5-Hydroxymethylfurfural reduces skeletal muscle superoxide production and modifies force production in rats exposed to hypobaric hypoxia.

Decreased blood-tissue oxygenation at high altitude (HA) increases mitochondrial oxidant production and reduces exercise capacity. 5-Hydroxymethylfurfural (5-HMF) is an antioxidant that increases hemoglobin's binding affinity for oxygen. For these reasons, we hypothesized that 5-HMF would improve muscle performance in rats exposed to a simulated HA of ~5500 m. A secondary objective was to measure mitochondrial activity and dynamic regulation of fission and fusion because they are linked processes impacted by HA. Fisher 344 rats received 5-HMF (40 mg/kg/day) or vehicle during exposure to sea level or HA for 72 h. Right ankle plantarflexor muscle function was measured pre- and post-exposure. Post-exposure measurements included arterial blood gas and complete blood count, flexor digitorum brevis myofiber superoxide production and mitochondrial membrane potential (ΔΨm), and mitochondrial dynamic regulation in the soleus muscle. HA reduced blood oxygenation, increased superoxide levels and lowered ΔΨm, responses that were accompanied by decreased peak isometric torque and force production at frequencies >75 Hz. 5-HMF increased isometric force production and lowered oxidant production at sea level. In HA exposed animals, 5-HMF prevented a decline in isometric force production at 75-125 Hz, prevented an increase in superoxide levels, further decreased ΔΨm, and increased mitochondrial fusion 2 protein expression. These results suggest that 5-HMF may prevent a decrease in hypoxic force production during submaximal isometric contractions by an antioxidant mechanism.

Comparison of treatment recompression tables for neurologic decompression illness in swine model.

BACKGROUND: Significant reductions in ambient pressure subject an individual to risk of decompression illness (DCI); with incidence up to 35 per 10,000 dives. In severe cases, the central nervous system is often compromised (>80%), making DCI among the most morbid of diving related injuries. While hyperbaric specialists suggest initiating recompression therapy with either a Treatment Table 6 (TT6) or 6A (TT6A), the optimal initial recompression treatment for severe DCI is unknown. METHODS: Swine were exposed to an insult dive breathing air at 7.06 ATA (715.35 kPa) for 24 min followed by rapid decompression at a rate of 1.82 ATA/min (184.41 kPa/min). Swine that developed neurologic DCI within 1 hour of surfacing were block randomized to one of four United States Navy Treatment Tables (USN TT): TT6, TT6A-air (21% oxygen, 79% nitrogen), TT6A-nitrox (50% oxygen, 50% nitrogen), and TT6A-heliox (50% oxygen, 50% helium). The primary outcome was the mean number of spinal cord lesions, which was analyzed following cord harvest 24 hours after successful recompression treatment. Secondary outcomes included spinal cord lesion incidence and gross neurologic outcomes based on a pre- and post- modified Tarlov assessment. We compared outcomes among these four groups and between the two treatment profiles (i.e. TT6 and TT6A). RESULTS: One-hundred and forty-one swine underwent the insult dive, with 61 swine meeting inclusion criteria (43%). We found no differences in baseline characteristics among the groups. We found no significant differences in functional neurologic outcomes (p = 0.77 and 0.33), spinal cord lesion incidence (p = 0.09 and 0.07), or spinal cord lesion area (p = 0.51 and 0.17) among the four treatment groups or between the two treatment profiles, respectively. While the trends were not statistically significant, animals treated with TT6 had the lowest rates of functional deficits and the fewest spinal cord lesions. Moreover, across all animals, functional neurologic deficit had strong correlation with lesion area pathology (Logistic Regression, p < 0.01, Somers' D = 0.74). CONCLUSIONS: TT6 performed as well as the other treatment tables and is the least resource intensive. TT6 is the most appropriate initial treatment for neurologic DCI in swine, among the tables that we compared.

Exercise in African American and White Colorectal Cancer Survivors: A Mixed Methods Approach.

BACKGROUND: African-American (AA) colorectal cancer (CRC) survivors tend to be more obese and less physically active compared to white survivors. PURPOSE/OBJECTIVE: To test the feasibility of an aerobic exercise program as well as explore perceptions about supervised exercise among AA CRC survivors. METHODS: A prospective supervised exercise intervention performed on a cycle ergometer 2 days/week for 12 weeks. Peak (VO2peak) and sub-maximal exercise (6MWT) along with questionnaires (SF-36, Memorial Sloan Kettering Cancer Center Bowel Function Instrument (BFI), Functional Assessment of Cancer Therapy Scale-Colorectal (FACT-C) and Fatigue (FACIT-F), Brief Symptom Inventory (BSI). A second group of survivors participated in an interview evaluating perceptions regarding exercise. DESIGN: Prospective case series and qualitative interview. SETTING: Research university and academic medical center. PATIENTS: African American and white colorectal cancer survivors. RESULTS: Quantitative: A total of 237 letters were mailed to CRC survivors (112 white, 126 AAs). From the letters, 25 white and 15 AAs expressed interest; only five white (4.5%) and four AAs (3.2%) enrolled. Two AAs and five white survivors (7/9) finished the program. There was an improvement in peak exercise (p=0.011) and quality of life (QoL) (SF-36 total, p=0.035) post-training. Qualitative: 30 CRC survivors (12 AA and 18 white) participated in qualitative interviews and selected co-morbidity, motivation and location as primary barriers to exercise. LIMITATIONS: Small sample size. CONCLUSIONS: Recruiting CRC survivors (regardless of race) into an exercise program is challenging, however, there are exercise and QoL benefits associated with participation. Barriers to exercise are similar between AA and white CRC survivors.

ß-Alanine supplementation increased physical performance and improved executive function following endurance exercise in middle aged individuals.

BACKGROUND: Sarcopenia, a reduction in muscle mass and function seen in aging populations, may be countered by improving systemic carnosine stores via beta-Alanine (ß-alanine) supplementation. Increasing systemic carnosine levels may result in enhanced anti-oxidant, neuro-protective and pH buffering capabilities. This enhancement should result in improved exercise capacity and executive function. METHODS: Twelve healthy adults (average age = 60.5 ± 8.6 yrs, weight = 81.5 ± 12.6 kg) were randomized and given either 2.4 g/d of ß-alanine (BA) or Placebo (PL) for 28 days. Exercise capacity was tested via bouts on a cycle ergometer at 70% VO2 peak. Executive function was measured by Stroop Tests 5 min before exercise (T1), immediately before exercise (T2), immediately following fatigue (T3), and 5 min after fatigue (T4). Lactate measures were taken pre/post exercise. Heart rate, Rating of Perceived Exertion (RPE) and VO2 were recorded throughout exercise testing. RESULTS: PRE average time-to-exhaustion (TTE) for the PL and BA group were not significantly different (Mean ± SD; 9.4 ± 1.4mins vs 11.1 ± 2.4mins, respectively, P = 0.7). POST BA supplemented subjects cycled significantly longer than PRE (14.6 ± 3.8mins vs 11.1 ± 2.4mins, respectively, P = 0.04) while those given PL did not (8.7 ± 2.4mins vs 9.4 ± 1.4mins, respectively, P = 0.7). PL subjects were slower in completing the Stroop test POST at T4 compared to T3 (T3 = - 13.3 ± 8.6% vs T4 = 2.1 ± 8.3%, P = 0.04), while the BA group (T3 = - 9.2 ± 6.4% vs T4 = - 2.5 ± 3.5%, P = 0.5) was not. POST lactate production expressed a trend when comparing treatments, as the BA group produced 2.4 ± 2.6 mmol/L more lactate than the PL group (P = 0.06). Within group lactate production for BA (P = 0.4) and PL (P = 0.5), RPE (P = 0.9) and heart rate (P = 0.7) did not differ with supplementation. CONCLUSION: BA supplementation increased exercise capacity and eliminated endurance exercise induced declines in executive function seen after recovery. Increased POST TTE coupled with similar PRE vs POST lactate production indicates an improvement in the ability of BA to extend exercise durations. Furthermore, by countering endurance exercise's accompanying deficits in executive function, the aging population can maintain benefits from exercise with improved safety.

Immunological consequences of interleukin 12 administration after autologous stem cell transplantation.

PURPOSE: The purpose is to determine the immunological effects of recombinant human interleukin (rhIL)-12 therapy after autologous stem cell transplantation. EXPERIMENTAL DESIGN: Twelve patients (8 non-Hodgkin's lymphoma, 2 Hodgkin's disease, and 2 plasma cell myeloma) were treated with rhIL-12 by bolus i.v. injection in doses of 30, 100, or 250 ng/kg starting at a median of 66 days posttransplant. Immunological assays were performed using serum and peripheral blood mononuclear cell (PBMC) samples obtained on study. RESULTS: Dose-dependent increases in the total lymphocyte count occurred during rhIL-12 therapy. The absolute number of peripheral blood CD4 T cells increased up to 16.3-fold, CD8 T cells up to 20.5-fold, B cells up to 11-fold, and natural killer (NK) cells up to 12.3-fold during rhIL-12 administration and returned to pretreatment baseline levels after discontinuation of rhIL-12. CD56(bright) NK cells expanded dramatically in the blood of a patient with baseline lymphopenia before rhIL-12 therapy. In vitro proliferation of patient PBMCs in response to IL-12 was indistinguishable from that of PBMCs obtained from healthy control sub-jects. Moreover, spontaneous in vitro proliferation of patient PBMCs increased significantly during rhIL-12 therapy. Increased levels of IFN-gamma and IL-18 were detected in the serum of patients treated in the 100 and 250 ng/kg dose cohorts during the first multiple dose cycle. CONCLUSIONS: Expansion of T, B, and NK cells occurs in vivo during rhIL-12 therapy after autologous stem cell transplantation for hematological malignancies. In contrast to their striking defect in IL-12-induced IFN-gamma production, posttransplant patient PBMCs exhibit normal proliferative responses to IL-12 in vitro. Additional investigation of rhIL-12 for posttransplantation immunotherapy is warranted.