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Biomedical subjects

Y Cheng

Publications and source records attributed to Y Cheng.

At least 73 records · Page 4Linked to original sources

[Effects of glutamate and glutamine on learning and memory of rats].

The effects of glutamate (Glu) and glutamine (Gln) on learning and memory of rats and the mechanism involved were examined. Three groups of rats were fed with stock diet (control group), and the diets supplemented with 2% Glu (Glu group) or 2% Gln (Gln group) respectively. Compared with control group, the active avoidance response rats of Gln group in shuttle box test was significantly elevated while the time of passive avoidance response shortened. The contents of brain free amino acids, such as Gln, Glu, aspartic acid and arginine, activity of brain nitric oxide synthase (NOS), Bmax of N-methyl-D-aspartate(NMDA) receptors in hippocampus of Gln group were all increased significantly. Such changes were not observed in Glu group. The results suggested that Gln could improve the learning ability and memory of rats, which might be related to the change of amino acids composition of brain, the synthesis of messenger nitric oxide and the binding capacity of NMDA receptor in hippocampus.

Animals↗

Serological and histological findings in infection and transmission of GBV-C/HGV to macaques.

Seven healthy macaques were inoculated with the GBV-C/HGV-RNA serum from a non-A-E hepatitis patient. The serology and pathology of the liver in the animals were observed. The results indicated that all inoculated animals were infected with a GBV-C/HGV-RNA viremia and had mildly abnormal alanine transaminase levels during the infectious period. The histology, immuno-histochemistry, and in situ hybridization in the liver tissues of the inoculated animals also showed that there was a very mild hepatitis with the positive antigenic expression and the genome of GBV-C/HGV-NS5 in hepatocytes. The pathological changes in the infected animals appeared to become normal whether or not GBV-C/HGV-RNA viremia persisted. There is a possibility that the mild virulence of the GBV-C/HGV to the host became harmless with time after inoculation. Infection and the transmission of the GBV-C/HGV virus in the macaques provides an appropriate animal model and new information about GBV-C/HGV infection in both humans and animals. It is possible that this virus is a mild and self-limited pathogenic agent to the hepatic cells of primates.

Alanine Transaminase↗

A functional investigation of tumor suppressor gene activities in a nasopharyngeal carcinoma cell line HONE1 using a monochromosome transfer approach.

Monochromosome transfers of selected chromosomes into a nasopharyngeal carcinoma (NPC) cell line were performed to determine if tumor suppressing activity for NPC mapped to chromosomes 9, 11, and 17. Current information from cytogenetic and molecular allelotyping studies indicate that these chromosomes may harbor potential tumor suppressor genes vital to NPC. The present results show the importance of CDKN2A on chromosome 9 in NPC development. There was no functional suppression of tumor development in nude mice with microcell hybrids harboring the newly transferred chromosome 9 containing an interstitial deletion at 9p21, whereas transfection of CDKN2A into the NPC HONE1 cells resulted in obvious growth suppression. Whereas intact chromosome 17 transfers into HONE1 cells showed no functional suppression of tumor formation, chromosome 11 was able to do so. Molecular analysis of chromosome 11 tumor segregants indicated that at least two tumor suppressive regions mapping to 11q13 and 11q22-23 may be critical for the development of NPC.

Animals↗

Phylogeny of taxaceae and cephalotaxaceae genera inferred from chloroplast matK gene and nuclear rDNA ITS region.

