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Deitelzweig Steve Luo Xuemei Nguyen Jennifer L. Malhotra Deepa Emir Birol Russ Cristina Li Xiaoyan Lee Theodore C. Ferri Mauricio Wiederkehr Danny Reimbaeva Maya Barnes Geoffrey D. Piazza Gregory 《Journal of thrombosis and thrombolysis》2022,54(4):696-696
Journal of Thrombosis and Thrombolysis - 相似文献
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Theodore C. Bania MD MS Tom Ashar MD Gregory Press MD Patricia M. Carey MD 《Academic emergency medicine》2003,10(7):697-704
Long-term daily use of gamma-hydroxybutyrate (GHB) and related compounds has recently been associated with a withdrawal syndrome. To the best of the authors' knowledge, there are currently no animal models of GHB withdrawal. OBJECTIVES: The authors studied and described the effect of chronic dosing of GHB (3-6 days) on tolerance and withdrawal in a rat model. METHODS: Rats were administered GHB every three hours via intraperitoneal catheter. Groups of rats (2 per group) were dosed with GHB for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The GHB dose was 0.25 g/kg for doses 1-8, 0.75 g/kg for doses 9-12, 1 g/kg for doses 13-16, 1.25 g/kg for doses 17-24, 1.5 g/kg for doses 25-32, 1.75 g/kg for doses 33-40, and 2 g/kg for doses 41-48. Following the last dose of GHB, the rats were scored using a 16-point ethanol intoxication-withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24. RESULTS: Tolerance: Rats dosed with GHB for more days were less intoxicated one hour after their last GHB dose despite receiving higher doses. WITHDRAWAL: The scores for all rats dosed with GHB increased at hours 4 (p = 0.028), 5 (p = 0.037), 6 (p = 0.007), and 9 (p = 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of GHB dosing at hours 3 (p < 0.000), 4 (p = 0.004), 5 (p = 0.002), and 12 (p = 0.039) as well as prior to the last dose at hour 0 (p = 0.000). No rats developed seizures. CONCLUSIONS: Tolerance and mild withdrawal in rats can be induced by administering intraperitoneal GHB every three hours for 3-6 days. More prolonged dosing and higher doses of GHB may be necessary to induce severe withdrawal. 相似文献
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C. M. Gordon E. Binello M. S. LeBoff M. E. Wohl C. J. Rosen A. A. Colin 《Osteoporosis international》2006,17(5):783-790
Introduction Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss
are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients
between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA)
and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α,
and interleukin-6.
Methods We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous
samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum
IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations
were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse
correlation between IL-1β and BMD at all sites.
Results In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate
models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant
independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits
in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD.
Conclusions These findings may have therapeutic implications for enhancing bone density in these patients. 相似文献
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