bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct vascular effects of HR780, a novel 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor
Authors: Wajima Teruaki , Makita Shigeki , Oshima Kenichi 
Published: December 2003

Summary1. We have examined the effects of HR780, a novel 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor, on porcine endothelial cell (EC) injury induced by xanthine (X)/xanthine oxidase (XO), a source of superoxide anion. Furthermore, the effects of HR780 on platelet‐derived growth factor (PDGF)‐induced migration and fetal calf serum (FCS)‐induced proliferation of rabbit smooth muscle cells (SMC) were investigated.2. Probucol, at 10 µmol/L, significantly (P < 0.001) and completely suppressed lactate dehydrogenase leakage induced by X/XO. At 10 µmol/L, HR780 significantly (P = 0.010) inhibited X/XO‐induced EC injury.3. HR780 dose‐dependently inhibited PDGF‐induced SMC migration and FCS‐induced SMC proliferation. The addition of mevalonate completely abolished the inhibitory effect of HR780 on SMC proliferation. Another HMG‐CoA reductase inhibitor, simvastatin (0.1–100 µmol/L), also inhibited the migration and proliferation responses as potently as HR780. In contrast, pravastatin (0.1–100 µmol/L) did not show any effects.4. This in vitro study provides the first evidence that HR780 protects the vascular endothelium from oxidant stress and inhibits the migration and proliferation of SMC.
Analgesic duration and kinetics of liposomal bupivacaine after subcutaneous injection in mice
Authors: Grant GJ , Piskoun B , Bansinath M 
Published: December 2003

Summary1. The objective of the present study was to assess the time‐course profile of analgesia and bupivacaine concentrations at the site of injection after subcutaneous administration of a single dose of standard bupivacaine or a novel controlled‐release liposomal bupivacaine formulation.2. Groups of mice were injected subcutaneously with 0.2 mL of 0.5% standard bupivacaine or 0.5, 1 or 2% liposomal bupivacaine.3. A prolonged duration of analgesia occurred in mice receiving liposomal bupivacaine. In the liposomal groups, the bupivacaine remained at the injection site for more than 96 h, compared with approximately 8 h in groups injected with standard bupivacaine.4. These results confirm that the prolonged analgesia observed after injection of the liposomal formulation is associated with sustained higher levels of bupivacaine at the site of injection.
Vascular non‐endothelial nitric oxide induced by swimming exercise stress in rats
Authors: Chies AB , Corrêa FMA , De Andrade CR , Rosa‐e‐Silva AAM , Pereira FC , De Oliveira AM 
Published: December 2003

Summary1. Herein, we report the effects of acute or chronic forced swimming on vascular responsiveness to angiotensin (Ang) II.2. The possible involvement of locally produced substances, such as nitric oxide (NO) and prostanoids, in these effects were studied in rat thoracic aorta and superior mesenteric arteries.3. Chronic, but not acute, swimming reduced the efficacy (maximal effect; Emax) of AngII in thoracic aorta and mesenteric arteries, either with intact or denuded endothelium.4. The efficacy of AngII was reduced in the presence of indomethacin in mesenteric arteries, but not in the aorta, from either control or chronically stressed rats.5. Treatment with NG‐monomethyl‐l‐arginine reversed the effect of chronic stress on the response to AngII, suggesting that chronic stress may increase non‐endothelial NO activity in both the aorta and mesenteric arteries.6. The effects of acute and chronic stress on vascular reactivity were selective for AngII because no changes were observed on the effects of phenylephrine.
Cosegregation analysis of natriuretic peptide genes and blood pressure in the spontaneously hypertensive rat
Authors: Ye Ping , West Malcolm J 
Published: December 2003

