αv integrins: key regulators of tissue fibrosis

Chronic tissue injury with fibrosis results in the disruption of tissue architecture, organ dysfunction and eventual organ failure. Therefore, the development of effective anti-fibrotic therapies is urgently required. During fibrogenesis, complex interplay occurs between cellular and extracellular matrix components of the wound healing response. Integrins, a family of transmembrane cell adhesion molecules, play a key role in mediating intercellular and cell-matrix interactions. Thus, integrins provide a major node of communication between the extracellular matrix, inflammatory cells, fibroblasts and parenchymal cells and, as such, are intimately involved in the initiation, maintenance and resolution of tissue fibrosis. Modulation of members of the αv integrin family has exhibited profound effects on fibrosis in multiple organs and disease states. In this review, we discuss the current knowledge of the mechanisms of αv-integrin-mediated regulation of fibrogenesis and show that the therapeutic targeting of specific αv integrins represents a promising avenue to treat patients with a broad range of fibrotic diseases

Developing a Worksite-based Culturally Adapted Smoking Cessation Intervention for Male Hispanic/Latino Construction Workers

Over 2.6 million Hispanic/Latino construction workers (CWs) live in the US; 91% of South Florida CWs are Hispanic/Latino. CWs have higher smoking and lower cessation rates than other workers. Limited access to cessation services, worksite turnover, and lack of interventions tailored to culture/occupation hinder cessation. Partnering with worksite food trucks to deliver unique cessation interventions may improve these efforts. Aims: To explore a novel cessation approach, assess worker/worksite acceptability, and seek input into intervention development. Methods: In 2016, we conducted five semi-structured focus groups with 37 smoking Hispanic/Latino CWs. Constant comparative analysis was used to examine a priori themes regarding smoking behaviours, cessation treatments, intervention delivery, cultural adaptation, and quit interest. Results: CWs reported tremendous job stress. Most smoking occurred during the workday and most CWs did not use nicotine replacement therapy with past quit attempts. Most CWs were open to a worksite face-to-face group cessation intervention before work (many underutilize breaks and feel pressure to keep working). CWs felt it unnecessary to tailor the intervention to Hispanics/Latinos indicating smokers are the same regardless of race/ethnicity. Conclusions: Findings demonstrate the need to consider work environments, job demands/stress, and worker preferences when developing accessible and acceptable cessation interventions

Agmatine reverses pain induced by inflammation neuropathy and spinal cord injury

Antagonists of glutamate receptors of the N-methyl-D-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG) an endogenous neuromodulator present in brain and spinal cord has both NMDAR antagonist and NOS inhibitor activities. We report here that AG exogenously administered to rodents decreased hyperalgesia accompanying inflammation normalized the mechanical hypersensitivity (allodyniayhyperalgesia) produced by chemical or mechanical nerve injury and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury. Originally published Proceedings of the National Academy of Sciences Vol. 97 No. 19 Sep 200

Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury

Antagonists of glutamate receptors of the N-methyl-D-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodyniayhyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury. Originally published Proceedings of the National Academy of Sciences, Vol. 97, No. 19, Sep 200