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Multiple sclerosis (MS) patients initiating IFN beta-1a, Avonex, therapy (Group 1, n = 30) or experiencing side effects after 6 months on therapy (Group 2, n = 30) were randomized for 5 weeks open label adjunct therapy to naproxen (Aleve), acetaminophen (Tylenol) or ibuprofen (Advil). Our hypothesis was that non-prescription pain medications are effective in decreasing or alleviating the side effects associated with IFN beta-1a therapy. Contrary to the hypothesis, most patients in both groups continued to report side effects on all pain medications. After 5 weeks, headache, fever, chills and injection site pain were low in< or = 50% of patients. Moderate to significant fatigue, muscle or joint pain continued in most patients. As a quality of life measure, the Modified Fatigue Impact Scale (mFIS) improved for Group 1 on naproxen or ibuprofen with greatest improvement in physical subset (P = 0.002 for naproxen and P<0.01 for ibuprofen). Total mFIS for Group 1 on acetaminophen improved (P = 0.04) due to improved cognitive subset rather than physical subset. Group 2, with side effects initially, reported less significant fatigue (severity 5-10) but more moderate fatigue (severity 2-4) at study end for all three medications. All medications improved cognitive subset (P = 0.05). Physical mFIS subset did not improve for Group 2 on acetaminophen, but did with naproxen (P = 0.05) or ibuprofen (P = 0.03). Naproxen and ibuprofen were more effective than acetaminophen in minimizing physical side effects of IFN beta-1a. None of the three pain medications tested were as effective as hypothesized for minimizing fatigue or muscle and joint pain.

Contraction of type I collagen gels is an in vitro model of tissue remodeling. In addition to fibroblasts, some epithelial cells can mediate this process. We therefore hypothesized that alveolar epithelial cells might contract extracellular matrices and have the potential to directly participate in the remodeling of the lung after alveolar injury. A549 cells were plated on top of collagen gels, and the gels were floated in culture medium. A549 cells contracted the gels in a time- and cell density-dependent manner. A549 cells, as well as human bronchial epithelial cells (HBEC) and rat alveolar epithelial cells (RalvEC) contracted collagen gels more when they were plated on top of the gel than when they were embedded inside, in contrast to human fetal lung fibroblast (HFL1), which contracted more when cast inside. The amount of hydroxyproline in the collagen gels remained unchanged throughout the contraction. Anti-beta(1) integrin antibody inhibited A549 cell-mediated contraction. Transforming growth factor beta augmented the contraction by A549 cells as well as that by HBEC and HFL1. Prostaglandin E(2) inhibited the contraction by HFL1 but did not affect the contraction by A549 cells, HBEC, or RalvEC. Cytomix (a mixture of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma) inhibited the contraction by HFL1 but strongly enhanced the contraction by A549 cells. Cytomix also caused a morphologic change of A549 cells from a polygonal to a spindle shape. Immunocytochemistry showed that cytomix induced alpha-tubulin expression in A549 cells, whereas cytokeratin, vimentin, smooth muscle actin, beta(1) integrin, and paxillin expressions were not changed. This study thus demonstrates that alveolar epithelial cells can cause contraction of extracellular matrices and that this process is modulated by exogenous mediators, which also modify the microtubular system. Such an activity might contribute to alveolar remodeling after injury.

Multiple sclerosis (MS) is an incurable neurodegenerative disease whose symptoms are only partially relieved by pharmaceutical intervention. Disability due to this disease process can impede activities of daily living and decrease quality of life, both for MS patients and for their care partners and families. A nonrandomized, nonblinded prospective cohort study of 45 patients with MS was undertaken to investigate the impact of an exercise program emphasizing resistance training on balance and gait. This article presents data for the first 33 participants to complete the study protocol. The exercise program consisted of twice-weekly 50-minute sessions for 6 months. At 3 months and 6 months, statistically significant improvements (P &lt; .05) from baseline were observed for the following measures: Nine-Hole Peg Test, 2- and 3-second Paced Auditory Serial Addition Test, Modified Fatigue Impact Scale, NeuroCom Balance Master (NeuroCom International, Inc, Clackamas, OR), Timed Up and Go test, and Berg Balance Scale. Three-dimensional biomechanical gait analysis showed increased knee power generation during midstance and increased hip power generation during terminal stance. To determine whether individuals with varying levels of disability responded to exercise in a similar fashion, participants were divided into two subgroups based on Expanded Disability Status Scale score: little or no disability (EDSS score 1.0–4.0) and mild-to-moderate disability (EDSS score 4.5–6.5). No statistically significant differences in results were found. The results of this study indicate that participation in a resistance training program improves MS patients' ability to walk and to generate muscular forces during locomotion.

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Using a calcium-sensitive electrode to monitor calcium movements, we found that neoplastic GH3 cells experienced a net accumulation of calcium when exposed to elevated (50 mM) K+. Acute prolactin (PRL) release was also stimulated under these conditions. Both calcium uptake and PRL release could be blocked by the calcium antagonist methoxyverapamil (D-600). Thyrotropin-releasing hormone (TRH) also stimulated PRL release but had no effect on cellular calcium accumulation. Likewise, D-600 had no effect on TRH-induced PRL release. Such results indicate that enhanced secretory activity does not require an increase in intracellular calcium content. The observation that secretagogues do not stimulate PRL release in the absence of extracellular calcium was investigated. When GH3 cells were placed in a Ca-free medium, they underwent a prompt and sustained loss of cellular calcium. The loss of such intracellular calcium could be blocked with D-600. We conclude that the inability of TRH to stimulate the release of PRL in Ca-free medium is due to the loss of intracellular calcium and not to the absence of external calcium per se.