Summary1. The natriuretic peptide precursor A (Nppa) and B (Nppb) genes are candidate genes for hypertension and cardiac hypertrophy in the spontaneously hypertensive rat (SHR). The purpose of the present study was to determine the role of the Nppa and Nppb genes in the development of hypertension in the SHR.2. A cohort (n = 162) of F2 segregating intercross animals was established between strains of hypertensive SHR and normotensive Wistar‐Kyoto rats. Blood pressure and heart weight were measured in each rat at 12–16 weeks of age. Rats were genotyped using 11 informative microsatellite markers, distributed in the vicinity of the Nppa marker on rat chromosome 5 including an Nppb marker. The phenotype values were compared with genotype using the computer package mapmaker 3.0 (Whitehead Institute, Boston, MA, USA) to determine whether there was a link between the genetic variants of the natriuretic peptide family and blood pressure or cardiac hypertrophy.3. A strong correlation was observed between the Nppa marker and blood pressure. A quantitative trait locus (QTL) for blood pressure on chromosome 5 was identified between the Nppa locus and the D5Mgh15 marker, less than 2 cM from the Nppa locus. The linkage score for the blood pressure QTL on chromosome 5 was 3.8 and the QTL accounted for 43% of the total variance of systolic blood pressure, 54% of diastolic blood pressure and 59% of mean blood pressure. No association was found between the Nppb gene and blood pressure. This is the first report of linkage between the Nppa marker and blood pressure in the rat. There was no correlation between the Nppa or Nppb genes or other markers in this region and either heart weight or left ventricular weight in F2 rats.4. These findings suggest the existence of a blood pressure‐dependent Nppa marker variant or a gene close to Nppa predisposing to spontaneous hypertension in the rat. It provides a strong foundation for further detailed genetic studies in congenic strains, which may help to narrow down the location of this gene and lead to positional cloning.
Morphological evidence of reinnervation of the baroreceptive regions in sinoaortic‐denervated rats
Authors: Cai Guo‐Jun , Li Ling , Xie He‐Hui , Xu Jia‐Jun , Miao Chao‐Yu , Su Ding‐Feng 
Published: December 2003

Summary1. The arterial baroreflex (ABR) plays an important role in the maintenance of the stability of blood pressure. Sinoaortic denervation (SAD) destroys the integrity of the reflex arc and produces severe organ damage in rats. However, partial recovery of ABR function has been observed following chronic denervation. The aim of the present study was to determine whether there was morphological evidence of reinnervation of the aortic arch and carotid sinus following SAD.2. A substantial body of physiological and morphological evidence suggests that substance P (SP) may be a neurotransmitter contained in first‐order sensory baroreceptor afferents; therefore, the patterns of vascular SP and neurofilament (NF) immunoreactive (IR) innervation of the aortic arch and carotid sinus were investigated in the present study.3. Ten‐week‐old male Sprague‐Dawley rats underwent SAD or sham operation. Whole mounts of carotid bifurcation and aortic arch were prepared for immunohistochemical study at various time points (1, 9 and 16 weeks after operation).4. The results of computerized image analysis show that the mean density of NF‐ and SP‐IR nerves of SAD rats 9 and 16 weeks after operation increased gradually and significantly compared with that of rats 1 week after operation.5. In conclusion, the results indicate that there is reinnervation of the aortic arch and carotid sinus by NF‐ and SP‐IR fibres in SAD rats, which may be the morphological basis for the partial restoration of ABR function over time after SAD.
Phytosterol additives increase blood pressure and promote stroke onset in salt‐loaded stroke‐prone spontaneously hypertensive rats
Authors: Ogawa Hiroshi , Yamamoto Kazuo , Kamisako Toshinori , Meguro Tadamichi 
Published: December 2003

Summary1. To assess the effect of dietary phytosterol on stroke and the lifespan of salt‐loaded stroke‐prone spontaneously hypertensive rats (SHRSP), we investigated the effects of the addition of phytosterol to soybean oil (phytosterol content: 0.3%) on stroke onset, lifespan following onset of stroke and overall lifespan compared with canola oil (phytosterol content: 0.9%).2. Six‐week‐old male SHRSP were fed a test diet prepared by the addition of canola oil (CA diet), soybean oil (SO diet), soybean oil plus 0.6% phytosterol (SO + 0.06P diet) or soybean oil plus 4.5% phytosterol (SO + 0.45P diet) as a 10% fat source.3. Systolic blood pressure (SBP) increased in the SO + 0.06P and SO + 0.45P groups compared with the SO group and the increase was dependent on the amount of phytosterol added, indicating that the addition of phytosterol to soybean oil may promote an increase in SBP in salt‐loaded SHRSP.4. The onset of stroke was shortest in the SO + 0.45P group and survival after the onset of stroke was shortest in the CA group. Consequently, the SO + 0.45P and CA groups showed marked lifespan shortening, indicating that a fivefold greater amount of phytosterol was required to produce an effect equivalent to that of canola oil.5. Investigation of the mRNA expression of ATP‐binding cassette (ABC) transporters involved in intestinal phytosterol absorption indicated significant decreases in the intestinal mRNA expression of Abcg5 and Abcg8 in SHRSP and Wistar‐Kyoto rats compared with Wistar rats.6. In conclusion, the addition of phytosterol to soybean oil elevated SBP and promoted the onset of stroke, which may cause a reduction in survival time. However, a fivefold greater amount of phytosterol was required to produce an effect that was equivalent to the survival time‐shortening effect of canola oil. The significant decrease in the intestinal mRNA expression of Abcg5 and Abcg8 in SHRSP may be responsible, at least in part, for the unfavourable effects observed following the addition of phytosterol.
Effect of salt and water intake on epithelial sodium channel mRNA abundance in the kidney of salt‐sensitive Sabra rats
Authors: Nicco Carole , Bankir Lise , Bouby Nadine 
Published: December 2003

