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Inuence of male alcoholism on pregnancy and progeny. Exp. Pathol., 12, 3845. Kleiman, S.E., Yogev, L., Gamzu, R. et al. 1999 ; Genetic evaluation of infertile men. Hum. Reprod., 14, 3338. Kola, I., Kirby, C., Shaw, J. et al. 1988 ; Vitrication of mouse oocytes results in aneuploid zygotes and malformed fetuses. Teratology, 38, 467474. Kuleshova, L., Gianaroli, L., Magli, C. et al. 1999 ; Birth following vitrication of a small number of human oocytes: case report. Hum. Reprod., 14, 30773079. Lanzendorf, S.E., Mayer, J.F., Toner, J. et al. 1999 ; Pregnancy following transfer of ooplasm from cryopreserved-thawed donor oocytes into recipient oocytes. Fertil. Steril., 71, 575577. Leibovitz, B. and Siegel, B.V. 1980 ; Aspect of free radical reactions in biological systems. Aging J. Gerontol., 35, 4556. Lemoine, P.I., Harousseau, H., Borteyru, J.P. et al. 1968 ; Les enfants de parents alcooliques: anomalies observees. A propos de 127 cas. Ouest Med., 25, 476482. Leonard, C., Bisson, J.P. and David, G. 1979 ; Male sterility associated with familial translocation heterozygosity: t 8; 15 ; q22; p11 ; . Arch. Androl., 2, 269275. Li, F.P., Gimbrere, K., Gelber, R.D. et al. 1987 ; Outcome of pregnancy in survivors of Wilms' tumor. JAMA, 257, 216219. Lindbohm, M.L. 1995 ; Effects of parental exposure to solvents on pregnancy outcome. J. Occup. Environ. Med., 37, 908914. Little, J. and Vainio, H. 1994 ; Mutagenic lifestyles ? A review of evidence of associations between germ-cell mutations in humans and smoking, alcohol consumption an use of `recreational' drugs. Mutat. Res., 313, 131151. Little, R.E. and Sing, C.F. 1985 ; Father's drinking and infant birth weight: report of an association. Teratology, 36, 5965. Liu, J., Van Den Abbeel, E. and Van Steirteghem, A. 1993 ; Assessment of ultrarapid and slow freezing procedures for 1-cell and 4-cell mouse embryos. Hum. Reprod., 8, 11151119. Lord, B.I., Woolford, L.B., Wang, L. et al. 1998 ; Induction of lymphohaematopoietic malignancy: Impact of preconception paternal irradiation. Int. J. Radiat. Biol., 74, 721728. Lorenzo, A.V., Gewirtz, M. and Averill, D. 1978 ; CNS lead toxicity in rabbit offspring. Environ. Res., 17, 131150. Lowery, M.C., Au, W.W., Adams, P.M. et al. 1990 ; Male-mediated behavioral abnormalities. Mutat. Res., 229, 213229. Lutwak-Mann, C., Schmid, K. and Keberle, H. 1967 ; Thalidomide in rabbit semen. Nature, 214, 10181020. Magistrini, M. and Szollosi, D. 1980 ; Effects of cold and isopropyl-Nphenylcarbamate on the second meiotic spindle of mouse oocytes. Eur. J. Cell Biol., 22, 699707. Mahadevan, M.M., McIntosh, A., Miller, M.M. et al. 1998 ; Formaldehyde in cryoprotectant propanediol and effect on mouse zygotes. Hum. Reprod., 13, 979982. Mandelbaum, J., Junca, A.M., Tibi, C. et al. 1987 ; La congelation de l'ovocyte. Fertil. Contracept. Sex., 15, 792795. Mankes, R.F., LeFevre, R., Benitz, K.F. et al. 1982 ; Paternal effects of ethanol in the Long-Evans rat. J. Toxicol. Environ. Health, 10, 871878. Mann, T. and Lutwak-Mann, C. 1982 ; Passage of chemicals into human and animal semen: mechanisms and signicance. Crit. Rev. Toxicol., 2, 114. Manuel, C., Choquet, M. and