Monoamine metabolism and behavioral responses to ethanol in mitochondrial aldehyde dehydrogenase knockout mice

BACKGROUND: It is widely accepted that, in addition to removing acetaldehyde produced during the metabolism of ethanol, mitochondrial aldehyde dehydrogenase (ALDH2) functions in the pathway by which aldehyde metabolites of the monoamines dopamine (DA) and serotonin (5-HT) are converted to their acidic metabolites. Moreover, studies of ALDH2 inhibitors used for treating alcoholism suggest that their antidipsotropic effects may be related to inhibition of monoamine metabolism. Therefore, we examined the hypothesis that altered brain monoamine metabolism is related to the influence of ALDH2 on behavioral responses to ethanol. METHODS: Mice were generated with a gene-trap mutation of the ALDH2 gene. ALDH2 mRNA was absent in ALDH2-/- mice. Western blot analysis of liver mitochondria confirmed the absence of ALDH2 protein in the ALDH2-/- mice. Wild-type and ALDH2-deficient mice were tested for the effects of different doses of ethanol on locomotor activity, ataxia, and a 2-bottle ethanol-water preference test. RESULTS: Wild-type and ALDH2+/- mice preferred ethanol to water. However, ALDH2-/- mice drank significantly less ethanol than wild-type or ALDH2+/- mice. Locomotor activity and ataxia were significantly more affected by ethanol in ALDH2-/- mice than in wild-type or ALDH2+/- mice. There was no effect of genotype on levels of 5-HT, DA, or their precursors or metabolites in several brain regions, as measured by HPLCec. CONCLUSIONS: The results indicate that: (1) the effect of the mutant genotype on behavioral responses to ethanol is unrelated to altered brain monoamine metabolism and (2) ALDH2 is not required for the metabolism of brain monoamines in vivo.     

利用丙酮酸脱氢酶复合物原核表达产物检测原发性胆汁性肝硬变患者血清自身抗体

目的 建立一种利用重组表达的丙酮酸脱氢酶复合物E2亚单位(PDC-E2)和E3结合蛋白(PDC-E3BP)检测原发性胆汁肝硬变(PBC)患者血清的方法。方法 以适当的条件诱导PDC-E2和PDC-E3BP表达质粒pExSecI/PDC-E2和pET28/E3BP,利用表达产物通过酶联免疫吸附试验检测PBC、正常人及其他原因肝硬变患者血清,并与欧盟的检测试剂盒比较。结果 显示PDC-E2和PDC-E3BP表达产物检测PBC患者血清中的自身抗体阳性率为93.3％,与欧盟试剂盒比较,总符合率为98.03％。结论 建立了利用重组表达丙酮酸脱氢酶复合物E2亚单位和E3结合蛋白检测PBC患者血清中自身抗体的方法,且获得PDC-E2和PDC-E3BP的高效表达产物。     

脑脊液NSE、LDH对化脓性脑膜炎与病毒性脑膜炎的鉴别诊断价值

目的测定化脓性脑膜炎与病毒性脑膜炎患儿脑脊液神经元烯醇化酶（NSE）、乳酸脱氢酶（LDH）活力变化并探讨其鉴别诊断价值。方法选择化脓性脑膜炎31例,病毒性脑膜炎33例,对照组22例,采用化学发光法测定NSE活力,速率法测定LDH活力。结果①NSE、LDH含量：化脓性脑膜炎组高于病毒性脑膜炎组和对照组（P〈0．01）,病毒性脑膜炎组高于对照组（P〈0．01）。②若以阳性标准NSE≥15．3μg/L判断,NSE诊断化脓性脑膜炎的灵敏度、特异性分别为58．06％,86．36％;NSE诊断病毒性脑膜炎的灵敏度、特异性分别为39．33％、86．36％。③若以阳性标准LDH≥29．2U／L判断,LDH诊断化脓性脑膜炎的灵敏度、特异性分别为100％,80．95％;LDH诊断病毒性脑膜炎的灵敏度、特异性分别为66．67％、90．9％。结论联合测定NSE、LDH活力,有助于鉴别诊断化脓性脑膜炎与病毒性脑膜炎。     

Unraveling a case of 46,XY DSD due to 17ß-Hydroxysteroid Dehydrogenase type 3 mutations at the age of 49

17-ß Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is an enzyme transforming Delta 4 androstenedione into testosterone. It is involved in the early development of the male genital tract. In this case report, we describe a 46,XY Difference of Sexual Development (DSD) individual with a female phenotype, primary amenorrhea, facial dysmorphia and mental retardation. Gene sequencing using a panel of genes involved in DSD revealed two heterozygous loss-of-function mutations in the HSD17B3 enzyme. Furthermore, a microarray analysis revealed a 37Mb segmental 3p duplication and a recurrent 16p13.11 microduplication. The large 3p duplication is responsible for her mental retardation and her facial dysmorphia. Interestingly, HSD17B3 mutations were identified only in adulthood, at the age of 49. Furthermore, the patient's severe mental retardation and facial dysmorphia are due to genetic abnormalities different from the ones involved in her DSD.     

The pro-inflammatory cytokine IL-Iβ alteration by deer (Rusa unicolor) antler extract on osteoarthritis rat model

Osteoarthritis is a disease associated with articular cartilage degradation, intra-articular area inflammation, and subchondral bone replacement. Cytokine IL-1β has a prominent function in the inflammations process that passes in the joints. The 70% ethanol extracts of deer antler (250 and 500 mg/kg BW) and glucosamine sulfate (250 kg/BW) were evaluated for four weeks in reducing cytokine IL-1β to rat model OA-induced Monosodium iodoacetate. Measurements of joint diameter in rat’s knee and hyperalgesia were performed on weeks 0, 1, 2, 3, 4, 5, 6, and 7. The presence of a significant difference in the stimulation thermal latency (p = 0.00) and the resulting increase in swelling of joint diameter (p = 0.00) are evidence that MIA has successfully induced the rat modeling of OA. A significant decrease in cytokine IL-Iβ levels was shown on week 3 after MIA injection (p = 0.00). Both concentrations of deer extracts significantly reduced knee joint diameter (p = 0.00), latency thermal stimulation (p = 0.00), and cytokine IL-1β levels (p = 0.00). Based on the results, it can be concluded that the 70% ethanol extract of deer antler is a potential medicine for OA therapy.