Analysis of treatment methods and prognostic factors in 354 cases of hilar cholangiocarcinoma: A cohort study

Context: Better management strategies are needed to improve the survival of patients with hilar cholangiocarcinoma (HCCA). Aims: This study was designed to examine the effects of different treatment methods on survival and prognostic factors in HCCA. Settings and Design: We retrospectively analyzed the clinical data of 354 patients with HCCA treated at our institution from 2003 to 2013. Materials and Methods: Patients were divided into three groups according to the treatment: the radical resection group, the nonradical resection group, and the biliary drainage-only group. Statistical Analysis Used: The Kaplan–Meier method was used to compare survival rates between the groups, and the independent prognostic factors were assessed using the Cox proportional hazards model. Results: There were 110 patients in the radical resection group, 93 patients in the nonradical resection group, and 151 patients in the biliary drainage-only group, and they showed differing survival rates: 1-year survival rates of 70.7%, 49.5%, and 31.3%; 2-year survival rates of 62.9%, 24.7%, and 9.0%; 3-year survival rates of 34.7%, 4.0%, and 0%; and median survival of 21.7 months, 13.6 months, and 8.7 months, respectively. The radical resection group had the longest overall survival (P< 0.001). Treatment method, albumin (ALB), total bilirubin (TBIL), postoperative pathological T-stage, and distant metastasis were identified as independent prognostic indicators of survival. Conclusions: Radical resection significantly increases survival in patients with HCCA, and an increase in ALB and a decrease in TBIL improve the prognosis of patients with HCCA

The application of left anterior minimally invasive thoracotomy to surgical repair of subarterial ventricular septal defect in children / 中国胸心血管外科临床杂志

@#Objective    To summarize the application and clinical effect of left anterior minimally invasive thoracotomy to surgical repair of subarterial ventricular septal defect (VSD) in children. Methods    From October 2015 to April 2019, 21 children with subarterial VSD underwent surgical repair via left anterior minimally invasive thoracotomy. There were 13 males and 8 females, aged 5-13 (9.1±2.2) years, and weighing 22-55 (35.6±9.5) kg. The diameter of subarterial VSD was 4-15 (9.1±3.3) mm. Eight patients had right coronary valve prolapse, and 4 aortic valve regurgitation (3 mild and 1 mild-to-moderate). The minimally invasive surgery was performed via left parasternal thoracotomy through the second or third intercostal space. The peripheral perfusion was performed with femoral arterial and venous cannulation. After aortic cross-clamp (ACC), subarterial VSD was performed with direct suture of patch closure through an incision on the root of pulmonary artery. Results    All patients successfully underwent surgical repair (patch closure, n=15; direct suture, n=6) of subarterial VSD through left anterior minimally invasive thoracotomy. The cardiopulmonary bypass time was 45-68 (57.1±6.3) min. The ACC time was 23-40 (32.6±4.7) min. The postoperative ventilation time was 5-9 (6.3±1.3) h, postoperative in-hospital time was 5-8 (5.7±1.0) d and drainage volume was 33-105 (57.5±17.7) mL in postoperative 24 h. No death, residual VSD shunt, atrioventricular block, wound infection or thoracic deformity occurred during the perioperation or follow-up. Only one patient still had trivial aortic valve regurgitation. Conclusion    Left anterior minimally invasive thoracotomy could be safely and effectively applied to surgical repair of subarterial VSD in children, with satisfactory early- and mid-term outcomes.

Crebanine N-oxide, a natural aporphine alkaloid isolated from Stephania hainanensis, induces apoptosis and autophagy in human gastric cancer SGC-7901 cells

Objective: To investigate the cytotoxic effects and the potential mechanisms of crebanine N-oxide in SGC-7901 gastric adenocarcinoma cells. Methods: The cytotoxicity of crebanine N-oxide was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and cellular morphology was observed under a microscope. Cell apoptosis was determined by flow cytometry using propidium iodide staining. The expression levels of apoptotic-related proteins, cleaved caspase-3, cytochrome C, p53 and Bax, and autophagyrelated proteins p62, beclin1 and LC3 were detected by Western blotting assays. Results: Crebanine N-oxide treatment significantly inhibited the proliferation of SGC-7901 cells in a dose-dependent and timedependent manner via induction of G2-phase cell cycle arrest, apoptosis, and autophagy in SGC-7901 cells. Conclusions: Crebanine N-oxide could inhibit the growth of gastric cancer cells by promoting apoptosis and autophagy and could be used as a potential agent for treating gastric cancer.

