ObjectiveTo observe the expression of syntaxin-1 in hippocampus of adult rats with hypothyroidism and the role of different doses of thyroid hormone replacement therapy,further to explore the molecular mechanism of brain damage.MethodsAll 44 male adult SD rats were randomly divided into 4 groups according to their body mass(250 - 300 g):hypothyroidism group,routine dosage thyroxine treatment group,high dosage thyroxine treatment group and control group (11 in each group).Hypothyroidism group,routine dosage thyroxine treatment group and high dosage thyroxine treatment group received daily intraperitoneal injection of propylthiouracil (PTU) 10 mg/kg.Hypothyroidism group was given PTU by intraperitoneal injection for two weeks after the previous four week treatment,the routine dosage thyroxine treatment group and the high dosage thyroxine treatment group were given 50,200 μg/kg L-thyroxine daily intraperitoneally for two weeks; the control group received daily intraperitoneal injection of saline.The levels of serum T3,T4 were assayed by radioimmunoassay method,and the level of syntaxin-1 in hippocampus was analyzed by immunohistochemistry.ResultsIn the hypothyroidism group,the levels of serum T3,T4[(0.34 ± 0.04),(43.01 ± 2.95)nmol/L] were significantly lower than those in the control group[(0.65 ± 0.05),(55.20 ± 3.56)nmol/L,all P ＜ 0.05].In the routine dosage of thyroxine treatment group,the levels of serum T3,T4[(0.63 ± 0.05),(55.04 ± 3.77)nmol/L] were not significantly different compared to the control group (all P ＞ 0.05 ).In the high dosage thyroxine thyroid hormone treatment group,the levels of serum T3,T4[(1.11 ± 0.10),(96.68 ± 6.42)nmol/L] were significantly higher than those in the control group(all P ＜ 0.05).The levels of syntaxin-1 protein in the CA1,CA3 and dentate gyrus(DG) of all layer regions of hippocampus (0.059 ± 0.016,0.064 ± 0.014,0.068 ± 0.016,0.069 ± 0.017,0.072 ± 0.016,0.070 ± 0.011,0.051 ± 0.012,0.072 ± 0.017) were significantly higher compared to the control group(0.037 ± 0.008,0.045 ± 0.010,0.042 ±0.009,0.040 ± 0.010,0.053 ± 0.009,0.042 ± 0.009,0.032 ± 0.007,0.047 ± 0.010,all P ＜ 0.05).In the routine dosage and the high dosage thyroxine thyroid hormone treatment group,the level of syntaxin-1 in CA1,CA3and DG regions(0.041 ± 0.011,0.046 ± 0.017,0.044 ± 0.014,0.037 ± 0.008,0.051 ± 0.010,0.043 ± 0.010,0.033 ± 0.011,0.045 ± 0.014 and 0.040 ± 0.010,0.045 ± 0.011,0.043 ± 0.010,0.033 ± 0.009,0.050 ± 0.010,0.041 ± 0.009,0.032 ± 0.009,0.046 ± 0.009)were not significantly different compare to the control group(all P＞0.05).ConclusionThe expression of syntaxin-1 in hippocampus of adult-onset hypothyroidism is increased,which can be reversed by routine dosage treatment of thyroxine.

OBJECTIVETo investigate the effect of triptolide (TPL) on the renal tissue of diabetic rats and its possible mechanisms.

METHODSSD rats were randomly divided into the normal control group (as the normal group), the diabetic model group (the model group), the low dose TPL treatment group (the low dose TPL group, TPL 0.2 mg/kg by gastrogavage), the high dose TPL treatment group (the high dose TPL group, TPL 0.4 mg/kg by gastrogavage). Equal volume of normal saline was given to rats in the normal group and the model group. Five rats were randomly selected from each group at week 4, 8, and 12 of the experiment to detect body weight, kidney weight, 24 h urinary albumin (24 h UAL), plasma glucose (FBG), total cholesterol (TC), total triglyeride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell (WBC), and hemoglobin A1c (HbA1c). The mRNA and protein expression of regulated upon activation normal T-cell expressed and secreted (RANTES) in the renal tissue was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). The renal tissue was pathologically stained by HE, PAS, and Masson staining. The glomerular and renal tubular interstitial lesions were observed at each time point. The glomerular sclerosis index (GSI) was observed by PAS staining, and the renal interstitial filrosis index (RIFI) was calcutated.

