Discovery medicine
-
Review Case Reports
Evolving paradigms for desensitization in managing broadly HLA sensitized transplant candidates.
The broadly human leukocyte antigen (HLA) sensitized patient awaiting organ transplantation remains a persistent and significant problem for transplant medicine. Sensitization occurs as a consequence of exposure to HLA antigens through pregnancy, blood and platelet transfusions, and previous transplants. Early experience with desensitization protocols coupled with improved diagnostics for donor-specific antibodies (DSAs) and renal pathology have greatly improved transplant rates and outcomes for patients once considered un-transplantable or at high risk for poor outcomes. ⋯ Current desensitization therapies include high-dose intravenous immunoglobulin (IVIG), plasma exchange (PLEX) with low-dose IVIG, and IVIG combined with rituximab. Developing therapies include proteasome inhibitors aimed at plasma cells and modifiers of complement-mediated injury. Here we discuss the important advancements in desensitization including defining the risk for antibody-mediated rejection prior to transplantation and the evolution of therapies aimed at reducing the impact of antibody injury on allografts.
-
Elevated numbers of blood and tissue eosinophils are present in allergic diseases and experimental evidence suggests that eosinophils play an important pathogenic role in these conditions. Regulation of eosinophil maturation, recruitment, and survival is under the control of a small group of factors, including interleukin-5 (IL-5). Given the probable importance of eosinophils to allergy and other associated disorders, IL-5 has been proposed as a potential molecular target in the treatment of these diseases. ⋯ In patients with severe, refractory asthma associated with eosinophilia, however, clinical trials have demonstrated significant reductions in asthma exacerbations. Clinical studies in other disorders, particularly eosinophilic esophagitis and hypereosinophilic syndrome, have also shown significant improvements in blood and/or tissue eosinophilia and variable alterations in clinical disease activity. Strategies aimed at the inhibition of IL-5 may hold great promise in the treatment of eosinophilic diseases.
-
The prevalence of type 1 diabetes is escalating worldwide. Novel therapies and management strategies are needed to reduce associated morbidity. Aggressive blood glucose lowering using conventional insulin replacement regimens is limited by the risk of hypoglycemia. ⋯ So far, closed-loop prototypes have been evaluated under controlled conditions suggesting improved glucose control and a reduced risk of hypoglycemia. Limitations include suboptimal accuracy and reliability of continuous glucose monitors and delays associated with subcutaneous insulin delivery. Outpatient evaluation is required as the next step, leading to deployment into clinical practice.
-
Rapid advances in brain imaging chronic pain patients have yielded exciting data sets that could provide the basis for the development of chronic pain biomarkers that could increase the probability of success in analgesic drug development, aid clinicians in understanding, tracking, and treating disease, and link patients to the most effective therapies for their pain conditions. This review explores the potential of brain imaging techniques to detect functional, morphometric, and chemical changes that could serve as biomarkers for disease state and therapeutic efficacy. An important area for future research is to image clinical ongoing pain to further our knowledge of brain function in different pain states and the effects of treatment.
-
Currently, light therapies are widely used in both human and veterinarian medicine. The application of light to clinical therapeutics includes: photodynamic therapy, used to kill cancer cells; UVA therapies, used to treat a variety of skin diseases; and photobiomodulation, used to promote cell growth and recovery from injury. Photobiomodu-lation uses light emitting diodes (LEDs) or low energy lasers, which emit light in the visible red to near infrared range. ⋯ And third, low intensity light enhances nitric oxide synthesis by cytochrome c oxidase without altering its ability to reduce oxygen. From these findings, we propose that cytochrome c oxidase functions in photobiomodulation by producing nitric oxide, a signaling molecule which can then function in both intra- and extracellular signaling pathways. We also propose that the effectiveness of photobiomodulation is under the control of tissue oxygen and nitrite levels.