The conformation and movement of Na+ channel inactivation gate peptide in linker between domain III and IV during inactivation by NMR spectroscopy and molecular modeling study

Abstract: A model peptide that their sequence corresponds to the linker part between domain III and IV of rat brain type IIA Na⁺ channel has been synthesized for the conformational affect study corresponded to different gated states of Na⁺ channel. Nuclear magnetic resonance spectra of local anesthetic (LA) diphenyl drugs, such as phenytoin, in presence of a model peptide in both phosphate buffer and phospholipid bicelles (dimyristotl phosphocholine/dihexanoyl phospholcholine), which micelles serve to mimic the peptide–lipid interactions, have been measured to obtain information of the interactions between selected drugs and model peptide. Molecular modeling is performed to help to provide possible conformational information about the polypeptide L_III–IV that may be critical for recognition and signal transduction of inactivated Na⁺ channel. The voltage‐sensing mechanism of Na⁺ channel involves the movement of the inactivation particles (Ile, Phe, and Met) in the L_III–IV while binding to S4–S5 intracellular region within DIII and DIV. The movement of L_III–IV making its C‐terminal residues, including Glu¹⁴⁹² and Glu¹⁴⁹³, may aligned near and stabilize the LAs bound with their receptors.     

The Stigma of Mental Illness on Children of Color

Children and adolescents who have been designated as mentally ill, mentally retarded, juvenile delinquent, poor, homeless, or sexually abused at some point in their lives experience a great deal of difficulty in removing such labels. Society has persisted in using these labels even when the designated person is engaged in many of the things taken for granted among "normal" persons of their age and culture. The author discusses the stigma that results from unreliable, invalid, unstandardized identification of psychiatric disorders, particularly among children from ethnic minority groups. Research is needed that improves clinical information processing, particularly among the multicultural population of the United States. For too long majority-based norms have been the focus of research, with little consideration given to the creative adaptations that have occurred among ethnic minority groups.     

Interferon alfa-2a in the treatment of exudative age-related macular degeneration

Nineteen patiens (20 eyes) with the exudative form of macular degeneration were treated with parenteral interferon alfa-2a. Fifteen patients (16 eyes) had adequate follow-up for evaluation of outcome of the exudative macular lesion. The average follow-up was 8 months (range 5-11 months). Color photographs and fluorescein angiograms were evaluated independently by two masked readers for change in size, presence of fibrosis, and leakage of the neovascular lesion. During the follow-up, none of the exudative lesions resolved: one lesion became smaller, four remained the same, nine enlarged, and two could not be graded based on the photographs. Visual acuity remained 20/40 or better in four eyes. The proportion of eyes with visual acuity of 20/200 or worse increased from 35% at the initial visit to 59 % at the final visit. Ten patients experienced significant but reversible side effects, including weight loss, depression, and/or hematopoietic suppression. The data from these cases do not support any significant treatment benefit from interferon alfa-2a at the doses used in exudative macular degeneration.     

糖皮质激素抑制缓激肽引起的PC12细胞外钙内流与蛋白激酶C有关

缓激肽（BK）可引起PC12细胞的[Ca2＋]i；升高，该作用不通过电压敏感性钙通道，而是由G蛋白转导，通过内钙释放和外钙内流引起的。BK的作用可受到皮质疏（B）的快速抑制。本研究利用无钙／再加钙方法，把BK对内钙释放和外钙内流作用分开来进行研究。结果发现：（1）B可以抑制BK引起的外钙内流，对内钙释放影响不明显；（2）B－BSA（牛血清白蛋自偶联的皮质疏）对BK所引起外钙内流的抑制作用与游离的B作用类似；（3）PKC激活剂（PMA）可以模拟，而PKC的抑制剂G66976可以逆转B的抑制作用；（4）百日咳毒素（PTX）预处理可以阻断B抑制BK引起的外钙内流。结果提示：B可能作用在膜受体上，通过PTX敏感的G蛋白-PKC途径抑制BK引起的外钙内流。     

Bacterial growth in secretions and on suctioning equipment of orally intubated patients: a pilot study.

BACKGROUND: Contamination of equipment, colonization of the oropharynx, and microaspiration of secretions are causative factors for ventilator-associated pneumonia. Suctioning and airway management practices may influence the development of ventilator-associated pneumonia. OBJECTIVES: To identify pathogens associated with ventilator-associated pneumonia in oral and endotracheal aspirates and to evaluate bacterial growth on oral and endotracheal suctioning equipment. METHODS: Specimens were collected from 20 subjects who were orally intubated for at least 24 hours and required mechanical ventilation. At baseline, oral and sputum specimens were obtained for culturing, and suctioning equipment was changed. Specimens from the mouth, sputum, and equipment for culturing were obtained at 24 hours (n=18) and 48 hours (n=10). RESULTS: After 24 hours, all subjects had potential pathogens in the mouth, and 67% had sputum cultures positive for pathogens. Suctioning devices were colonized with many of the same pathogens that were present in the mouth. Nearly all (94%) of tonsil suction devices were colonized within 24 hours. Most potential pathogens were gram-positive bacteria. Gram-negative bacteria and antibiotic-resistant organisms were also present in several samples. CANCLUSIONS: The presence of pathogens in oral and sputum specimens in most patients supports the notion that microaspiration of secretions occurs. Colonization is a risk factor for ventilator-associated pneumonia. The equipment used for oral and endotracheal suctioning becomes colonized with potential pathogens within 24 hours. It is not known if reusable oral suction equipment contributes to colonization; however, because many bacteria are exogenous to patients' normal flora, equipment may be a source of cross-contamination.     