RESULTSCompared with the same group at week 4, the expression of 24 h UAL, RANTES, GSI, and RIFI at week 12 significantly decreased in two TPL groups (P <0.01). Compared with the same group at week 8, the expression of 24 h UAL, RANTES, GSI, and RIFI at week 12 also significantly decreased in the two TPL groups (P <0. 05, P <0.01). Compared with the normal group, body weight and the kidney weight obviously decreased at week 4, 8, and 12 in the model group (P <0. 01); 24 h UAL, FBG, TG, TC, HbA1c, RANTES, GSI, and RIFI were obviously elevated (P <0.01). Compared with the model group, 24 h UAL, RANTES, GSI, and RIFI also decreased in the two TPL treatment groups (P <0.01). Compared with the low dose TPL group, they were attenuated in the high dose TPL group (P <0. 05, P <0. 01).

CONCLUSIONTPL could not only inhibit the over-expression of RANTES, but also improve the glomerular sclerosis and renal interstitial fibrosis in the renal tissue of diabetic rats.

Animals ; Chemokine CCL5 ; drug effects ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetic Nephropathies ; drug therapy ; Diterpenes ; pharmacology ; Drugs, Chinese Herbal ; metabolism ; Epoxy Compounds ; pharmacology ; Glycated Hemoglobin A ; metabolism ; Immunosuppressive Agents ; pharmacology ; Kidney ; drug effects ; Kidney Diseases ; drug therapy ; Kidney Glomerulus ; metabolism ; Kidney Tubules ; metabolism ; Phenanthrenes ; pharmacology ; RNA, Messenger ; genetics ; Rats

Objective To observe the expression of synaptotagmin I(syt I)protein in the prefrontal cortex of adult-onset hypothyroidism rats and the effects of replicated therapy in different doses of thyroid hormone on the syt I protein.Methods All 44 aduh male Sprague-Dawley rats were divided into 4 groups randomly according to their body mass:hypothyroidism group,routine dosage thyroxine treatment group,high dosage thyroxine treatment group and control group.The adult male Sprague-Dawley rats were replicated to the adult-onset hypothyroidism and treatment models with propyhhiouracil(PTU).The levels of serum T3,T4 were assayed by the radioimmunoassay method and the level of the syt I protein in the molecular layer,external granular layer,external pyramidal layer,internal granular layer and internal pyramidal layer in prefrontal cortex was analyzed by immunohistochemistry.Results In the hypothyroidism group,the levels of serum T3 and T4[(0.34±0.04),(43.01±2.95)nmol/L]were significantly lower than those in the control group[(0.65±0.15), (55.20±3.56)nmol/L, F value: 6.026,5.940,4.503,P<0.05 or <0.01 ], the levels of the syt I protein in the molecular layer(0.018±0.010), external granular layer (0.020±0.007), external pyramidal layer(0.013±0.008), internal granular layer(0.011±0.005), internal pyramidal layer(0.024±0.013) of prefrontal lobe were significantly lower compared to the control group[(0.028±0.010,0.031 ± 0.010,0.028 ± 0.010,0.022 ± 0.008,0.038 ± 0.013), F value: 5.697,8.965,14.668,13.597,6.807,P<0.05 or <0.01 ]. In the routine dosage of the thyroxine treatment group, the levels of serum T3,T4 [(0.63 ±0.05), (55.04 ± 3.77)nmol/L] were not significantly different compared to the control group(F value: 3.162,0.367,all P>0.05), and the level of the syt I protein in the molecular layer, external granular layer, external pyramidal layer, internal granular layer and internal pyramidal layer in prefrontal cortex showed a significant improvement of the syt I protein(0.027 ± 0.013,0.025 ± 0.009,0.022 ± 0.008,0.020 ± 0.010,0.033 ± 0.010), which were similar to that of the control group(F value: 0.094,2.208,2.467,0.350,0.693, all P>0.05). In the high dosage thyroxine thyroid hormone treatment group, the levels of serum T3 and T4[ (1.11 ± 0.10), (96.68 ± 6.42)nmoL/L] were higher than the control group(F value: 6.291,12.031, all P<0.01), the expression of the syt I protein(0.028 ± 0.008,0.031 ±0.011,0.026 ± 0.012,0.023 ± 0.011,0.038 ± 0.010) were not significantly different compare to the control group (F value: 0.001,0.019,0.111,0.061,0.001, all P>0.05). Conclusions The expression of the syt I protein in the prefrontal cortex of adult-onset hypothyroidism can be decreased, which can be reversed by routine dosage of thyroxine treatment.