Influencing factors of the purchase of supplementary insurance for adverse events following immunization by parents in Changsha / 预防医学

Objective@#To learn the status and influencing factors of the purchase of supplementary insurance for adverse events following immunization ( AEFI ) by parents in Changsha, so as to provide basis for the development of compensatory strategies.@*Methods@#Stratified random sampling method was used to select the parents who lived in Changsha for more than six months and had children under seven years old as subjects. A questionnaire survey was conducted to collect the information about demographic features, awareness of AEFI and the purchase of supplementary insurance. Logistic regression model was used to analyze the influencing factors for purchasing supplementary insurance. @*Results@#Among 712 respondents ( response rate, 94.93% ) , 354 ( 49.72% ) purchased supplementary insurance. The results of multivariate logistic regression analysis showed that the parents aged 36-71 years ( OR=0.325, 95%CI: 0.144-0.732 ) were less likely to purchase supplementary insurance; the parents who were aware of supplementary insurance ( OR=3.622, 95%CI: 2.218-5.913 ) and compensation range ( OR=1.332, 95%CI: 1.164-1.524 ) , and who scored higher in the knowledge and attitude of AEFI ( OR=1.137, 95%CI: 1.049-1.231 ) were more likely to purchase supplementary insurance.@*Conclusion @#About 49.72% of the parents purchased of supplementary insurance. Age, awareness of supplementary insurance and compensation range,as well as knowledge and attitude of AEFI were associated with the purchase of supplementary insurance.

Effects of selectively resecting the lower half of stellate ganglion on fast ventricular rate in canines with persistent atrial fibrillation / 中国胸心血管外科临床杂志

@#Objective To determine the effects of resecting the lower half of left stellate ganglion (LSG) on fast ventricular rate (VR) in persistent atrial fibrillation (AF) and its mechanism. Methods Twelve mature healthy male beagle dogs (15–25 kg) were studied. They were randomly divided into two groups (an experimental group and a control group, 6 dogs in each group). The control group were merely performed with rapid left atrial pacing to induce persistent AF. The experimental group were disposed with rapid left atrial pacing and received resection of the lower half of LSG after the persistent AF was documented. Simultaneously the ventricular rates were monitored separately before anesthesia, after anesthesia, 30 minutes and one month after LSG resection. The forward passing effective refractory period (ERP) of the canine atrioventricular node (AVN) was also measured. Results Each dog was documented with persistent AF after 3–6 weeks’ left atrial pacing. After resecting the lower half of LSG for 30 minutes (the control group was only observed for 30 minutes without LSG resection), the average VR of the control group attained 144.5±4.2 beats/min, while that of the experimental group was 121.5±8.7 beats/min (P<0.001). After resecting the lower half of LSG for one month (the control group was observed for one month without LSG resection), the average VR of the control group was 139.2±5.6 beats/min, while that of the experimental group was 106.5±4.9 beats/min (P<0.001). Meantime, the forward passing ERP of AVN of the experimental group was significantly prolonged than that of the control group (265.6±7.8 msvs.251.1±4.6 ms, P=0.003). Conclusion Resection of the lower half of LSG is efficient in reducing VR in canines with persistent AF, one of the mechanisms of which may be prolonging the forward passing ERP of AVN.

Expression and clinical significance of proline-rich tyrosine kinase 2 and phospho-protein kinase B in tongue squamous cell carcinoma / 华西口腔医学杂志

OBJECTIVE@#This study aimed to investigate the expression and clinical significance of proline-rich tyrosine kinase 2 (Pyk2) and phospho-protein kinase B (p-AKT) in tongue squamous cell carcinoma (TSCC) and adjacent nontumor tissues.@*METHODS@#The Pyk2 and p-AKT protein levels were detected via immunohistochemistry in 45 cases of TSCC tissues and 30 cases of adjacent nontumor tissues. The relationships of the two protein levels and clinicopathological characteristics were also analyzed.@*RESULTS@#Pyk2 and p-AKT levels were significantly higher in the TSCC tissues than in the adjacent nontumor tissues (P<0.05). Nontumor tissues showed poor or no expression. The expression levels of the two proteins were positively correlated (γs=0.412). The expression of Pyk2 was associated with histopathological differentiation type, regional lymph node metastasis, and TNM staging (P<0.05), but not with age and gender. The expression of p-AKT was only related to histopathological differentiation types (P<0.05).@*CONCLUSIONS@#The abnormal expression of Pyk2 and p-AKT proteins might be closely related to the development and progression of TSCC. Joint detection can be used as an indicator to estimate the degree of TSCC.

