Effect of pulsed electromagnetic field treatment on programmed resolution of inflammation pathway markers in human cells in culture.

Inflammation is a complex process involving distinct but overlapping biochemical and molecular events that are highly regulated. Pulsed electromagnetic field (PEMF) therapy is increasingly used to treat pain and edema associated with inflammation following surgery involving soft tissue. However, the molecular and cellular effects of PEMF therapy on pathways involved in the resolution of inflammation are poorly understood. Using cell culture lines relevant to trauma-induced inflammation of the skin (human dermal fibroblasts, human epidermal keratinocytes, and human mononuclear cells), we investigated the effect of PEMF on gene expression involved in the acute and resolution phases of inflammation. We found that PEMF treatment was followed by changes in the relative amount of messenger (m)RNAs encoding enzymes involved in heme catabolism and removal of reactive oxygen species, including an increase in heme oxygenase 1 and superoxide dismutase 3 mRNAs, in all cell types examined 2 hours after PEMF treatment. A relative increase in mRNAs encoding enzymes involved in lipid mediator biosynthesis was also observed, including an increase in arachidonate 12- and 15-lipoxygenase mRNAs in dermal fibroblasts and epidermal keratinocytes, respectively. The relative amount of both of these lipoxygenase mRNAs was elevated in mononuclear cells following PEMF treatment relative to nontreated cells. PEMF treatment was also followed by changes in the mRNA levels of several cytokines. A decrease in the relative amount of interleukin 1 beta mRNA was observed in mononuclear cells, similar to that previously reported for epidermal keratinocytes and dermal fibroblasts. Based on our results, we propose a model in which PEMF therapy may promote chronic inflammation resolution by mediating gene expression changes important for inhibiting and resolving inflammation.

An open-label pilot study of pulsed electromagnetic field therapy in the treatment of failed back surgery syndrome pain.

Persistent pain following back surgery remains a major treatment challenge. The primary objective of this open-label exploratory study was to investigate the analgesic effectiveness of pulsed electromagnetic field therapy administered twice daily over a 45-day period in 34 subjects (68% female) with persistent or recurrent pain following back surgery. A secondary goal was to guide the design of future randomized controlled trials that could target responsive subpopulations. All predefined primary and secondary outcomes, including change in pain intensity (PI), physical function (Oswestry Disability Index), analgesic consumption, and overall well-being (Patient Global Impression of Change), are reported. A responder analysis (≥30% reduction in PI versus baseline) was added as a post hoc evaluation. Safety outcomes, as well as results of a cost-avoidance survey, are also summarized. Of the 30 per-protocol subjects who completed the study, 33% reported a clinically meaningful (≥30%) reduction in PI. A higher response rate (60%) was reported for subjects who had undergone discectomy prior to the trial compared to subjects who had undergone other types of surgical interventions (decompression or fusion) without discectomy. Improvements in PI were paralleled by improvements in secondary outcomes. Relative to baseline, responders reported an average 44% and 55% reduction in back PI and leg PI (respectively), and an average 13% improvement in Oswestry Disability Index scores. In the per-protocol population, 50% of responders and 12% of nonresponders reported less analgesia consumption at the end of treatment versus baseline. Sixty-seven percent of per-protocol responders and 0% of nonresponders reported clinically meaningful improvement in overall well-being on the Patient Global Impression of Change scale.

Meta-analysis of clinical efficacy of pulsed radio frequency energy treatment.

OBJECTIVE: To statistically evaluate published clinical efficacy data related to the use of pulsed radio frequency energy (PRFE) therapy in 3 clinical applications. BACKGROUND: Numerous clinical studies have reported efficacy outcomes for PRFE therapy use in the palliative treatment of both postoperative and nonpostoperative pain and edema, and for its use as an adjunctive wound-healing (WH) therapeutic. Although diverse in design and endpoint, these studies are amenable to systematic review using both a vote-counting and P-value combination meta-analytic technique. METHODS: A meta-analysis of efficacy outcomes reported in clinical trials was performed using a vote-counting procedure. In addition, when possible, the sum of logs method of P-value combination was used to determine a significance level for the combined evidence within each endpoint and clinical area. RESULTS: Of the 186 clinical articles identified after application of selection criteria, there were 25 controlled trials that met criteria for inclusion in vote-counting and P-value combination methods and were used for formal statistical analysis. In total, 1332 patients receiving PRFE treatment were studied. Vote-counting procedure applied to clinical outcomes from controlled studies resulted in a greater number of positive outcomes than neutral outcomes, and zero negative outcomes, for each of the clinical application groups evaluated. The sum of logs P-value method found statistically significant improvement in pain, reduction in edema, and improvement in WH outcomes. CONCLUSIONS: On the basis of statistical evaluation of published clinical efficacy data, there is strong statistical evidence that PRFE therapy is effective in the treatment of postoperative and nonpostoperative pain and edema and in WH applications.

Pulsed radio frequency energy (PRFE) use in human medical applications.

A number of electromagnetic field-based technologies are available for therapeutic medical applications. These therapies can be broken down into different categories based on technical parameters employed and type of clinical application. Pulsed radio frequency energy (PRFE) therapy is a non invasive, electromagnetic field-based therapeutic that is based on delivery of pulsed, shortwave radio frequency energy in the 13-27.12 MHz carrier frequency range, and designed for local application to a target tissue without the intended generation of deep heat. It has been studied for use in a number of clinical applications, including as a palliative treatment for both postoperative and non postoperative pain and edema, as well as in wound healing applications. This review provides an introduction to the therapy, a summary of clinical efficacy studies using the therapy in specific applications, and an overview of treatment-related safety.

Luman, a new partner of HIV-1 TMgp41, interferes with Tat-mediated transcription of the HIV-1 LTR.

In our search for new partners of the HIV-1 envelope glycoprotein (Env), we found that the cytoplasmic domain of the TMgp41 (TMgp41 CD) subunit of HIV-1 Env interacted with Luman, a transcription factor of the CREB/ATF family. Luman is anchored in the endoplasmic reticulum membrane and subjected to activation by regulated intramembrane proteolysis (RIP). The RIP process permits the release of the activated amino-terminal fragment of Luman into the cytoplasm, and its import into the nucleus. Here, we demonstrate that interaction between the TMgp41 CD and Luman requires a region encompassing the b-Zip and TM domains of Luman and decreases the stability of this factor. Moreover, we found that overexpression of a constitutively active form of Luman in cells transfected with HXB2R HIV-1 provirus decreased the intracellular expression of Gag and Env and led to a decrease in virion release. This negative effect of activated Luman on HIV-1 production was correlated to the inhibition of Tat transactivation of the HIV-1 LTR, which might be related to an interaction of activated Luman with Tat. Altogether, these results show that Luman acts as a partner of two major HIV-1 proteins: the TMgp41 Env subunit and Tat. The interaction between the TMgp41 subunit of Env and Luman affects the stability of the full-length Luman protein, the precursor of the activated, nuclear form of Luman, which acts negatively on Tat-mediated HIV-1 transactivation.