Bone-resorbing activity of thyroid hormones is related to prostaglandin production in cultured neonatal mouse calvaria

The bone-resorbing activity of thyroid hormones was evaluated in neonatal mouse calvaria maintained in organ culture for 96 h. Thyroxine (T4) between 10(-8) and 10(-5) mol/liter and triiodothyronine (T3) between 10(-8) and 10(-7) mol/liter caused a dose-dependent release of calcium from cultured bone. The thyroid hormone effect was delayed in onset for at least 24 h, and after 96 h of culture amounted to 50-90% of the bone-resorbing activity of 10(-8) mol/liter parathyroid hormone (PTH). The bone-resorbing action of T4 as well as of T3 was completely blocked by 100 U/ml interferon-gamma (IF-gamma) or 20 mU/ml salmon calcitonin (CT). "Escape" from CT inhibition, which is a well-known phenomenon in the action of PTH, was not observed with thyroid hormone-mediated bone resorption. Thyroid hormone treatment of cultured calvaria resulted in a gradual increase between 48 and 96 h of medium concentrations of prostaglandin (PG) E2 and particularly of 6-keto-PGF1 alpha, the inactive metabolite of prostacyclin (PGI2). The release of PGF2 alpha in general was not significantly affected. Although the effect of thyroid hormones on PG release from cultured calvaria was completely abolished by 5 x 10(-7) mol/liter indomethacin, in some experiments indomethacin reduced thyroid hormone-mediated bone resorption by only 50%. This indicates that thyroid hormone action on bone is also mediated by a PG-independent mechanism.     

Rous sarcoma virus p19 binds to specific double-stranded regions of viral RNA: effect of p19 on cleavage of viral RNA by RNase III.

The extent of binding of purified RSV(Pr-C) p19 and p12 to a variety of RNAs was measured using a sensitive nitrocellulose filter binding assay which is capable of detecting binding reactions with association constants as low as 3 × 10⁶ liters × mol^?1 (Hizi, A., Leis, J. P., and Joklik, W. K. 1977). RSV p19 bound 60 and 34 S RSV (Pr-C) RNA with association constants of 5.1 × 10¹¹ and 1.8 × 10¹⁰ liters × mol^?1. RSV p19 bound preferentially to specific double-stranded regions of the RNA since: (a) The association constant for Neurospora nuclease-digested 34 S RNA was the same as for untreated RNA; (b) the association constant for 34 S RNA partially digested with Escherichia coli RNase III (which is specific for double-stranded RNA regions) was 30-fold lower than for untreated RNA; (c) p19 prevented cleavage of 34 S RSV-RNA by E. coli RNase III; (d) p19 bound cell precursor RNAs containing RNase III-sensitive sites, but not mature RNAs lacking RNase III-sensitive sites. On the other hand, purified RSV p12 bound all RNAs tested with association constants roughly proportional to their molecular weights. A possible function for p19 in regulating the processing of viral RNA and its subsequent translation has been proposed.     

Effect of creatine supplementation during rapid body mass reduction on metabolism and isokinetic muscle performance capacity

Well-trained subjects (n=6) were studied before and after losing a mean 3.0%–4.3% of body mass to determine whether muscle performance could be maintained or even enhanced by dietary creatine supplementation. During a 5-day period of loss of mass the subjects were randomly assigned to a creatine or placebo supplemented diet. All the subjects were measured before and after loss of mass on both supplements for isokinetic peak torque (PT) and work at peak torque (W _PT) of knee extensors, also for intermittent high intensity working capacity of the same muscle group. The latter test consisted of submaximal isokinetic knee extensions at an angular velocity of 1.57 rad?·?s^?1 for 45 s at the rate of 30 contractions each min (submaximal work, W _{s max} ) followed by 15-s maximal effort (maximal work, W _max ). Total duration of the test was 3 min. Haematocrit was measured and haemoglobin, ammonia, lactate, glucose and urea concentrations were analysed in blood samples obtained at rest and after cessation of muscle performance tests. The results indicated that creatine supplementation in comparison with placebo treatment during rapid body mass reduction may help to maintain muscle PT and W _PT at high angular velocities, not influencing W _max and the rate of fatigue development during W _max , but affecting adversely W _{s max} . Within the limitations of the present study the reasons for the partially detrimental effect of creatine administration remain obscure, but it is suggested that impaired creatine uptake in muscle during body mass loss as well as creatine induced changes in muscle glucose and glycogen metabolism may be involved.     