Using the theory and method of health economics,we analyzed CER and ICER in early elimination stage (2005-2009),the late elimination stage (2015-2010) and the post elimination phase (2016-).Results showed that annual total cost of investment was as following:64 235 144.8 Yuan in early elimination stage,11 250 248 Yuan in the late elimination stage,and 11 075 228.8 Yuan the post elimination phase.Effect analysis showed that the difference of the three-stage monitoring measures was statistically significant (P＜0.01).Number of cases within 3 days of onset (rate) prompt monitoring measures had the best effect in the late elimination stage,number of blood tests (rates),number of cases reported (rates) and number of cases within 1 days of onset (rate).Prompt monitoring measures had the best effect in the post elimination phase.CER and IC-ER showed that taking the number of blood test as the effect index,the monitoring measures in the late elimination stage were more cost effective.The number of cases reported,number of cases within 3 days of onset and number of cases within 1 day of onset were as the effect index,the monitoring measures in the post elimination phase were more cost effective.The elimination effect for monitoring measures after stage was optimal,cost the least,and might be the most effective.The study provides basic data for Fujian Province to strengthen the monitoring of imported cases of malaria on the construction of the management mechanism,and scientific and effective evaluation of monitoring measures,which has very important practical value and significance.

OBJECTIVETo observe blood uric acid levels and Goldstein grading, as well as their correlation in Wilson's disease (WD) patients with different Chinese medical syndrome types.

METHODSTotally 906 WD patients in line with inclusive criteria were assigned to 6 groups, i.e., the heart spirit confused by phlegm group (HSCP, 26 cases), the phlegm-fire disturbing heart group (PFDH, 90 cases), the retention of damp-heat group (RDH, 113 cases), deficiency of qi and blood group (DQB, 168 cases), the deficiency of Gan-yin and Shen-yin group (DGYSY, 327 cases), the deficiency of Gan and Shen group (DGS, 182 cases) due to different Chinese medical syndrome types. Recruited were another 160 healthy subjects having similar ages and diet structures, who came for medical examinations, as the healthy control group. Venous blood was collected from the medial cubital vein of each-patient on an empty stomach in early mornings to detect blood uric acid levels. Results Blood uric acid levels were lower in each syndrome type group than in the healthy control group (146.08 +/- 67.24 micromol/L in the HSCP group; 157.08 +/- 69.77 micromol/L in the PFDH group; 162.58 +/- 97.72 micromol/L in the RDH group; 156.20 +/- 62.63 micromol/L in the DQB group; 161.83 +/- 111.23 micromol/L in the DGYSY group; 194.41 +/- 90.01 micromol/L in the DGS group; 242.39 +/- 87.55 micromol/L in the healthy control group, P < 0.01). Blood uric acid levels were higher in the DGYSY group than in the other 5 syndrome groups (P < 0.01). Correlation analyses between Goldstein grading and blood uric acid showed that, along with increased Goldstein grade (that was aggravating disease conditions), WD patients' blood uric acid levels decreased (P < 0.01).

CONCLUSIONSWD patient's blood uric acid levels decreased more. Blood uric acid levels and Goldstein grading were different in various Chinese medical syndrome types. Blood uric acid levels had certain value in assessing the severity of WD.

