Effects of L-lysine monohydrochloride on insulin and blood glucose levels in spinal cord injured rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hyperglycemia in brain and spinal cord could aggravate neurologic impairment. Recent studies showed that L-lysine monohydrochloride (LMH) could increase the insulin secretion and regulate the blood glucose level. The aim of the present study was to investigate the effects of LMH on pancreatic islet B cells, the levels of endogenous insulin and blood glucose in spinal cord injured rats.</p><p><b>METHODS</b>Forty male Wistar rats were divided into four groups, namely, normal control group, model group, high-dose LMH group (621.5 mg/kg equal to LMH 1/8 LD50), and low-dose LMH group (310.8 mg/kg equal to LMH 1/16 LD50). The model of spinal cord injured rat was established by hemi-transection at the lower right thoracic spinal cord. LMH was administered via intraperitoneal injection once spinal cord injury was produced in rats. All rats were sacrificed 48 hours after spinal cord injured. The effects of LMH on pancreatic islet B cells, the content of endogenous insulin, and the level of blood glucose were observed with immunohistochemical method, radioimmunoassay method, and biochemical analyzer, respectively.</p><p><b>RESULTS</b>The insulin immunohistochemical intensities of islet B cells were significantly weaker in model group than those in normal control group (P < 0.01). The levels of endogenous insulin were significantly lower and the blood glucose levels were significantly higher in model group than those in normal control group (P < 0.01). The insulin immunohistochemical intensities of islet B cells were significantly stronger in high-dose LMH group than those in model group (P < 0.05). In addition, we found that the levels of endogenous insulin were significantly higher and the blood glucose levels were significantly lower in high-dose LMH group than those in model group (P < 0.05). There were no significant differences in the insulin immunohistochemical intensities of islet B cells, the levels of endogenous insulin and the blood glucose between low-dose LMH group and model group (P > 0.05).</p><p><b>CONCLUSION</b>LMH, but dose-dependent, might participate in the regulation of pancreatic islet B cells, and then reduce the blood glucose levels in the spinal cord injured rats.</p>

Desferoxamine preconditioning protects against cerebral ischemia in rats by inducing expressions of hypoxia inducible factor 1 alpha and erythropoietin / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To investigate whether desferoxamine (DFO) preconditioning can induce tolerance against cerebral ischemia and its effect on the expression of hypoxia inducible factor 1alpha (HIF-1alpha) and erythropoietin (EPO) in vivo and in vitro.</p><p><b>METHODS</b>Rat model of cerebral ischemia was established by middle cerebral artery occlusion with or without DFO administration. Infarct size was examined by TTC staining, and the neurological severity score was evaluated according to published method. Cortical neurons were cultured under ischemia stress which was mimicked by oxygen-glucose deprivation (OGD), and the neuron damage was assessed by MTT assay. Immunofluorescent staining was employed to detect the expressions of HIF-1alpha and EPO.</p><p><b>RESULTS</b>The protective effect induced by DFO (decreasing the infarction volume and ameliorating the neurological function) appeared at 2 d after administration of DFO (post-DFO), lasted until 7 d and disappeared at 14 d (P < 0.05); the most effective action was observed at 3 d post-DFO. DFO induced tolerance of cultured neurons against OGD: neuronal viability was increased 23%, 34%, 40%, 48% and 56% at 8 h, 12 h, 24 h, 36 h, and 48 h, respectively, post-DFO (P < 0.05). Immunofluorescent staining found that HIF-1alpha and EPO were upregulated in the neurons of rat brain at 3 d and 7 d post-DFO; increase of HIF-1alpha and EPO appeared in cultured cortex neurons at 36 h and 48 h post-DFO.</p><p><b>CONCLUSION</b>DFO induced tolerance against focal cerebral ischemia in rats, and exerted protective effect on OGD cultured cortical neurons. DFO significant induced the expression of HIF-1alpha and EPO both in vivo and in vitro. DFO preconditioning can protect against cerebral ischemia, which may be associated with the synthesis of HIF-1alpha and EPO.</p>

Correlation of free radical level and apoptosis after intracerebral hemorrhage in rats / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To investigate the correlation of perihematomal free radical level and neuronal apoptosis following the intracerebral hemorrhage (ICH).</p><p><b>METHODS</b>Animals were randomly divided into 4 groups: sham operation group, model group, 1 mg/kg edaravone group, and 3 mg/kg edaravone group. Each group was then divided into seven subgroups, in which the rats were correspondingly killed at 6 h, 12 h, 24 h, 48 h, 72 h, 7 d or 14 d (n = 1 in each subgroup of the sham group, and n = 6 in each subgroup of the other 3 groups). By Horseley-Clarke technique, autoblood (80 microL) were administered into the left caudate putamen of SD rats in a double administration-withdrawal way. Rats in the sham group were needled in but not administered with autoblood. The ICH model was then evaluated by Bederson's scale. Around the hematoma, the levels of malonaldehyde (MDA) and hydroxyl radical were tested by spectrophotometer, and the process of apoptosis was tested by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) method.</p><p><b>RESULTS</b>(1) ICH significantly increased the levels of MDA and hydroxyl radicals. Significant differences in MDA and hydroxyl radical contents were observed among the four groups. (2) In the sham group, a small number of TUNEL-positive cells were found. In the other three groups, the TUNEL-positive cells were observed at 6 h, increased significantly at 24 h, and reached peak level at 3 d, then fell profoundly at 7 d, but remained detectable at 14 d. (3) The positive correlation existed between apoptosis and free radical level (r = 0.2003), and existed between apoptosis and MDA content (r = 0.6563) in the brain.</p><p><b>CONCLUSION</b>Post-hemorrhagic apoptosis was related to the production of free radicals, indicating that the elevated free radicals following the ICH could induce neuron and glial cell apoptosis.</p>