Summary1. The level of mRNA expression of epithelial sodium channel (ENaC) subunits was studied in a salt‐dependent hypertensive rat strain (Sabra). These rats exhibit high vasopressin levels compared with their normotensive counterparts. We also investigated whether this expression is influenced by changes in the sodium intake/aldosterone axis or in the fluid intake/vasopressin axis.2. A higher expression of β‐ and γ‐subunit mRNA was found in salt‐sensitive compared with salt‐resistant rats on a normal salt diet. A high‐sodium diet did not alter mRNA abundance in either substrain. In contrast, water supplementation in salt‐sensitive rats fed the high‐sodium diet induced a marked reduction in mRNA abundance of β‐ and γ‐subunits.3. The present study provides evidence that β‐ and γ‐subunits of ENaC are differently expressed in the kidney of salt‐sensitive and salt‐resistant Sabra rats and that their abundance is regulated by vasopressin, not by sodium intake. These results are consistent with the hypothesis that increased vasopressin‐dependent ENaC expression and activity may contribute to the pathogenesis of hypertension in salt‐sensitive Sabra rats.
Role of angiotensin AT1 and AT2 receptors in cardiac hypertrophy and cardiac remodelling
Authors: Zhu Yi‐Chun , Zhu Yi‐Zhun , Lu Ning , Wang Ming‐Jie , Wang Yan‐Xia , Yao Tai 
Published: December 2003

Summary1. Left ventricular hypertrophy (LVH) is an independent cardiovascular risk factor. Angiotensin AT1 receptor antagonism has been considered as a specific approach to block the renin–angiotensin system and been demonstrated to be able to prevent or regress LVH by interfering with the remodelling process of the heart.2. Angiotensin AT1 receptor blockade induces a marked increase in angiotensin (Ang) II, which may stimulate the AT2 receptors. Gene expression of AT1 and AT2 receptors increases in a time‐dependent manner in cardiac remodelling following myocardial infarction.3. Considerable efforts have been made to clarify the role of AT2 receptors in cardiac hypertrophy and remodelling since the mid‐1990s, resulting in controversial reports: the AT2 receptor mediates actions either opposite to or in coordination with those of the AT1 receptor. Moreover, there are many reports of no significant effects mediated by AT2 receptors.4. Based on the studies reviewed in the present article, we assume that the predominant effect of AngII in cardiac hypertrophy and cardiac remodelling is growth promoting and that this effect is mediated mainly via AT1 receptors. The AT2 receptors may affect the hypertrophic process by interacting with other cardiac membrane proteins, enzymes and autacoids. Before coming to a conclusion as to whether AT2 receptor stimulation or antagonism is beneficial to the heart, more studies should be performed in different LVH models, especially long‐term treatment protocols in vivo.
Therapeutic options for esophageal cancer
Authors: LAW SIMON , WONG JOHN 
Published: December 2003

AbstractOptions for the treatment of esophageal cancer used to be very limited, with surgical resection and radiotherapy methods aimed at both cure or palliation, and, in those unfortunate patients with severe dysphagia, intubation with a plastic prosthesis to restore esophageal luminal patency. Progress in the management of this cancer in the past two decades includes refinement in surgical techniques and perioperative care, better radiological staging methods, enhanced means of planning and delivering radiotherapy, multimodality treatments, and better designs in esophageal prosthesis. For individual patients, a stage‐directed therapeutic plan can be used. Long‐term survival, however, remains suboptimal for this deadly disease. The current review presents an overview of the commonly employed therapeutic options for esophageal cancer at the beginning of the 21st century.
Expression of Mg2+‐dependent, HCO3–‐stimulated adenine triphosphatase in the human duodenum
Authors: KONNO YUTAKA , KATO KATSUAKI , DAIRAKU NAOHIRO , KOIKE TOMOYUKI , IIJIMA KATSUNORI , IMATANI AKIRA , SEKINE HITOSHI , OHARA SHUICHI , SHIMOSEGAWA TOORU 
Published: December 2003

