Association between the MnSOD Ala-9Val polymorphism and development of schizophrenia and abnormal involuntary movements in the Xhosa population

Reactive oxygen species (ROS)-mediated damage has been hypothesized to play a role in the development and poor outcome of schizophrenia, as well as the development of neuroleptic-induced abnormal involuntary movements. Recently, the functional polymorphism (Ala-9Val) in the manganese superoxide dismutase (MnSOD) gene (part of the antioxidant defense mechanism) was found to be associated with schizophrenia in a Turkish population. This study was aimed at replicating this finding in a Xhosa population. In addition, the role of Ala-9Val in abnormal involuntary movement and tardive dyskinesia development in the Xhosa population was also investigated. The schizophrenic patient group (n=286) and a healthy control group (n=243) were genotyped for the Ala-9Val polymorphism using heteroduplex-single stranded conformational polymorphism (HEX-SSCP) analysis. No significant difference in genotype or allele frequency could be observed between the schizophrenia and control group (P=0.294 and P=0.528 respectively). In addition no association could be found between the polymorphism and symptom severity (SANS and SAPS). The Xhosa schizophrenia patient group with abnormal involuntary movements (n=54) and a subgroup with tardive dyskinesia (n=30) was found to significantly differ in Ala-9Val genotype frequency (P=0.008 and P=0.011 respectively) compared to the Xhosa schizophrenia patient group without abnormal involuntary movements (n=204). However, no significant difference was found for the allele frequencies (P=0.955 and P=0.161). Further, using ANCOVA no association was found between AIMS score and genotype in the group with abnormal involuntary movements (P=0.1234). However, in the patient group with tardive dyskinesia an association was observed between genotype and AIMS score (P=0.0365). These results do not support a major role of the MnSOD Ala-9Val polymorphism in the development of schizophrenia or symptom severity in the Xhosa population. Yet it seems to be involved in the development of abnormal involuntary movements and tardive dyskinesia and may even modulate the severity of tardive dyskinesia.     

气相色谱-质谱联用技术分析3种耳蕨根脂溶性成分

目的研究革叶耳蕨、黑鳞耳蕨和三叉耳蕨根的脂溶性成分。方法用索氏提取法提取3种耳蕨根的脂溶性成分,甲酯化处理后,采用气相色谱-质谱联用技术（GC—MS法）对3种蕨类根中脂溶性成分进行分析和鉴定。结果3种耳蕨根主要的脂肪酸成分一致,有显著差异的成分是甾醇类化合物。结论3种耳蕨根均具有药用价值。     

开封产紫白菊花脂溶性成分研究

目的对开封产紫白色菊花脂溶性成分进行初步研究。方法采用索氏提取法从紫白色菊花中提取脂溶性成分,用气相色谱-质谱联用检测其化学成分。结果从紫白色菊花中分离出56个化学成分,鉴定了其中的43个,占色谱总馏分出峰面积的83．92％。其中鉴定了18个脂肪酸成分。结论紫白色菊花脂溶性成分中主要为脂肪酸类（34．81％）,其次为烷烃类（29．83％）、萜类（13．39％）、甾醇类（5．89％）。     

Molecular recognition of long chain fatty acids by peroxisome proliferator-activated receptor α

In the present study, flexible ligand docking and multiple scoring were used to study the binding of long-chain fatty acid (LCFAs) to the peroxisome proliferator-activated receptor α (PPARα). The calculations indicated that LCFAs bind PPARα in nanomolar affinities, which is in agreement with the intracellular concentrations of LCFAs. Calculated binding affinities were linearly related with the chain length up to 20 carbon atoms. The best correlation between the rank order of experimentally detected binding affinities and the predicted scores was found with the internal coordinate mechanics (ICM) binding energy method. This study contributes molecular insight into the binding process, which is of pivotal importance for designing new ligands interfering with lipid and glucose homeostasis.     

Bioavailability of salvianolic acid B and effect on blood viscosities after oral administration of salvianolic acids in beagle dogs

Salvianolic acid B (SalB) is an active component isolated from Chinese herbal medicine Salvia miltiorrhiza. The aim of this study was to investigate the extent of absolute oral bioavailability (F) of SalB in beagle dogs and the effect on blood viscosity after intravenous and oral administration of Salvianolic acids (SAs). A gradient elution HPLC method was developed and validated to determine the concentration of SalB and its three possible metabolites in plasma. After SAs (180 mg/kg, p.o.; 9 mg/kg, i.v.) were given, the AUCs of SalB were 1680 ± 670 and 7840 ± 1140 ng/mL·h, respectively. The F of SalB in dogs was calculated to be only 1.07 ± 0.43%. The blood viscosity was remarkably decreased after a single intravenous injection of SAs (9 mg/kg). However, no significant change of blood viscosity was observed after a single oral administration of SAs (180 mg/kg). The results suggested that the F of SalB was extremely low and single oral administrated SAs had no effect on ameliorating blood viscosity in beagle dogs.     