Anti-oxidant effects of Tongxinluo on ATPase in focal brain ischemia-reperfusion rats / 中南大学学报(医学版)

OBJECTIVE@#To explore the effects of Tongxinluo on adenosine triphosphatase (ATPase), anti-oxidant enzymes activities, and lipid peroxidation of mitochondria or brain homogenate in focal brain ischemia-reperfusion rats.@*METHODS@#The models of the focal brain ischemia-reperfusion rats were made by the middle cerebral artery occlusion (MCAO). Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and ATPase and malonaldehyde (MDA) levels of mitochondria or brain homogenate were measured by biochemical methods.@*RESULTS@#Tongxinluo significantly inhibited the decrease of activities of SOD and the increase of MDA levels, but had no difference in GSH-Px in brain homogenate. It also inhibited the decrease of activities of SOD, GSH-Px, ATPase, and the increase of MDA levels in mitochondria.@*CONCLUSION@#The protective mechanisms of Tongxinluo against mitochondrial injuries in focal ischemia-reperfusion rats may be derived from reducing lipid peroxides, scavenging free radicals and improving the energy metabolism.

The Role of CD40-CD40L in Artherosclerosis and Thrombosis / 国际脑血管病杂志

Recent studies have confirmed that both CD40 molecule and its ligand CD40L played important roles in various stages of atherosclerosis.The critical cell component of atherosclerosis- endothelial cells,macrophages,and smooth muscle cells on which there are expressions of CD40 and CD40L.The combination of both induces human vascular endothelial cells expressing various active media,participating in the formation of atherosclerosis.However,blocking the CD40-CD40L pathway can prevent atherosclerosis or prevent the plaques from progressing.CD40L may participate in thrombosis and activation of platelet.The soluble CD40L levels increase persistently in patients with acute cerebral infarction and acute coronary syndrome.Some drugs may down-regulate CD40L level.It has provided a new approach for preventing the occurrence of vascular events.

The alpha-synuclein gene microsatellite polymorphism and late-onset sporadic Parkinson's disease susceptibility / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the association of the microsatellite polymorphisms in the promoter region of alpha-synuclein gene with the late-onset sporadic Parkinson's disease (PD) susceptibility.</p><p><b>METHODS</b>The microsatellite polymorphism of alpha-synuclein gene was analyzed with amplified fragment length polymorphism (Amp-FLP) and semiautomatic fluorescent labeled genotyping technique. Association analysis was performed in 135 unrelated late-onset sporadic PD patients and 170 age-matched healthy controls.</p><p><b>RESULTS</b>The distribution of the alleles of the dinucleotide repeats variants of alpha-synuclein gene promoter region in PD cases was significantly different from that in the healthy controls. The most frequent allele in PD patients was allele 269 bp, but in controls it was the 271 bp allele. Alleles of <or=267 bp showed positive correlation with PD risk (OR=5.228, 95%CI: 1.248-27.202, chi-square=6.416, P=0.011), while the 273 bp allele was negatively correlated to PD (OR=0.638, 95%CI: 0.440-0.926, chi-square=5.644, P=0.018). Furthermore, no difference of genotype polymorphism distribution was shown between the two groups (chi-square=16.368, df=12, P=0.175). But the genotypes containing <or=267 bp allele may increase the susceptibility to PD (OR=4.594, 95%CI: 0.94-22.49, chi-square=4.224, P=0.04). Heterozygosity was 40% in PD patients, and 50% in controls.</p><p><b>CONCLUSION</b>alpha-synuclein microsatellite polymorphism might be a genetic susceptibility factor for late-onset sporadic PD.</p>

