Disruption in bone marrow fat may attenuate testosterone action on muscle size after spinal cord injury: a case report.

BACKGROUND: Mesenchymal stem cells can be differentiated into muscle satellite cells. Testosterone replacement therapy (TRT) promotes the differentiation of satellite cells into muscle cells. CASE REPORT: A 31-year-old male with a T4 complete chronic spinal cord injury (SCI) had fixation for a mid-shaft fracture of the left femur. The participant received transdermal testosterone patches (4 mg/day) daily for 16 weeks. Skeletal muscle and yellow bone marrow adiposity cross-sectional areas (CSAs) of both thighs were measured using magnetic resonance imaging. CLINICAL REHABILITATION IMPACT: The yellow bone marrow CSA was 67-69% lower in the left femur compared to the right femur. Following intervention, a discrepancy was noted between the whole skeletal muscle CSAs of the right (+13%) and left (+6%) thighs. The right knee extensor CSA increased by 7% with no changes in the left CSA. Disruption in bone marrow fat may attenuate the systemic effects of TRT on muscle size.

Neuromuscular electrical stimulation and testosterone did not influence heterotopic ossification size after spinal cord injury: A case series.

Neuromuscular electrical stimulation (NMES) and testosterone replacement therapy (TRT) are effective rehabilitation strategies to attenuate muscle atrophy and evoke hypertrophy in persons with spinal cord injury (SCI). However both interventions might increase heterotopic ossification (HO) size in SCI patients. We present the results of two men with chronic traumatic motor complete SCI who also had pre-existing HO and participated in a study investigating the effects of TRT or TRT plus NMES resistance training (RT) on body composition. The 49-year-old male, Subject A, has unilateral HO in his right thigh. The 31-year-old male, Subject B, has bilateral HO in both thighs. Both participants wore transdermal testosterone patches (4-6 mg/d) daily for 16 wk. Subject A also underwent progressive NMES-RT twice weekly for 16 wk. Magnetic resonance imaging scans were acquired prior to and post intervention. Cross-sectional areas (CSA) of the whole thigh and knee extensor skeletal muscles, femoral bone, and HO were measured. In Subject A (NMES-RT + TRT), the whole thigh skeletal muscle CSA increased by 10%, the knee extensor CSA increased by 17%, and the HO + femoral bone CSA did not change. In Subject B (TRT), the whole thigh skeletal muscle CSA increased by 13% in the right thigh and 6% in the left thigh. The knee extensor CSA increased by 7% in the right thigh and did not change in the left thigh. The femoral bone and HO CSAs in both thighs did not change. Both the TRT and NMES-RT + TRT protocols evoked muscle hypertrophy without stimulating the growth of pre-existing HO.

Cytogenetic evaluation of malathion-induced toxicity in Sprague-Dawley rats.

Malathion is a well known pesticide and is commonly used in many agricultural and non-agricultural settings. Its toxicity has been attributed primarily to the accumulation of acetylcholine (Ach) at nerve junctions, due to the inhibition of acetylcholinesterase (AChE), and consequently overstimulation of the nicotinic and muscarinic receptors. However, the genotoxicity of malathion has not been adequately studied; published studies suggest a weak interaction with the genetic material. In the present study, we investigated the genotoxic potential of malathion in bone marrow cells and peripheral blood obtained from Sprague-Dawley rats using chromosomal aberrations (CAs), mitotic index (MI), and DNA damage as toxicological endpoints. Four groups of four male rats, each weighing approximately 60 ± 2g, were injected intraperitoneally (i.p.) once a day for five days with doses of 2.5, 5, 10, and 20mg/kg body weight (BW) of malathion dissolved in 1% DMSO. The control group was made up of four animals injected with 1% DMSO. All the animals were sacrificed 24h after the fifth day treatment. Chromosome preparations were obtained from bone marrow cells following standard protocols. DNA damage in peripheral blood leukocytes was determined using alkaline single-cell gel electrophoresis (comet assay). Malathion exposure significantly increased the number of structural chromosomal aberrations (CAs) and the percentages of DNA damage, and decreased the mitotic index (MI) in treated groups when compared with the control group. Our results demonstrate that malathion has a clastogenic/genotoxic potential as measured by the bone marrow CA and comet assay in Sprague-Dawley rats.

