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Background:. Norepinephrine infusion decreases hypotension after spinal anesthesia during cesarean section. This study aimed to compare the efficacy of norepinephrine infusion and ephedrine bolus against post-spinal hypotension in parturients. Methods:. In this double-blinded, randomized controlled clinical trial, parturients scheduled for elective cesarean section were randomly allocated to receive norepinephrine infusion (0.05 μg·kg−1·min−1) just before spinal anesthesia continuing for 30 min or ephedrine bolus (0.15 mg/kg) just before spinal anesthesia. A rescue bolus (5 μg norepinephrine for the norepinephrine group, and 5 mg ephedrine for the ephedrine group) was administered whenever hypotension occurred. Our primary outcome was the incidence of hypotension within 30 min of spinal anesthesia administration. Secondary outcomes included maternal and neonatal outcomes 30 min after spinal block, and neonatal cerebral oxygenation 10 min after birth. Results:. In total, 190 patients were enrolled; of these patients, 177 were included in the final analysis. Fewer patients suffered hypotension in the norepinephrine group than in the ephedrine group (29.5% vs. 44.9%, odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.28–0.95, P = 0.034). Moreover, the tachycardia frequency was lower in the norepinephrine group than in the ephedrine group (OR: 0.22, 95% CI: 0.11–0.44, P

Background: Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lowergrade gliomas that carry IDH2 mutations. Methods: Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test. Results: Totally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively). Conclusions: IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation. Key words: Isocitrate dehydrogenase 1; Isocitrate dehydrogenase 2; Telomerase reverse transcriptase; Glioma; Oligodendroglioma

Background: Excessive reactive oxygen species (ROS) may lead to a number of reproductive diseases such as polycystic ovary syndrome. This study aimed to establish an animal model of ovarian oxidative stress and to assess the protective effect of curcumin against oxidative injury. Methods: Ovarian oxidative stress was induced in female Kunming mice (n = 40) with intraperitoneal injection of 8 mg/kg sodium arsenite (As) once every other day for 16 days; meanwhile, they were, respectively, treated by intragastric administration of 0, 100, 150, or 200 mg/kg (n = 10/group) curcumin once per day for 21 days. Ten normal mice were used as control. Then, the mice were injected intraperitoneally with BrdU and sacrificed; the right ovaries were collected for hematoxylin and eosin (HE) staining and BrdU immunohistochemistry, and the left ovaries for enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses. Results: The ELISA results showed that ROS (11.74 ± 0.65 IU/mg in 8 mg/kg AS + 0 mg/kg curcumin group vs. 10.71 ± 0.91 IU/mg in control group, P = 0.021) and malondialdehyde (MDA) (0.32 ± 0.02 nmol/g in 8 mg/kg AS + 0 mg/kg curcumin group vs. 0.27 ± 0.02 nmol/g in control group, P = 0.048) increased while superoxide dismutase (SOD) (3.96 ± 0.36 U/mg in 8 mg/kg AS + 0 mg/kg curcumin group vs. 4.51 ± 0.70 U/mg in control group, P = 0.012) and glutathione peroxidase (17.36 ± 1.63 U/g in 8 mg/kg AS + 0 mg/kg curcumin group vs. 18.92 ± 1.80 U/g in control group, P = 0.045) decreased in the ovary after injection of As, indicating successful modeling of oxidative stress. Curcumin treatment could considerably increase SOD (4.57 ± 0.68, 4.49 ± 0.27, and 4.56 ± 0.25 U/mg in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively, all P < 0.05) while significantly reduce ROS (10.64 ± 1.38, 10.73 ± 0.71, and 10.67 ± 1.38 IU/mg in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively, all P < 0.05) and MDA (0.28 ± 0.02, 0.25 ± 0.03, and 0.27 ± 0.04 nmol/g in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively; both P < 0.05) in the ovary. HE staining and BrdU immunohistochemistry of the ovarian tissues indicated the increased amount of atretic follicles (5.67 ± 0.81, 5.84 ± 0.98, and 5.72 ± 0.84 in 100 mg/kg, 150 mg/kg, and 200 mg/kg curcumin group, respectively, all P < 0.05), and the inhibited proliferation of granular cells under oxidative stress would be reversed by curcumin. Furthermore, the Western blotting of ovarian tissues showed that the p66Shc expression upregulated under oxidative stress would be lowered by curcumin. Conclusion: Curcumin could alleviate arsenic-induced ovarian oxidative injury to a certain extent.