Asian Continental Ancestry Group ; Heart ; Hepatolenticular Degeneration ; blood ; classification ; diagnosis ; Humans ; Medicine, Chinese Traditional ; Syndrome ; Uric Acid ; blood

This study was purposed to investigate the molecular genetics basis for para-Bombay phenotype. The para-Bombay phenotype of two probands was identified by routine serological techniques. The full coding region of alpha (1, 2) fucosyltransferase gene (FUT1 and FUT2) in the probands was amplified by polymerase chain reaction and the amplified fragments were directly sequenced, meanwhile the mutations of FUT1 were also identified by TOPO TA cloning sequence method. The results indicated that two heterozygous mutations were detected by directly sequencing in two probands: AG deletion at position 547 - 552 and C to T mutation at position 658. Two different mutations were confirmed to be true compound heterozygotes with each mutation on a separate homologous chromosome by TOPO TA cloning sequence method. AG deletion at position 547 - 552 caused a reading frame shift and a premature stop codon. C658T mutation resulted in Arg-->Cys at amino acid position 220. It is suggested that the FUT1 mutation of two probands are compound heterozygous mutation with different chromosomes, which are named h1h3 and may be the genetics basis of para-Bombay phenotype.
ABO Blood-Group System ; genetics ; Alleles ; Frameshift Mutation ; Fucosyltransferases ; genetics ; Gene Deletion ; Heterozygote ; Humans ; Male ; Mutation, Missense

OBJECTIVETo investigate the effects of heme oxygenase 1 inducer hemin on protection of ischemia-reperfusion injury in rats and its mechanisms.

METHODSThe Langendorff model of isolated rat heart was used; the left anterior descending coronary artery was occluded for 30 min and subsequently reperfused for 2 h. Then the ventricular function and infarct size were measured.

RESULTHemin preconditioning prevented the increase in LVEDP, decrease in LVDP and +/- dp/dt(max) in the isolated ischemia-reperfusion rat hearts. The leakage of LDH and CK in the coronary effluent was significantly declined in hemin-treated rat hearts. And the infarct size was also reduced. Administration of a blocker of mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) 5-HD (5 mg/kg) before hemin preconditioning increased the LVEDP, and reduced the LVDP and +/- dp/dt(max). The leakage of LDH and CK in the coronary effluent and the infarct size were also increased compared with only hemin-treated rat hearts. Pretreatment of the rats with a blocker of sarcolemmal ATP-sensitive potassium channel (sarcK(ATP)) HMR-1098 (6 mg/kg) before hemin preconditioning also abolished the protective effect. Infusion of paxilline (1 micromol/L), a blocker of calcium activated potassium channel (K(Ca)) for 10 min before ischemia/reperfusion led to larger infarct size and poorer myocardial performance as compared with the hemin group. The leakage of LDH and CK in the coronary effluent was also increased.

CONCLUSIONBoth mitoK(ATP)and sarcK(ATP)channels activation are required for the delayed cardioprotection induced by hemin. The opening of K(Ca) channels-dependent mechanism may be involved in the protection.

Animals ; Cardiotonic Agents ; pharmacology ; Heme Oxygenase-1 ; biosynthesis ; Hemin ; pharmacology ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Infarction ; metabolism ; Myocardial Reperfusion Injury ; metabolism ; physiopathology ; prevention & control ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Potassium Channels, Calcium-Activated ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the correlation between cyclin E protein overexpression and centrosome amplification in oral squamous cell carcinoma (OSCC).

METHODSFormalin-fixed, paraffin-embedded tissues from 12 normal oral epithelium cases and 46 cases of OSCC were studied. Their centrosome status was analyzed by indirect immunofluorescence double staining with antibodies to centrosome protein gamma-tubulin and cytokeratin. The expression of cyclin E protein was studied by immunohistochemical methods. The correlation between cyclin E protein expression and centrosome amplification in OSCC was statistically analyzed by SPSS 12.0.