Phylogeny of the Taxaceae genera and the monotypic family Cephalotaxaceae has been extraordinarily controversial. In this paper chloroplast matK genes and nuclear ITS sequences were determined for all six genera of the two families and representatives of other conifer families. Analysis using either the nonsynonymous sites or the deduced amino acid sequences of matK genes strongly indicates that taxad genera and Cephalotaxaceae are monophyletic, with the Taxodiaceae/Cupressaceae clade as their sister group. Cephalotaxus is basal to the taxad genera, among which two clades, Torreya/Amentotaxus and Taxus/Pseudotaxus/Austrotaxus, are resolved. They correspond to Janchen's two tribes, Torreyeae and Taxeae. In Taxeae, Austrotaxus is the first to branch off. Analyses of the nuclear ITS sequence data corroborated the topology of the matK gene tree. These results refute the views that Cephalotaxaceae has no alliance with Taxaceae and that Austrotaxus and Amentotaxus should be excluded from the Taxaceae. We estimated the divergence time between the Taxodiaceae/Cupressaceae and the Cephalotaxaceae/Taxaceae clades to be 192-230 Myr ago and the divergence time between taxads and Cephalotaxus to be 149-179 Myr ago. Soon after the latter divergence event, within 6-8 Myr, the two taxad tribes originated. In conclusion, our data do not support Florin's claim that taxads could be traced to Devonian psilophytes (359-395 Myr ago).

Base Sequence↗

Efficacy and safety of preoperative lobar or segmental ablation via transarterial administration of ethiodol and ethanol mixture for treatment of hepatocellular carcinoma: clinical study.

Transarterial embolization (TAE) using various thrombotic substances for unresectable hepatocellular carcinoma (HCC) performed on many patients has resulted in a better survival rate. We evaluated the efficacy and clinical safety of using an Ethiodol-ethanol mixture as the embolizer for treatment of HCC and the possibility of a surgical approach for inoperable tumors after TAE. Twenty patients with HCC who underwent TAE and tumor resection were included in the study. Initially, eight had increased retention rate of indocyanine green dye via intravenous injection (0.5 mg/kg) at 15 minutes (ICGR15), and six had an insufficient residual volume that precluded them from undergoing tumor resection. TAE was performed by slowly infusing the mixture of Ethiodol and ethanol into the artery supplying the tumor until dual hepatic artery and portal vein embolization was achieved. Serum levels of alanine aminotransferase increased after embolization, but all biochemistry studies reverted to normal within 2 weeks. A decreased tumor size (n = 15), improved ICG (n = 8), and increased volume of the nonembolized lobe (n = 10) were noted. The operations performed were right lobectomy (n = 11), extended right lobectomy (n = 3), left lobectomy (n = 2), extended left lobectomy (n = 2), and wedge resection (n = 2), which included patients who did not want to undergo major hepatectomy. Complete tumor necrosis was found in seven cases. All patients survived with no associated complications. The 1-year survival rate was 95%. Transarterial Ethiodol and ethanol administration creating dual hepatic artery and portal vein embolization was a safe and efficacious method for treating HCC. It effectively decreases tumor size, causes compensatory hepatic hypertrophy, and improves the ICGR15, which allows a wider range of patients to undergo liver surgery and achieve better survival.

Adult↗

Dose escalation and pharmacokinetic study of irinotecan in combination with paclitaxel in patients with advanced cancer.

PURPOSE: Based on preclinical data demonstrating synergy between camptothecin analogues and taxanes, we determined the maximum tolerated dose (MTD) of irinotecan that could be given in combination with a fixed dose of paclitaxel of 75 mg/m2, when both drugs were delivered on a weekly schedule. The pharmacokinetics of this combination were explored to determine whether the sequence of administration affected the elimination of irinotecan. METHODS: For the first cycle patients with advanced cancer were treated with irinotecan given as a 90-min infusion followed immediately by paclitaxel given at a dose of 75 mg/m2 over 1 h. The sequence of drug administration was reversed in subsequent cycles for most patients. Chemotherapy was given weekly for 4 weeks, followed by a 2-week rest. In selected patients, plasma concentrations of irinotecan were determined by high-performance liquid chromatography during the first 24 h of cycle 1 and after the first dose of cycle 2 to determine whether the order of drug administration affected the elimination of irinotecan, or the toxicologic effects of the chemotherapy. RESULTS: A total of 53 cycles were delivered to 21 patients. Reversible neutropenia was dose-limiting. Suppression of the other blood cell elements was modest. There was one partial response in a man with a previously treated cholangiocarcinoma that lasted 26 weeks. Prolonged stabilization of disease (6 months or more) was observed in five of the patients (24%). At the recommended dose of irinotecan (50 mg/m2), transfusions of red cells and platelets were not required. The sequence of drug administration produced no significant differences in the pharmacokinetic parameters of irinotecan or SN-38, which were similar to the values reported when irinotecan is administered alone. The most prominent nonhematologic toxicities were mild diarrhea and fatigue. CONCLUSIONS: The recommended dose of irinotecan on this schedule is 50 mg/m2. The sequence of drug administration affects neither the elimination of irinotecan nor the chemotherapy-related toxicity. This combination is well tolerated and causes minimal clinical side effects.