AbstractBackground and Aim:  Mg2+‐dependent, HCO3–‐stimulated adenine triphosphatase (Mg2+‐HCO3–‐ATPase) is an enzyme that catabolizes ATP in the presence of HCO3– and Mg2+. The activity of this ATPase is known to be present in the duodenum, but its physiological role remains unclear. In the present study, the aim was to study the distribution and biochemical profiles of Mg2+‐HCO3–‐ATPase in the human duodenum.Methods:  The histochemistry of Mg2+‐HCO3–‐ATPase, its localization using electron microscopy (EMS), and the measurement of enzyme activity were carried out by using mucosal samples of the bulb, and the second and third portions of the duodenum, obtained from six volunteers by endoscopic biopsy.Results:  The Mg2+‐HCO3–‐ATPase was detected in the brush border along the luminal surface of human duodenal epithelial cells. The EMS confirmed its localization to the surface of microvilli. The activity of Mg2+‐HCO3–‐ATPase was higher in the distal portions of the human duodenum than in the bulb. Its maximal activity was obtained under a pH of 8.5, and in the presence of 1.0 mmol/L MgCl2 and 50 mmol/L NaHCO3, but the activity was undetectable in pH <7.4 or >9.5.Conclusion:  The results of the present study suggested that Mg2+‐HCO3–‐ATPase may work for luminal alkalization in the distal portions of the human duodenum and may contribute to maintaining the activity of pancreatic digestive enzymes.
Cost‐effectiveness of colorectal cancer screening: Comparison of community‐based flexible sigmoidoscopy with fecal occult blood testing and colonoscopy
Authors: O'LEARY BETH A , OLYNYK JOHN K , NEVILLE A MUNRO , PLATELL CAMERON F 
Published: December 2003

AbstractBackground and Aims:  To determine the cost‐effectiveness of screening for colorectal cancer using flexible sigmoidoscopy once every 10 years, compared with annual and biennial rehydrated Hemoccult fecal occult blood testing and colonoscopy once every 10 years, or no screening.Methods:  A Markov model was developed in order to simulate the progression of a cohort of asymptomatic, average‐risk individuals aged 55–64 years who were moving through a defined series of states towards death. The main outcome measures were: cases of colorectal cancer averted, colorectal cancer deaths averted, and cost per life‐year saved.Results:  Colonoscopy averted the greatest number of cases of colorectal cancer (35%), followed by flexible sigmoidoscopy (25%), and annual (24%) and biennial (14%) fecal occult blood testing. Colonoscopy averted the greatest number of deaths from colorectal cancer (31%), followed by annual fecal occult blood testing (29%), flexible sigmoidoscopy (21%) and biennial fecal occult blood testing (19%). Flexible sigmoidoscopy was the most efficient in terms of cost per life‐year saved (A$16 801), followed by colonoscopy (A$19 285), biennial (A$41 183), and annual (A$46 900) fecal occult blood testing.Conclusions:  Flexible sigmoidoscopy and colonoscopy are cost‐effective strategies for reducing the disease burden of colorectal cancer.
Digital quantification of fibrosis in liver biopsy sections: Description of a new method by Photoshop software
Authors: DAHAB GAMAL M , KHERIZA MOHAMED M , EL‐BELTAGI HUSSIEN M , FOUDA ABDEL‐MOTAAL M , EL‐DIN OSAMA A SHARAF 
Published: December 2003

AbstractBackground:  The precise quantification of fibrous tissue in liver biopsy sections is extremely important in the classification, diagnosis and grading of chronic liver disease, as well as in evaluating the response to antifibrotic therapy. Because the recently described methods of digital image analysis of fibrosis in liver biopsy sections have major flaws, including the use of out‐dated techniques in image processing, inadequate precision and inability to detect and quantify perisinusoidal fibrosis, we developed a new technique in computerized image analysis of liver biopsy sections based on Adobe Photoshop software.Methods:  We prepared an experimental model of liver fibrosis involving treatment of rats with oral CCl4 for 6 weeks. After staining liver sections with Masson's trichrome, a series of computer operations were performed including (i) reconstitution of seamless widefield images from a number of acquired fields of liver sections; (ii) image size and solution adjustment; (iii) color correction; (iv) digital selection of a specified color range representing all fibrous tissue in the image and; (v) extraction and calculation.Results:  This technique is fully computerized with no manual interference at any step, and thus could be very reliable for objectively quantifying any pattern of fibrosis in liver biopsy sections and in assessing the response to antifibrotic therapy. It could also be a valuable tool in the precise assessment of antifibrotic therapy to other tissue regardless of the pattern of tissue or fibrosis.
Five‐lipoxygenase‐activating protein inhibitor MK‐886 induces apoptosis in gastric cancer through upregulation of p27kip1 and bax
Authors: FAN XIAO MING , TU SHUI PING , LAM SHIU KUM , WANG WEI PING , WU JING , WONG WAI MAN , YUEN MAN FUNG , LIN MARIE CHIA MI , KUNG HSIANG FU , WONG BENJAMIN CHUN‐YU 
Published: December 2003