Minimally invasive surgery through right lateral thoracotomy for atrial septal defect combined with atrial fibrillation in adults / 中国胸心血管外科临床杂志

@#Objective     To explore the technique of performing minimally invasive Cox Maze Ⅳ procedure by bipolar clamp through right lateral minithoracotomy for atrial septal defect (ASD) combined with atrial fibrillation (AF) in adults. Methods     Thirty-five patients (21 males, 14 females with age ranging from 45 to 73 years) with ASD and persistent or long-standing persistent AF received minimally invasive Cox Maze Ⅳ procedure and ASD closure from August 2012 to April 2016 at Department of Cardiothoracic Surgery, Xinhua Hospital. Diameter of left atrium ranged from 39 to 60 mm and left ventricle ejection fraction (LVEF) ranged from 48% to 62%. Diameter of ASD ranged from 20 to 35 mm. Cox-maze Ⅳ procedure was performed through right minithoracotomy entirely by bipolar radiofrequency clamp. Then, mitral or tricuspid valvuloplasty and surgical ASD closure was performed through right minithoracotomy.   Results     All patients successfully underwent this minimally invasive surgery. No patient needed conversion to sternotomy. The mean cardiopulmonary bypass time was 120.1±14.1 min. The mean aortic cross-clamp time was 79.5±12.2 min. There was no early death or pacemaker implantation perioperatively. The average length of hospital stay was 10.1±2.7 d. At a mean follow-up of 22.8±12.2 months, sinus rhythm was restored in 32 patients (32/35, 91.4%). Cumulative maintenance of normal sinus rhythm without AF recurrence at 2 years postoperatively was 89.1%±6.0%. Conclusion     The minimally invasive Cox Maze Ⅳprocedure performed by bipolar clamp through right minithoracotomy is safe, feasible, and effective for adult patients with ASD combined with AF.

Progressive volume deflation followed by rate reduction in weaning intra-aortic balloon pump / 中国胸心血管外科临床杂志

@#Objective    To investigate the changes of hemodynamics in patients weaning intra-aortic balloon pump (IABP) by using progressive volume deflation followed by rate reduction. Methods    We retrospectively analyzed the clinical data of 36 patients aged 68.9±4.7 years, 22 males and 14 females, who underwent progressive volume deflation followed by rate reduction for IABP weaning in Xinhua Hospital between September 2006 and January 2016. Progressive volume deflation followed by rate reduction was used to wean IABP and collect hemodynamics parameters of each time point. Results    All the patients successfully weaned IABP. One patient got re-IABP assistant 36 hours after the first successful weaning. One early death and three patients (8%) with postoperative IABP-related complications were embolization of the toe artery. One was in ipsilateral limb, and two of contralateral limb. One patient with acute hepatic insufficiency and one patient with acute renal insufficiency cured after treatment. Conclusion    Intra-aortic balloon pump weaning is successful by using volume deflation followed by rate reduction which allowed better hemodynamic parameters.

Construction of recombinant plasmids Egr1-XPO4 and its synergic inhibition with 5-FU against hepatocarcinoma SK-Hep1 cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To construct recombinant plasmid Egr1-XPO4 and evaluate its synergic inhibition with 5-FU against hepatocarcinoma SK-Hep1 cells. Methods: The XPO4 gene was inserted into vector carrying promoter Egr1 to construct a new recombinant vector, Egr1-XPO4, which was then transfected into human hepatocarcinoma cell line SK-Hep1 and sensitized with chemotherapeutic drug 5-FU. Western blotting was adopted to examine the protein expression of XPO4; CCK assay was used to detect SK-Hep1 cell proliferation after transfection, and Flow Cytometry with Annexin V-FITC/PI staining was used to detect the apoptosis of SK-Hep1 cells. SKHep1 cell xenograft model was constructed on nude mice, and the effect of Egr1-XPO4 in combination with 5-FU on the growth of xenograft was observed. Results: The recombinant plasmid Egr1-XPO4 was successfully constructed.With the sensitization of 5-FU, the expression of XPO4 protein in SK-Hep1 cells was significantly elevated after Egr1-XPO4 transfection, and the evlevation was in a 5FU dose-depend manner.The combined treatment of Egr1-XPO4 and 5-FU produced a significantly stronger inhibition against SKHep1 cell proliferation and greatly promoted apoptosis of SK-Hep1cells compared with 5-FU or pEgr-XPO4 mono-treatment group (all P<0.05). And in vivo antitumor experiment showed that the tumor volume in Egr1-XPO4+5-FU treatment group was significantly smaller than that of Egr1-XPO4 or 5-FU mono-treatment group (P<0.05). Conclusion: The recombinant plasmid Egr1-XPO4 in combination with 5-FU could exertsynergic inhibitionagainst hepatocarcinomaSK-Hep1 cells.

Expression of autophagy-related proteins PTEN and MAP1LC3 in tongue squamous cell carcinoma / 口腔疾病防治

Objective @#This study ai ms to evaluate the expression of autophagy-related protein cancer phosphatase and tensinhomology deleted on chromosome ten (PTEN) and microtubule-associated protein 1 light chain 3 (MAP1LC3) and investigate its significance in tongue squamous cell carcin oma (TSCC). @*Methods @#About 46 TSCC samples, 13 cases of precancerous lesion and 13 cases of adjacent tissues were enrolled. Immunohistochemistry were performed to examine the expression of PTEN, MAP1LC3. Statistical analyses were carried out to assess the associations among clinic pathologic parameters. @*Results @# The positive expression rate of PTEN (34.78%) in TSCC was significantly lower than that in adjacent tissues (69.23%, χ2 = 4.926, P = 0.026) and precancerous lesions (76.92%, χ2 = 7.302, P = 0.007). The positive expression rate of MAP1LC3 (28.26%) in TSCC was significantly lower than that of adjacent tissues (61.53%, χ2 = 4.896, P = 0.027) and precancerous lesions (69.23%, χ2 = 7.275, P = 0.007), the difference was statistically significant. The expression of PTEN and MAP1LC3 was not correlated with age, sex, smoking, alcohol consumption and cell differentiation (P > 0.05). There was a significant difference in the expression of PTEN and MAP1LC3 in subgroup with different clinical stage and in subgroup with or without lymph node metastasis (P < 0.05). There is a significant difference in the tumor recurrence between PTEN protein expression positive subgroup and PTEN protein expression negative subgroup (χ2 = 4.629,P = 0.039), and there was no significant difference in the tumor recurrence between MAP1LC3 protein expression positive subgroup and MAP1LC3 protein expression negative subgroup (χ2 = 0.343,P = 0.453). There was a positive correlation between PTEN and MAP1LC3. @*Conclusion@#The expression of PTEN and MAP1LC3 suggested that autophagy associated proteins play a pivotal role in the progression, diagnosis and prognosis of TSCC. Down-regulation of PTEN and MAP1LC3 was observed in TSCC.

Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice

ABSTRACT PURPOSE: To investigate the hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mice. METHODS: Fifteen nude mice were grafted subcutaneously in the left flank with MDA-MB-231 cells, then all mice were divided into control group (PBS), 3BP group (8 mg/kg), positive group (DNR: 0.8 mg/kg) when tumor volume reached approximately 100 mm3. 28 days later, tumors, livers and kidneys were stored in 4 % formalin solution and stained with hematoxylin and eosin staining. The Kunming mice experiment included control group (PBS), 3BP group (4mg/kg; 8mg/kg; 16mg/kg), positive group (DNR: 0.8 mg/kg). 24 hours later, the blood were used for the determination of hepatic damage serum biomarkers. Livers were stored in 4 % formalin solution for the later detection. RESULTS: 3BP at the dose of 8mg/kg had a good effect on inhibiting tumor growth in nude mice and did not damage liver and kidney tissues. Kunming mice experiment showed 3BP at the dose of 16mg/kg did damage to liver tissues. CONCLUSION: 3-Bromopyruvate at the dose of suppressing tumor growth did not exhibit hepatotoxicity and nephrotoxicity in nude mice, and the effect on liver was confirmed in Kunming mice.

The intervention research on treatment by Xianchen to rabbits model of chemotherapeutic phlebitis

ABSTRACT PURPOSE: To develop a chemotherapeutics induced phlebitis and explore the effects of Xianchen on the phlebitis treatment. METHODS: Forty-eight rabbits were divided into two series. Phlebitis model induced by vincristine was established at each series. The first series had 24 rabbits, which were divided into four groups (6 hours, 12 hours, 18 hours, 24 hours) after vincristine infusion. The grades of phlebitis through visual observation and histopathological examination were observed. The second series had also 24 rabbits. Interventions were performed 12 hours after vincristine infusion. These rabbits were randomly divided into four groups, according to treatment: Hirudoid (bid), Xianchen (daily), Xianchen (tid), Xianchen (five times a day). Four days after intervention, the venous injury through visual observation and histopathological examination were evaluated. RESULTS: Series 1: Phlebitis appeared 12 hours after infusion of vincristine through visual observation. There was a significant difference (p<0.05) between 6 hours and 24 hours, 6 hours and 18 hours through visual observation. However, the inflammation happened 6 hours after infusion, the loss of venous endothelial cells demonstrated differences among four groups through histopathological evaluation (p<0.05). There were significant differences (p<0.05) after 4 days among the intervention groups through visual observation, the effects of Xianchen group (five times a day) were better than Xianchen group (tid) (p<0.01). The treatment of edema demonstrated differences among groups through histopathological evaluation (p<0.05), Xianchen (five times a day) better relieved the degree of edema (p<0.05). CONCLUSIONS: The study showed that inflammatory reaction of phlebitis appeared early. Xianchen can treat vincristine induced phlebitis, as well as Hirudoid. It is particularly effective in the treatment of edema, and there is a remarkable dose-response relationship.

Endoplasmic reticulum stress and renal lesion in mice with combination of high-fat diet and streptozotocin-induced diabetes

ABSTRACT PURPOSE : To investigate in the kidney the pathologic changes and expression of GRP78 and CHOP in the Kunming (KM) mice with combination of high-fat diet and streptozotocin-induced diabetes. METHODS : Sixty two male KM mice were randomly divided into a normal control (NC) group (n=20) and a high-fat diet (HFD) group (n=42). After a four-week dietary manipulation, the KM mice in the HFD group were injected intraperitoneally with streptozotocin to induce diabetes. After diabetic models were successfully established, the kidneys were excised and conserved for further test. RESULTS : No significant difference in the body weight was observed after the dietary manipulation (p=0.554). After the streptozotocin was injected, fasting blood glucose levels in the diabetes group (DM) were significantly higher than that in the NC group (p＜0.0001). Glomerular atrophy observed under light microscope in the DM group was more serious compared with the NC group. The expression of GRP78 and CHOP in the kidneys of the mice in the DM group were higher compared with the NC group. CONCLUSION : Renal lesion occurs in the diabetic Kunming mice induced by combination of high-fat diet and low-dose streptozotocin, and endoplasmic reticulum stress and CHOP may contribute to the injury process.

Biomineralization processes of calcite induced by bacteria isolated from marine sediments

Biomineralization is a known natural phenomenon associated with a wide range of bacterial species. Bacterial-induced calcium carbonate precipitation by marine isolates was investigated in this study. Three genera of ureolytic bacteria, Sporosarcina sp., Bacillus sp. and Brevundimonas sp. were observed to precipitate calcium carbonate minerals. Of these species, Sporosarcina sp. dominated the cultured isolates. B. lentus CP28 generated higher urease activity and facilitated more efficient precipitation of calcium carbonate at 3.24 ± 0.25 × 10−4 mg/cell. X-ray diffraction indicated that the dominant calcium carbonate phase was calcite. Scanning electron microscopy showed that morphologies of the minerals were dominated by cubic, rhombic and polygonal plate-like crystals. The dynamic process of microbial calcium carbonate precipitation revealed that B. lentus CP28 precipitated calcite crystals through the enzymatic hydrolysis of urea, and that when ammonium ion concentrations reached 746 mM and the pH reached 9.6, that favored calcite precipitation at a higher level of 96 mg/L. The results of this research provide evidence that a variety of marine bacteria can induce calcium carbonate precipitation, and may influence the marine carbonate cycle in natural environments.