Aged↗

Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression.

Matrix metalloproteinase 9 (MMP-9, also known as gelatinase B or 92-kd Type IV collagenase) is overexpressed in many human and murine cancers. We induced carcinomas in mice carrying a transgene that links the MMP-9 promoter to the reporter ss-galactosidase so that activation of the MMP-9 promoter would be indicated by ss-galactosidase. Mammary carcinomas were induced by mating the MMP-9 promoter reporter transgenic mice with mice carrying a transgene for murine mammary tumor virus promoter linked to polyoma middle T antigen, a transgene that leads to rapid development of mammary tumors in female mice. None of the hyperplastic mammary glands and none of the carcinomas in situ expressed ss-galactosidase. However, all invasive tumors had evidence of ss-galactosidase expression. In addition to the breast carcinomas, a malignant teratoma in a female and a papillary adenocarcinoma in the pelvic region of a male arose and were also ss-galactosidase positive. We also induced skin tumors in the mice with the MMP-9 reporter transgene with 7, 12-dimethylbenz[a]anthracene (DMBA) treatment followed by phorbol 12 myristate 13-acetate (TPA). None of the papillomas or in situ carcinomas showed any ss-galactosidase expression, but expression was seen in invasive carcinoma. Although normal skin epithelial cells did not express ss-galactosidase, we did find staining in a few cells at the duct of the sebaceous gland at the base of the hair follicles. The MMP-9 reporter transgene did not lead to expression in the alveolar macrophages, confirming that additional upstream sequences are required for expression in macrophages. These experiments have revealed that MMP-9 promoter activity is induced coincident with invasion during tumor progression. Furthermore, this indicates that the more proximal upstream elements of the promoter are sufficient for MMP-9 transcription during tumor progression.

Animals↗

Three-dimensional reconstruction of the actin cytoskeleton from stereo images.

In eucaryotic cells, actin filaments are abundant components in the cytoskeleton where they form a complex three dimensional (3D) structural network that provides the cell with its shape and mechanical properties. However, understanding the structural and mechanical properties of actin filaments composing the cell cytoskeleton is often hampered by the inability to faithfully reconstruct the three-dimensional geometric relationships. This paper presents a vision-based reconstruction approach that automatically reconstitutes the three-dimensional structures of cytoskeletal polymers from stereo image pairs taken at the different tilt angles. The approach finds corresponding points between two images and recovers the depth information about the structures. The computational process consists of three major procedures: feature representation, stereo matching, and disparity refinement, implemented in a multi-resolution manner based on a coarse-to-fine strategy. The reconstruction depicts the three-dimensional structure of cytoskeletal polymers and their geometric relationships. New and useful information becomes available and allows quantitative analysis of the structure. Measurement of the cytoskeleton geometrical properties and the filament concentration in a defined volume are obtained by direct calculation.

Actins↗

Discrete membrane arrays.

This review describes various methods for the attachment of phospholipid bilayers to solid supports. The simplest approach involves vesicle unrolling onto a surface that has been previously modified with a continuous self-assembled monolayer (SAM). The choice of a suitable SAM can lead to the formation of attached bilayers that have the desired biomimetic properties and are suitable for studying transmembrane proteins. However, there are intrinsic problems associated with this approach if one is interested in studying ion transport phenomena. In particular, the relatively low resistance values found for such bilayers do not permit studies of single ion channels. For such studies to be carried out the background leakage through the lipid film must be greatly reduced. In an attempt to reduce the problems of leakage we have formed patterned SAMs in which a blocking, hydrophobic, layer covers 90% of the electrode surface. The remaining portion of the surface, which is hydrophilic, supports the formation of a bilayer. This approach has led to an improvement in the quality of the bilayers formed but has still not provided bilayers with sufficiently high specific resistances to study single ion channels. Finally, we describe new approaches based on the formation of bilayers suspended over small apertures. These 'suspended' bilayers are similar in structure to those used in black lipid membrane experiments and give rise to highly blocking bilayer membranes. Unfortunately, this approach requires the use of solvents to create the suspended bilayer and they are relatively fragile.

