Purine nucleoside phosphorylase inhibition is an effective approach for the treatment of chemical hemorrhagic cystitis.

Hemorrhagic cystitis may be induced by infection, radiation therapy, or medications or may be idiopathic. Along with hemorrhagic features, symptoms include urinary urgency and frequency, dysuria (painful urination), and visceral pain. Cystitis-induced visceral pain is one of the most challenging types of pain to treat, and an effective treatment would address a major unmet medical need. We assessed the efficacy of a purine nucleoside phosphorylase inhibitor, 8-aminoguanine (8-AG), for the treatment of hemorrhagic/ulcerative cystitis. Lower urinary tract (LUT) function and structure were assessed in adult Sprague-Dawley rats, treated chronically with cyclophosphamide (CYP; sacrificed day 8) and randomized to daily oral treatment with 8-AG (begun 14 days prior to CYP induction) or its vehicle. CYP-treated rats exhibited multiple abnormalities, including increased urinary frequency and neural mechanosensitivity, reduced bladder levels of inosine, urothelial inflammation/damage, and activation of spinal cord microglia, which is associated with pain hypersensitivity. 8-AG treatment of CYP-treated rats normalized all observed histological, structural, biochemical, and physiological abnormalities. In cystitis 8-AG improved function and reduced both pain and inflammation likely by increasing inosine, a tissue-protective purine metabolite. These findings demonstrate that 8-AG has translational potential for reducing pain and preventing bladder damage in cystitis-associated LUT dysfunctions.

Dietary factors in experimental autoimmune encephalomyelitis and multiple sclerosis: A comprehensive review.

BACKGROUND: Dietary intervention in multiple sclerosis carries potential therapeutic implications. While studies utilizing animal models of multiple sclerosis (MS) have demonstrated intriguing findings, well-designed clinical trials are few in number. OBJECTIVE: The objective of this study is to review the animal model and clinical literature regarding dietary factors in experimental autoimmune encephalitis (EAE) and MS. METHODS: This manuscript provides a comprehensive review of current animal model and clinical knowledge related to dietary factors in MS. RESULTS: While there is currently little data for any specific diet in MS, there is growing evidence that certain dietary factors may influence the disease. CONCLUSIONS: Definitive information regarding dietary factors as a modifiable risk factor in MS will require larger randomized clinical trials.

Integration of leadership training into a problem/case-based learning program for first- and second-year medical students.

PURPOSE: The evolution of health care systems in response to societal and financial pressures has changed care delivery models, which presents new challenges for physicians. Leadership training is increasingly being recognized as an essential component of medical education training to prepare physicians to meet these needs. Unfortunately, most medical schools do not include leadership training. It has been suggested that a longitudinal and integrated approach to leadership training should be sought. We hypothesized that integration of leadership training into our hybrid problem-based learning (PBL)/case-based learning (CBL) program, Patient-Centered Explorations in Active Reasoning, Learning and Synthesis (PEARLS), would be an effective way for medical students to develop leadership skills without the addition of curricular time. METHODS: We designed a unique leadership program in PEARLS in which 98 medical students participated during each of their six courses throughout the first 2 years of school. A program director and trained faculty facilitators educated students and coached them on leadership development throughout this time. Students were assessed by their facilitator at the end of every course on development of leadership skills related to teamwork, meaningful self-assessment, process improvement, and thinking outside the box. RESULTS: Students consistently improved their performance from the first to the final course in all four leadership parameters evaluated. The skills that demonstrated the greatest change were those pertaining to thinking outside the box and process improvement. CONCLUSION: Incorporation of a longitudinal and integrated approach to leadership training into an existing PBL/CBL program is an effective way for medical students to improve their leadership skills without the addition of curricular time. These results offer a new, time-efficient option for leadership development in schools with existing PBL/CBL programs.