Animals ; Calcitonin Gene-Related Peptide ; pharmacology ; Ischemic Postconditioning ; Male ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley

Background The domestic and international researches discovered that many proteins and enzymes of the extracellular matrix (ECM) participate in the sclera remodeling by affecting the collagen typeⅠand fibronectin.Objective This study was to investigate the effect of matrixmetalloproteinase-2 (TIMP-2) on expression of collagen typeⅠand fibronectin of ECM in the posterior sclera by injecting liposomes containing tissue inhibitor of TIMP-2 gene into suprachoroidal space of the form-deprivation myopia in guinea pig.Methods Form-deprivation myopia was induced by translucent goggles in 36 clean guinea pig for 2 weeks.Then the animals were randomly assigned to TIMP-2 group,empty plasmid group,saline group and 12 for each group.Liposomes of 5μl containing TIMP-2 gene,empty plasmid and saline were suprachoroidally injected in the right eye respectively,and the left eyes without any treatment were used as self-control group.Other 12 matched guinea pigs only covered the right eyes through out the experimental duration as model control group.The guinea pigs were sacrificed and the posterior sclera tissue of the eyeballs were collected at 2,7 and 14 days after injection of drug.The expressions of collagen typeⅠmRNA and fibronectin mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).This study followed the Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results The expression level of collagen type Ⅰ mRNA in the posterior sclera of guinea pig was lower but that of fibronectin mRNA was higher in TIMP-2 group than self-control group,showing significant differences between them (P＜0.05).The expression level of collagen type Ⅰ mRNA in the posterior scleral tissue began to increase from the 2nd day after drug injection and was obviously elevated at the 7th day and then gradually decreased at the 14th day.However,the expression level of fibronectin mRNA in the posterior scleral tissue showed the opposite pattern.The expression levels of collagen typeⅠmRNA and fibronectin mRNA at the 7th after drug injection were significantly lower than that at the 2nd day or 14th day (P＜0.01).Conclusion Suprachoroidal injection of TIMP-2 in form-deprivation myopia could up-regulate the expression of collagen typeⅠmRNA and down-regulate the expression of fibronectin mRNA in the posterior scleral tissue.It may slow down the sclera remodeling of form-deprivation myopia in guinea pig in the early stage.

The major objective was to explore the effect of early hyperbaric oxygen (HBO) therapy on the tissue structure, apoptosis, and metalloproteinases of kidney cells in Goto-Kakizaki (GK) rats with type 2 diabetes mellitus. GK rats (n = 24) were divided randomly and evenly into model, metformin hydrochloride (MH), and hyperbaric oxygen (HBO) groups, while healthy Wistar rats (n = 8) were used as normal control group. The healthy rats in the normal control group and the GK rats in the model group were both intragastrically administered with purified water (5 mL/kg) once per day. Meanwhile, the rats in the MH group received intragastric administration of MH (250 mg/kg) once daily, while the rats in the HBO group inhaled pure oxygen under a constant pressure (0.15 MPa) for 30 min. After 3 weeks of treatment, the body weight of each rat was measured, and the blood samples were collected from tails. Subsequently, the kidneys of all rats were excised for weighing mass and further examination. For each renal sample, the sections were firstly embedded with paraffin and sliced to prepare histopathologic sections stained using HE, PAS and Masson, respectively, for subsequent observation with optical microscopy. Later, the apoptosis of kidney cells was examined using the TUNEL method by computing the apoptotic index. Furthermore, the histopathologic sections were also examined using the immunohistochemistry approach with Caspase-3, MMP-2, and TIMP-2 antibodies, respectively. At the same time, the plasma concentration of TGF-β1 of the rats in each group was detected using ELISA method. These resultant data showed that the pathological changes of the HBO group were less than those of the model group with respect to increased glomerular volume density of mesangial cells, broadening mesangial matrix and thickening basement membrane as well as swelling renal tubular epithelial cells. The index of cell apoptosis and Caspase-3 expression in the HBO group showed no significant differences (P > 0.05) compared with those in the normal control and MH groups respectively, but demonstrated significant decrease compared with that in the model group (P < 0.01). Meanwhile, the MMP-2 and TIMP-2 expressions of the HBO group were stronger than those in the model and MH groups, but weaker than those in the normal control group (P < 0.05). Although the plasma concentration of TGF-β1 in HBO, MH and model groups was greater than that in the normal control group, no significant statistical difference was distinguished among these four groups (P > 0.05). These results indicate that the HBO treatment can inhibit the apoptosis and Caspase-3 expression of renal cells of GK rats, adjust the activity of MMP-2 and its inhibitors, and reduce the accumulation of extracellular matrix. This implies that the HBO treatment might protect renal tissues, thus delaying occurrence and retaining development of diabetic nephropathy.
Animals ; Apoptosis ; Caspase 3 ; metabolism ; Diabetes Mellitus, Experimental ; physiopathology ; Diabetes Mellitus, Type 2 ; physiopathology ; Diabetic Nephropathies ; therapy ; Hyperbaric Oxygenation ; Kidney ; cytology ; Matrix Metalloproteinase 2 ; metabolism ; Oxygen ; administration & dosage ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Transforming Growth Factor beta1

BACKGROUNDKnowledge about factors influencing the prognosis of resective epilepsy surgery can be used to identify which patients are most suitable for surgical treatment. The aim of this study was to identify preoperative prognostic factors associated with the chance of achieving long-term seizure freedom.

