Recently, we showed that supplementation with nitric oxide (NO) via donor nitroglycerin (NG) alleviated the ovariectomy and corticosteroid-induced bone loss in rats. In humans, high doses or frequent applications of NG (i.e., for angina) lead to rapid loss of its efficacy in relieving angina. To examine whether there is a similar effect on the loss of efficacy of NG on bone, we examined the frequency-dependent effects of NG on bone mineral density (BMD), bone mass, trabecular bone volumes (BV/TV), and blood pressure in rats. Thirty 7-month-old female Brown Norway rats underwent ovariectomy, and an additional six rats were shamoperated. The ovariectomized rats were treated either with vehicle (ovariectomized control), 17␤-estradiol (E 2 ; positive control), or 0.2 mg NG (via dermal application) once, twice, or three times a day. Before and at the end of the 10-week treatment period, BMD of the lumbar spine was measured by dual-energy X-ray absorptiometric (DXA) scanning and expressed as a percentage change. BMD in ovariectomized rats was significantly lower (؊2.5 ؎ 2.0%) compared with the sham-operated rats (؉6.3 ؎ 5.3%; p < 0.01). Estrogen therapy completely abolished the ovariectomy-induced potential bone loss (؉5.9 ؎ 3.4%). Application of NG once daily also completely prevented (؉6.2 ؎ 2.8%; p < 0.01) the ovariectomy-induced bone loss (i.e., it was as effective as estrogen). However, the beneficial effects of NG on BMD were significantly reduced with increased frequency of application of NG (؉1.9 ؎ 2.1%, twice a day and ؊0.2 ؎ 3.3% three times a day). Estrogen or once daily administration of NG preserved femur weights, BV/TV, and decreased urinary deoxypyridinoline levels as expected. However, a higher level of serum osteocalcin and bone-specific alkaline phosphatase levels were maintained only with once daily administration of NG. There were no adverse effects of these doses of NG on blood pressure, but a tendency to lower blood pressure was noticed with increased frequency of NG. These results confirmed our previous findings that NO donors counteract the bone loss associated with estrogen deficiency. However, these beneficial effects of maintaining BMD are lost with increased frequency of NG application. (J Bone Miner Res 2000;15:1119 -1125) Key words: bone mineral density, osteoporosis, postmenopausal bone loss, osteocalcin, estrogen, nitric oxide synthase.

J. Wimalawansa. Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI. J. Appl. Physiol. 86(6): 1841-1846, 1999.-Microgravity causes rapid decrement in musculoskeletal mass is associated with a marked decrease in circulatory testosterone levels, as we reported in hindlimb-suspended (HLS) rats. In this model which simulates microgravity, we hypothesized that testosterone supplementation should prevent these losses, and we tested this in two studies. Muscle volumes and bone masses were quantitated by using magnetic resonance imaging (MRI) on day 12. In the first study, 12-wk-old Sprague-Dawley rats that were HLS for 12 days lost 28.5% of muscle volume (53.3 Ϯ 4.8 vs. 74.5 Ϯ 3.6 cm 3 in the ground control rats; P Ͻ 0.001) and had a 5% decrease in bone mineral density (BMD) (P Ͻ 0.05). In the second study, 30 male 12-wk-old Wistar rats were HLS and were administered either a vehicle (control), testosterone, or nandrolone decanoate (ND). An additional 20 rats were used as ground controls, one-half of which received testosterone. HLS rats had a significant reduction in muscle volume (42.9 Ϯ 3.0 vs. 56 Ϯ 1.8 cm 3 in ground control rats; P Ͻ 0.01). Both testosterone and ND treatments prevented this muscle loss (51.5 Ϯ 2 and 51.6 Ϯ 1.2 cm 3 , respectively; a 63% improvement; P Ͻ 0.05). There were no statistical differences between the two active treatment groups nor with the ground controls. Similarly, there was an 85% improvement in BMD in the testosterone group (1.15 Ϯ 0.04 vs. 1.04 Ϯ 0.04 density units in vehicle controls; P Ͻ 0.05) and a 76% improvement in the ND group (1.13 Ϯ 0.07 density units), whereas ground control rats had a BMD of 1.17 Ϯ 0.03 density units. Because serum testosterone levels are markedly reduced in this model of simulated microgravity, androgen replacement seems to be a rational countermeasure to prevent microgravity-induced musculoskeletal losses. osteoporosis; microgravity; bone turnover; bone mineral density; anabolic steriod; disuse atrophy DECREMENTS IN BONE AND MUSCLE mass are major concerns in extended space missions (1,8,9,38,49). Immobilization (e.g., bed rest or restricted movements of limbs) can also cause rapid losses in muscle or bone mass (6,9,25,26). Immobilization, prolonged bed rest, and spaceflight conditions inducing microgravity conditions can lead to the general or selective loss of muscle volume and mass. In addition, these conditions lead to negative calcium balance and loss of bone mineral density (BMD) (11,13,32,33). A similar reduction in musculoskeletal mass has been reported due to the immobilization of extremities seen in external bandaging, casting, or neural resectioning (13,25,27,(39)(40)(41)(42)(43). Both mineralization and collagen metabolism seem to be impaired in animals during the first few days of spaceflight (34). Urine analysis in Skylab astronauts has shown a significant loss of minerals, including calcium (10, 37). Reduction of muscle forces leads to a decrease in bone formation and BMD in the os calcis and an i...

