Muscle Cramps Do Not Improve With Correction of Vitamin D Insufficiency.

BACKGROUND: Minimal treatment options exist for idiopathic muscle cramps. OBJECTIVE: We evaluated whether correction of vitamin D insufficiency relieved muscle cramps in postmenopausal women. METHODS: We conducted a post hoc analysis of a randomized, double-blind, placebo-controlled trial at a single academic medical center in the Midwest to evaluate the benefits of treating vitamin D insufficiency. Two hundred thirty postmenopausal women participated. Eligible women were ≤75 years old, 5 years past menopause or oophorectomy, or ≥60 years if they had previously undergone hysterectomy without oophorectomy. Women had vitamin D insufficiency at baseline (25-hydroxyvitamin D 14-27 ng/mL). We excluded subjects with a glomerular filtration rate <45 mL/minute. INTERVENTIONS FOR CLINICAL TRIALS: Participants completed food diaries, laboratory studies, and functional tests including the Timed Up and Go test, Physical Activity Scale for the Elderly, Health Assessment Questionnaire (a measure of disability), and pain scores. Subjects recorded muscle cramp frequency and severity using a standardized form at 6 visits over 1 year. RESULTS: During the trial, over half of participants (n=121, 53%) reported muscle cramps. Despite unequivocal vitamin D repletion, vitamin D had no effect on muscle cramps. Pain levels, disability, and dietary potassium predicted presence of cramps. Serum albumin and physical activity were inversely associated with, and disability was positively associated with, severity of muscle cramps. CONCLUSIONS: Further studies are needed to evaluate the link between pain, disability, dietary potassium intake, and muscle cramps.

Adoptive transfer of lymphocytes isolated from simian immunodeficiency virus SIVmac239Δnef-vaccinated macaques does not affect acute-phase viral loads but may reduce chronic-phase viral loads in major histocompatibility complex-matched recipients.

The live attenuated simian immunodeficiency virus (SIV) SIVmac239Δnef is the most effective SIV/human immunodeficiency virus (HIV) vaccine in preclinical testing. An understanding of the mechanisms responsible for protection may provide important insights for the development of HIV vaccines. Leveraging the uniquely restricted genetic diversity of Mauritian cynomolgus macaques, we performed adoptive transfers between major histocompatibility complex (MHC)-matched animals to assess the role of cellular immunity in SIVmac239Δnef protection. We vaccinated and mock vaccinated donor macaques and then harvested between 1.25 × 10(9) and 3.0 × 10(9) mononuclear cells from multiple tissues for transfer into 12 naive recipients, followed by challenge with pathogenic SIVmac239. Fluorescently labeled donor cells were detectable for at least 7 days posttransfer and trafficked to multiple tissues, including lung, lymph nodes, and other mucosal tissues. There was no difference between recipient macaques' peak or postpeak plasma viral loads. A very modest difference in viral loads during the chronic phase between vaccinated animal cell recipients and mock-vaccinated animal cell recipients did not reach significance (P = 0.12). Interestingly, the SIVmac239 challenge virus accumulated escape mutations more rapidly in animals that received cells from vaccinated donors. These results may suggest that adoptive transfers influenced the course of infection despite the lack of significant differences in the viral loads among animals that received cells from vaccinated and mock-vaccinated donor animals.

Extralymphoid CD8+ T cells resident in tissue from simian immunodeficiency virus SIVmac239{Delta}nef-vaccinated macaques suppress SIVmac239 replication ex vivo.

Live-attenuated vaccination with simian immunodeficiency virus (SIV) SIVmac239Deltanef is the most successful vaccine product tested to date in macaques. However, the mechanisms that explain the efficacy of this vaccine remain largely unknown. We utilized an ex vivo viral suppression assay to assess the quality of the immune response in SIVmac239Deltanef-immunized animals. Using major histocompatibility complex-matched Mauritian cynomolgus macaques, we did not detect SIV-specific functional immune responses in the blood by gamma interferon (IFN-gamma) enzyme-linked immunospot assay at select time points; however, we found that lung CD8(+) T cells, unlike blood CD8(+) T cells, effectively suppress virus replication by up to 80%. These results suggest that SIVmac239Deltanef may be an effective vaccine because it elicits functional immunity at mucosal sites. Moreover, these results underscore the limitations of relying on immunological measurements from peripheral blood lymphocytes in studies of protective immunity to HIV/SIV.