METHODSWe retrospectively reviewed seizure outcomes and clinical, electroencephalography (EEG), magnetic resonance imaging (MRI), histopathology, and surgical variables from 99 epilepsy surgery patients with at least one year of postoperative follow-up. Seizure outcomes were categorized based on the modified classification by the International League Against Epilepsy.

RESULTSWe found that the seizure-free rate was 27.9% after one year, and that it stabilized at about 20.0% between two and six years after surgery. Univariate analysis showed that medial temporal lobe epilepsy with hippocampal sclerosis, MRI with visible focal lesions concordant with EEG, and regional ictal EEG and electrocorticography patterns were associated with a favorable surgical outcome. On the other hand, seizure recurrence within six months, incomplete focus resection, and surgical complications were associated with a poor outcome. Multivariate analysis showed that medial temporal lobe epilepsy with hippocampal sclerosis and MRI with visible focal lesions were independent presurgical predictors of a favorable outcome (P < 0.01). Seizure recurrence within six months was the only significant independent predictor associated with a poor outcome (P < 0.01).

CONCLUSIONHippocampal sclerosis and abnormal MRI findings are strongly associated with a favorable surgical outcome, whereas seizure recurrence within six months is associated with a poor outcome.

Adolescent ; Adult ; Child ; Epilepsy ; surgery ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Chemical and Drug Induced Liver Injury ; Hair Dyes ; toxicity ; Humans ; Liver ; drug effects ; pathology ; Liver Diseases ; diagnosis ; drug therapy ; etiology ; Male ; Young Adult

Objective To investigate the effect of seafood intake on the urinary iodine level in women for exploring an alternative to iodine supplementation.Methods Healthy pregnant women and non-pregnant women, aged 20～40 years,were selected during their health examination in local women'S health care in 2006.The types of seafood and its intake frequency were recorded from these women.and urine and kitchen salt samples were collected for iodine determination.Results A total of 198 women including 148 pregnant and 50 non-pregnant women were recmitod for this study;they had a median level of urine iodine of 87.51 mg/L.The median levels of urine iodine of83.49,91.52,166.45μg/L in three group women classified as hardly,seldom and often intake of see food showed significant difference(X2=6.202,P<0.05).Urine iodine level in non-pregnant women taking seafood (90.94μg/L)was higher than that in pregnant women(84.79μg/L),the difference being statistically significant (U=3318.00,P<0.05).The urine iodine in pregnant women with seldom intake of seafood(94.46 μg/L)was significantly higher than that in the hardly intake women(83.28 μg/L),the difference being statistically significant (U=1257.5,P<0.05).During late period of gestation,the urinary iodine in the women ofthree statUS of hardly. Seldom and often intake of seafood were 81.93,97.97 and 140.18 μg/L,respective,with significant differences among them.Conclusions A certain amount of seafood taken every week Can increase urine iodine levels,and a direct relationship Was observed.Therefore,we suggest that it is necessary to advocate taking seafood to pregnant women for prevention of cretinism,particularly in the air.as where iodized salt was difficult to implement.

OBJECTIVETo develop a model of SHIV-KB9/Chinese origin rhesus (Ch Rh) macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus (Ind Rh) macaques.

METHODSSeven mamu-A*01 negative Ch Rh macaques were inoculated intravenously with 1-10000 MID50 of SHIV-KB9. The monkeys were monitored for viral load, CD4, CD8, SHIV-specific antibody and virus genetic variation. The results were compared with those previously observed in Ind Rh macaques.

RESULTSAs compared to that observed in Ind Rh macaques, SHIV-KB9 in Ch Rh macaques displayed three identical disease progression patterns. However, the primary pattern was not identical between the two subspecies. The level of plasma viremia differed in SHIV-KB9-infected Ch Rh macaques which exhibited different outcomes from those in Ind Rh macaques. Generally, the values of viral load and the maintenance of CD4+ T cells were associated with humoral responses. Otherwise, the viral genetic distances (divergence, diversity) were larger in animals (M419, M425) with their CD4+ T cells profoundly depleted.

CONCLUSIONThe model of SHIV-KB9/Ch Rh macaques displays a relatively slow progression to AIDS compared with Ind Rh macaques, which may more accurately reflect the potential of candidate vaccines in humans.