Lipid Bilayers↗

Enzymatic degradation of guar and substituted guar galactomannans.

Enzymatic degradation of guar galactomannan is studied using gel permeation chromatography (GPC) and steady shear viscometry. In very dilute polymer solutions, reaction rate increases with first-order kinetics with substrate concentration. In the intermediate concentration regime, the enzyme/polymer binding saturates, and the degradation kinetics is zero-order. The observations are in accord with a Michaelis-Menton kinetics model. The Michaelis-Menton parameter, Km and Vmax, were determined to be 0.6 mM and 7.8 x 10(-10) mol/(mL s) for guar at pH = 7, where the maximal velocity of the reaction, Vmax, was measured in terms of the molar concentration of glycosidic bonds broken per unit time. However, as the solution increases in concentration, the reaction rate decreases and the enzyme diffusion through the concentrated polymer gel becomes a limiting factor. A reaction-diffusion model is presented to express the competition between enzyme reaction and diffusion. The scaling theory and kinetic data are used to define the boundaries of the polymer concentration regimes between substrate (i.e., polymer strand) limited reactions, enzyme limited reactions, and hindered diffusion limited reactions. The influence of polymer derivatization on the degradation kinetics was also explored. The degradation rate was shown to be greatly affected by the type of substituent groups as well as the degree of substitution. The triggering mechanism and controlled degradation were found for the enzymatic hydrolysis of cationically derivatized guar solutions.

Algorithms↗

Pilocytic astrocytomas do not show most of the genetic changes commonly seen in diffuse astrocytomas.

AIMS: While it is well known that pilocytic astrocytomas are clinically distinct from diffuse astrocytomas, few comprehensive studies have focused on their genetic differences. The aim of this study was to examine pilocytic astrocytomas for genetic alterations that are commonly seen in diffuse astrocytomas. METHODS AND RESULTS: By using molecular genetic and immunohistochemical techniques, we evaluated p16, p53, CDK4 and PTEN genes in 29 pilocytic astrocytomas. Mutation screening of p53 and PTEN was performed by single strand conformation polymorphism analysis followed by direct sequencing. Loss of heterozygosity (LOH) of p53, p16 and 10q23-25 loci was performed with microsatellite markers and genomic microsatellite instability (MSI) was also screened. Protein expression of p16, p53, CDK4 and PTEN was examined by immunohistochemistry. Five tumours were found to have single genetic alterations, which included a p53 mutation, a PTEN mutation, MSI at a single microsatellite marker of the p16 locus, and one single LOH at each p16 and 10q23 loci. Protein expressions of p16, CDK4 and PTEN were detected in 73%, 61% and 38% of tumours, respectively. Significantly and in sharp contrast to diffuse astrocytomas, no pilocytic astrocytoma in our series stained for p53 protein. CONCLUSION: Pilocytic astrocytomas have neither MSI phenotype nor recurrent alterations of the p53 and p116 genes. However, altered expression of PTEN may be important in the genesis of pilocytic astrocytomas. We conclude that pilocytic astrocytomas are genetically distinct from diffuse astrocytomas. Lack of p53 mutation/immunostaining may serve as a diagnostic adjunct for differentiating pilocytic astrocytomas from diffuse astrocytomas in small neurosurgical biopsies.

Adolescent↗

Bacteriology and antimicrobial choice in hepatolithiasis.

