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Effects of nitric oxide (NO) on thiopental-induced general anesthesia in the mouse
ARTICLE IN PRESS Poster presentations
S53
Effects of nitric oxide (NO) on thiopental-induced general anesthesia in the mouse
Antiosteoporotic effects of the special Cimicifuga racemosa extract BNO 1055
G. Sadeghi Hashjina, A. Najafpourb, E. Azizib
D. Seidlova ´-Wuttke, W. Wuttke
a
Department of Endocrinology, University Medical Center, Georg-August-University Go ¨ttingen, Go ¨ttingen, Germany
Veterinary Pharmacology, University of Tehran, Tehran, Islamic Republic of Iran b Veterinary Medicine, Urmia Azad University, Urmia, Islamic Republic of Iran Introduction: Nowadays, an increased demand for various surgical operations has raised a need of knowledge over principles and methods used to induce local and general anesthesia. Nevertheless, it is also necessary to gain a deep knowledge over positive or negative interactions of the endogenous biogenic substances on the process of general anesthesia. NO is one of these chemicals that has been paid a special attention during last 30 years. Materials and methods: To study the role of NO in the process of general anesthesia and, meanwhile, gaining a suitable method in the administration of anesthetic agents as well as finding a new combination to induce anesthesia, three drugs were administered to mice prior to sodium thiopental injection. For this purpose, 60 male mice were used in three periods of studies (20 animals per study). Every 20 animals were divided into four experimental groups of five each. Each group received either of the following drugs via the subcutaneous route once daily for 3 days: L-arginine (a precursor of NO, 10 mg/kg), nitroglycerine (a donor of NO, 1 mg/kg), methylene blue (an inhibitor of guanylyl cyclase, 10 mg/kg). Anesthesia was induced by intraperitoneal injection of thiopental on days 3 and 4. In the first, second, and third sets of experiments, doses of 40, 60, and 80 mg/kg of thiopental were used, respectively. Results: After recording and analysis of data, it became evident that methylene blue owed the most prominent and consistent effect among the chemicals used. After this, nitroglycerine stood on the second order; it potentiated the anesthetic effect of thiopental so that an accelerated anesthesia induction, an increased duration of hypnosis, a prolonged recovery period, and a deeper level of anesthesia were observed. Nitroglycerine, as an NO donor, increased the anesthetic effect of thiopental. This implies that methylene blue should have decreased the anesthesia parameters as it opposes the effect of NO, whereas, similar to what seen with methylene blue, it also increased the duration of anesthesia. Conclusion: In conclusion, nitroglycerine, and perhaps other nitrovasodilators, which release NO in physiological environment, may be used as adjuncts to sodium thiopental as an anesthetic agent. The lack of an expected, inhibitory, effect by methylene blue can be related to extra mechanisms implicated in the effects of this chemical. 10.1016/j.eujim.2008.08.102
We and others have recently shown that extracts of the rhizome of black cohosh (Cimicifuga racemosa ¼ CR) contains one or several substance(s) that prevent osteoporosis in gonadectomized female and male rats. In two doubleblind placebo-controlled trials in postmenopausal women, surrogate parameters of bone metabolism were also improved, indicating the reduction of osteoclasts and a stimulation of osteoblast activity. The mechanisms of actions, however, still remained unknown. It is known that osteoblasts produce the ligand for the receptor activator of NF-kB (Rank), which stimulates osteoclastogenesis and function. Osteoprotegerin (OPG) is another osteoblast product and is a decoy receptor for RANKL. Its high production prevents RANKL to activate RANK and thereby OPG inhibits osteoclastogenesis and function. Furthermore, osteoblasts produce Osteocalcin, a protein that is essential for proper bone formation. To elucidate the function of the special CR extract BNO 1055 serum concentrations of RANKL, OPG and Osteocalcin were measured in female and male rats treated with 33 mg of the CR extract BNO 1055 orally over a period of 3 months. For positive control purposes, female ovariectomized rats were substituted with estradiol (E2) and males with E2 and testosterone (T). E2 and CR BNO 1055 suppressed serum RANKL concentrations in the serum significantly while E2 inhibited CR BNO 1055-stimulated Osteocalcin production, reflecting an increased serum concentration. The production of OPG was also inhibited by E2 but unaffected by CR BNO 1055. Quantitative computer tomography and histomorphometry indicated significantly less deterioration of the trabecular apparatus in the tibia in both CR BNO 1055- and E2- treated animals in comparison to castrated controls. These data indicate a specific effect of substances in CR BNO 1055, which inhibits osteoblast RANKL production. Thereby osteoclastogenesis and function are also inhibited, which may in part explain the antiosteoporotic effects of the CR extract. In addition, the stimulation of Osteocalcin points to a stimulatory effect of CR BNO 1055 on bone formation. Thus, the effects of CR BNO 1055 and E2 differ in that E2 suppresses all osteoblast parameters and thereby also osteoclastogenesis, whereas CR BNO 1055 appears to inhibit osteoclastogenesis and function but simultaneously stimulates osteoblasts and thereby possibly osteogenesis. 10.1016/j.eujim.2008.08.103