This study examined the effects of simulated weightlessness on serum hormone levels and their relationship to bone mineral density (BMD). The tail-suspended (i.e., hindlimb suspended, HLS) rat model was used to simulate weightless conditions through hindlimb unloading to assess changes in hormonal profile and the associated bone loss. In the first study, 24 adult male rats were assigned to two groups with 12 rats being HLS for 12 d, and the remaining 12 rats serving as ground controls. On d 0, 6, and 12, blood samples were taken to estimate circulating hormone levels. HLS rats had significant reductions in testosterone, 1,25 (OH)2 vitamin D, and thyroxine levels by d 6 (p<0.01); their testosterone levels were almost undetectable by d 12 (p<0.001). Serum cortisol levels in these rats were elevated on d 6 (p<0.02), but returned to normal levels by d 12. No changes were observed with serum ionized calcium and other hormones examined, as well as the body weights, and weights of thymus, heart, and brain. In the second study, eight rats were ground controls, while an additional eight rats were HLS for 12 d before being removed from tail-suspension and maintained for a further 30 d. Blood samples were collected every 6th d for 42 d. This study showed that both serum thyroxine and 1,25(OH)2 vitamin D levels returned to normal levels soon after hind limb unweighting, while serum testosterone levels matched normal levels only after a further 3-4 wk. These studies showed a significant decrease of femur weights, but not weights of humeri in HLS rats suggesting that this is a specific effect on unloaded bones. On d 12 in both studies, a significant reduction in the lumbar spine (p<0.05) and the femoral neck (p<0.01) BMD appeared in HLS rats. This was confirmed in the second study, where HLS led to a significant decrease in BMD even extending to d 42. Previous studies have shown that space flight and tail-suspension lead to marked reductions in bone formation with little effect on bone resorption. Recently, we reported that androgen replacement can indeed prevent bone losses in this animal model. Therefore, it seems logical to propose that the significant decreases of serum testosterone observed in these tail-suspended animals are, at least in part, responsible for the losses of BMD seen in their affected weight-bearing bones (i.e., lumbar spine and the femur). Considering that 1. testosterone is anabolic to osteoblasts and also decreases the rate of bone turnover 2. serum testosterone levels are markedly suppressed in simulated weightlessness, and 3. testosterone replacement therapy prevented the bone loss in HLS rats, we propose that the testosterone deficiency in this animal model is related to their bone loss.

The popularity of cosmetic surgery has increased around the world, and whereas in the past, the patient base consisted of mainly Caucasian individuals, interest in this field has grown among persons of varying ethnic backgrounds. Growing interest enables ethnic populations to contribute to the economic growth of the cosmetic surgery industry and impact the direction of the field in the future. Minority populations accounted for 22% of the cosmetic procedures performed in 2007, with the most common being liposuction, Botox((R)) generic botulinum toxin type A (Allergan, Inc., Irvine, CA), and chemical peels. Ultimately, changes in the population characteristics of the plastic surgery patient will alter the techniques of plastic surgeons that treat ethnic patients to cater to their physical differences. Factors such as increased cultural acceptance of plastic surgery, growing ethnic populations, and media emphasis on personal appearance have contributed to the increase in minorities seeking out cosmetic surgery. Escalating economic power within these populations has created an additional potentially lucrative market for interested plastic surgeons.

The rat femoral artery (RFA) anastomosis model has been the gold standard in microsurgical simulation training. While effective, live animal use requires animal use committee regulation and costly maintenance. Our institution's animal laboratory is remote to the hospital, limiting access by our busy surgical residents with their limited duty hours. We present an alternative convenient, cost-effective model. Ten frozen turkey wings were divided into distal and proximal segments. Vessel diameter, length, and anastomosis perfusion were assessed. Proximal brachial arteries ("humeral" segments) measured 8.85 ± 1.14 cm long with diameter 1.69 ± 0.27 mm. Distal brachial arteries ("forearm") measured 10.5 ± 2.06 cm long with diameter 1.25 ± 0.25 mm. An 8-lb box (~20 wings) cost $13.76. Separate use of the segments provides two training sessions with $0.35 per session effective cost. Our average cost for RFA microsurgical training sessions was $120 dollars for a single rat 2-hour session and $66 per rat if a maximum crate load of six rats was used. Besides significant cost, not all training programs are equipped to house, care for, and use rats in microsurgical training. We now use turkey wings for microvascular training. They are cheap, abundant, readily accessible for training, and consistent with tissue quality and vessel size approximating human systems.