Czyba, J.C. 1986 ; L'enfant ne apres insemination articielle avec sperme de donneur IAD ; . Hormones, 3, 133135. Marmor, D. 1999 ; Fonction gonadique et reproduction apres traitement antimitotique. Reprod. Hum. Horm., XII, 559567. Martin, R.H. 1993 ; Detection of genetic damage in human sperm. Reprod. Toxicol., 7, 4752. Matsuda, Y., Seki, N., Utsugi-Takeuchi, T. et al. 1989 ; X-ray- and mitomycin C MMC ; -induced chromosome aberrations in spermiogenic germ cells and the repair capacity of mouse eggs for the X-ray and MMC damage. Mutat. Res., 211, 6575. McDiarmid, M.A. 1993 ; Occupational exposure to pharmaceuticals: antineoplastics, anesthetic agents, sex steroid hormones. In Paul, M. ed. ; , Occupational and Environmental Reproductive Hazards: A Guide for Clinicians. Williams & Wilkins, Baltimore, pp. 280295. Meistrich, M.L. 1993 ; Potential genetic risks of using semen collected during chemotherapy. Hum. Reprod., 8, 810. Mieusset, R., Quintana Casares, P.I., Sanchez-Partida, L.V. et al. 1992 ; Effects of heating on the testes and epididymes of rams by scrotal insulation on fertility and embryonic mortality in ewes inseminated with frozen semen. J. Reprod. Fertil., 94, 337343.
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Coupling Mature bone is a continuously remodeling tissue in which resorption and formation take place sequentially throughout life. The process whereby this sequential coordination between osteoclastmediated resorption and osteoblast-mediated formation is maintained is termed coupling. The coupling of osteoblast and osteoclast function is brought about by a number of mechanisms. Possibly the most important is the fact that the major hormones PTH and vitamin D ; and local factors IL1 ; that stimulate bone resorption do not have their receptors on the osteoclasts but instead on the bone lining cells. Thus the signal for bone resorption by the osteoclast is mediated by the osteoblast cell lineage. This signalling involves the release of soluble factors produced by the bone lining cells MCSF and osteoprotegerin ; and the interaction of cell surface molecules on the bone lining cells TRANCE ; and recruited osteoclasts RANK ; . In addition, the osteoclasts will not bind to bone surfaces covered by unmineralized osteoid, but first require the bone lining cells to degrade the osteoid to expose underlying mineral. Demineralization of bone by the osteoclast releases matrix constituents such as BMP and TGF ; that can stimulate the differentiation and proliferation of osteoblast progenitors or stimulate matrix production by the osteoblasts, and so initiate new bone formation. Osteoclast action is terminated by apoptosis programmed cell death ; and the prevention of new recruitment by osteoprotegerin production by the osteoblasts. Thus each cycle of bone remodeling involves the sequential steps of activation-resorption-formation ARF ; , carried out by the bone lining cells, osteoclasts and osteoblasts, respectively. In the young healthy adult resorption and formation are balanced such that bone mass remains constant. Pathological states develop when resorption and formation are unbalanced, as either excessive bone loss or excessive formation can occur.
