Foot forces during exercise on the International Space Station.

Long-duration exposure to microgravity has been shown to have detrimental effects on the human musculoskeletal system. To date, exercise countermeasures have been the primary approach to maintain bone and muscle mass and they have not been successful. Up until 2008, the three exercise countermeasure devices available on the International Space Station (ISS) were the treadmill with vibration isolation and stabilization (TVIS), the cycle ergometer with vibration isolation and stabilization (CEVIS), and the interim resistance exercise device (iRED). This article examines the available envelope of mechanical loads to the lower extremity that these exercise devices can generate based on direct in-shoe force measurements performed on the ISS. Four male crewmembers who flew on long-duration ISS missions participated in this study. In-shoe forces were recorded during activities designed to elicit maximum loads from the various exercise devices. Data from typical exercise sessions on Earth and on-orbit were also available for comparison. Maximum on-orbit single-leg loads from TVIS were 1.77 body weight (BW) while running at 8mph. The largest single-leg forces during resistance exercise were 0.72 BW during single-leg heel raises and 0.68 BW during double-leg squats. Forces during CEVIS exercise were small, approaching only 0.19 BW at 210W and 95RPM. We conclude that the three exercise devices studied were not able to elicit loads comparable to exercise on Earth, with the exception of CEVIS at its maximal setting. The decrements were, on average, 77% for walking, 75% for running, and 65% for squats when each device was at its maximum setting. Future developments must include an improved harness to apply higher gravity replacement loads during locomotor exercise and the provision of greater resistance exercise capability. The present data set provides a benchmark that will enable future researchers to judge whether or not the new generation of exercise countermeasures recently added to the ISS will address the need for greater loading.

Foot forces during typical days on the international space station.

Decreased bone mineral density (BMD) in astronauts returning from long-duration spaceflight missions has been well documented, but the altered mechanical loading environment experienced by the musculoskeletal system, which may contribute to these changes, has not been well characterized. The current study describes the loading environment of the lower extremity (LE) during typical days on the International Space Station (ISS) compared to similar data for the same individuals living on Earth. Data from in-shoe force measurements are also used as input to the enhanced daily load stimulus (EDLS) model to determine the mechanical "dose" experienced by the musculoskeletal system and to associate this dose with changes in BMD. Four male astronauts on approximately 6-month missions to the ISS participated in this study. In-shoe forces were recorded using capacitance-based insoles during entire typical working days both on Earth and on-orbit. BMD estimates from the hip and spine regions were obtained from dual energy X-ray absorptiometry (DXA) pre- and post-flight. Measurable loading was recorded for only 30% of the time assigned for exercise. In-shoe forces during treadmill walking and running on the ISS were reduced by 25% and 46%, respectively, compared to similar activities on Earth. Mean on-orbit LE loads varied from 0.20 to 1.3 body weight (BW) during resistance exercise and were approximately 0.10 BW during bicycle ergometry. Application of the EDLS model showed a mean decrease of 25% in the daily load experienced by the LE. BMD decreased by 0.71% and 0.83% per month during their missions in the femoral neck and lumbar spine, respectively. Our findings support the conclusion that the measured ISS exercise durations and/or loading were insufficient to provide the loading stimulus required to prevent bone loss. Future trials with EDLS values closer to 100% of Earth values will offer a true test of exercise as a countermeasure to on-orbit bone loss.

Erythropoietin decreases cytotoxicity and nitric oxide formation induced by inflammatory stimuli in rat oligodendrocytes.

In the present study, we investigated whether erythropoietin (Epo) has a protective effect against cytotoxicity induced by interferon-gamma (IFN-gamma ) and lipopolysaccharide (LPS) in primary rat oligodendrocyte cultures. The possible modulatory effect of erythropoietin on inducible nitric oxide synthase (iNOS) mRNA expression and nitrite production were also analyzed. Erythropoietin exerted a significant protective effect against IFN-gamma and LPS-induced oligodendrocyte injury as determined by lactate dehydrogenase assay. Treatment with erythropoietin inhibited the expression of iNOS mRNA and nitrite production resulting from proinflammatory stimulation by IFN-gamma and LPS. These results suggest that erythropoietin has protective effects against inflammatory oligodendrocyte injury in vitro and may play a protective role in neurological disorders characterized by oligodendrocyte death, such as multiple sclerosis.

Does sucralfate prevent apoptosis occurring in the ischemia/reperfusion-induced intestinal injury?

