Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Effects of curcumin on methyl methanesulfonate damage to mouse kidney

Methylmethane sulfonate (MMS) is an alkylating agent that may react with DNA and damage it. We investigated histological changes and apoptosis caused by MMS and the effects of curcumin on MMS treated mouse kidneys. Twenty-four mice were divided into four equal groups: controls injected with saline, a group injected with 40 mg/kg MMS, a group injected with 40 mg/kg MMS and given 100 mg/kg curcumin by gavage, and a group given 100 mg/kg curcumin by gavage. MMS caused congestion and vacuole formation, and elevated the apoptotic index significantly, but had no other effect on kidney tissue. Curcumin improved the congestion and vacuole formation caused by MMS and decreased the apoptotic index. Curcumin administered with MMS appears to decrease the deleterious effects of MMS on the kidney.     

Follicular development and ovulation in Macaca fascicularis,Saimiri sciureus and Galago senegalensis

A technique utilizing laparoscopy to determine the precise time of ovulation in three species is described. Determination is based on morphological changes that occur 24 to 36 hours before ovulation. This technique, coupled with mating sessions of short-duration, has been used to produce precisely defined pregnancies; the implications of this technique in reproduction research and teratology are discussed. A comparison of ovulation times in Macaca fascicularis indicates that ovulation normally occurs on day 13 of animals having a cycle length from 25 to 28 days. In animals with a cycle length from 31 to 34 days, ovulation occurred on day 14.8. Evidence presented does not substantiate previous claims for alternation between ovaries in consecutive cycles.     

Variations in soil N cycling and trace gas emissions in wet tropical forests

We used a previously described precipitation gradient in a tropical montane ecosystem of Hawai’i to evaluate how changes in mean annual precipitation (MAP) affect the processes resulting in the loss of N via trace gases. We evaluated three Hawaiian forests ranging from 2200 to 4050 mm year⁻¹ MAP with constant temperature, parent material, ecosystem age, and vegetation. In situ fluxes of N₂O and NO, soil inorganic nitrogen pools (NH₄⁺ and NO₃⁻), net nitrification, and net mineralization were quantified four times over 2 years. In addition, we performed ¹⁵N-labeling experiments to partition sources of N₂O between nitrification and denitrification, along with assays of nitrification potential and denitrification enzyme activity (DEA). Mean NO and N₂O emissions were highest at the mesic end of the gradient (8.7±4.6 and 1.1±0.3 ng N cm⁻² h⁻¹, respectively) and total oxidized N emitted decreased with increased MAP. At the wettest site, mean trace gas fluxes were at or below detection limit (≤0.2 ng N cm⁻² h⁻¹). Isotopic labeling showed that with increasing MAP, the source of N₂O changed from predominately nitrification to predominately denitrification. There was an increase in extractible NH₄⁺ and decline in NO₃⁻, while mean net mineralization and nitrification did not change from the mesic to intermediate sites but decreased dramatically at the wettest site. Nitrification potential and DEA were highest at the mesic site and lowest at the wet site. MAP exerts strong control N cycling processes and the magnitude and source of N trace gas flux from soil through soil redox conditions and the supply of electron donors and acceptors.     

Spontaneous cytotoxicity and tumor necrosis factor production by peripheral blood monocytes from AIDS patients

Peripheral blood monocytes (PBM) from AIDS patients have exhibited defects in some but not all of the immune functions yet tested. This study has examined the capacity of AIDS PBM to lyse tumor target cells as well as their ability to secrete TNF. Untreated PBM from AIDS patients were significantly cytotoxic to U937 target cells and responded to IFN-gamma pretreatment with augmented cytotoxicity. Both the spontaneous and IFN-gamma-stimulated cytotoxic activity was significantly (p less than 0.01) higher than that observed with normal PBM. The cytotoxic activity depended on the E:T ratio used and was higher in AIDS PBM at all ratios tested (10:1 to 40:1). Because TNF has been implicated in macrophage cell-mediated cytotoxicity, we examined whether the elevated cytotoxic activity of AIDS PBM was associated with an increase in TNF production. Supernatants from PBM cultured overnight with or without IFN-gamma were tested in a bioassay measuring cytotoxicity against U937 target cells as well as in an RIA specific for TNF. Supernatants derived from either unstimulated or IFN-gamma-treated AIDS PBM exhibited significantly higher levels of cytotoxicity than supernatants from normal macrophages. Both normal and AIDS PBM produced higher levels of cytotoxic factors in response to IFN-gamma. As determined by the RIA, AIDS PBM spontaneously released high levels of TNF whereas little TNF was produced by normal PBM. Treatment with IFN-gamma augmented the level of TNF production in both AIDS and normal PBM. These results demonstrate that PBM from AIDS patients have undergone in vivo activation as manifested by both cytotoxicity against tumor target cells and production of TNF. Target cell lysis by both AIDS PBM and their supernatants was inhibited by monoclonal anti-rTNF, suggesting that the increase in PBM cell-mediated cytotoxicity was caused by an increase in TNF production. The significance of these findings in the pathogenesis of the disease is discussed.     

The contribution of cell death to medium-released fractions of cell cultures

Summary Cell death was estimated by prelabeling primary chick embryo skeletal muscle cell cultures with [³H]thymidine and by subsequently measuring the release of label into complete culture medium or serum-and embryo-extract-free medium for a 6 h period. Cultures of the established muscle cell line L6 and the fibroblastic cell line 3T3 were used for comparative purposes. Comparison of the nigrosin exclusion test with the thymidine release test shows that the former underestimates cell death because it measures only the instantaneously occurring cell death. The [³H]thymidine release test estimates the cumulative amount of cell death. From cumulative cell death estimates it is calculated that 12.0 and 17.8% of the³H-fucosylated medium-released fractions from primary cell cultures are the result of cell death contamination when release occurs in complete or macromolecule-free media, respectively. High speed centrifugation is shown to eliminate most contamination from cell death. Evidence is presented that the absence of macromolecules in the culture medium has little effect on the release process. Contamination of the released fraction resulting from cell death is much less in the established cell lines than in the primary cells. It is concluded that the release process can be studied in primary muscle cell cultures and especially in established cell lines if adequate precautions are taken and if corrections for cell death contamination are taken into account. This research benefited from use of the Cell Culture Facility supported by National Cancer Institute Grant CA 14733. This research was supported by a Muscular Dystrophy Association Grant to Dr. Heinz Herrmann and by American Cancer Society Grant RDP 8 and was submitted in partial fulfillmant of a Ph.D. degree at the University of Connecticut (T. C. Doetschman).