Role of nitric oxide in wound healing

Chronic wounds mainly affect elderly individuals and persons with comorbid diseases due to a compromised immune status. An age-related decline in immune function deters proper healing of wounds in an orderly and timely manner. Thus, older adults with 1 or more concomitant illnesses are more likely to experience and sufferfrom a nonhealing wound, which may drastically decrease their quality of life and financial resources. Novel therapies in wound care management rely heavily on our current knowledge of wound healing physiology. It is well established that normal wound healing occurs sequentially and is strictly regulated by pro-inflammatory cytokines and growth factors. A multitude of commercial products such as growth factors are available; however, their effectiveness in healing chronic wounds has yet to be proven. Recently, investigators have implicated nitric oxide (NO) in the exertion of regulatoryforces on various cellular activities of the inflammatory and proliferative phases of wound healing. Gene therapy in animal studies has shown promising results and is furthering our understanding of impaired wound healing. The purpose of this article is to review the literature on NO and its role in wound healing. A discussion of the physiology of normal healing and the pathophysiology of chronic wounds is provided.     

Cineplasty as a control input for externally powered prosthetic components

To achieve significant improvement in the function of electric-powered, upper-limb prostheses, we believe it is necessary to develop better control interfaces with inherent sensory feedback. Small cineplasties, or other surgical procedures that also externalize the force and excursion of a muscle, could potentially provide this superior control. Connecting a muscle to a prosthetic component via a controller that embodies the concept of extended physiological proprioception (EPP) would enable the physiological sensory feedback inherent in the skin, muscle, and other tissues of the cineplasty to inform the user of the state of the prosthesis. Multiple miniature forearm tunnel cineplasties, each with an EPP controller, might enable meaningful independent multifinger control of hand prostheses. At higher levels of amputation (e.g., transhumeral), small pectoral or deltoid cineplasties could augment existing control sources to improve control of multifunctional total arm prostheses. To explore the feasibility of these ideas, we quantified the control capabilities of individuals with preexisting biceps muscle tunnel cineplasties with the use of pursuit tracking experiments. A "proof-of-concept" EPP electric hand prosthesis was also successfully developed for a subject with agonist-antagonist, forearm tendon exteriorization cineplasties. The results of the tracking studies demonstrate numerically the efficacy of control by cineplastized muscles relative to other control approaches.     

A paradox resolved: Sulfide acquisition by roots of seep tubeworms sustains net chemoautotrophy

Vestimentiferan tubeworms, symbiotic with sulfur-oxidizing chemoautotrophic bacteria, dominate many cold-seep sites in the Gulf of Mexico. The most abundant vestimentiferan species at these sites, Lamellibrachia cf. luymesi, grows quite slowly to lengths exceeding 2 meters and lives in excess of 170-250 years. L. cf. luymesi can grow a posterior extension of its tube and tissue, termed a "root," down into sulfidic sediments below its point of original attachment. This extension can be longer than the anterior portion of the animal. Here we show, using methods optimized for detection of hydrogen sulfide down to 0.1 microM in seawater, that hydrogen sulfide was never detected around the plumes of large cold-seep vestimentiferans and rarely detectable only around the bases of mature aggregations. Respiration experiments, which exposed the root portions of L. cf. luymesi to sulfide concentrations between 51-561 microM, demonstrate that L. cf. luymesi use their roots as a respiratory surface to acquire sulfide at an average rate of 4.1 micromol x g(-1) x h(-1). Net dissolved inorganic carbon uptake across the plume of the tubeworms was shown to occur in response to exposure of the posterior (root) portion of the worms to sulfide, demonstrating that sulfide acquisition by roots of the seep vestimentiferan L. cf. luymesi can be sufficient to fuel net autotrophic total dissolved inorganic carbon uptake.     

Role of conditioning factors in the development of drug dependence

Conditioned opioid phenomena have now been documented in both opiate-dependent and abstinent patients. Although the existence of these phenomena is generally accepted, their potential role in drug use and relapse is still under study. Our own research indicates that both physiologic and subjective responses may be conditioned, and that these responses are present in a significant proportion of patients who abuse opiates. Patients' responsivity (for example, craving or a reduction in skin temperature) may vary depending upon mood, cognitive set, and the individual relevance of the drug-related stimuli. Extinction procedures have been developed that are effective in reducing both subjective and physiologic conditioned responses. The clinical impact of these extinction procedures is now being assessed in a large-scale treatment-outcome study with abstinent patients. The results of this project will help determine the actual clinical significance of these complex but potentially important phenomena.     

Causes of colonization of autografted burn wounds

The progression of autograft colonization to infection presents significant problems in the care of grafted burn wounds. To determine whether graft colonization arises from self-contamination or from some exogenous source, we characterized pregraft and graft Candida albicans isolates through serotyping and biotyping (Leicester system) and Pseudomonas aeruginosa isolates through serotyping (Japan Pseudomonas aeruginosa Society system). In 21 of 24 patients, the serotype/biotype of the graft isolate was the same as the serotype/biotype of a C. albicans strain previously isolated from the same patient. Fifteen of 16 P. aeruginosa graft contaminants also showed the same serotype as that in a pregraft isolate. Therefore, whereas it has long been surmised that the grafts of patients with burns are self-colonized, this study provides definite data showing that most C. albicans and P. aeruginosa autograft isolates are indeed self-contaminants.     

Arginine supplementation does not enhance serum nitric oxide levels in elderly nursing home residents with pressure ulcers

The purpose of this study was to determine whether arginine supplementation enhances in vitro (neutrophil burst and mitogen-induced lymphocyte proliferation) and in vivo (delayed-type hypersensitivity [DTH] and serum nitric oxide) measures of immune function in nursing home elders with pressure ulcers. Twenty-six elders, 65 years of age or older, with one or more pressure ulcers, were randomized to receive 8.5 g of arginine or an isonitrogenous supplement for 4 weeks. Immune function studies and serum arginine, ornithine, citrulline, and nitric oxide were measured at baseline, 4 weeks postsupplementation (Week 4) and after a 6-week washout (Week 10). At Week 4, serum ornithine increased (p = .01) and arginine trended to increase (p = .055), but there was no increase in citrulline or nitric oxide with arginine supplementation. There were no differences in neutrophil burst or DTH responses between groups. Whole blood mitogen-induced proliferation decreased significantly at Week 10 in the isonitrogenous but not in the arginine-supplemented group. There is mounting concern that arginine supplementation during an inflammatory state could be detrimental due to overwhelming nitric oxide production. A key finding of this study is that arginine supplementation did not increase serum nitric oxide levels over that observed in elders with pressure ulcers given an isonitrogenous supplement.     

Conscious and unconscious brain responses to food and cocaine cues

Brain Imaging and Behavior - Visual presentation of appetitive and negative cues triggers fast responses in the human brain. Here we assessed functional MRI (fMRI) responses to food, cocaine, and...