A pedigree with myotonic dystrophy: non-CTG, non-CCTG repeat expansion / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Two genetic loci are associated with the myotonic dystrophy (DM) phenotype: DM1 DMPK on chromosome 19, and DM2 ZNF9 on chromosome 3. The aim of this study was to investigate the molecular genetics of a pedigree with DM.</p><p><b>METHODS</b>In twenty-six individuals from a family with DM, the CTG repeats in DMPK and CCTG repeats in ZNF9were evaluated genetically, using Long Expand trade mark Template polymerase chain reaction (PCR), Southern blotting and genomic scanning.</p><p><b>RESULTS</b>The numbers of CTG and CCTG repeat were all in normal range. There was no significant difference between the CTG repeat size in DMPK gene and that 4 years later from the same individual. The Lod score values with short tandem repeats STR markers chosen in 19q and 3q were all smaller than 1, which suggested that no STR marker was linked with this DM family.</p><p><b>CONCLUSION</b>There might be some other mutant in this DM pedigree. Further study should be done to find the genetic basis of this pedigree.</p>

Preliminary clinical and genetic study of a family with ophthalmoplegia,dysphagia and facial weakness / 中华神经科杂志

Objective To investigate the features of familiar facial palsy,ophthalmoplegia and dysphagia characterized by autosomal dominant inheritance in a family and to discuss the classification and pathogenesis of the disease.Methods Clinical,electrophysiological,pathological examinations were performed and blood samples were obtained from 5 patients and 26 family members.PCR protocol was used to identify a certain gene. Results In the 5 patients receiving physical examination,all had ptosis,external ophthalmoplegia,facial paralysis,dyphagia,hoarseness,decreased pharyngeal reflex;4 had amyotrophy of muscle of tongue,temporal nuscle,masseter and muscles of distal lower limbs;3 had proximal limb asthenia and distal limbs amyotrophy.Compared to those of oculopharyngeal muscular dystrophy(OPMD)with similar symptoms and signs,both electrophysiological manifestation and pathological findings of the family members supported the diagnosis of muscular dystrophy,but the(GCG)6(GCA)3GCG in the first exon of PABPN1 mutated neither in normal family members nor in patients.Conclusions This family presents clinical manifestations somewhat resembling to those of OPMD and distinctive to other disorders,but has a totally different genetic background from OPMD.It may be a new subtype of muscular dystrophy.

Clinical and gene study on one pedigree of hereditary spinocerebellar ataxia type 7 / 中华神经科杂志

Objective To summarize the clinical characteristics and make genetic diagnosis in the patients with hereditary spinocerebellar ataxia type 7 (SCA7).Methods Pedigree analysis and clinical examination were performed in one family with SCA7 by clinical findings,of which retinal morphology and visual electrophysiology were available on part numbers.The polymorphic cytosine adenine guanine (CAG) repeats in the encode region of SCA7 gene were detected by combining polymerase chain reaction with deoxyribonucleic acide (DNA) sequencing on 19 familial numbers and 12 controls.Results 6 patients were identified,who manifesting cerebellar ataxia,decreased visual acuity and colour vision defect,as was pigmentary retinopathy on fundoscopy;The 6 patients had not only extinction of the electroretinogram (ERG) but also remarkably reduced amplitudes of oscillatory potentials and flash-visual evoked potentials. On normal alleles CAG repeat size ranges from 8 to 25 repeats,wherease on mutated alleles of the 6 numbers it ranges from 50 to 97 repeats.The 6 numbers were diagnosised as SCA7 patients.One asymptomatic individual of this family,who displayed a normal allele with 18 CAG repeats and another containing abnormal expantion of 56 repeats,was diagnosised as a asymptomatic carrier whose age maybe still below the age of onset.Conclusion The clinical manifestations of SCA7 are heterogeneous,and the detection of CAG repeats can provide an effective way for the gene diagnosis and the prediction of asymptomatic patients.

Effect of brain-derived neurotrophic factor genetically modified neural stem cells transplantation on cerebral ischemic injury in rats / 中华神经科杂志

Objective To investigate the effect of brain-derived neurotrophic factor (BDNF) gene modified neural stem cells (NSCs)transplantation on cerebral ischemic injury in rats.Methods NSCs from newborn rat hippocampus were isolated,cultured in a medium containing fibroblast factor (FGF) in vitro. Their proliferation and differentiation were detected by immunohistochemistry.Virus vectors pLXSN-BDNF were built and BDNF were transfected into NSCs.Biological activity were detected to obtained engineering stem cells of BDNF protein with secretary activity.Middle cerebral artery occlusion (MCAO) models were made and transplanted with NSCs-BDNF by stereotaxic technique.The effect of transplantation on MCAO models was evaluated histologically and behaviorally.Results Statistical analysis showed that the behavioral performance of the animals improved after transplantation (Longa mark being 1.343?0.293 four weeks after stem cell transplantation).The number of hippocampal dentate gyrus neurons increased to 87.5%?6.6% , four weeks after stem cell transplantation on Nissle stained hippocampal sections,which was significantly different from that of controls.Positively BrdU stained neural stem cells revealed by immunohistochemistry in the cultured cells and in the transplanted brain sections,indicated that the engineering cells transplanted had survived in the host brain and began to proliferate.Conclusion Transplantation of BDNF genetically modified NSCs can effectively promote the recovery from cerebral ischemic injury.