槟榔中与烯丙基焦儿茶酚具有协同抗疟疾作用化合物的生物活性导向分离

目的:从槟榔中筛选出能与烯丙基焦儿茶酚具有协同抗疟疾的化合物。方法:运用生物活性导向分离的方法,把从槟榔的甲醇提取物中分离的各组分进行体外抗疟疾试验,找出活性单体。结果:筛选出能与烯丙基焦儿茶酚具有协同抗疟疾作用的两个化合物,他们与烯丙基焦儿茶酚在一定浓度下单独给药体外抗疟疾效果很差,但是联合给药具有较好的体外协同抗疟疾作用。     

Effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients

BACKGROUND: Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine (L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase. METHODS: A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24-52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD. The drug was administered orally 30 min before the start of each HD period in both studies. Doses of 400 mg of L-DOPS or placebo were given to HD patients with OH (45 and 41 patients, respectively) in the double-blind study, and doses of 200 or 400 mg of L-DOPS were given to 74 HD patients in the long-term study. RESULTS: In the double-blind study, L-DOPS significantly ameliorated subjective symptoms related to OH, including dizziness/light-headed feeling, and malaise, throughout the interdialytic period. For 19 patients with delayed-type OH, hypotension with the lowest blood pressure recorded 10 min after standing, the decrease in blood pressure was suppressed significantly after L-DOPS treatment (10 patients) as compared with the placebo-treated group (9 patients). In the long-term study, the efficacy of L-DOPS was not attenuated, and the marked fluctuations in the plasma L-DOPS and norepinephrine levels were not noted after long-term use, without increases in incidence or severity of adverse reactions. CONCLUSIONS: These results indicate that L-DOPS is effective for improving OH-related interdialytic subjective symptoms in HD patients after short-term as well as after long-term administration.     

Lymphatic absorption of docosahexaenoic acid given as monoglyceride,diglyceride, triglyceride,and ethyl ester in rats

Lymphatic absorption of docosahexaenoic acids (DHA) given as monoglyceride (MG), consisting of 1(or 3)-species (9 1.4%), 2-species (4.2%) and diglyceride (DG) consisting of 1,3-species (70.8%), 1(or 3),2-species (28.6%), were investigated in comparison with that of triglyceride (TG) and ethyl ester (EE). Rats were infused with a lipid emulsion containing 200 mg of DHA-MG, DG, TG, or EE via a gastric cannula. Lymph was collected through the thoracic lymph duct at 2 h intervals for 10 h and at a single collection from 10 to 30 h. Physiological saline containing glucose was infused (2 mL/h) throughout the lymph collection. The overall recovery of DHA at 30 h after its infusion was significantly higher in the rank order DHA-MG>DG>TG=EE. Moreover, time-dependent changes in recovery rates from 2 to 10 h of DHA given as MG were significantly higher than those of the corresponding DG, TG, and EE. These results indicate that DHA-MG and DG are absorbed and transported more effectively than TG and EE forms under restricted water supply, even if they mainly consist of 1(or 3)-species. Lymph lipids were mainly transported as TG, and a large amount of DHA was incorporated into a TG fraction in all fat types examined. Furthermore, the intramolecular distribution of DHA in lymph TG was similar in all groups. docosahexaenoic acid, monoglyceride, diglyceride triglyceride, ethyl ester     

Role of heparan sulfate proteoglycan (syndecan-1) on the renal epithelial cells during calcium oxalate monohydrate crystal attachment

We have reported that heparan sulfate (HS)/heparan sulfate proteoglycan (HSPG, syndecan-1) expression significantly increased in the rat kidney during calcium oxalate (CaOx) nephrolithiasis. Although the exact role of syndecan still remains unclear, HS/syndecan-1 is thought to have some important role in the CaOx crystal formation. Mardin-Darby canine kidney (MDCK) cells are most commonly used in kidney stone research. It was reported that MDCK cells do not express syndecan-1. In the present study, we established a novel MDCK cell line (KIC-synd-1) that expressed the human syndecan-1 gene. In this cell line, we confirmed stable expression of both sndecan-1 gene and core protein. Immunohistochemical study revealed positive staining of syndecan-1 monoclonal antibody in the basolateral and cytosolic area of the KIC-synd-1 cells. We also investigated the composition of glycosaminoglycans (GAGs) side chains in MDCK cells and KIC-synd-1 cells by using high-performance liquid chromatography (HPLC). Four types of HS chains were identified in both cells as follows; delta diHS-NS, delta diHS-6S, delta diHS-diS1, delta diHS-diS2. Increased production of delta diHS-NS and delta diHS-diS2 were shown in KIC-synd-1 cells compared with production in MDCK cells (p < 0.05). In contrast, only a small amount of delta diHS-6S and delta diHS-diS1 was contained in both cell lines. Total amount of HS was significantly increased in the KIC-synd-1 cells compare with that in the wild type MDCK cells (p < 0.05). Scanning electron microscopy revealed no significant difference between cell surface of wild type MDCK cells and that of KIC-synd-1 cells in normal conditions. However, calcium oxalate crystal attachment was apparently decreased in the KIC-synd-1 cells. These results suggested that cell surface HS/syndecan-1 has preventive role for calcium oxalate nephrolithiasis via creation of a charge barrier against COM crystal attachment.     

