Disorders of pyruvate carboxylase and the pyruvate dehydrogenase complex

Summary The most common defect associated with deficiency of the pyruvate dehydrogenase (PDH) complex occurs in the E₁ component, specifically due to mutations in the X-linked E₁ gene. Clinical sequelae of these mutations, which range from severe neonatal lactic acidosis to carbohydrate-sensitive ataxia, can be different in males and females depending on the nature of the mutation and, in the case of females, on the X-inactivation pattern in different tissues. Males have a high representation of missense mutations among the patient cohort, while females are much more likely to have DNA rearrangements, particularly toward the 3 end of the coding sequence of the gene. Missplicing mutations involving exon 6 deletion have been reported, as has a missense mutation conferring true thiamin-responsiveness of the enzyme and the patient's clinical symptoms.Pyruvate carboxylase deficiency, on the other hand, is a true autosomal recessive disease, though it has high occurrences in particular ethnic groups, especially in Algonkian-speaking Amerindians and in Arabs. In the former group the defect is a simple type in which material cross-reactive to pyruvate carboxylase antibody is present in cultured cells (CRM^+ve). In the latter group, cross-reacting material is rarely present (CRM^–ve). The CRM^+ve patients can survive into teenage years with careful supervision, while the CRM^–ve patients have complications due to hyperammonaemia and dysfunction of the urea cycle and rarely survive beyond 3 months of life.     

Selective neuronal survival and upregulation of PCNA in the rat inner retina following transient ischemia

In this study we investigated the extent and time course of neuronal cell death and the regulation of the proliferating cell nuclear antigen (PCNA) in the different retinal cell layers following ischemia-reperfusion injury. Retinal ischemia was induced by controlled elevation of the intraocular pressure for a duration of 60 min. Changes in thickness and cell numbers in the retinal cell layers were analyzed at various time points (1 h to 4 weeks) after reperfusion. In parallel, apoptotic cell death was determined by the TUNEL method and the expression of PCNA analyzed by immunocytochemistry. In addition, we tested whether PCNA is expressed in neurons by double immunocytochemistry. The reduction in thickness was found to be less pronounced in the inner nuclear layer (INL). Correspondingly, cell numbers decreased by only 33% in the inner retina, but by more than 80% in the outer nuclear layer (ONL). Alterations in glial cell numbers did not contribute significantly to postischemic changes in the INL and ONL as assessed by using immunocytochemical markers for microglial and Müller cells. The time course of cell death determined by the TUNEL technique also differed markedly in the retinal layers being rapid and transient in the inner retina but delayed and prolonged in the ONL. PCNA immunoreactivity was undetectable in the normal retina, but was specifically induced in neurons of the inner retina within 1 h after reperfusion and was sustained for at least 4 weeks. We conclude that in contrast to photoreceptors in the ONL, a significant proportion of inner retinal neurons is resistant to ischemic insult induced by transiently increased intraocular pressure and that PCNA may possibly play a role in the selective postischemic survival of these cells.     

第二信使系统和其介导的基因表达对针灸效应影响的研究

从微观水平研究针灸效应对揭示其机理有重要的意义。本文从第二信使系统和其介导的基因表达对针灸效应影响的研究方面综述了针灸效应的终结反映于细胞内生物效应的变化(即对机体不同器官组织细胞内的物质代谢调节 ) ,从一个侧面提示 ,针灸对机体各系统的调节作用最终是在细胞通过胞内信息传导系统实现的     

疏肝起萎汤配合夫妻性感集中训练疗法治疗心因性勃起功能障碍147例疗效观察

目的:观察疏肝起萎汤配合夫妻性感集中训练疗法治疗心因性勃起功能障碍的临床疗效。方法:将406例患者随机分为3组,治疗组147例采用疏肝起萎汤(由柴胡、枳壳、白芍、淫羊藿、蜈蚣、川芎、陈皮、炙甘草组成)配合夫妻性感集中训练疗法治疗;对照Ⅰ组132例采用疏肝起萎汤治疗;对照Ⅱ组127例采用家庭性感集中训练疗法治疗。观察3组综合疗效和症状改善情况。结果:治疗组痊愈99例,好转37例,痊愈率67.35％,总有效率92.52％;对照Ⅰ组痊愈49例,好转34例,痊愈率37.12％,总有效率62.88％;对照Ⅱ组痊愈53例,好转36例,痊愈率41.70％,总有效率70.08％。治疗组与对照Ⅰ组、对照Ⅱ组痊愈率、总有效率比较,差异均有显著性意义(P<0.05)。结论:疏肝起萎汤配合夫妻性感集中训练疗法治疗心因性勃起功能障碍,疗效确切。     

血能达片对小鼠的急性毒性和抗栓疗效

目的：测定血能达片的急性毒性和验证其抗栓疗效及选药提供依据。方法：小白鼠一次Ig血能达26g/kg；五组动物分别给血能达（XND）3g/kg,溶栓胶种（RSC）1．25g/kg，复方丹参（CDDP）1．25g/kg，消栓通络（XSTL）2．5g/kg和NS Ig,qd 1次，连续7d。第7日药后1h,IV Collagen-Adr诱发血栓[1]，观察死亡数；用毛细血管法测凝血时间，扭体法测痛。结果：小白鼠口服最大耐受量为26g/kg，临床用量的866．7倍；4种药物除消栓通络外，均有明显的抗栓作用（P＜0．05－0．01）；还证中、高剂量血能达尚有延长凝血时间和镇痛作用（P＜0．05－0．01），其余3种药则没有。结论：血能达毒性小，具有溶栓胶囊，复方丹参等效的抗栓疗效，还能抗凝和镇痛。     

硫色满酮3位Mannich碱衍生物的合成及其抗真菌活性

目的 设计、合成硫色满酮3位Mannich碱类化合物，并对其抗真菌活性进行初步评价。方法 以对氟苯硫酚为原料，经多步反应合成目标化合物，并测定目标化合物的抗真菌活性。结果共合成了10个未见文献报道的新化合物，经红外光谱、核磁共振氟谱及元素分析确证了其结构。其中化合物3对大部分供试真菌活性强于或相当于对照品克霉唑。结论 硫色满目3位取代Mannich碱具有较强的抗真菌活性。     

Synchronous coexpression of epidermal growth factor receptor and cyclooxygenase-2 in carcinomas of the uterine cervix: a potential predictor of poor survival.

PURPOSE: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients. EXPERIMENTAL DESIGN: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b). the EGFR-negative/COX-2-positive group (n = 8); (c). the EGFR-positive/COX-2-negative group (n = 27); and (d). the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared. RESULTS: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R(2) = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03). CONCLUSIONS: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.     

Radial forearm free flap for salvage of Achilles-tendon repair wounds

Achilles-tendon repair wounds are prone to breakdowns and secondary infections, compromising the integrity of the repair and the ultimate function of the repaired tendon. Unlike defects resulting from tumor excision, burns, or trauma, Achilles-tendon repair wounds have their own special considerations. The dissection needed for the repair of the tendon often denudes the tendon of the peritenon blood supply and creates a sub-tendinous dead space. Anatomic topography unique to the Achilles region makes the choice of flap coverage crucial in terms of function and cosmesis. Considering all the flap options utilized in the past, the radial forearm free flap is the most logical choice, offering the advantage of thin, supple, vascularized tissue. The flap can also be elevated easily for secondary reconstructions, when simultaneous tendon reconstruction and coverage are not possible. The authors present their experience utilizing the radial forearm flap as the flap of choice for salvage of the complicated wounds of Achilles tendon repair.