Animals ; CD4-CD8 Ratio ; China ; Disease Progression ; India ; Macaca mulatta ; Simian Acquired Immunodeficiency Syndrome ; pathology ; Species Specificity ; Viral Load

OBJECTIVETo observe the changes in the hemodynamics of rats with immunological liver fibrosis and explore the pathogenesis of "blood stasis" in liver fibrosis.

METHODSRat models of liver fibrosis were established by multiple intraperitoneal injections of pig serum. The hematocrit, blood viscosity at the shear rate of 150/s, 30/s, 5/s, and 1/s, serum markers for liver fibrosis, and serum transaminase levels were measured in the control and model rats.

RESULTSThe hematocrit, blood viscosity at different shear rates, hyaluronic acid (HA), laminin (LN), procollagen type III (PCIII), type IV collagen (CIV), glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST) increased significantly in the rats with experimental liver fibrosis appeared as compared with those in the control rats. Positive correlations were noted between blood viscosity at different shear rates and serum concentrations of the fibrosis markers (HA, LN, PCIII, and CIV) in the model rats.

CONCLUSIONThe changes in the hemodynamics in rats with immunological liver fibrosis suggests the role of "blood stasis" in the pathogenesis of liver fibrosis and provide experimental evidence for therapies to "activate the blood circulation and dissipate blood stasis" for treatment of liver fibrosis.

Animals ; Blood Viscosity ; Diagnosis, Differential ; Female ; Hemodynamics ; physiology ; Liver Cirrhosis, Experimental ; blood ; immunology ; Male ; Medicine, Chinese Traditional ; Random Allocation ; Rats ; Rats, Sprague-Dawley

As part of our ongoing influenza surveillance program in South China, 19 field strains of H9N2 subtype avian influenza viruses (AIVs) were isolated from dead or diseased chicken flocks in Guangdong province, South China, between 2012 and 2013. Hemagglutinin (HA) genes of these strains were sequenced and analyzed and phylogenic analysis showed that 12 of the 19 isolates belonged to the lineage h9.4.2.5, while the other seven belonged to h9.4.2.6. Specifically, we found that all of the viruses isolated in 2013 belonged to lineage h9.4.2.5. The lineage h9.4.2.5 viruses contained a PSRSSRdownward arrowGLF motif at HA cleavage site, while the lineage h9.4.2.6 viruses contained a PARSSRdownward arrowGLF at the same position. Most of the isolates in lineage h9.4.2.5 lost one potential glycosylation site at residues 200-202, and had an additional one at residues 295-297 in HA1. Notably, 19 isolates had an amino acid exchange (Q226L) in the receptor binding site, which indicated that the viruses had potential affinity of binding to human like receptor. The present study shows the importance of continuing surveillance of new H9N2 strains to better prepare for the next epidemic or pandemic outbreak of H9N2 AIV infections in chicken flocks.
Animals ; *Chickens ; China ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/*genetics/metabolism ; Influenza A Virus, H9N2 Subtype/*genetics/metabolism ; Influenza in Birds/virology ; Phylogeny ; Poultry Diseases/*virology ; Sequence Analysis, RNA/veterinary

OBJECTIVETo investigate in vivo inhibitory effect of histone deacetylase (HDAC) inhibitor valproic acid (VPA) on xenografted Kasumi-1 tumor in nude mice and its mechanism.

METHODSXenografted Kasumi-1 tumor mouse model was established by subcutaneous inoculation of Kasumi-1 cells. Xenotransplanted nude mice were assigned into control or VPA treatment groups. Volume of the xenografted tumors was measured and compared between the two groups. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) was applied to detection of tumor cell apoptosis. The gene expression of GM-CSF, HDAC1, Ac-H3 and survivin was studied with semi-quantitative RT-PCR and Western blotting. ChIP method was used to assay the effects of VPA on acetylation of histone H3 within GM-CSF promoter region.

RESULTS(1) VAP significantly inhibited xenografted Kasumi-1 tumor growth. The calculated inhibition rate was 57.25%. (2) Morphologic study showed that VPA induced differentiation and apoptosis of Kasumi-1 tumor cells. The apoptosis index of VAP treatment group [(3.661 +/- 0.768)%] was significantly higher than that of control group [(0.267 +/- 0.110)%]. (3) Comparing to those in control group, the level of nuclear HDAC1 protein was significantly decreased, the Ac-H3 protein expression level was increased, the mRNA and protein expression levels of GM-CSF and acetylation of histone H3 were remarkably increased, and the gene expression level of survivin significantly decreased in VPA treatment group.

CONCLUSIONVAP significantly inhibits xenografted Kasumi-1 tumor growth and induces tumor cell differentiation and apoptosis. The mechanism may be decrease of survivin gene expression, inhibition of nuclear expression of HDAC, promotion of histone protein acetylation level and acetylation of histone H3 within GM-CSF promoter region, and increase of GM-CSF transcription.

Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Mice ; Mice, Nude ; Valproic Acid ; pharmacology ; Xenograft Model Antitumor Assays