Vitamin D Receptor Signaling Enhances Locomotive Ability in Mice

Bone fractures markedly reduce quality of life and life expectancy in elderly people. Although osteoporosis increases bone fragility, fractures frequently occur in patients with normal bone mineral density. Because most fractures occur on falling, preventing falls is another focus for reducing bone fractures. In this study, we investigated the role of vitamin D receptor (VDR) signaling in locomotive ability. In the rotarod test, physical exercise enhanced locomotive ability of wild‐type (WT) mice by 1.6‐fold, whereas exercise did not enhance locomotive ability of VDR knockout (KO) mice. Compared with WT mice, VDR KO mice had smaller peripheral nerve axonal diameter and disordered AChR morphology on the extensor digitorum longus muscle. Eldecalcitol (ED‐71, ELD), an analog of 1,25(OH)₂D₃, administered to rotarod‐trained C57BL/6 mice enhanced locomotor performance compared with vehicle‐treated nontrained mice. The area of AChR cluster on the extensor digitorum longus was greater in ELD‐treated mice than in vehicle‐treated mice. ELD and 1,25(OH)₂D₃ enhanced expression of IGF‐1, myelin basic protein, and VDR in rat primary Schwann cells. VDR signaling regulates neuromuscular maintenance and enhances locomotive ability after physical exercise. Further investigation is required, but Schwann cells and the neuromuscular junction are targets of vitamin D₃ signaling in locomotive ability. © 2014 American Society for Bone and Mineral Research.     

Detection of varicella-zoster virus DNA in cultured cells and tissue specimens by in situ hybridization using biotin-labeled probes

A method of in situ hybridization with biotinylated probes is described for specific detection of varicella-zoster virus (VZV) DNA in infected cell cultures and in human biopsied or autopsied materials. From molecularly cloned EcoRI-fragments of VZV DNA, we selected as probes for in situ hybridization three fragments (B, H, and K) which had any detectable homology neither with human cell DNA nor with DNAs of VZV-related viruses (herpes simplex virus type 1, type 2 and human cytomegalovirus). The procedure of in situ hybridization was based on that of Brigati et al. (Virology 126, 32-50, 1983), but following modifications were made. 1) The concentration of probe DNA was lowered to 100 ng per ml. 2) Streptavidin-biotin system was used for detection of hybridization. 3) Acid phosphatase was used to generate color development discernible from melanin present in skin. 4) Before hybridization, deparaffinized sections were treated with trypsin by the procedure routinely employed for detection of viral antigens in paraffin-embedded sections.     

Ala601-Thr type dysplasminogenaemia genetically diagnosed in patients with retinochoroidal vascular disorders

Dysplasminogenaemia has been reported in patients with retinochoroidal vascular disorders. The precise genetic defects of these cases, however, remain unclear because of the limitations of conventional diagnostic techniques. In this study, three patients with these diseases were investigated at the DNA level for the first time to define the molecular bases of these disorders. Polymerase chain reaction–restriction fragment length polymorphism analysis revealed that all three cases carried the same Ala601-Thr mutation. This defect may also play a role in the pathogenesis of circulation disorders in small local vessels because of reduced fibrinolytic activity due to decreased functional plasminogen levels.     

Hemorrhagic acquired factor XIII (13) deficiency and acquired hemorrhaphilia 13 revisited

Coagulation factor XIII (F13) circulates in blood as a heterotetramer composed of an A subunit dimer and a B subunit dimer. It is activated by thrombin and crosslinks fibrin monomers. Congenital F13 deficiency demonstrates a lifelong bleeding tendency, abnormal wound healing, and recurrent miscarriages, and it first manifests as umbilical bleeding after birth. In contrast, secondary F13 deficiencies due to its overconsumption and/or hypobiosynthesis by disseminated intravascular coagulation, major surgery, liver diseases, and other disorders are rather common but rarely complicated with bleeding symptoms. Recently, consultations with physicians who have patients with hemorrhagic-acquired F13 deficiency with anti-F13 inhibitors (acquired hemorrhaphilia 13) have indicated an increase in this disease in Japan. We performed a nationwide survey, supported by the Japanese Ministry of Health, Welfare and Labor and confirmed 21 Japanese cases of this disease with anti-F13 inhibitors. Because neither prolonged clotting times nor reduced platelet counts are observed in patients with this disease, many more cases may have been overlooked. Physicians must be mindful of acquired hemorrhaphilia 13 when seeing such patients and should measure F13 activity. Products containing F13 are effective for hemostasis generally, and immunosuppressive therapy must be started immediately to eradicate anti-F13 antibodies.     