Contact area, contact pressure, and pressure patterns of the tendon-bone interface after rotator cuff repair

BACKGROUND: The contact pressure and contact area at the tendon-bone interface after the most commonly used rotator cuff repair methods have not been investigated. HYPOTHESIS: There are no significant differences among the transosseous, the single-row suture anchor, and the double-row suture anchor techniques in terms of contact pressure, contact area, and pressure patterns at the tendon-bone interface. STUDY DESIGN: Controlled laboratory study. METHODS: After creating a full-thickness supraspinatus tendon tear in 10 cadaveric shoulder specimens, we inserted pressure-sensitive film between the tendon stump and the bone, and we repaired the tear by (1) transosseous, (2) single-row suture anchor, and (3) double-row suture anchor techniques. RESULTS: The contact area of the double-row technique was 42% greater than that of the transosseous technique (P < .0001) and 60% greater than that of the single-row technique. The contact area of the transosseous technique was 31% greater than that of the single-row technique (P = .0015). The average pressures of the single-row and double-row techniques were 18% (P = .014) and 16% (P = .03) greater, respectively, than that of the transosseous technique, but there was no significant difference between the single-row and double-row techniques (P = .915). CONCLUSIONS: The double-row technique produced the greatest contact area and the second-highest contact pressure, whereas the single-row technique created the highest contact pressure and the least contact area. The transosseous technique produced the second-greatest contact area and the least contact pressure. CLINICAL RELEVANCE: The double-row suture anchor technique and the transosseous technique may provide a better environment for tendon healing.     

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer: the Fukuoka Colorectal Cancer Study

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism, which affects DNA synthesis and methylation. This study investigated the relation of MTHFR C677T and A1298C polymorphisms to colorectal cancer in a case-control study in Fukuoka, Japan. The subjects comprised 685 incident cases of histologically confirmed colorectal adenocarcinomas and 778 community controls selected randomly in the study area. The genotype was determined by the PCR-RFLP method using genomic DNA extracted from buffy coat. Alcohol use was ascertained by in-person interview. Statistical adjustment was made for gender, age class, area, and alcohol use. The MTHFR 677TT genotype was associated with a statistically significant decrease in the risk with an adjusted odds ratio of 0.69 (95% confidence interval 0.51-0.93) compared with the 677CC and 677CT combined, and the decrease was most evident in individuals with no alcohol consumption. While the A1298C polymorphism showed no measurable association with the overall risk of colorectal cancer, the 1298CC genotype was associated with a statistically significant increase in the risk when alcohol consumption was high, and was also associated with an approximately 2-fold increase in the risk of each of proximal and distal colon cancer. The findings add to evidence that individuals with the MTHFR 677TT genotype have a decreased risk of colorectal cancer in the absence of folate depletion, suggesting a protective role of folate by ensuring a sufficient thymidylate pool for DNA synthesis. Because very few individuals had the 1298CC genotype, the findings regarding the A1298C polymorphism need careful interpretation and confirmation in larger studies.     

Crystal structure of the Pyrococcus horikoshii DNA primase-UTP complex: implications for the mechanism of primer synthesis

BACKGROUND: In chromosomal DNA replication, DNA primase initiates the synthesis of a dinucleotide on a single-stranded template DNA, and elongates it to form a primer RNA for the replicative DNA polymerase. Although the apo-structure of an archaeal primase has been reported, the mechanism of primer synthesis by the eukaryotic-type primase still remains to be elucidated. RESULTS: In this study, we present the crystal structure of the eukaryotic-type DNA primase from the hyperthermophilic archaeon (Pyrococcus horikoshii) with the uridine 5'-triphosphate (UTP). In the present primase-UTP complex, the primase binds the triphosphate moiety of the UTP at the active site, which includes Asp95, Asp97, and Asp280, the essential residues for the nucleotidyl transfer reaction. CONCLUSION: The nucleotide binding geometry in this complex explains the previous biochemical analyses of the eukaryotic primase. Based on the complex structure, we constructed a model between the DNA primase and a primer/template DNA for the primer synthesis. This model facilitates the comprehension of the reported features of DNA primase.     

Delayed potassium current and non-specific outward current in pyramidal neurones acutely dissociated from rat hippocampus

The electrical property of delayed K+ currents (IKD) was studied in pyramidal neurones freshly isolated from the rat hippocampal CA1 region. The IKD was separated pharmacologically from other membrane currents. Activation and inactivation processes of the IKD were highly voltage-dependent in the potential range between -30 and +20 mV. The steady-state inactivation of IKD was observed at -100 mV or more positive potentials. The potential for half steady-state inactivation was -65 mV. The IKD was fully inactivated around -20 mV. Reactivation of IKD consisted of two exponential components. After pharmacological suppression of IKD, the small amount of residual voltage-dependent outward current (one-fifteenth to one-twentieth of IKD amplitude) was observed. The current kinetics was similar to that of IKD and greatly reduced by substitution of internal K+ with N-methyl-D-glucamine+. It was concluded that the properties of IKD was basically similar to those of IKD in other excitable tissues and that the residual current might be non-specific outward current.