BACKGROUND/PURPOSE: We have shown in a previous study that sucralfate is beneficial in the prophylaxis and treatment of hypoxia/reoxygenation-induced intestinal injury. The aim of this study is to investigate whether sucralfate has any effect on the prevention of apoptosis in the ischemia/reperfusion (I/R)-induced intestinal injury. METHODS: Rats were randomized into three groups. Group 1 and 2 were subjected to I/R. Group 1 (treatment group) received sucralfate while group 2 (treatment control group) did not. Group 3 served as a normal control group (sham group). The terminal ileum was harvested for histopathologic investigation by light microscopy. The presence of apoptotic enterocytes (DNA fragmentation in cell nuclei) was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) reaction. RESULTS: In treatment control group, 3 of 7 rats had severe inflammation. None of the sucralfate-treated rats showed severe inflammation, 6 of them only showed mild inflammatory changes (p < 0.05). The apoptotic percentage was found to be 37.1 +/- 9.4 in the sucralfate-treated group (group 1), whereas it was 45.4 +/- 3.9 in the untreated group (group 2) (p < 0.05). The sham group had a completely normal intestinal architecture. CONCLUSIONS: The present study shows that 1) the experimental model of I/R-induced intestinal injury induces enterocyte apoptosis; 2) sucralfate decreases enterocyte apoptosis in the experimental model of I/R-induced intestinal injury which may play a key role in the pathophysiological events leading to failure of the intrinsic gut barrier defense mechanisms.

Erythropoietin exerts neuroprotection in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated C57/BL mice via increasing nitric oxide production.

Erythropoietin (EPO), produced by the kidney and fetal liver, is a cytokine-hormone that stimulates erythropoiesis under hypoxic conditions. It has been shown that EPO is produced in the central nervous system and its receptor is expressed on neurons. Since EPO has neuroprotective effects in vitro and in vivo against brain injury, we investigated the effect of EPO treatment on locomotor activities of animals, survival of nigral dopaminergic neurons and nitrate levels in substantia nigra and striatum in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of Parkinsonism in C57/BL mice. Our findings suggest that EPO has protective and treating effect in MPTP-induced neurotoxicity in this mouse model of Parkinson's Disease via increasing nitric oxide production.

Monocyte activation in multiple sclerosis.

Monocytes, macrophages, and microglia have a central role in the CNS inflammation of MS. Monocytes are important in the earliest events in MS. Peripheral blood monocytes secrete prostaglandins before MS attacks. During clinical activity monocyte activation markers increase and IL-1 and TNF-alpha levels are elevated. Other monocyte products such as IL-10 reduce inflammation. IL-10 mRNA in MNC is increased during stable disease. Manipulation of monokine secretion and expression of monocyte surface proteins are reasonable approaches for immune therapy of MS.

Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy.

Costimulatory molecules help determine T cell responses. CD80 (B7-1) and CD86 (B7-2), costimulatory proteins on antigen-presenting cells, bind to CD28 on T cells. When costimulation is coupled with a signal through the T cell receptor (TCR), T cell proliferation and cytokine secretion are induced. However, TCR signaling without CD80/CD86CD28 costimulation causes anergy. During multiple sclerosis (MS) exacerbations, circulating immune cells are activated, Th1 cytokine levels in the blood are elevated, and blood-derived immune cells destroy brain oligodendroglia. In the experimental autoimmune encephalomyelitis model of MS, CD80 on antigen-presenting cells induces Th1 cell responses; CD86 enhances generation of Th2 cells. Variation in CD80 and CD86 expression is likely to influence immune regulation in MS. We demonstrate that the number of circulating CD80(+) lymphocytes is increased significantly during MS exacerbations, but is normal in stable MS. These CD80(+) lymphocytes are predominantly B cells, based on two-color flow cytometry. The number of CD71(+) and HLA-DR+ lymphocytes and monocytes is also increased in active MS. Therapy with IFN beta-1b markedly reduces the number of circulating CD80(+) B cells and increases CD86(+) monocyte number. HLA-DR+, CD71(+), and CD25(+) mononuclear cell numbers are also reduced by therapy. The number of CD80(+) cells may be a useful surrogate marker during IFN-beta therapy, and reduction of CD80-mediated costimulation may be one therapeutic mechanism by which IFN-beta acts in MS.

Splenoptosis (wandering spleen).

Splenoptosis which is a congenital fusion anomaly of dorsal mesogastrium in children is a very rare entity. In the literature cases are usually diagnosed at operation and it is noted that in former years splenectomy had a special place among various methods of treatment. In this report, a 7-year-old case of splenoptosis diagnosed on ultrasonography and isotope scintigraphic methods preoperatively and treated by splenopexy is presented. In cases with splenoptosis the clinical and radiologic diagnostic criteria are given and the importance of splenopexy in treatment is emphasized.