Background: Inconsistencies in the use of the vasoactive agent therapy to treat shock are found in previous studies. A descriptive study was proposed to investigate current use of vasoactive agents for patients with shock in Chinese intensive care settings. Methods: A nationwide survey of physicians was conducted from August 17 to December 30, 2012. Physicians were asked to complete a questionnaire which focused on the selection of vasoactive agents, management in the use of vasopressor/inotropic therapy, monitoring protocols when using these agents, and demographic characteristics. Results: The response rate was 65.1% with physicians returning 586 valid questionnaires. Norepinephrine was the first choice of a vasopressor used to treat septic shock by 70.8% of respondents; 73.4% of respondents favored dopamine for hypovolemic shock; and 68.3% of respondents preferred dopamine for cardiogenic shock. Dobutamine was selected by 84.1%, 64.5%, and 60.6% of respondents for septic, hypovolemic, and cardiogenic shock, respectively. Vasodilator agents were prescribed by physicians in the management of cardiogenic shock (67.1%) rather than for septic (32.3%) and hypovolemic shock (6.5%). A significant number of physicians working in teaching hospitals were using vasoactive agents in an appropriate manner when compared to physicians in nonteaching hospitals. Conclusions: Vasoactive agent use for treatment of shock is inconsistent according to self-report by Chinese intensive care physicians; however, the variation in use depends upon the form of shock being treated and the type of hospital; thus, corresponding educational programs about vasoactive agent use for shock management should be considered.

Although some studies have reported that aquaporin-4 (AQP4) plays an important role in the brain edema after traumatic brain injury (TBI), little is known about the AQP4 expression in the early stage of TBI, or about the correlation between the structural damage to the blood-brain barrier (BBB) and angioedema. The aim of this project was to investigate the relationship between AQP4 expression and damage to the BBB at early stages of TBI.One hundred and twenty healthy adult Wistar rats were randomly divided into two groups: sham operation group (SO) and TBI group. The TBI group was divided into five sub-groups according to the different time intervals: 1, 3, 6, 12, and 24 hours. The brains of the animals were taken out at different time points after TBI to measure brain water content. The cerebral edema and BBB changes in structure were examined with an optical microscopy (OM) and transmission electron microscopy (TEM), and the IgG content and AQP4 protein expression in traumatic brain tissue were determined by means of immunohistochemistry and Western blotting. The data were analyzed with SPSS 13.0 statistical software.In the SO group, tissue was negative for IgG, and there were no abnormalities in brain water content or AQP4 expression. In the TBI group, brain water content significantly increased at 6 hours and peaked at 24 hours following injury. IgG expression significantly increased from 1 to 6 hours following injury, and remained at a high level at 24 hours. Pathological observation revealed BBB damage at 1 hour following injury. Angioedema appeared at 1 hour, was gradually aggravated, and became obvious at 6 hours. Intracellular edema occurred at 3 hours, with the presence of large glial cell bodies and mitochondrial swelling. These phenomena were aggravated with time and became obvious at 12 hours. In addition, microglial proliferation was visible at 24 hours. AQP4 protein expression were reduced at 1 hour, lowest at 6 hours, and began to increase at 12 hours, showing a V-shaped curve.The angioedema characterized by BBB damage was the primary type of early traumatic brain edema. It was followed by mixed cerebral edema that consisted of angioedema and cellular edema and was aggravated with time. AQP4 expression was down-regulated during the angioedema attack, but AQP4 expression was upregulated during intracellular edema.

The cytosine arabinoside (Ara-C)-based chemotherapy is the major remedial measure for acute myeloid leukemia (AML). Deoxycytidine kinase (DCK) and cytidine deaminase (CDA) are the key enzymes in the metabolism of Ara-C. Many single nucleotide polymorphisms (SNPs) and haplotypes of DCK and CDA, which contribute to susceptibility to Ara-C, have been identified in Africans and Europeans. However, there has been no report about the relation among three SNPs in DCK (rs115543896, rs72552079, and rs111454937) and two SNPs in CDA (rs2072671 and rs60369023), and their clinical response to Ara-C for a Chinese population. In this study, we aimed to investigate whether these five SNPs are associated with the therapeutic outcomes of Ara-C-based chemotherapy regimens in patients with AML.A total of 151 Chinese patients with AML were enrolled in our study. SNPs genotyping were performed using the MassARRAY system by means of the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) method.The results illustrated that DCKrs111454937 AA genotype was more frequent in patients with higher platelet count, and A allele frequency was significantly higher in the group £40 years, lower white blood cell (WBC) count patients group and the group with platelet counts60'10(9)/L. Meanwhile, both DCKrs72552079 TC (OR = 1.225, 95%CI = 1.225 - 9.851, P = 0.0192) and CDArs60369023 GA (OR = 9.851, 95%CI = 1.31 - 77.93, P = 0.0263) significantly improved Ara-C-based chemotherapy response. While DCKrs11554389 AA (OR = 0.147, 95%CI = 0.027 - 0.801, P = 0.0267) was associated with the decrease of Ara-C-based chemotherapy response.It is evident that the DCK and CDA polymorphisms might be the important markers for the AML patients' therapy outcomes in a Chinese population.

Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population.Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment.The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c2=3.96, P=0.0465).These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.

Aspirin and clopidogrel resistance plays a significant role in the development of cardiovascular ischemic events for ninety patients undergoing percutaneous coronary intervention. Recent studies have indicated that increasing the dose of antiplatelet drugs maybe a potent method to improve the inhibition of platelet aggregation.Thrombelastograph (TEG) determinations were used to evaluate the effect of antiplatelet therapy. According to the results, 90 patients were divided into three groups and given different doses of aspirin and clopidogrel. Thirty patients with both an inhibition rate of aspirin50% and an inhibition rate of clopidogrel50% were defined as the control group. Sixty patients with an inhibition rate for aspirin50% and an inhibition rate for clopidogrel50% were defined as the resistance group. Patients in resistance group were randomly assigned to be given a routine dose (100 mg aspirin plus 75 mg clopidogrel per day, which we called a resistance plus routine dose group, R + R) and a loading dose (200 mg aspirin and 150 mg clopidogrel per day, which we called resistance plus loading dose group, R + L) of antiplatelet therapy. A 12-month follow-up was observed to examine the change of inhibition rate of antiplatelet therapy and to estimate the relationship between inhibition rate and the occurrence of cardiovascular ischemic events.After 6 months of antiplatelet therapy, the inhibition rate of aspirin in the R + L group increased from (31.4 ± 3.7)% to (68.6 ± 7.1)%, which was significantly higher than that in R + R group, (51.9 ± 8.2)% (P0.01). The inhibition rate of clopidogrel in the R + L group increased from (22.1 ± 3.8)% to (60.2 ± 7.4)%, which was significantly higher than in the R + R group, (45.9 ± 4.3)% (P0.01). The occurrence rates of cardiovascular ischemic events, stent thrombosis, recurrent unstable angina and myocardial infarction in the R + R group were 20%, 36% and 17%, respectively. Occurrence was significantly increased compared with that in the control group, 3%, 10% and 1%, respectively (P0.01). In contrast, the occurrence rates in the R + L group (10%, 23% and 6%, respectively) were attenuated compared with those in the R + R group (P0.01), although still higher than in the control group (P0.01).Almost all of the cardiovascular ischemic events occurred in the first six months after percutaneous coronary intervention. According to the result of TEG determinations, earlier application of a loading dose of aspirin and clopidogrel can decrease the rate of recurrent cardiovascular ischemic events.

Platinum-based chemotherapeutics are the most common regimens for advanced non-small-cell lung cancer (NSCLC) patients, and genetic factors are thought to represent important determinants of drug efficacy. We prospectively assessed the status of the XPC Ala499Val and Lys939Gln gene polymorphisms and investigated whether these SNPs can predict the response to cisplatin/carboplatin-based regimens in advanced NSCLC patients in a Chinese population.The treatment outcomes of 96 advanced NSCLC patients who were treated with platinum-based chemotherapy were evaluated. The polymorphic status of xeroderma pigmentosum group C (XPC) gene was genotyped by the 3-D polyacrylamide gel-based DNA microarray method.The distributions of XPC Lys939Gln genotypes differed significantly between the response group (complete + partial responses) and the non-response group (stable + progressive disease; P = 0.022). The heterozygous A/C genotype carriers had a poorer response rate than the wild A/A genotype carriers in stage III (OR, 0.074; 95%CI, 0.008 - 0.704; P = 0.023). The XPC Ala499Val polymorphisms were not associated with response to platinum-based chemotherapy.Polymorphisms of the XPC gene, Lys939Gln, may be a predictive marker of treatment response for advanced NSCLC patients in stage III.

Although some studies have reported that aquaporin-4 (AQP4) plays a role in the post-ischemic edema formation and diffusion-weighted imaging (DWI), little is known about the AQP4 expression in stage of the reperfusion following acute cerebral ischemia, as well as the correlation between histopathology and DWI. The aim of the study was to investigate the correlation among DWI, histopathology and the AQP4 expression in the reperfused rat brain tissues following acute ischemia.Seventy Wistar rats were randomly divided into a control group (group A), and several occluded and reperfusion groups. They had their middle cerebral artery unilaterally occluded (MCAO) for 30 minutes (group B) followed by 30 minutes (group D) or 60 minutes (group E) of reperfusion, or 60 minutes of MCAO (group C) followed by 30 minutes (group F), or 60 minutes (group G) of reperfusion (n = 10 for each group). All rats underwent DWI scanning. The relative apparent diffusion coefficient (rADC) value of each rat was calculated. All the rats were sacrificed and the cerebral ischemic tissues were examined for histopathology. Real-time fluro-quantitative polymerase chain reaction (RT-PCR) and Western-blotting were performed. The amount of AQP4 mRNA (Ex(-ΔΔCt)) and AQP4 protein (Q) was statistically analyzed. The correlation between rADC values and AQP4 mRNA expression was analyzed with the Pearson correlation test.In all the reperfusion groups, the areas of hyper-intensity signal in DWI were decreased, and the rADC value increased and the AQP4 expression decreased significantly compared with the occluded group (t = 26.89, t = 18.26, P0.01). There was a negative correlation between AQP4 mRNA expression and rADC values (r = -0.72, P0.01). A mixed edema, composed of cerebral intracelluar edema and vasogenic brain edema, was observed in all the reperfusion groups. It was more prevalent in groups D and F than in the groups E and G. With the reperfusion time postponed, the cerebral intracelluar edema of the rat was significantly mitigated, but the vasogenic brain edema was not significantly changed.There is a close correlation between AQP4 expression and the cerebral intracellular edema. The change of ADC values may indirectly reflect the level of the AQP4 expression. DWI may become a promising, noninvasive imaging modality to predict early stroke and reperfusion injury.