BACKGROUND AND AIMS: Hepatolithiasis is prevalent in southeast Asia and presents a difficult management problem. Acute repeated episodes of cholangitis are frequently manifested in patients with hepatolithiasis. Without proper treatment, such infection can lead to liver abscess, secondary biliary cirrhosis, portal hypertension, and death from sepsis or hepatic failure. In addition to clearance of the stones and relief of bile stasis either by surgery or by interventional radiologic manipulation, effective antimicrobial therapy also plays a crucial role in the treatment of patients with hepatolithiasis. The aim of this study is to clarify the bacteriology in hepatolithiasis and to provide the information for an appropriate antimicrobial choice. METHODS: From July 1993 to June 1996, 150 patients with hepatolithiasis underwent surgical intervention. Bile specimens were routinely obtained by syringe aspiration from common bile duct. The syringe was immediately capped, and the bile was subsequently cultured for both aerobes and anaerobes. RESULTS: Bacteria were present in the bile of all patients. The bacteria most frequently found were gram-negative bacteria such as Klebsiella sp, Escherichia coli, and Pseudomonas sp, and the gram-positive Enterococcus sp. Bacteroides sp were the most frequently found anaerobes. CONCLUSIONS: This study demonstrated the close relationship between acute cholangitis in hepatolithiasis and enteric bacteria and also displayed the detailed antibiotic sensitivity results. Armed with this fruitful information, we believe the antibiotic treatment for acute cholangitis in hepatolithiasis should first aim at enteric bacteria and be adjusted later according to the results of bacteriologic cultures and clinical situation to achieve an effective microbial control.

Adult↗

Development of a syngeneic mouse model for events related to ovarian cancer.

Mouse ovarian surface epithelial cells (MOSEC) were obtained from virgin, mature mice by mild trypsinization and were repeatedly passaged in vitro. Early passage cells (<20 passages) exhibited a cobblestone morphology and contact inhibition of growth. After approximately 20 passages in vitro, cobblestone morphology and contact inhibition of growth was lost. Tumor forming potential was determined by s.c. and i.p. injection of early and late passage cells into athymic and syngeneic C57BL6 mice. Subcutaneous tumors formed in approximately 4 months and were present only at the injection site. Intraperitoneal injection of late passage MOSEC into athymic and syngeneic mice resulted in growth of tumor implants throughout the abdominal cavity, and production of hemorrhagic ascitic fluid. Early passage MOSEC did not form tumors in vivo. Histopathologic analysis of tumors revealed a highly malignant neoplasm containing both carcinomatous and sarcomatous components. Late passage MOSEC expressed cytokeratin and did not produce ovarian steroids in response to gonadotropin stimulation in vitro. Ten clonal lines were established from late passage MOSEC. Each clone formed multiple peritoneal tumors and ascitic fluid after i.p. injection into C57BL6 mice. Three cell lines examined cytogenetically were polyploid with near-tetraploid modal chromosome numbers. Common clonal chromosome gains and losses included +5, +15, +19 and -X, -3, -4. One cell line had a clonal translocation between chromosomes 15 and 18 and another had a small marker chromosome; common structural abnormalities were not observed. These data describe the development of a mouse model for the study of events related to ovarian cancer in humans. The ability of the MOSEC to form extensive tumors within the peritoneal cavity, similar to those seen in women with Stage III and IV cancer, and the ability of the MOSEC to produce tumors in mice with intact immune systems, makes this model unique for investigations of molecular and immune interactions in ovarian cancer development.

Animals↗

Antiproliferative effects of trapidil in vascular smooth muscle cells are associated by inhibition of MAPK and P34(cdc2) activity.