Reduced difference of α<Subscript>2</Subscript>-plasmin inhibitor levels between plasma and serum in patients with severe factor XIII deficiency,including autoimmune hemorrhaphilia due to anti-factor XIII antibodies

Coagulation factor XIII/13 (FXIII/13) stabilizes fibrin molecules by creating crosslinks with other fibrin molecules as well as with α₂-plasmin inhibitor (α₂-PI). “Hemorrhagic acquired FXIII/13 deficiency” was formerly considered rare, but has been increasing recently in Japan. During the 10 months of our nationwide campaign, we diagnosed five new patients with “acquired hemorrhaphilia due to anti-FXIII/13 autoantibodies,” after examining 20 newly suspected cases of “hemorrhagic acquired FXIII/13 deficiency.” When FXIII/13 activity was reduced to less than 50% of normal, it was proportional to the difference in α₂-PI levels between plasma and serum (plasma–serum α₂-PI), likely due to its cross-linking to fibrin by activated FXIII/13. Accordingly, decreased amounts of the plasma–serum α₂-PI ex vivo may reflect reduced FXIII/13 activity in vivo. The plasma–serum α₂-PI may thus also be a useful diagnostic marker for severe FXIII/13 deficiency.     

Caregiving and cardiovascular disease risk factors in male and female Luo elders from Kenya

Background: The HIV/AIDS pandemic has created over 11 million orphans, who are primarily being cared for by grandparents. It has been suggested that this renewed parenting responsibility presents elders with added stressors. Few studies have systematically examined the impact of caregiving on health outcomes.

Aim: The aim of this study was to examine the impact of caregiving on cardiovascular risk. It was hypothesized that caregiving would increase cardiovascular disease risk as measured by Framingham risk scores.

Subjects and method: 386 Luo elders (age = 73±8), divided into caregiving and non-caregiving groups, were recruited from the Nyanza Province, Kenya. Data were obtained from the participants including: Total cholesterol, HDL cholesterol, glucose, blood pressure, age, sex and smoking status.

Results: No significant difference was found between the Framingham risk scores of caregivers and non-caregivers. Among women increased BMI was positively associated with Framingham score (p=0.017), and among men increased waist circumference was positively associated with the score (p<0.001). Among women, the number of orphans under one's care lowered the risk of falling into the top quartile of the Framingham score while being a caregiver increased the risk of falling into the top quartile.

Conclusion: This study demonstrates that there is not a simple relationship between caregiving and cardiovascular risk.     

Comparison of pain and dyspnea perceptual responses in healthy subjects

Dyspnea and pain have a number of similarities. Recent brain imaging experiments showed that similar cortical regions are activated by the perceptions of dyspnea and pain. We tested the hypothesis that an individual’s pain sensitivity might parallel the individual’s dyspnea sensitivity. Studies were carried out in 52 young healthy subjects. Each subject experienced experimentally induced pain and dyspnea. Pain was induced by a cold-pressor test and dyspnea was induced by breathholding while the unpleasant experience of pain and dyspnea was assessed by using a Visual Analogue Scale (VAS). The times from the start of cold stimulation and breathholding to the onset of uncomfortable sensation (pain threshold time and the period of no respiratory sensation, respectively) and to the limit of tolerance (pain endurance time and total breathholding time, respectively) were also measured. In response to cold pain stimulation, a behavioral dichotomy (pain-tolerant and pain-sensitive) was observed. The period of no respiratory sensation was significantly shorter in the PS (pain-sensitive) group than in the PT (pain-tolerant) group (16.9 ± 3.8 vs. 19.6 ± 5.3 s: P < 0.05), whereas no significant difference in the total breathholding time was found between the PT and PS groups. A significant correlation was observed between the pain threshold time and the period of no respiratory sensation in both the PT and PS groups. However, no significant association was observed between pain and dyspnea tolerance in both groups. In conclusion, an individual’s pain threshold is correlated to the individual’s dyspnea threshold, but the individual’s pain tolerance is not consistently correlated to the individual’s dyspnea tolerance.