In vitro and in vivo antitumor activity of oridonin nanosuspension

The aim of the present study was to evaluate the antitumor activity of an oridonin (ORI) nanosuspension relative to ORI solution both in vitro and in vivo. ORI nanosuspension with a particle size of 897.2 ± 14.2 nm was prepared by the high pressure homogenization method (HPH). MTT assay showed that ORI nanosuspension could significantly enhance the in vitro cytotoxicity against K562 cells compared to the ORI solution, the IC₅₀ value at 36 h was reduced from 12.85 μmol/L for ORI solution to 8.11 μmol/L for ORI nanosuspension. Flow cytometric analysis demonstrated that the ORI nanosuspension also induced a higher apoptotic rate in K562 cells compared to ORI solution. In vivo studies in a mouse model of sarcoma-180 solid tumors demonstrated significantly greater inhibition of tumor growth following treatment with ORI nanosuspension than ORI solution at the same dosage. The mice injected with ORI nanosuspension showed a higher reduction in tumor volume and tumor weight at the dose of 20 mg/kg compared to the ORI solution (P < 0.01), with the tumor inhibition rate increased from 42.49% for ORI solution to 60.23% for the ORI nanosuspension. Taken together, these results suggest that the delivery of ORI in nanosuspension is a promising approach for the treatment of the tumor.     

挤压综合征合并急性肾衰竭病人的护理研究

挤压综合征（crus syndrome，CS）合并急性肾衰竭（acute rehal failure，ARF）是一种外科严重创伤加内科急症的重危病症，病情严重复杂，并发症多，死亡率高，因而治疗和护理尤为重要。我科于2005年10月-2007年5月收治10例挤压综合征合并AFR病人经内、外科联合治疗和阶段化个体化整体护理，效果良好，现将护理介绍如下。     

基因转染促骨髓间质前体细胞体外向软骨的分化**☆

目的：骨髓中包含的间质前体细胞在适宜的条件下可以被许多细胞因子诱导分化为软骨。采用基因转染技术观察转化生长因子β2对体外培养的骨髓间质前体细胞向软骨分化的影响。 方法：实验于2005-12/2007-01在中日友好医院临床研究所骨科实验室完成。①骨髓标本来源于6名志愿者，对治疗及实验均签署知情同意书，实验经医院医学伦理委员会批准。②实验方法：志愿者局麻下行骨髓穿刺，抽取7.0~10.0 mL骨髓抗凝，以密度梯度离心法分离人骨髓间质前体细胞，通过脂质体介导转染技术，将pcDNA3.1(+)TGF-β2载体导入骨髓间质前体细胞中，体外单层培养。③实验评估：利用RT-PCR、Western Blotting和免疫组化法检测转化生长因子β2和软骨相关基因、蛋白的表达情况。 结果：①转染后48 h，可检测到明显的转化生长因子β2 mRNA表达，Ⅱ型胶原A1和Aggrecan mRNA均有轻微表达；转染后4周，转化生长因子β2 mRNA表达稍有降低，Ⅱ型胶原A1和Aggrecan mRNA表达均明显上调。②转染后48 h和4周，间质前体细胞培养上清液中均有转化生长因子β2蛋白的表达。③转染后48 h部分细胞显示Ⅱ型胶原蛋白免疫组化阳性信号，转染后4周Ⅱ型胶原蛋白阳性细胞数增加。 结论：pcDNA3.1(+)/TGF-β2真核表达载体在骨髓间质前体细胞内可获得短暂和长期表达。在单层培养的情况下，骨髓间质前体细胞可被转化生长因子β2诱导向软骨方向分化。     

Plasma volume during heat stress and exercise in women

Summary Five women were studied during exercise and passive heating to determine whether PV dynamics were affected by the menstrual cycle. The exercise bout (80% peak) on a modified cycle ergometer and the passive heat stress were done in a hot environment (T_a=50°C, P_w=1.61kPa) during the follicular and luteal phase. Esophageal temperature (T_es) was measured continuously. Blood samples were drawn after each 0.2° C increase in T_es and was measured at that time. Initial PV was estimated at rest during the follicular phase. PV changes from rest were calculated at each T_es from Hb and Hct. During passive heating, PV decreased by a mean volume of 156 (±80) ml to 2.83 (±0.09)l in the follicular phase. During the luteal phase, there was a larger volume reduction (300±100 ml) during passive heating, and the final PV was lower than in the follicular phase and averaged 2.47±0.181. During exercise, PV decreased 463 (±90) ml to 2.50 (±0.11) l in the follicular and 381 (±70) ml to 2.50 (±0.23) l in the luteal phase. These data indicate that there is a menstrual cycle effect on PV dynamics during passive heating such that more fluid is shifted out of the vasculature during the luteal phase. During severe exercise there is a greater fluid loss during the follicular phase, yet the final PV is not different between phases.