Gamma-hydroxybutyric Acid Tolerance and Withdrawal in a Rat Model

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.     

Revascularized fibula for tibia replacement in adamantinoma

Adamantinoma of long bones is one of the rarest of malignant bone tumors; it is commonly located in the middle or lower third of the diaphysis of the tibia. A case with multiple occurrences affecting both the tibia and fibula is presented. En bloc resection with wide operative margins was performed, and a large tibial defect of 23 cm was effectively bridged by a revascularized free fibular flap. At 13 months follow-up, there was no sign of local recurrence or metastasis, and the patient was mobile.     

Lugol液染色对食管早期癌和癌前病变的诊断价值

目的 探讨Lugol液染色对食管早期癌和癌前病变的诊断价值。方法 对45例食管黏膜可疑病变经内镜以2％Lugol液喷洒染色，观察黏膜染色情况，并取活检送病理组织学检查。结果 45例食管病变染色后，39例呈浅染色或不染色，其中食管癌8例（食管早期癌5例，进展期癌3例），Barrett食管5例，轻至中度不典型增生1l例。本组Lugol液染色对食管早期癌和癌前病变的检出率达46．7％。结论 内镜下应用Lugol液染色结合活检有助于食管早期癌和癌前病变的诊断，且操作简便，具有重要的临床价值。     

彩色多普勒超声在Graves''''病诊断中的作用

目的:探讨彩色多普勒超声在Graves’病(又称弥漫性甲状腺肿)诊断中的作用。方法:用能量多普勒超声观察40例Graves’病患者及40例正常对照组双侧甲状腺组织的血液供应及分布情况;用脉冲多普勒测量颈总动脉的收缩期峰值流速(VPS),甲状腺上动脉的收缩期峰值流速(VPS)及阻力指数(RI),测量甲状腺上动脉的内径。结果:Graves’病组甲状腺实质内的血供极为丰富,血流分级以Ⅲ级为主,呈“火海征”,Graves’病组与正常对照组相比有显著性差异,P<0.005。Graves’病组颈总动脉的收缩期峰值流速为(162.1±31.5)cm/s,正常对照组颈总动脉的收缩期峰值流速为(98.2±20.9)cm/s,Graves’病组甲状腺上动脉的收缩期峰值流速(108.7±35.6)cm/s,正常对照组甲状腺上动脉的收缩期峰值流速(42.1±15.1)cm/s,以上各参数Graves’病组甲状腺上动脉的阻力指数为0.55±0.11,正常对照组甲状腺上动脉的阻力指数为0.73±0.19。Graves’病组与正常对照组相比有显著性差异P<0.01。Graves’病组甲状腺上动脉的内径为3.34±1.16mm,正常对照组甲状腺上动脉的内径为1.62±1.24mm。Graves’病组与正常对照组相比有显著性差异P<0.01。结论:彩色多普勒超声在Graves’病诊断中有重要的作用。     

丹参对持续癫痫幼鼠脑损伤保护作用的实验研究

目的 探讨丹参对持续癫痫发作诱发幼鼠脑神经元损伤是否具有保护作用。方法 皮下及腹腔注射贝美格针诱发健康幼龄鼠癫痫持续状态发作。光镜下观察神经元病变情况；电镜观察海马神经元超微结构的改变。结果 持续癫痴组幼鼠脑组织光镜下可见明显的神经元病变。电镜下可见海马区神经元的超微结构病变。丹参治疗组神经元病变均轻于持续癫痴组；而正常对照组未见类似病变。结论 丹参在组织、细胞和亚细胞水平对持续癫病幼鼠脑神经元损伤具有一定的保护作用，为临床有效防治小儿惊厥性脑损伤提供了可靠的实验依据。     

PET imaging of the dopamine transporter with 18F-FECNT: a polar radiometabolite confounds brain radioligand measurements.

18F-2beta-Carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (18F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. METHODS: Two rats were infused with 18F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with 18F-FECNT and scanned kinetically, with serial arterial blood analysis. RESULTS: At 60 min after the injection of rats, 18F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was 18F-fluoroacetaldehyde, the product expected from the N-dealkylation of 18F-FECNT, or its oxidation product, 18F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 +/- 0.1-fold (mean +/- SD; n = 3) in nonhuman primates between 60 and 240 min after injection. CONCLUSION: An 18F-fluoroalkyl metabolite of 18F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of 18F-FECNT will be prone to more errors than analysis with a measured arterial input function.