Trapidil (Tra) is a potent coronary vasodilator. Recent studies have shown that Tra possesses antiproliferative activity in glioma cells and vascular smooth muscle cells (VSMCs). These studies were undertaken to determine the effects of Tra on the cell cycle of cultured rat VSMCs, in particular, the effects on two key enzymes responsible for cell-cycle control in cultured rat VSMCs. VSMCs were synchronized by serum deprivation and then stimulated to enter the cell cycle by serum refeeding; the cell-cycle distribution was subsequently measured by flow cytometry, and VSMCs pretreated with 5, 50, and 500 microM Tra showed a decrease in S-phase cell-cycle distribution, 13.1, 18.7, and 58.6%, respectively. In addition, the mitotic activity (S + G2/M) decreased 12.9, 18.7, and 49.6%, respectively after Tra treatment. The protein expression of p34cdc2 was determined by Western blot analysis, and Tra treatment did not affect its expression even at 500 microM. Mitogen-activated protein kinase (MAPK) activity and p34cdc2 kinase activity were assayed by phosphorylation of their specific substrates, myelin basic protein (MBP) and histone H1, after immunoprecipitation. Exposure of VSMCs to Tra resulted in a significant decrease in serum-stimulated MAPK and p34cdc2 activity. The inhibitory rates of 50 and 500 microM Tra on MAPK activity were 59.2 and 80.9%, respectively. Tra concentrations of 5, 50, and 500 microM inhibited p34cdc2 activity by 16.4, 22.6, and 40.8%, respectively. Furthermore, 500 microM Tra inhibited the basal kinase activities of MAPK and p34cdc2 in the cells that were not serum stimulated. These findings demonstrate that Tra significantly decreases the mitotic activity of cultured VSMCs, and that this effect is associated with the inhibitory role of Tra on the kinase activities of MAPK and p34cdc2.

Animals↗

Acute cardiovascular effects of the alpha2-adrenoceptor antagonist, idazoxan, in rats: influence of the basal sympathetic tone.

Intravenous administration of the alpha2-adrenoceptor antagonist, idazoxan, elicits variable cardiovascular effects, depending on experimental conditions. In this study, the effects of idazoxan were investigated in rats with high, low, or no basal sympathetic tone. In a group of conscious Sprague-Dawley rats (n = 9), mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nervous activity (RSNA) were recorded. Idazoxan (250 microg/kg, i.v.) induced a transient decrease in MAP (-12+/-3 mm Hg) that was accompanied by increases in HR (49+/-14 beats/min) and RSNA (53+/-14%). In six of nine rats, a light pentobarbitone anesthesia was given. Basal RSNA was decreased (6.0+/-1.3 microV from 12.8+/-4.1 microV; p<0.05), and the depressor effect of idazoxan was reversed to a pressor effect (21+/-6 mm Hg) associated with bradycardia (-16+/-8 beats/min) and sympathoinhibition (-56+/-15%). In eight conscious intact rats, idazoxan (250 microg/kg, i.v.) attenuated by approximately 40% the pressor response to the selective alpha1-adrenoceptor agonist, cirazoline (0.5 microg/kg, i.v.). In three groups of six to seven ganglion-blocked (chlorisondamine, 2.5 mg/kg, i.v.) conscious rats, idazoxan dose-dependently increased mean arterial pressure (MAP: 39+/-2, 55+/-3, and 69+/-4 mm Hg at 125, 250, and 500 microg/kg, i.v., respectively) with minimal changes in HR. In contrast, the noradrenaline-releasing agent, tyramine (62.5, 125, and 250 microg/kg, i.v.), dose-dependently increased both MAP and HR. The alpha1-adrenoceptor antagonist, prazosin (1 mg/kg, i.v.; n = 8) blunted by approximately 70% (p<0.01) the pressor effect of 250 microg/kg idazoxan. It is concluded that in rats with high sympathetic tone, idazoxan has depressor effects, most likely related to its peripheral alpha-adrenoceptor antagonist properties. In rats with low or no sympathetic tone, idazoxan induced pressor responses mainly secondary to its partial agonist activity at vascular postjunctional alpha1-adrenoceptors.

Acute Disease↗

Direct evidence of the role of virtual electrode-induced phase singularity in success and failure of defibrillation.