Evaluation of Body Composition,Physical Activity,and Food Intake in Patients with Inborn Errors of Intermediary Metabolism

Children with inborn errors of intermediary metabolism (IEiM) must follow special diets that restrict their intake of essential nutrients and may compromise normal growth and development. We evaluated body composition, bone mineral density, physical activity, and food intake in IEiM patients undergoing dietary treatment. IEiM patients (n = 99) aged 5–19 years and healthy age- and sex-matched controls (n = 98) were recruited and underwent dual-energy X-ray absorptiometry to evaluate anthropometric characteristics and body composition. Data on food intake and physical activity were also collected using validated questionnaires. The height z-score was significantly lower in IEiM patients than controls (−0.28 vs. 0.15; p = 0.008), particularly in those with carbohydrate and amino acid metabolism disorders. Significant differences in adiposity were observed between patients and controls for the waist circumference z-score (−0.08 vs. −0.58; p = 0.005), but not the body mass index z-score (0.56 vs. 0.42; p = 0.279). IEiM patients had a significantly lower total bone mineral density (BMD) than controls (0.89 vs. 1.6; p = 0.001) and a higher risk of osteopenia (z-score < −2, 33.3% vs. 20.4%) and osteoporosis (z-score < −2.5, 7.1% vs. 0%), but none presented fractures. There was a significant positive correlation between natural protein intake and BMD. Our results indicate that patients with IEiM undergoing dietary treatment, especially those with amino acid and carbohydrate metabolism disorders, present alterations in body composition, including a reduced height, a tendency towards overweight and obesity, and a reduced BMD.     

Predictors of Hand Function Following Digit Replantation: Quantitative Review and Meta-Analysis

Background: Digit replantation affords the opportunity to restore hand function following amputation. To date, however, few studies have evaluated functional outcomes following replantation. Therefore, it was the objective of this study to perform a meta-analysis to better characterize the predictors of hand function. Methods: A literature search was performed using the PubMed database to identify studies that focused on digit amputation/replantation and functional outcomes. Studies were evaluated for patient- and injury-related factors and their respective effects on clinical outcomes of sensation, grip strength, and Disabilities of the Arm, Shoulder, and Hand (DASH) scores. Statistical analysis was conducted across the pooled data set to identify significant trends. Results: Twenty-eight studies representing 618 replanted digits were included in this study. We found the average grip strength was 78.7% (relative to contralateral), the average 2-point discrimination (2PD) was 7.8 mm, and the average DASH score was 12.81. After conducting statistical analysis, we found patients with more proximal injuries had lower grip strength scores (P < .05). We found 2PD scores were influenced by age, mechanism of injury, and amputation level (P < .05). Finally, we found DASH scores after replantation were predicted by mechanism of injury and level of amputation (P < .05). The following variables did not influence outcomes: gender, tobacco use, ischemia time, and digit number. Conclusions: Digit replant does not restore premorbid hand function but does result in adequate hand function. Expected functional outcomes following replant should be considered in the decision-making process. These data can help risk-stratify patients, guide postreplant expectations, and influence the decision for replantation.     

Towards a Neurotransmitter-Based Retinal Prosthesis Using an Inkjet Print-head

Electronic chips that provide a patterned stimulus to cells in the retina may provide a viable treatment for age-related macular degeneration. A surrogate MEMS device, in the form of a print-head from a desktop printer, has been used to eject a pattern of neurotransmitters (bradykinin) onto living rat pheochromocytoma (PC12) cells. Fluorescent calcium imaging was used to measure the patterned stimulation of individual cells. The chemical stimulation of cells by directed microfluidic delivery may have applications in retinal prosthetic devices, and in other prosthetic implants in the nervous system.