RESULTSThirty-seven of the 46 OSCC cases (80.4%) studied showed evidence of centrosome amplification, as signified by enlargement and/or increase in number of centrosomes, while normal oral epithelium possessed centromeres of normal size and number. Positive staining for cyclin E protein was observed in 30 of the 46 OSCC cases (65.2%), while all the normal oral epithelium cases were cyclin E protein-negative. The percentage of centrosome amplification in OSCC with positive cyclin E protein staining (90.0%, 27/30) was higher than that in OSCC with negative cyclin E protein staining (62.5%, 10/16) (chi(2) = 5.014, P < 0.05). Centrosome amplification showed positive correlation with cyclin E protein overexpression (r = 0.330, P < 0.05).

CONCLUSIONUp-regulation of cyclin E protein may represent one of the possible mechanisms for centrosome amplification in OSCC.

Carcinoma, Squamous Cell ; metabolism ; pathology ; surgery ; Centrosome ; pathology ; ultrastructure ; Cyclin E ; metabolism ; Epithelium ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Microscopy, Confocal ; Mouth Mucosa ; metabolism ; pathology ; Mouth Neoplasms ; metabolism ; pathology ; surgery ; Up-Regulation

OBJECTIVETo investigate the cell proliferation and differentiation in the developing brain of mouse.

METHODSC57/BL6 mice were divided into 3 groups at random. Bromodeoxyuridine (BrdU) was injected into the brains in different development periods once a day for 7 d. The brains were retrieved 4 weeks after the last BrdU injection. Immunohistochemical and immunofluorescent studies were carried out for detecting cell proliferation (BrdU) and cell differentiation (NeuN, APC, Iba1, and S100beta), respectively.

RESULTSThe number of BrdU labeled cells decreased significantly with the development of the brain. Cell proliferation was prominent in the cortex and striatum. A small portion of BrdU and NeuN double labeled cells could be detected in the cortex at the early stage of development, and in the striatum and CA of the hippocampus in all groups. The majority of BrdU labeled cells were neuroglia, and the number of neuroglia cells decreased dramatically with brain maturation. Neurogenesis is the major cytogenesis in the dentate gyrus.

CONCLUSIONThese results demonstrated that cell proliferation, differentiation and survival were age and brain region related.

Animals ; Animals, Newborn ; Brain ; cytology ; growth & development ; Bromodeoxyuridine ; Cell Count ; Cell Differentiation ; physiology ; Cell Proliferation ; Cerebral Cortex ; cytology ; growth & development ; Corpus Striatum ; cytology ; growth & development ; Fluorescent Antibody Technique ; Hippocampus ; cytology ; growth & development ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; metabolism ; Neuroglia ; cytology ; physiology ; Neurons ; cytology ; physiology ; Nuclear Proteins ; metabolism

AIMTo determine the protective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia induced by endothelin-1 in rats.

METHODSSlow microinjection of endothelin-1 (120 pmol in 6 microL, for > 6 min) into the region near the middle cerebral artery was used to induce focal cerebral ischemia. ONO-1078 (0.1 mg.kg-1) was i.p. injected 1 h before endothelin-1 injection. Neurological symptoms, brain edema, brain infarction size, and the survival neurons in cortex and striatum were observed 24 h after ischemia.

RESULTSIntracerebral microinjection of endothelin-1 induced remarkable neurological symptoms, brain infarction, brain edema, and decrease of survival neurons in the cortex and striatum. In rats pretreated with ONO-1078, endothelin-1-induced brain edema and brain infarction size were decreased. The numbers of survival neurons in striatum and cortex were increased significantly. The neurological symptoms were improved but not significantly.

CONCLUSIONONO-1078 possesses neuroprotective effect against cerebral ischemic injury induced by endothelin-1, therefore, leukotrienes may play a role in the injury of cerebral ischemia.

Animals ; Behavior, Animal ; drug effects ; Brain Edema ; pathology ; Brain Ischemia ; chemically induced ; pathology ; Cerebral Cortex ; pathology ; Cerebral Infarction ; pathology ; Chromones ; pharmacology ; Corpus Striatum ; pathology ; Endothelin-1 ; Leukotriene Antagonists ; pharmacology ; Male ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley