This study tested the hypothesis that reactive oxygen intermediates present in unfatigued skeletal muscle act to enhance contractile function. Fiber bundles from rat diaphragm were incubated with exogenous catalase (an antioxidant enzyme that dehydrates hydrogen peroxide to molecular oxygen and water) to decrease the tissue concentration of reactive oxygen intermediates. Catalase (10(3) U/ml) significantly decreased twitch characteristics (time to peak tension, half-relaxation time, peak force, and twitch-to-tetanus force ratio), thereby shifting the force-frequency relationship to the right. Catalase effects were dose dependent. Concentrations of 1 to 10(5) U/ml progressively depressed submaximal (30-Hz) tetanic stress, whereas concentrations > 10(5) U/ml were toxic, inhibiting maximal (200-Hz) tetanic stress (P < 0.0001). Exogenous hydrogen peroxide (10(-4) to 10(-2)M) increased peak twitch stress (P < 0.03) and lengthened both time to peak tension (P < 0.02) and half-relaxation time (P < 0.02). Selective removal of superoxide anion radicals with the use of superoxide dismutase produced dose-dependent contractile inhibition similar to that produced by catalase. We conclude that the reactive oxygen intermediates present in unfatigued skeletal muscle have a positive effect on excitation-contraction coupling and are obligatory for optimal contractile function.

We have tested the hypothesis that diaphragm muscle fibers release superoxide anion radicals (O2-.) into the extracellular space. Fiber bundles were isolated from rat diaphragm and incubated in Krebs-Ringer solution containing cytochrome c (10(-5) M), a standard assay for O2-.. Bundles were either passive or active, i.e., directly stimulated to contract rhythmically. After 1 h, absorbance of reduced cytochrome c in the incubation medium was measured at 550 nm. Absorbance was greater in medium exposed to passive muscle than in medium without muscle (P < 0.01), indicating O2-. release by passive muscle. Absorbance was greater in medium exposed to active muscle than in that exposed to passive muscle (P < 0.01), an increase inhibited by superoxide dismutase (10(3) U/ml). Active bundles fatigued; bundles developing the lowest final stresses produced the greatest absorbance increases (P < 0.001), suggesting that the magnitude of fatigue was inversely related to O2-. release. We conclude that O2-. is released by diaphragm myocytes into the interstitium and surrounding medium, a process accelerated by fatiguing muscular contractions.

Elevated circulating levels of TNF-alpha provoke contractile dysfunction in the diaphragm through an endocrine mechanism thought to be mediated by oxidative stress.

BACKGROUND The current study was conducted to assess the feasibility of laparoscopy in the treatment of women with early stage endometrial carcinoma and to compare the surgical outcome, cost, and quality of life among these patients with those treated with laparotomy. METHODS A prospective study was conducted over 2 years in which all women with early stage endometrial carcinoma who could tolerate laparoscopic surgery were treated with laparoscopically assisted vaginal hysterectomy (LAVH), bilateral salpingo‐oophorectomy (BSO), and lymphadenectomy. Women with a similar disease stage who underwent similar surgical procedures through laparotomy in the previous 2 years were used as the control group. Both groups were compared with regard to their characteristics, surgical outcome, and cost and were interviewed regarding their quality of life. RESULTS Eighty‐six of 90 women with endometrial carcinoma underwent LAVH. The procedure was converted to laparotomy in 5 patients (5.8%). Laparoscopic surgery thus was successful in 90% of the women. There were no significant differences noted between those women who underwent LAVH and those who underwent total abdominal hysterectomy (TAH) (n = 57) with regard to patient characteristics, type of surgical procedure, preoperative and postoperative hematocrit, complications, patient recall of postoperative pain, and tumor recurrence. LAVH patients had significantly smaller body mass indices, a longer surgical time, more pelvic lymph nodes, a smaller decrease in postoperative hematocrit, received less pain medication, had a shorter hospital stay, an earlier return to full activity and work, and a higher level of satisfaction with their treatment, although their procedures had a higher cost compared with TAH patients. CONCLUSIONS The majority of women with early stage endometrial carcinoma can be treated with laparoscopy with an excellent surgical outcome, shorter hospitalization, earlier recovery, and improved quality of life, but with a higher financial cost. Cancer 2001;91:378–87. © 2001 American Cancer Society.

Objective To develop a new bioactive gas delivery method using echogenic liposomes (ELIP) as the gas carrier. Background Nitric oxide (NO) is a bioactive gas with potent therapeutic effects. Bioavailability of NO by systemic delivery is low with potential systemic effects. Methods Liposomes containing phospholipids and cholesterol were prepared using a new freezing under pressure method. The encapsulation and release profile of NO from NO containing-ELIP (NO-ELIP) or a mixture of NO/Argon (NO/Ar-ELIP was studied. Uptake of NO from NO-ELIP by cultured vascular smooth muscle cells (VSMC) both in the absence and presence of hemoglobin was determined. The effect of NO-ELIP delivery to attenuate intimal hyperplasia in a balloon-injured artery was determined. Results Coencapsulation of NO with argon (Ar) enabled the adjustment the amount of encapsulated NO. A total of 10 µl of gas can be encapsulated into 1 mg liposomes. The release profile of NO from NO-ELIP demonstrated an initial rapid release followed by a slower release over 8 hours. Sixty-eight percent of cells remained viable when incubated with 80 µg/ml of NO/Ar-ELIP for 4 hours. NO delivery to VSMC using NO/Ar-ELIP was 7-fold higher than unencapsulated NO. NO/Ar-ELIP remained effective NO delivery to VSMC even in the presence of hemoglobin. Local NO-ELIP administration to balloon-injured carotid arteries attenuated the development of intimal hyperplasia and reduced arterial wall thickening by 41±9%. Conclusions Liposomes can protect and deliver a bioactive gas to target tissues with the potential for both visualization of gas delivery and controlled therapeutic gas release.