Malathion-induced oxidative stress, cytotoxicity, and genotoxicity in human liver carcinoma (HepG2) cells.

Malathion is an organophosphate pesticide that is known for its high toxicity to insects and low to moderate potency to humans and other mammals. Its toxicity has been associated with the inhibition of acetylcholinesterase activity, leading to the interference with the transmission of nerve impulse, accumulation of acetylcholine at synaptic junctions, and subsequent induction of adverse health effects including headache, dizziness, nausea, vomiting, bradycardia, and miosis. Oxidative stress (OS) has been reported as a possible mechanism of malathion toxicity in humans. Hence, the aim of this study was to examine the role of OS in malathion-induced cytotoxicity and genotoxicity. To achieve this goal, MTT, lipid peroxidation, and single cell gel electrophoresis (Comet) assays were performed, respectively, to evaluate the levels of cell viability, malondialdehyde (MDA) production, and DNA damage in human liver carcinoma (HepG(2)) cells. Study results indicated that malathion is mitogenic at lower levels of exposure, and cytotoxic at higher levels of exposure. Upon 48 h of exposure, the average percentages of cell viability were 100% +/- 11%, 117% +/- 15%, 86% +/- 15%, 35% +/- 9%, and 27% +/- 7% for 0, 6, 12, 18, and 24 mM, respectively. In the lipid peroxidation assay, the concentrations of MDA produced were 12.55 +/- 0.16, 20.65 +/- 0.27, 31.1 +/- 0.40, 34.75 +/- 0.45, and 15.1 +/- 0.20 muM in 0, 6, 12, 18, and 24 mM malathion, respectively. The Comet assay showed a significant increase in DNA damage at the 24 mM malathion exposure. Taken together, our results indicate that malathion exposure at higher concentrations induces cytotoxic and genotoxic effects in HepG(2) cells, and its toxicity may be mediated through OS as evidenced by a significant production of MDA, an end product of lipid peroxidation.

Global-World HIV/AIDS Alliance (GHAA): charting healthy pathways for vulnerable populations.

The Global-World HIV/AIDS Alliance (GHAA) is a collaboration of representatives from civil society, faith-based organizations, institutions of higher education, and government agencies who are pooling resources specific to their respective organizations' missions to assist with enhancing education and early treatment for HIV/AIDS in marginalized and medically underserved communities worldwide. The Alliances' partnerships are divided into five geographically oriented operational groups (called clusters), which are the Africa Regional Cluster, Asia Regional Cluster, Europe Regional Cluster, Latin-Caribbean Cluster, and United States Cluster. The purpose of this collaborative effort, which relies on the expertise and services of agencies and institutions from 26 countries, is to mobilize experts from various fields to share lessons learned about effective (and ineffective) strategies for reaching those most neglected, to ultimately realize a decline in HIV/AIDS infection and death rates. It is hoped the sharing of culturally sensitive educational materials and prevention strategies will decrease new HIV cases, increase participation in clinical trials, and mobilize grassroots efforts to affect health policy. Emerging from GHAA is the Charting Healthy Pathways for Vulnerable Populations, a 15-year initiative scheduled for 2006 through 2020. The inaugural launching took place in Hyderabad, India, in February 2006, and the first biennial global conference was held in October 2007 in Richard's Bay, South Africa. Several regional cluster meetings are scheduled in various countries before the second global conference in China in October 2009. In the meantime, cluster countries' representatives will be engaging in various forms of dialogue to promote innovative prevention/awareness strategies, identification of resources and services to be rendered, potential research collaborations, and networking to engage others in the cause of GHAA as we move to become the "global voice for vulnerable HIV populations".