Hypergravity modulates behavioral nociceptive responses in rats.

Hypergravity (2G) exposure elevated the nociceptive threshold (pain suppression) concomitantly with evoked neuronal activity in the hypothalamus. Young Wistar male rats were exposed to 2G by centrifugal rotation for 10 min. Before and after 2G exposure, the nociceptive threshold was measured as the withdrawal reflex by using the von Frey type needle at a total of 8 sites of each rat (nose, four quarters, upper and lower back, tail), and then rats were sacrificed. Fos expression was examined immunohistochemically in the hypothalamic slices of the 2G-treated rats. When rats were exposed to 2G hypergravity, the nociceptive threshold was significantly elevated to approximately 150 to 250% of the 1G baseline control levels in all the examination sites. The 2G hypergravity remarkably induced Fos expression in the paraventricular and arcuate nuclei of the hypothalamus. The analgesic effects of 2G hypergravity were attenuated by naloxone pretreatment. Data indicate that hypergravity induces analgesic effects in rats, mediated through hypothalamic neuronal activity in the endogenous opioid system and hypothalamo-pituitary-adrenal axis.

Gravity stress elevates the nociceptive threshold level with immunohistochemical changes in the rat brain.

Young Wistar male rats were exposed to 2G hypergravity by continuous centrifugation for 15 minutes. The nociceptive threshold was measured by using the von Frey type filament on the rat skin surfaces after hypergravity exposure. Following the hypergravity exposure, rats were sacrificed with anesthesia, then perfused and fixed for immunohistochemical examination. The 2G hypergravity elevated the nociceptive threshold up to 2-fold and induced analgesic effects on rats that remained for 2 hours after termination of centrifugation. Expression of Fos-immunoreactive proteins was prominently induced by 2G hypergravity in the arcuate nucleus and the paraventricular nucleus of the hypothalamus. The 15-minute flash exposure to 2G hypergravity induced pain suppression in rats, which might be attributed to change of neuronal activity in rat hypothalamus.

Hypergravity and opioid-mediated pain suppression in rats.

It is known that pain suppression in animals is induced by certain environmental stimulus. However, little is known about the effects of gravitational alteration on the nociceptive responses in rats. A recent study indicated that Fos protein expression was strongly induced in the vestibular-related brainstem regions of rats that were exposed to 2 G hypergravity (Gustave Dit Duflo et al., 2000). A number of studies indicate that Fos expression is induced in the brain by various kinds of stress. We showed that either long-term exposure or short-term exposure to 2 G hypergravity elevated the nociceptive threshold in the rat skin surfaces, in concomitant with Fos induction in the hypothalamus including the arcuate nucleus and paraventricular nucleus (Kumei et al., 2000). We have examined the possible involvement of beta-endorphin, an endogenous opioid, in the hypergravity-induced analgesic effects on rats and its counteraction by naloxone, an opioid receptor antagonist.

Decreased bone mineral density associated with early menopause progresses for at least ten years: cross-sectional comparisons between early and normal menopausal women.

To establish whether early onset of menopause carries an increased risk of osteoporosis, we compared the bone mineral density (BMD) of the second to fourth lumbar vertebrae (L2-4) between 18 women who had menopause before 43 years of age (early menopause group) and 19 women who had menopause after reaching 43 years of age (normal menopause group). Serum levels of calcium, phosphorus, calcitonin, intact parathyroid hormone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and alkaline phosphatase activity were measured, and urine samples were analyzed to derive calcium/creatinine, hydroxyproline/creatinine, pyridinoline/creatinine, and deoxypyridinoline/creatinine (D-Pyr/Cr) ratios. Mean BMD was significantly lower in the early menopause group than in the normal menopause group, and individual BMD values in about half of the subjects in the former group were below the fracture threshold for Japanese women. Serum concentrations of LH, FSH, and E2 were slightly, but not significantly, lower in the early menopause group than in the normal menopause group. The D-Pyr/Cr ratio was significantly higher in the early menopause group than in the normal menopause group. There was no correlation between L2-4 BMD and age or the number of years after menopause in the normal menopause group, but both age and the number of years after menopause were negatively correlated with L2-4 BMD in the early menopause group. These results indicate that BMD in women who have early menopause continues to decline for up to 10 years, and that menopause and aging increase the risk of osteoporosis.