INTRODUCTION: We recently demonstrated that virtual electrode-induced phase singularity is responsible for arrhythmogenesis during T wave shocks and explains the upper and lower limits of vulnerability. Furthermore, we suggested that the same mechanism might be responsible for defibrillation failure. The aim of this study was to experimentally support this hypothesis. METHODS AND RESULTS: We used the voltage-sensitive dye di-4-ANEPPS and fast imaging to assess electrical activity in Langendorff-perfused rabbit hearts. Ventricular arrhythmias were induced by monophasic shocks applied during T wave. Three types of defibrillation shocks (n = 79) were delivered from an intravenous right ventricular electrode: monophasic (8 msec), optimal biphasic (8/8 msec, 2/1 leading-edge voltage ratio), and nonoptimal biphasic (8/8 msec, 1/1 leading-edge voltage ratio). We found that a monophasic shock extinguished arrhythmic pattern of electrical activity via a virtual electrode polarization effect. However, the virtual electrode polarization was likely to produce phase singularities, leading to another arrhythmia and defibrillation failure. Nonoptimal biphasic shocks produced similar effects. Optimal biphasic shocks were successful because the first phase of the shock erased the arrhythmia via the virtual electrodes effect, whereas the second phase canceled the virtual electrodes, eliminating the substrate for phase singularities and arrhythmia resulting from them. CONCLUSION: Our data provide the first experimental support of the hypothesis implicating virtual electrode-induced phase singularity in defibrillation failure in the Langendorff-perfused rabbit heart. Optimal biphasic shock has a higher defibrillation efficacy because it does not produce virtual electrode-induced phase singularities.

Animals↗

Reversal of repolarization gradient does not reverse the chirality of shock-induced reentry in the rabbit heart.

INTRODUCTION: Two hypotheses have been proposed to explain the mechanisms of vulnerability and related failure of defibrillation therapy: the cross-field-induced critical point hypothesis and the virtual electrode-induced phase singularity hypothesis. These two hypotheses predict the opposite effect of preshock repolarization on the chirality (direction of rotation) of shock-induced reentry. The former suggests its reversal upon reversal of repolarization, whereas the latter suggests its preservation. The aim of this study was to determine, by reversing the repolarization sequence, which of the mechanisms is responsible for internal shock-induced arrhythmia in the Langendorff-perfused rabbit heart. METHODS AND RESULTS: We used high-resolution optical mapping to assess the chirality of postshock reentry in 11 hearts. Hearts were paced at a coupling interval of 300 msec at various sites around the field of view (13.5 x 13.5 to 16.5 x 16.5 mm). Cathodal monophasic implantable cardioverter defibrillator shocks (-100 V, 8 msec) were applied during the T wave from a 10-mm coil electrode placed into the right ventricular cavity. We used 3.5 +/- 0.8 different pacing sites per heart. Change in direction of repolarization did not result in change of chirality. Chirality was constant in all 11 hearts despite the complete reversal of activation and repolarization patterns. However, the position of resulting vortices depended on transmembrane polarization gradient inverted delta Vm and amplitude of negative polarization Vm (deexcitation). Stronger gradients and deexcitation produced earlier epicardial break excitation (P = 0.04 and P < 0.0001, respectively). CONCLUSION: Virtual electrode-induced phase singularity mechanism underlies internal shock-induced arrhythmia in this model.

Animals↗

Does physical activity reduce the risk of developing peptic ulcers?

BACKGROUND: Although Helicobacter pylori has been identified as a major cause of chronic gastritis, not all infected patients develop ulcers, suggesting that other factors such as lifestyle may be critical to the development of ulcer disease. AIM: To investigate the role physical activity may play in the incidence of peptic ulcer disease. METHODS: The subjects were men (8529) and women (2884) who attended the Cooper Clinic in Dallas between 1970 and 1990. The presence of gastric or duodenal ulcer disease diagnosed by a doctor was determined from a mail survey in 1990. Subjects were classified into three physical activity groups according to information provided at the baseline clinic visit (before 1990): active, those who walked or ran 10 miles or more a week; moderately active, those who walked or ran less than 10 miles a week or did another regular activity; the referent group consisting of those who reported no regular physical activity. RESULTS: With the use of gender specific proportional hazards regression models that could be adjusted for age, smoking, alcohol use, body mass index, and self reported tension, active men were found to have a significant reduction in risk for duodenal ulcers (relative hazard (95% confidence interval) for the active group was 0.38 (0.15 to 0.94) and 0.54 (0.30 to 0.96) for the moderately active group). No association was found between physical activity and gastric ulcers for men or for either type of ulcer for women. CONCLUSIONS: Physical activity may provide a non-pharmacological method of reducing the incidence of duodenal ulcers among men.

Adult↗