Intractable secondary glaucoma with severe ocular contusion involving the posterior segment is difficult to treat. In this study, we evaluated the safety and efficacy of combined trabeculectomy and vitrectomy for intractable glaucoma with severe ocular contusion involving the posterior segment.This retrospective interventional study enrolled 18 eyes from 18 consecutive cases with uncontrolled intraocular pressure, angle recession exceeding 180°, dense vitreous hemorrhage, and/or limited retinal detachment after severe ocular contusion. Combined trabeculectomy and vitrectomy was performed after giving the patient sufficient anti-inflammatory and intraocular pressure (IOP)-lowering medication. Follow-up averaged 26.2 (range, 6.0- 48.0) months.The mean IOP decreased from (36.4 ± 10.0) mmHg on maximum IOP-lowering medications to (14.6 ± 4.4) mmHg on (0.7 ± 1.2) topical medications at the final follow-up (P0.0001). During the first postoperative month, four eyes (22%) had a short hypertensive phase and six eyes (33%) had early hypotony, including one case (5.6%) of bleb leakage. Seven eyes (39%) developed recurrent hypertension 3- 6 months postoperatively, five of which were controlled by topical medications. Ten (55.6%) eyes were classified as a complete success, five (27.8%) as a qualified success, and three eyes (16.7%) as failures. Kaplan-Meier survival analysis for complete and cumulative success showed 53.5% and 80.0% survival at 48 months, respectively. Visual acuity was improved in 15 eyes (83.3%). Three eyes (16.7%) had unchanged visual acuity, one (5.6%) of which developed atrophia bulbi despite a normal intraocular pressure. No recurrent retinal detachment or vitreous hemorrhage developed.Combined trabeculectomy and vitrectomy is a viable surgical procedure for the management of intractable glaucoma with severe ocular contusion involving the posterior segment in selected cases.

As an uncommon presentation, occult primary breast cancer remains a diagnostic and therapeutic challenge in clinical practice. This study aimed to retrospectively assess the feasibility of breast magnetic resonance imaging (MRI) in patients with malignant axillary lymphadenopathy and unknown primary malignancy, and correlation with histopathological characteristics.A total of 35 women with occult breast carcinoma were evaluated with dynamic contrast-enhanced breast MRI. Whole seriate section was used in all cases. MRI performance was assessed and correlated with histopathological findings.Twenty-one of 35 patients were found to have primary breast carcinoma histologically. Twenty of the 21 patients had abnormal MR findings and 1 patient had a normal MRI study. Of the remaining 14 patients, 10 were negative on both MRI and surgery. Four had suspicious enhancement on MRI and no corresponding tumor was found. Lesions with mass enhancement were found in 55% (11/20) and ductual and segmental enhancement in 45%. The average diameter of the primary tumors was 15 mm. Invasive ductal carcinomas were found in 81% (17/21). One of 17 invasive ductual carcinomas was too small to be graded. Fourteen of the remaining 16 were classified as grade II and 2 as grade I. Thirty-two of the 35 patients had received estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 examinations and the 12 of 32 were triple-negative breast carcinoma.Mass lesions with small size and lesions with ductal or segment enhancement are common MRI features in patients with occult breast cancer. The dominant types of primary tumors are invasive ductal carcinoma with moderate histopathological grade. The rate of triple-negative breast carcinoma may be higher in occult breast cancer.

Background The baseline characteristics of patients in a multinational trial are possibly related to cardiovascular outcome. This study compared the baseline characteristics of patients recruited in China with those recruited in other countries. Methods A total of 508 Chinese hypertensive men and 728 women over the age of 80 years who entered the Hypertension in the Very Elderly Trial (HYVET) were compared with those in 860 men and 1348 women who entered the trial in other countries. Results The Chinese subjects were slightly younger, had less previous hypertension but more previous strokes than the subjects from other countries. The Chinese subjects smoked more than those from other countries, but drank less alcohol. They had less previous episodes of myocardial infarction and were, on average, lighter and shorter. The Chinese had lower mean concentrations of blood urea, uric acid and creatinine as well as higher concentrations of high density lipoprotein (HDL) cholesterol. The concentration of total cholesterol was, on average, lower in the Chinese subjects as was blood glucose. The levels of serum sodium and potassium, blood hematocrit and hemoglobin were all, on average, lower in the Chinese subjects. Conclusions Calorie restriction, compared with the rest of the world, may have resulted in lower stature and weight, and recent increases in calorie intake have not changed the metabolic profile of the very elderly hypertensive patients in China. Some of these biochemical differences may reflect different dietary lifestyle in the Chinese. Chin Med J 2008;121(16):1509-1512