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93. PURPOSE: We evaluated the erectogenic properties of a new cyclic alpha-melanocytestimulating hormone analogue, Melanotan-II, to treat men with psychogenic erectile dysfunction. MATERIALS AND METHODS: Ten men with erectile dysfunction of no known organic cause were entered in a double-blind, placebo controlled crossover study in which the erectogenic properties of Melanotan-II and a vehicle placebo were compared using realtime RigiScan monitoring. The presence, duration and rigidity of erections were recorded during a 6-hour period. RESULTS: In 8 of men treated with Melanotan-II clinically apparent erections developed. Mean duration of tip rigidity greater than 80% was 38.0 minutes with Melanotan-II and 3.0 with placebo p 0.0045 ; . Transient side effects of nausea, stretching and yawning, and decreased appetite were reported more frequently after injections of Melanotan-II than placebo but none required treatment. CONCLUSIONS: Melanotan-II is a potent initiator of erections in men with psychogenic erectile dysfunction and has manageable side effects at a dose of 0.025 mg. kg. Wessells, H., D. Gralnek, et al. 2000 ; . "Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction." Urology 56 4 ; : 641-6. OBJECTIVES: To assess the safety, erectogenic properties, and effect on sexual desire of Melanotan II, a synthetic melanotropic initiator of erection, in men with erectile dysfunction and organic risk factors. METHODS: Ten subjects were enrolled in a double-blind, placebocontrolled, crossover study. Melanotan II 0.025 mg kg ; and vehicle were each administered twice by subcutaneous injection; real-time RigiScan monitoring and a visual analog were used to quantify the erections during a 6-hour period. The level of sexual desire and side effects were recorded with a questionnaire. RESULTS: Melanotan II initiated subjectively reported erections in 12 of injections versus only 1 of 21 doses of placebo. The mean rigidity score of the responders was 6.9 on a scale of 0 to 10. The mean duration of tip rigidity greater than 80% was 45.3 minutes with Melanotan II versus 1.9 for placebo P 0.047 ; . The level of sexual desire after injection was significantly higher after Melanotan II administration than after placebo. Nausea and stretching yawning occurred more frequently with Melanotan II, and 4 of 19 injections were associated with severe nausea. CONCLUSIONS: The erectogenic properties of Melanotan II are not limited to cases of psychogenic erectile dysfunction; men with a variety of organic risk factors developed penile erections. The finding of increased sexual desire warrants further investigation of centrally acting agents on disorders of sexual desire. Wessells, H., V. J. Hruby, et al. 2003 ; . "MT-II induces penile erection via brain and spinal mechanisms." Ann N Y Acad Sci 994: 90-5. alpha-Melanocyte-stimulating hormone induces penile erection via melanocortin MC ; receptors in areas surrounding the third ventricle, but spinal and peripheral mechanisms have not been demonstrated. We used pharmacological strategies to localize the site of the proerectile action of the melanocortin receptor agonist MT-II. We administered MT-II intracerebroventribularly i.c.v. ; , intrathecally i.th. ; , and intravenously i.v. ; and scored penile erection and yawning for 90 min in awake male rats. In some animals i.c.v. or i.th. SHU-9119 was injected 10 minutes before i.c.v. and i.th. MT-II to confirm the MC receptor action of the agonist and to distinguish spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracorporal pressure responses to intracavernosal injection of MT-II in the anesthetized rat. MT-II induced penile erections in a dose-dependent fashion, with optimal response at 1 microg for both i.c.v. and i.th. routes. Supraspinal MT-II-induced erections were completely suppressed by 1 microg SHU-9119 i.c.v. Yawning was observed with i.c.v. and i.v. MT-II, whereas spinal injection did not produce this behavior. SHU-9119 blocked the erectile responses to i.th. MT-II when injected i.th. but not i.c.v. Intracavernosal MT-II neither increased intracorporal pressure nor augmented neurostimulated erectile responses. The lumbosacral spinal cord contains MC receptors that can initiate penile erection independent of higher centers. We confirmed the supraspinal proerectile action of MT-II. These results provide insight into the central melanocortinergic pathways that mediate penile erection and may allow for more efficacious melanotropin-based therapy for erectile dysfunction. Wessells, H., V. J. Hruby, et al. 2003 ; . induces penile erection via brain and spinal melanocortin receptors." Neuroscience 118 3 ; : 755-62. Penile erection induced by alpha-melanocyte-stimulating hormone and melanocortin receptors MC-R ; in areas of the spinal cord and periphery has not been demonstrated. To elucidate sites of the proerectile action of melanocortin peptides, in awake male rats we administered the MC-R agonist 2 ; MT-II ; i.c.v., intrathecal i.th. ; and i.v. and scored penile erection and yawning. Injection of the MC-R antagonist Ac-Nle-c[Asp-His-DNal 2' ; -Arg-Trp-Lys]-NH 2 ; SHU-9119 ; i.c.v. or i.th. in combination with i.th. MT-II differentiated spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracavernous pressure responses to intracavernosal injection of MT-II in the anesthetized rat.I.c.v., i.th., and i.v. MT-II induced penile erections.
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