Cloning and characterization of a growth factor-inducible cyclooxygenase gene from rat intestinal epithelial cells.

Growth factors have been shown to play a role in intestinal epithelial growth regulation and transformation. Utilizing standard differential cloning techniques, we have isolated a growth factor-inducible gene (RS-2) from rat intestinal epithelial cells that has approximately 95% homology to the mouse mitogen-inducible cyclooxygenase (COX-2) at the amino acid level. This cDNA hybridizes to a approximately 4.5-kb mRNA from transforming growth factor (TGF)-alpha-stimulated rat intestinal epithelial (RIE-1) cells and is constitutively expressed in vivo in adult rat kidney and brain. Nuclear run-on experiments demonstrate that the increase of RS-2 mRNA after TGF-alpha stimulation is in part due to an increased transcription rate of the gene. The coding region for RS-2 was subcloned into a pCMV-2 expression vector, and the RS-2 protein was expressed in COS-1 cells. Microsomal fractions isolated from the COS-1 cells transfected with the RS-2 expression vector contained cyclooxygenase activity. In addition to the production of prostaglandins, the recombinant RS-2 protein also catalyzed the formation of three other eicosanoid products. In summary, we have cloned a mitogen-inducible cyclooxygenase gene from rat intestinal cells that is induced following growth factor stimulation.

[Influences of menopause and oophorectomy on bone metabolism and spinal bone mineral content].

The present study was performed on bone metabolism and spinal bone mineral content (BMC) in 3 groups of age- and body size-matched subjects: Thirty-three postmenopausal subjects, 37 oophorectomized (OPX) subjects and 22 premenopausal subjects. Serum levels of Alp and osteocalcin (OC) as indices of bone formation, U-Ca/cr and U-hydroxyproline (Hpr)/cr as indices of bone resorption, and Ca-regulating hormones, M-PTH, calcitonin (CT) and 1,25(OH)2D; were measured and spinal BMC was determined by QCT. Alp and OC levels were slightly higher in the postmenopausal group than in the OPX group and, in contrast, U-Ca/cr and U-Hpr/cr were slightly higher in the latter. The M-PTH level was slightly higher in the latter, and the CT level in the former. There was no difference in the 1,25(OH)2D level between two groups. For BMC, there was no difference between the two groups. The above results corresponded to the previously reported significant reductions in sex steroids. OPX seemed to affect bone metabolism more than menopause, there was no specific influence of OPX on spinal BMC as compared with QCT findings in postmenopausal subjects. Our previous study and the present study demonstrated that, at an interval of about 3 years after menopause or OPX, the endocrine system and bone metabolism tended to be more affected by OPX. However, BMC did not reflect any influence of OPX, or of menopause. There was no clear clinical difference between postmenopausal subjects and the OPX subjects with regard to the osteoporotic condition.

Scintigraphic manifestation of fibrous dysplasia.

Scintigraphic manifestations of fibrous dysplasia were analyzed in 59 lesions of 26 patients (12 monostotic, 14 polystotic). Bone imaging with Tc-99m MDP revealed a high percentage of increased uptake of radioisotope in the lesions of fibrous dysplasia. Four (14%) of 29 cystic lesions and two (7%) of 30 lesions with the appearance of ground glass showed no increase in radioisotope uptake, although roentgenograms showed marked changes. Therefore, care must be taken in the diagnosis of fibrous dysplasia with bone imaging alone. Nuclear methods, however, are indispensable in evaluating the dynamic aspects of bone mineral behavior and in demonstrating disease where none was suspected, or in visualizing polyostotic involvement in those cases where only monostotic disease was suspected clinically. It is concluded that both scintigrams and roentgenograms are complementary procedures in the diagnosis of fibrous dysplasia.