BACKGROUND Aberrant DNA methylation plays a key role in human carcinogenesis. 5-aza-2'-deoxycytidine inhibits DNA methylation and induces the expression of genes putatively silenced by promoter methylation in vitro. There are few studies of the biological and clinical significance of 5-aza-2'-deoxycytidine in human hepatocellular carcinoma. This study explored the mechanism of 5-aza-2'-deoxycytidine targeting transcriptional repressor complexes affecting global gene expression in hepatocellular carcinoma cell line. METHODS High density oligonucleotide gene expression microarrays were used to examine the effects of 5-aza-2'-deoxycytidine treatments on human hepatocellular carcinoma cell line SMMC-7721. The 5' ends of the genes upregulated or downregulated in this manner were compared with BLAST database to determine whether they might have promoter CpG islands. Flow cytometry was used to detect stages of the cell cycle and apoptosis of SMMC-7721 after being treated with 5-aza-2'-deoxycytidine. RESULTS Data obtained 3 days after 4 days of treatment with 5-aza-2'-deoxycytidine showed that more genes were induced in tumorigenic cells including genes that function in cell proliferation, differentiation, regulation of transcription, and cytokine signalling. Approximately 30% of induced genes did not have CpG islands within their 5' regions, suggesting that some genes activated by 5-aza-2'-deoxycytidine may not result from the direct inhibition of promoter methylation. This phenomenon may contribute to a number of upregulated genes involving regulation of transcription in the treated cell. Results showed that 100 micromol/L 5-aza-2'-deoxycytidine blocked cell cycle at S/G2-M phase increasing rate of apoptosis. Notably, we found differential expression of molecular action in the methylation although DNA methyltransferases did not show significant difference in the treated cell line. CONCLUSION 5-aza-2'-deoxycytidine could restore some silenced genes expression independently of DNA methylation inhibition and expression of DNA methyltransferases.

To investigate the rule of the aquaporin-4 (AQP4) expression in acute ischemic brain edema, and to study the correlation between AQP4 expression and diffusion-weighted imaging (DWI).Thirty-six Wistar rats were divided into 2 groups randomly, control group (n = 12) and operation group (n = 24) in which right middle cerebral artery of each animal had been occluded unilaterally (MCAO) at interval times of: 15 minutes, 30 minutes, 1 hours, 3 hours, 6 hours and 24 hours, respectively. The operation process of the control group was the same as the operation group except for the MCAO. All groups were examined using DWI. The apparent diffusion coefficient (ADC), relative density (rd) and relative area (rs) of the biggest hyperintensity signal layer on DWI were measured. After that the animals were sacrificed and perfused with the mixture solution consisting of TTC. The biggest layers of the ischemic cerebral tissues in each rat corresponding to the DWI were stained with TTC and examined with immunochemistry (DeltaS), in situ hybridization (alpha) and histology.There was no significant change in the control group. In the operation group, a hyperintensity signal was found in the DWI of the right MAC territory at 15 minutes after MCAO. The ADC value decreased quickly within one hour after MCAO, while the AQP4 expression, rd-DWI and rs-DWI increased rapidly during this stage. As time progressed, the ADC value decreased further to (2.1 +/- 0.6) x 10(-4) mm(2)/s at 3 hours, and then began to increase slowly till 24 hours. But the AQP4 expression (DeltaS and alpha) and rd as well as the rs continuously increased slowly between 1 hour and 6 hours after MCAO, followed a peak after 6 hours. The AQP4 expression (alpha) showed a positive relationship with the rs-DWI, they all presented two peaks and a plateau. The corresponding sequential pathologic changes were a gradual increase of intracellular edema (within one hour), then an emergence of vasogenic edema (1-6 hours), and final necrosis and liquefaction (6 - 24 hours).Upregulated expression of AQP4 may play a significant role in acute ischemic brain edema, especially during the stages of intracellular edema and necrosis, but it has no correlation to vasogenic edema. Certainly, the high expression of AQP4 is perhaps one of the most important reasons of the decrease of ADC and hyperintensity on the DWI in the intracellular edema.