Aim To establish a rat model of Parkinsons disease by chronic subcutaneous injection of low-dose rotenone.Methods Lewis rats were randomly divided into two groups: vehicle-treated group and rotenone-treated group.Rotenone(1.0 mg?kg~(-1)?d~(-1)) was subcutaneously injected at 08:00 and 20:00 for 30 days with drug holidays every 7 days.Following 30 days of rotenone administration,neuronal loss in the substantia nigra(SN) was determined with tyrosine hydroxylase(TH) immunohistochemistry and Nissl staining.Aggregation of ?-synuclein in SN neurons was observed with a laser cofocal microscopy.Result Three rotenone-treated rats showed resting tremor.The number of TH-positive neurons in SN significantly reduced(P

Peroxisome prolifreator-activated receptors (PPARs) are ligand-activated nuclear transcription factors, members of nuclear hormone receptor superfamily. PPARs play critical roles in growth, proliferation and apoptosis of variety of cells. Recently, PPAR ligands have been reported to ameliorate neuronal damage in neurodegenerative diseases including Alzheim- ers disease, Parkinsons disease,cerebral ischemia and multiple sclerosis. PPAR agonists may have potential values in treatment of neurodegenerative diseases. In this paper, we reviewed recent findings on PPARs′ neuroprotective actions and their underlying mechanisms.

Matrix metalloproteinases (MMPs) are a family of Zn~ 2+ -dependent endopeptidases targeting extracellular matrix (ECM) compounds as well as a number of other proteins. Their proteolytic activity acts as an effector mechanism of tissue remodeling in physiologic and pathologic conditions, and as modulator of inflammation. Recently, it has been reported that MMPs play an important role in nervous diseases including cerebral ischemia, Alzheimers disease,multiple sclerosis and Parkinson′s disease.

Valproate (VPA) has long been used for the treatment of bipolar mood disorder. VPA is effective in control of mania and depression. Recent studies have demonstrated that VPA has profound neuroprotective effects in against various apoptotic stimuli. Moreover, VPA can promote neurogenesis, neuronal proliferation and differentiation. Although intensive research has been dedicated to VPA′s neuroprotection, the molecular mechanisms by which VPA protects neurons are still not fully understood. In this paper, recent progresses in the study of VPA′s neuroprotection and underlying mechanism are reviewed.

Huntington's disease is a fetal neurological disorder manifested as movement disorder accompanied by cognitive and psychological impairments. The disease is inherited as autosomal dominant. Huntington's disease is caused by an expansion of a polyglutamine tract in a protein named huntingtin. The length of polyglutamine tract in huntingtin in normal individual is less than 35 glutamines. In Huntington's disease patients the length of polyglutamine tract increases to more than 37 glutamines. The pathogenic mechanisms by which mutant huntingtin causes Huntington's disease have not been fully understood. This paper reviews main progresses in studying the pathogenic mechanisms of mutant huntingtin.

ObjectiveTo explore the value of Tth-single strand binding protein (SSB) used as an additive to improve the polymerase chain reaction (PCR) specificity for single nucleotide polymorphisms(SNP) alleles genotyping.MethodsTth-SSB plasmid was constructed and the protein was expressed,then the expressed Tth-SSB was added into PCR system detecting cytochrome P450 Protein ( CYP2C19 * 3,636G＞A)genotype to determine the optimal usage and condition.Then,the genotypes of 30 cerebral ischemia patients were tested with established methods and compared with direct sequencing to verify the accuracy of Tth-SSB as an additive into PCR for SNP genotyping.ResultsThe purity of Tth-SSB was 85％ and optimal dosage was 1 μg.The protein could improve the specificity and reduce the dimer when Tth-SSB was added into the PCR system.Thirty patients genotyping results as follow:26 patients belong to G/G homozygote,4 patients belong to G/A heterozygote,no body belong to A/A homozygote.The coincidence acquire 100％ with parallel sequencing.ConclusionAs an additive,Tth-SSB could significantly improve the accuracy of genotyping by eliminating non-specific bands.

Cobra venom secretory phospholipase A_2 (sPLA_2) is an important component of cobra venom which has a variety of biological activities. Recent studies are mainly focusing on each pharmacological active component of venom, SPLA_2 is one of them. This review summarized the structure, purification and biological activities of cobra venom sPLA_2 with emphasizing its diverse pharmacological effects and toxicity. In addition, some mechanisms of actions of sPLA_2 and possible applications of sPLA_2 were also discussed.

Autophagy occurs in all types of eukaryotic cells, which has a rigid connection with the normal or abnormal development of cells and is associated with many diseases. There're lots of molecular control elements and multiple signaling pathways involved in regulating autophagy. As a form of type Ⅱ programmed cell death, autophagy participates in maintaining cell homeostasis and pathogenesis of various of diseases through interacting with apoptotic pathway. Recent studies show that autophagy has effects on the occurrence and development of tumor cells through influencing on cell cycle, apoptosis-associated factors and angiogenesis.

Pulsatile drug delivery system,capable of releasing drug at the predetermined times according to clinical therapeutic requirements,can be used to treat several rhythmic diseases.Majority of individuals experience the rise in the blood pressure in the early morning hours,which potentially leads to serious cardiovascular complications.The purpose of the study was to develop pulsatile candesartan cilexetil core-in-cup tablets according to human circadian rhythm of blood pressure.The factors influencing t_(lag) were evaluated by in vitro drug release and tablet erosion observations.In addition,the jugular artery pressures vs times courses of rabbits were recorded after oral administration of commercial candesartan cilexetil tablets or the developed core-in-cup tablets.The quantity and characteristics of the excipients in top layers in the tablets were found to modify t_(lag).In vivo studies showed that the onset times indicating the decreases in the blood pressures of commercial tablets and core-in-cup tablets were (98 ± 17) min and (278 ±29) min,respevtively.In vivo t_(lag) of the prepared core-in-cup tablets was (180 ± 34) min in rabbits,which is consistent with the goal of design.