Mechanism of cytotoxic action of perfluorinated acids.: I. Alteration in plasma membrane potential and intracellular pH level

Perfluorinated (aliphatic) acids (PFAs) and congeners have many applications in various industrial fields and household for decades. Years later they have been detected in wildlife and this has spurred interest in environmental occurrence as well as influencing living organisms. PFAs were established as peroxisome proliferators and hepatocarcinogens. Amphipatic structure suggests that they may alter cell membrane potential (mbΔΨ) and/or induce changes in cytosolic pH (pHi). The aim of this study was to examine the correlation between changes of above parameters and PFAs structure (CF₆-CF₁₂) in human colon carcinoma HCT116 cells.mbΔΨ and pHi were measured by flow cytometry using fluorescence polarization of the plasma membrane probe 3,3′-dipentyloxacarbocyanine (DiOC₅(3)) and fluorescein diacetate (FDA), respectively. Dose- and time-dependent manner analysis revealed relatively fast depolarization of plasma membrane and acidification of cytosol both positively correlated with fluorocarbon chain length. mbΔΨ depletion after 4 h of incubation reached 8.01% and 30.08% for 50 μM PFOA and 50 μM PFDoDA, respectively. Prolonged treatment (72 h) led to dramatic dissipation of membrane potential up to 21.65% and 51.29% and strong acidification to pHi level at 6.92 and 6.03 at the presence of above compounds, respectively.The data demonstrate that PFAs can alter plasma membrane protonotrophy with the mode dependent on the compound hydrophobicity.     

The role of an alginate suspension on pepsin and bile acids – key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro‐oesophageal reflux disease?

Objectives During a reflux event the oesophagus is exposed to a heterogeneous mixture of gastric juice components. The role of non‐acid components of the refluxate in causing damage to the oesophagus is now well established but no therapeutic option exists to address this. Methods The role of Gaviscon Advance (GA), a raft‐forming alginate suspension, in protecting the oesophagus from damage by pepsin and bile acids (aggressors) was investigated using a series of in‐vitro models. Key findings GA was able to dose‐dependently inhibit pepsin activity over and above the neutralisation effect of the formulation. This was evident against both protein and collagen substrates using two distinct colorimetric assays. GA was able to retard the diffusion of pepsin and multiple bile acids using a Franz cell model. Using the raft‐forming mode of action GA was able to remove both pepsin and multiple bile acids from a simulated reflux event. There was capacity in the GA raft to accommodate aggressors from multiple reflux events. Conclusions GA can specifically remove both pepsin and bile acids from the refluxate, limit their diffusion and affect enzymatic activity of pepsin. There is a role for GA to reduce the damaging potential of the refluxate and thus protect the oesophagus.     

Development of an analytical method for the unambiguous structure elucidation of cyclic peptides with special appliance for hepatotoxic desmethylated microcystins

The periodical occurrence of harmful algal blooms (HABs) in freshwater lakes requires the determination of potential cyanobacterial toxins, especially microcystins (MCs). On demand of an adequate risk assessment, the high diversity of these hepatotoxic cyclic heptapeptides implicates the need of an unambiguous detection of their specific structural variants. Therefore, LC-MS and LC-MS/MS methods are the approaches of choice for determination of MCs. In contrast, even tandem mass spectromic fragmentation patterns are not even sufficient in any kind of structural determination requirements, whereas NMR methods require very high amounts of MCs. In this study, we present a novel method for chromatographic separation of desmethylated microcystins (dm-MCs). Based on the isolation of the specific structural variants using semi-preparative HPLC, a method was developed for the structure elucidation of cyclic peptides with special appliance for the determination of dm-MCs via analysis of the specific amino acid composition after peptide hydrolysis followed by stereospecific detection of the amino acids and resulting keto acids. On the basis of this method it is demonstrated that dm-MC-RR with the structure [Dha⁷]MC-RR represented the major compound in the microcystin pattern of Microcystis aeruginosa bloom events in 2005 and 2006 in Lake Senftenberg, Germany.     

Revealing the multiple structures of serine

We explored the conformational landscape of the proteinogenic amino acid serine [CH(2)OH CH(NH(2)) COOH] in the gas phase. Solid serine was vaporized by laser ablation, expanded in a supersonic jet, and characterized by Fourier transform microwave spectroscopy. In the isolation conditions of the jet there have been discovered up to seven different neutral (non-zwitterionic) structures of serine, which are conclusively identified by the comparison between the experimental values of the rotational and quadrupole coupling constants with those predicted by ab initio calculations. These seven forms can serve as a basis to represent the shape of serine in the gas phase. From the postexpansion abundances we derived the conformational stability trend, which is controlled by the subtle network of intramolecular hydrogen bonds formed between the polar groups in the amino acid backbone and the hydroxy side chain. It is proposed that conformational cooling perturbs the equilibrium conformational distribution; thus, some of the lower-energy forms are "missing" in the supersonic expansion.