The role of nitric oxide in melanoma.

Nitric oxide (NO) is a small gaseous signaling molecule that mediates its effects in melanoma through free radical formation and enzymatic processes. Investigations have demonstrated multiple roles for NO in melanoma pathology via immune surveillance, apoptosis, angiogenesis, melanogenesis, and on the melanoma cell itself. In general, elevated levels of NO prognosticate a poor outcome for melanoma patients. However, there are processes where the relative concentration of NO in different environments may also serve to limit melanoma proliferation. This review serves to outline the roles of NO in melanoma development and proliferation. As demonstrated by multiple in vivo murine models and observations from human tissue, NO may promote melanoma formation and proliferation through its interaction via inhibitory immune cells, inhibition of apoptosis, stimulation of pro-tumorigenic cytokines, activation of tumor associated macrophages, alteration of angiogenic processes, and stimulation of melanoma formation itself.

Blood vessel occlusion in peri-burn tissue is secondary to erythrocyte aggregation and mitigated by a fibronectin-derived peptide that limits burn injury progression.

Although vascular occlusion has long been noted in peri-burn tissue, the literature is inconsistent regarding the nature of the occlusion, with articles in the 1940s claiming that erythrocytes were the culprit and in the 1980s-1990s that microthrombi were responsible. To better define the nature of vessel occlusion, we studied two porcine burn models, a hot comb horizontal injury model and a vertical injury progression model. In both cases, tissue from the first two days after burn were stained with hemotoxylin and eosin, or probed for platelets or for fibrinogen/fibrin. Erythrocytes, identified as nonstained, clumped, anuclear, 5 µm cells, occluded most blood vessels (BVs) in both burn models. In contrast, platelet or fibrinogen/fibrin antibodies stained BV occlusions minimally at early time points, and only up to 16% of deep dermal BVs at 48 hours in the hot comb model and up to 7% at 24 hours in the vertical injury progression model. Treatment of animals with a fibronectin-derived peptide (P12), which limits burn injury progression and can dilate peripheral microvasculature, reduced erythrocyte occlusion by at least 50%, speeded healing and reduced scarring. Early erythrocyte aggregation, rather than thrombosis, explains the ineffectiveness of anticoagulants to prevent burn injury progression.

Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients.

INTRODUCTION: 5α-reductase inhibitors (5α-RIs), finasteride and dutasteride, have been approved for treatment of lower urinary tract symptoms, due to benign prostatic hyperplasia, with marked clinical efficacy. Finasteride is also approved for treatment of hair loss (androgenetic alopecia). Although the adverse side effects of these agents are thought to be minimal, the magnitude of adverse effects on sexual function, gynecomastia, depression, and quality of life remains ill-defined. AIM: The goal of this review is to discuss 5α-RIs therapy, the potential persistent side effects, and the possible mechanisms responsible for these undesirable effects. METHODS: We examined data reported in various clinical studies from the available literature concerning the side effects of finasteride and dutasteride. MAIN OUTCOME MEASURES: Data reported in the literature were reviewed and discussed. Results. Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship. CONCLUSIONS: We suggest discussion with patients on the potential sexual side effects of 5α-RIs before commencing therapy. Alternative therapies may be considered in the discussion, especially when treating androgenetic alopecia.

Phototherapy in Scleroderma.

Systemic and localized scleroderma are difficult to manage diseases with no accepted gold standard of therapy to date. Phototherapeutic modalities for scleroderma show promise. A PubMed search of information on phototherapy for scleroderma was conducted. The information was classified into effects on pathogenesis and clinical outcomes. Studies on photopheresis were excluded. There were no randomized, double-blind, placebo-controlled studies, and only three controlled studies. The vast majority of identified studies evaluated ultraviolet A1 (UVA1) phototherapy. More rigorous studies are needed to evaluate phototherapy in the treatment of scleroderma. Based on the limited studies available, 20-50 J/cm2 of UVA1 therapy 3-4 times a week for 30 treatments is recommended.

MicroRNA profiling of patient plasma for clinical trials using bioinformatics and biostatistical approaches.