S53
Effects of nitric oxide (NO) on thiopental-induced general anesthesia in the mouse
Antiosteoporotic effects of the special Cimicifuga racemosa extract BNO 1055
G. Sadeghi Hashjina, A. Najafpourb, E. Azizib
D. Seidlova ´-Wuttke, W. Wuttke
a
Department of Endocrinology, University Medical Center, Georg-August-University Go ¨ttingen, Go ¨ttingen, Germany
Veterinary Pharmacology, University of Tehran, Tehran, Islamic Republic of Iran b Veterinary Medicine, Urmia Azad University, Urmia, Islamic Republic of Iran Introduction: Nowadays, an increased demand for various surgical operations has raised a need of knowledge over principles and methods used to induce local and general anesthesia. Nevertheless, it is also necessary to gain a deep knowledge over positive or negative interactions of the endogenous biogenic substances on the process of general anesthesia. NO is one of these chemicals that has been paid a special attention during last 30 years. Materials and methods: To study the role of NO in the process of general anesthesia and, meanwhile, gaining a suitable method in the administration of anesthetic agents as well as finding a new combination to induce anesthesia, three drugs were administered to mice prior to sodium thiopental injection. For this purpose, 60 male mice were used in three periods of studies (20 animals per study). Every 20 animals were divided into four experimental groups of five each. Each group received either of the following drugs via the subcutaneous route once daily for 3 days: L-arginine (a precursor of NO, 10 mg/kg), nitroglycerine (a donor of NO, 1 mg/kg), methylene blue (an inhibitor of guanylyl cyclase, 10 mg/kg). Anesthesia was induced by intraperitoneal injection of thiopental on days 3 and 4. In the first, second, and third sets of experiments, doses of 40, 60, and 80 mg/kg of thiopental were used, respectively. Results: After recording and analysis of data, it became evident that methylene blue owed the most prominent and consistent effect among the chemicals used. After this, nitroglycerine stood on the second order; it potentiated the anesthetic effect of thiopental so that an accelerated anesthesia induction, an increased duration of hypnosis, a prolonged recovery period, and a deeper level of anesthesia were observed. Nitroglycerine, as an NO donor, increased the anesthetic effect of thiopental. This implies that methylene blue should have decreased the anesthesia parameters as it opposes the effect of NO, whereas, similar to what seen with methylene blue, it also increased the duration of anesthesia. Conclusion: In conclusion, nitroglycerine, and perhaps other nitrovasodilators, which release NO in physiological environment, may be used as adjuncts to sodium thiopental as an anesthetic agent. The lack of an expected, inhibitory, effect by methylene blue can be related to extra mechanisms implicated in the effects of this chemical. 10.1016/j.eujim.2008.08.102
We and others have recently shown that extracts of the rhizome of black cohosh (Cimicifuga racemosa ¼ CR) contains one or several substance(s) that prevent osteoporosis in gonadectomized female and male rats. In two doubleblind placebo-controlled trials in postmenopausal women, surrogate parameters of bone metabolism were also improved, indicating the reduction of osteoclasts and a stimulation of osteoblast activity. The mechanisms of actions, however, still remained unknown. It is known that osteoblasts produce the ligand for the receptor activator of NF-kB (Rank), which stimulates osteoclastogenesis and function. Osteoprotegerin (OPG) is another osteoblast product and is a decoy receptor for RANKL. Its high production prevents RANKL to activate RANK and thereby OPG inhibits osteoclastogenesis and function. Furthermore, osteoblasts produce Osteocalcin, a protein that is essential for proper bone formation. To elucidate the function of the special CR extract BNO 1055 serum concentrations of RANKL, OPG and Osteocalcin were measured in female and male rats treated with 33 mg of the CR extract BNO 1055 orally over a period of 3 months. For positive control purposes, female ovariectomized rats were substituted with estradiol (E2) and males with E2 and testosterone (T). E2 and CR BNO 1055 suppressed serum RANKL concentrations in the serum significantly while E2 inhibited CR BNO 1055-stimulated Osteocalcin production, reflecting an increased serum concentration. The production of OPG was also inhibited by E2 but unaffected by CR BNO 1055. Quantitative computer tomography and histomorphometry indicated significantly less deterioration of the trabecular apparatus in the tibia in both CR BNO 1055- and E2- treated animals in comparison to castrated controls. These data indicate a specific effect of substances in CR BNO 1055, which inhibits osteoblast RANKL production. Thereby osteoclastogenesis and function are also inhibited, which may in part explain the antiosteoporotic effects of the CR extract. In addition, the stimulation of Osteocalcin points to a stimulatory effect of CR BNO 1055 on bone formation. Thus, the effects of CR BNO 1055 and E2 differ in that E2 suppresses all osteoblast parameters and thereby also osteoclastogenesis, whereas CR BNO 1055 appears to inhibit osteoclastogenesis and function but simultaneously stimulates osteoblasts and thereby possibly osteogenesis. 10.1016/j.eujim.2008.08.103