Microbiologically induced deterioration of concrete: a review

Microbiologically induced deterioration (MID) causes corrosion of concrete by producing acids (including organic and inorganic acids) that degrade concrete components and thus compromise the integrity of sewer pipelines and other structures, creating significant problems worldwide. Understanding of the fundamental corrosion process and the causal agents will help us develop an appropriate strategy to minimize the costs in repairs. This review presents how microorganisms induce the deterioration of concrete, including the organisms involved and their colonization and succession on concrete, the microbial deterioration mechanism, the approaches of studying MID and safeguards against concrete biodeterioration. In addition, the uninvestigated research area of MID is also proposed.

Influence of Osteopontin Short Hairpin RNA on the Proliferation and Invasion of Human Renal Cancer Cells / 华中科技大学学报（医学）（英德文版）

The influence of short hairpin RNA(shRNA)-mediated osteopontin(OPN)gene silencing on the proliferation and invasion of human renal cancer ACHN cells was investigated.Four types of OPN shRNA recombinant plasmids were constructed and RT-PCR assays were used to screen the most highly functional shRNA recombinant plasmids,which were transferred into the cultured ACHN cells by LipofectamineTM 2000.The cells transfected by shRNA expression vectors(ACHN/OPN)were visualized under an inverted microscope and screened by G418.Untreated cells(ACHN)and cells transfected by mock vectors(ACHN/Vect)were used as control groups.The expression levels of OPN mRNA and protein were detected by real-time PCR and Western blot respectively.The cell cycle and ratios of apoptotic cells were assessed by flow cytometry.MTT method was used for drawing the growth curve and observing cell proliferation in vitro.The abilities of migration and invasion in three groups were measured by Transwell chamber test.The expression levels of matrix metalloproteinase(MMP)-2 and MMP-9 in three groups were examined by Western blot.Our results showed that the recombinant plasmid could be successfully transferred into ACHN cells by LipofectamineTM 2000.Compared with untreated cells,the expression levels of OPN mRNA and protein in ACHN/OPN cells were decreased by59.68% and 76.42%,respectively(P<0.05),ACHN/OPN cells were blocked in S phase and apoptotic ratio increased significantly(P<0.05),however,no significant differences were found between ACHN/Vect and ACHN.Recombinant plasmid significantly attenuated expression levels of MMP-2 and MMP-9 proteins and suppressed the proliferation,migration,and invasion of ACHN cells.This study suggested that OPN may play an important role in the growth and invasion of human renal cancer ACHN cells,and these processes are correlated with the activations of MMP-2 and MMP-9.Our data provided preliminary experimental evidence for the feasibility of RNA interference technology in gene therapy of human renal cancer.

Pretreatment with candesartan protects brain against ischemia in normotensive rats / 西安交通大学学报·英文版

Objective: Angiotensin II (Ang-II) increases NADPH oxidase activity and stimulates the production of reactive oxygen species (ROS) including superoxide anion through Ang II AT1-receptor (AT1-R) activation. ROS is involved in various pathological processes in brain ischemia. We investigated whether the AT1-R blocker (ARB) candesartan can protect normotensive rats against brain ischemia. Methods: After 2-week pretreatment with candesartan, rats were subjected to 2 hours middle cerebral artery occlusion-reperfusion (MCAO-R) and 24 hours later, the infarct volume, iNOS, and eNOS mRNA in the internal carotid artery was recorded and compared. Results: Candesartan pretreatment reduced cerebral ischemia and oxidative brain damage after MCAO-R in normotensive rats, resulting in a decreased cortical infarct volume [0.5 mg/kg candesartan, (46.8±13.2) mm3; 1.0 mg/kg candesartan, (19.3±15.3) mm3 vs. control, (111.7±14.3) mm3; P<0.05, P<0.01, respectively]. Candesartan pretreatment increased the eNOS mRNA level in the internal carotid artery. Conclusion: In normotensive rats exposed to MCAO-R, candesartan protectes against brain ischemia. This effect may represent a significant therapeutic advantage and may induce end-organ protection even at normal blood pressure.