AbstractBackground and Aim:  Products of the arachidonic acid metabolizing enzyme, 5‐lipoxygenase (5‐LOX), stimulate the growth of several cancer types. Inhibitors of 5‐LOX and 5‐LOX‐activating protein (FLAP) induce apoptosis in some cancer cells. Here, the authors investigated the effect of a FLAP inhibitor, MK‐886, on the inhibition of proliferation and induction of apoptosis in gastric cancer.Methods:  Cell proliferation in gastric cancer cells was measured using an 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide assay. Apoptosis was measured using acridine orange staining and flow cytometry. Protein expression of apoptosis‐related genes p53, p21waf1, p27kip1, bcl‐2 families, cytochrome c, and the caspases were examined using Western blotting. Caspase‐3 activity was measured using colorimetric assay of substrate cleavage.Results:  MK‐886 inhibited cell growth in a dose‐ and time‐dependent manner. Apoptosis was induced in gastric cancer cells and was characterized by upregulation of p27kip1 and bax, with release of cytochrome c from mitochondria into cytosol, which initiated caspase‐3 activation. Specific caspase‐3 inhibitors partially blocked MK‐886‐induced apoptosis.Conclusion:  The present results suggest that MK‐886 induces apoptosis in gastric cancer cells through upregulation of p27kip1 and bax, and that MK‐886 is a potentially useful drug in gastric cancer prevention and therapy.
Wireless capsule endoscopy: Experience in a tropical country
Authors: SRIRAM PVJ , RAO GV , REDDY D NAGESHWAR 
Published: December 2003

AbstractBackground and Aim:  Capsule endoscopy is fast becoming the procedure of choice for small bowel imaging, especially to investigate the cause of unexplained gastrointestinal (GI) bleeding. We report our experience with capsule endoscopy in 24 cases with various indications.Methods:  In patients with unexplained GI bleeding or chronic anemia, the cause could be established in nine of 12 cases (75%), which included angioectasiae, leiomyomata and parasitic infestation.Results:  The yield of capsule endoscopy was highest in patients presenting with chronic diarrhea and suspicion of small bowel mucosal disease, where Crohn's disease and tuberculosis could be diagnosed. However, in patients with unexplained abdominal pain, capsule endoscopy was found to be least useful because 5/7 patients in the study were normal, emphasizing the importance of case selection. Overall, capsule endoscopy yielded a positive diagnosis in 16 of the 24 cases (66.6%).Conclusions:  The experience of capsule endoscopy in a tropical clinical setting is no different from elsewhere, although certain conditions like worm infestation are more likely to be detected in this environment.
New indication for endoscopic treatment of colorectal carcinoma with submucosal invasion
Authors: SHIMOMURA TETSUYA , ISHIGURO SHINGO , KONISHI HIDEYUKI , WAKABAYASHI NAOKI , MITSUFUJI SHOJI , KASUGAI TSUTOMU , MANOU MASAYUKI , KODAMA TADASHI 
Published: December 2003

AbstractBackground and Aims:  Although an increasing number of early colorectal cancers (CRC) have been curatively treated by endoscopy, there have been no definitive criteria to decide the effectiveness of such therapy. We retrospectively analyzed clinicopathological factors to establish criteria for curative endoscopic treatment of early CRC.Methods:  First, risk factors of lymph node metastasis were analyzed in 171 patients who received surgery with postoperative histology of CRC submucosal invasion. The resultant new criteria were evaluated in another 60 patients who experienced endoscopic resection of CRC and surgery according to the current criteria most often used in Japan.Results:  In the first substudy, lymph node metastasis was present in 18 of 171 patients (10.5%). Lymphatic permeation, sprouting and infiltrative growth of cancer cells were identified as histological factors significantly related to lymph node metastasis, and observed in much higher rates when the depth of submucosal invasion was beyond 1500 micron. The minimum depth with positive lymph nodes was 1075 micron. In the second group of 60 patients, lymph node metastasis was recorded in none of nine patients who met our new criteria of complete endoscopic treatment: submucosal invasion below 1500 micron in depth, and no lymphatic permeation, sprouting or infiltrative growth pattern on tumor histology. Lymph node metastasis was positive in three of the other cases who did not meet our new criteria.Conclusions:  The present study showed that endoscopic treatment of early CRC may be considered complete when submucosal invasion beyond 1500 micron, lymphatic permeation, sprouting, and infiltrating growth are all denied.