BACKGROUND: MicroRNAs (miRNAs) are short noncoding RNAs that function to repress translation of mRNA transcripts and contribute to the development of cancer. We hypothesized that miRNA array-based technologies work best for miRNA profiling of patient-derived plasma samples when the techniques and patient populations are precisely defined. METHODS: Plasma samples were obtained from five sources: melanoma clinical trial of interferon and bortezomib (12), purchased normal donor plasma samples (four), gastrointestinal tumor bank (nine), melanoma tumor bank (ten), or aged-matched normal donors (eight) for the tumor bank samples. Plasma samples were purified for miRNAs and quantified using NanoString® arrays or by the company Exiqon. Standard biostatistical array approaches were utilized for data analysis and compared to a rank-based analytical approach. RESULTS: With the prospectively collected samples, fewer plasma samples demonstrated visible hemolysis due to increased attention to eliminating factors, such as increased pressure during phlebotomy, small gauge needles, and multiple punctures. Cancer patients enrolled in a melanoma clinical study exhibited the clearest pattern of miRNA expression as compared to normal donors in both the rank-based analytical method and standard biostatistical array approaches. For the patients from the tumor banks, fewer miRNAs (<5) were found to be differentially expressed and the false positive rate was relatively high. CONCLUSION: In order to obtain consistent results for NanoString miRNA arrays, it is imperative that patient cohorts have similar clinical characteristics with a uniform sample preparation procedure. A clinical workflow has been optimized to collect patient samples to study plasma miRNAs.

Tanning Bed Perception Survey: A Questionnaire-based Study.

OBJECTIVE: This study was intended to investigate the perception of tanning bed use among college students. DESIGN: A 15-question survey was given to young adults regarding tanning perceptions. SETTING: Rochester Community College in Rochester, Minnesota. PARTICIPANTS: Forty-four respondents between 18 and 51 years of age. MEASUREMENTS: Data was collected via a self-reported questionnaire. RESULTS: In this study, 50 percent of participants were not educated on the risks of melanoma, and 68 percent were not interested in receiving information on melanoma and completing a follow-up survey. More specifically, 63 percent versus 89 percent of participants with no tanning bed versus some tanning bed use did not want information regarding melanoma, respectively. This study also shows that more tanning bed users believe tanning helps prevent burning than non-tanning bed users. Fifty-seven percent of the 35 participants who had never used a tanning bed thought that they never prevent sunburn, while only 11 percent of the nine participants who had used a tanning bed in the past thought that they never prevent sunburn, which was statistically significant.

Osteopathic manipulative treatment as a useful adjunctive tool for pneumonia.

Pneumonia, the inflammatory state of lung tissue primarily due to microbial infection, claimed 52,306 lives in the United States in 2007 (1) and resulted in the hospitalization of 1.1 million patients (2). With an average length of in-patient hospital stay of five days (2), pneumonia and influenza comprise significant financial burden costing the United States $40.2 billion in 2005 (3). Under the current Infectious Disease Society of America/American Thoracic Society guidelines, standard-of-care recommendations include the rapid administration of an appropriate antibiotic regiment, fluid replacement, and ventilation (if necessary). Non-standard therapies include the use of corticosteroids and statins; however, these therapies lack conclusive supporting evidence (4). (Figure 1) Osteopathic Manipulative Treatment (OMT) is a cost-effective adjunctive treatment of pneumonia that has been shown to reduce patients' length of hospital stay, duration of intravenous antibiotics, and incidence of respiratory failure or death when compared to subjects who received conventional care alone (5). The use of manual manipulation techniques for pneumonia was first recorded as early as the Spanish influenza pandemic of 1918, when patients treated with standard medical care had an estimated mortality rate of 33%, compared to a 10% mortality rate in patients treated by osteopathic physicians (6). When applied to the management of pneumonia, manual manipulation techniques bolster lymphatic flow, respiratory function, and immunological defense by targeting anatomical structures involved in the these systems(7,8, 9, 10). The objective of this review video-article is three-fold: a) summarize the findings of randomized controlled studies on the efficacy of OMT in adult patients with diagnosed pneumonia, b) demonstrate established protocols utilized by osteopathic physicians treating pneumonia, c) elucidate the physiological mechanisms behind manual manipulation of the respiratory and lymphatic systems. Specifically, we will discuss and demonstrate four routine techniques that address autonomics, lymph drainage, and rib cage mobility: (1) Rib Raising, (2) Thoracic Pump, (3) Doming of the Thoracic Diaphragm, and (4) Muscle Energy for Rib 1.