) is a potent stimulus of connective tissue accumulation, and is implicated in the pathogenesis of scleroderma and other fibrotic disorders. Smad3 functions as a key intracellular signal transducer for profibrotic TGF-beta responses in normal skin fibroblasts. The potential role of Smad3 in the pathogenesis of scleroderma was investigated in Smad3-null (Smad3(-/-)) mice using a model of skin fibrosis induced by subcutaneous injections of bleomycin.

Evaluation of an instrumented glove for hand-movement acquisition.

Quantitative assessment of digit range of motion (ROM) is often needed for monitoring effectiveness of rehabilitative treatments and assessing patients' functional impairment. The objective of this research was to investigate the feasibility of using the Humanware Humanglove, a 20-position sensors glove, to measure fingers' ROM, with particular regard to measurement repeatability. With this aim, we performed a series of tests on six normal subjects.

Can physical activity attenuate aging-related weight loss in older people? The Yale Health and Aging Study, 1982-1994.

The purpose of this analysis was to determine the longitudinal relation between physical activity and the trajectory of weight change in an older cohort (> or =65 years) living in New Haven, Connecticut, who participated in the Established Populations for the Epidemiologic Study of the Elderly between 1982 and 1994 (n=2,812). The authors hypothesized that body weight would decline over the follow-up and that physical activity would play an important role in minimizing weight loss over time. Physical activity and other covariables were self-reported at baseline, while body weight was self-reported annually over 12 years.