Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50–97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l±35.0 nmol/l and 49.4 ng/l±23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels ( p =0.04), and positively and independently associated with 25(OH)D levels ( p =0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate ( r =–0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.     

Acute stages of batrachotoxin-induced neuropathy: a morphologic study of a sodium-channel toxin

Summary The acute effects of batrachotoxin, a steroidal neurotoxin which opens the membrane sodium channel, were observed morphologically at various time points up to 3 h after injection into rat peroneal nerve. Three changes were found. First, there was massive swelling of the axon at the node of Ranvier accompanied by retraction of paranodal myelin. Second, a similar swelling of unmyelinated axons was seen. Third, extracellular fluid accumulated along the internode in the adaxonal space, the intraperiod line of myelin and, rarely, the external mesaxon, with concomitant shrinkage of the axon. The first two changes might be explained on the basis of massive shift of sodium through the batrachotoxin-modified sodium channel into the axon and subsequent osmotic shift of fluid. The reason for the third change is not clear but probably also has a ionic basis.     

Injuries in youth football: a prospective observational cohort analysis among players aged 9 to 13 years

OBJECTIVE: To determine the risk of injury in youth football games. SUBJECTS AND METHODS: Nine hundred fifteen players aged 9 to 13 years on 42 teams participated, including 10 teams in each grade from grades 4 through 6 and 6 teams each in grades 7 and 8. The study was conducted in the fall of 1997. Injury incidence, prevalence, and severity were calculated for each grade level and player position. Additional analyses examined the number of injuries according to body weight. RESULTS: A total of 55 injuries occurred in games during the entire season (overall prevalence, 5.97%). Most injuries were mild, and the most common type was contusion, which occurred in 33 players (60%). Four injuries (7%) were severe enough to prevent players from participating for the rest of the season. All 4 severe injuries were fractures involving the ankle physis. The risk of injury increased as players matured in age and grade level. Injury risk for an eighth-grade player was 4 times greater than the risk of injury to a fourth-grade player. A trend was identified for heavier players to be at increased risk, but no significant correlation was evident between body weight and injury. CONCLUSION: Our prospective observational analysis showed that most youth football injuries are mild. Older and heavier players appear to be at higher risk.     

Reverse vaccinology approach to design a multi-epitope vaccine construct based on the Mycobacterium tuberculosis biomarker PE_PGRS17

Mycobacterium tuberculosis (Mtb) is responsible for high mortality rates in many low- and middle-income countries. This infectious disease remains accountable for around 1.4 million deaths yearly. Finding effective control measures against Mtb has become imperative. Vaccination has been regarded as the safe and lasting control measure to curtail the impact of Mtb. This study used the Mtb protein biomarker PE_PGRS17 to design a multi-epitope vaccine. A previous study predicted a strong antigenic property of PE_PGRS17. Immunogenic properties such as antigenicity, toxicity, and allergenicity were predicted for the PE_PGRS17 biomarker, specific B- and T-cell epitope sequences, and the final multiple epitope vaccine (MEV) construct. Algorithmic tools predicted the T- and B-cell epitopes and those that met the immunogenic properties were selected to construct the MEV candidate for predicted vaccine development. The epitopes were joined via linkers and an adjuvant was attached to the terminals of the entire vaccine construct. Immunogenic properties, and physicochemical and structural predictions gave insight into the MEV construct. The assembled vaccine candidate was docked with a receptor and validated using web-based tools. An immune simulation was performed to imitate the immune response after exposure to a dosed administrated predicted MEV subunit. An in silico cloning and codon optimisation gave insight into optimal expression conditions regarding the MEV candidate. In conclusion, the generated MEV construct may potentially emit both cellular and humoral responses which are vital in the development of a peptide-based vaccine against Mtb; nonetheless, further experimental validation is still required.

     

Multiple Sclerosis: Fas Signaling in Oligodendrocyte Cell Death

Fas is a cell surface receptor that transduces cell death signals when cross-linked by agonist antibodies or by fas ligand. In this study, we examined the potential of fas to contribute to oligodendrocyte (OL) injury and demyelination as they occur in the human demyelinating disease multiple sclerosis (MS). Immunohistochemical study of central nervous system (CNS) tissue from MS subjects demonstrated elevated fas expression on OLs in chronic active and chronic silent MS lesions compared with OLs in control tissue from subjects with or without other neurologic diseases. In such lesions, microglia and infiltrating lymphocytes displayed intense immunoreactivity to fas ligand. In dissociated glial cell cultures prepared from human adult CNS tissue, fas expression was restricted to OLs. Fas ligation with the anti-fas monoclonal antibody M3 or with the fas–ligand induced rapid OL cell membrane lysis, assessed by LDH release and trypan blue uptake and subsequent cell death. In contrast to the activity of fas in other cellular systems, dying OLs did not exhibit evidence of apoptosis, assessed morphologically and by terminal transferase–mediated d-uridine triphosphate-biotin nick-end-labeling staining for DNA fragmentation. Other stimuli such as C2-ceramide were capable of inducing rapid apoptosis in OLs. Antibodies directed at other surface molecules expressed on OLs or the M33 nonactivating anti-fas monoclonal antibody did not induce cytolysis of OLs. Our results suggest that fas-mediated signaling might contribute in a novel cytolytic manner to immune-mediated OL injury in MS.