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Research organisations and individual researchers increasingly choose to share their research findings by providing lists of their published works on the World Wide Web. To facilitate the exchange of ideas, the lists often include links to published papers in portable document format (PDF) or Postscript (PS) format. Generally, these publication Web sites are updated regularly to include new works. While manual monitoring of relevant Web sites is tedious, commercial search engines and information monitoring systems are ineffective in finding and tracking scholarly publications. Analyses the characteristics of publication index pages and describes effective automatic extraction techniques that the authors have developed. The authors' techniques combine lexical and syntactic analyses with heuristics. The proposed techniques have been implemented and tested for more than 14,000 Web pages and achieved consistently high success rates of around 90 percent. [ABSTRACT FROM AUTHOR]

The dynamic nature of information content on the Web has posed a serious problem to users who need constantly to keep track of the latest updates on specific information. Traditional search engines enable users to retrieve potentially relevant Web information, but they do not track and monitor Web pages based on users' interests. On the other hand, Web information monitoring systems are designed specifically to help users track and monitor Web information. However, to make Web monitoring effective, it is necessary to identify and understand typical Web page update characteristics so that useful monitoring features and functions can be designed and built into these systems. In this study, a total of 105 Web pages from the Internet were collected and monitored over a one-month period. These pages are selected from seven domains under Yahoo!'s directories. The analysis results are presented according to Web site domains, Web page types, Web page attributes and change frequency. Based on this study, different functions and features for a Web monitoring system are identified. These features have been incorporated into a Web monitoring system, WebMon, that has been developed at the School of Computer Engineering, Nanyang Technological University, Singapore. [ABSTRACT FROM AUTHOR]

In natural language processing, fact verification is a very challenging task, which requires retrieving multiple evidence sentences from a reliable corpus to verify the authenticity of a claim. Although most of the current deep learning methods use the attention mechanism for fact verification, they have not considered imposing attentional constraints on important related words in the claim and evidence sentences, resulting in inaccurate attention for some irrelevant words. In this paper, we propose a syntactic evidence network (SENet) model which incorporates entity keywords, syntactic information and sentence attention for fact verification. The SENet model extracts entity keywords from claim and evidence sentences, and uses a pre-trained syntactic dependency parser to extract the corresponding syntactic sentence structures and incorporates the extracted syntactic information into the attention mechanism for language-driven word representation. In addition, the sentence attention mechanism is applied to obtain a richer semantic representation. We have conducted experiments on the FEVER and UKP Snopes datasets for performance evaluation. Our SENet model has achieved 78.69% in Label Accuracy and 75.63% in FEVER Score on the FEVER dataset. In addition, our SENet model also has achieved 65.0% in precision and 61.2% in macro F1 on the UKP Snopes dataset. The experimental results have shown that our proposed SENet model has outperformed the baseline models and achieved the state-of-the-art performance for fact verification., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Detecting event triggers in biomedical texts, which contain domain knowledge and context-dependent terms, is more challenging than in general-domain texts. Most state-of-the-art models rely mainly on external resources such as linguistic tools and knowledge bases to improve system performance. However, they lack effective mechanisms to obtain semantic clues from label specification and sentence context. Given its success in image classification, label representation learning is a promising approach to enhancing biomedical event trigger detection models by leveraging the rich semantics of pre-defined event type labels., Results: In this paper, we propose the Biomedical Label-based Synergistic representation Learning (BioLSL) model, which effectively utilizes event type labels by learning their correlation with trigger words and enriches the representation contextually. The BioLSL model consists of three modules. Firstly, the Domain-specific Joint Encoding module employs a transformer-based, domain-specific pre-trained architecture to jointly encode input sentences and pre-defined event type labels. Secondly, the Label-based Synergistic Representation Learning module learns the semantic relationships between input texts and event type labels, and generates a Label-Trigger Aware Representation (LTAR) and a Label-Context Aware Representation (LCAR) for enhanced semantic representations. Finally, the Trigger Classification module makes structured predictions, where each label is predicted with respect to its neighbours. We conduct experiments on three benchmark BioNLP datasets, namely MLEE, GE09, and GE11, to evaluate our proposed BioLSL model. Results show that BioLSL has achieved state-of-the-art performance, outperforming the baseline models., Conclusions: The proposed BioLSL model demonstrates good performance for biomedical event trigger detection without using any external resources. This suggests that label representation learning and context-aware enhancement are promising directions for improving the task. The key enhancement is that BioLSL effectively learns to construct semantic linkages between the event mentions and type labels, which provide the latent information of label-trigger and label-context relationships in biomedical texts. Moreover, additional experiments on BioLSL show that it performs exceptionally well with limited training data under the data-scarce scenarios., (© 2024. The Author(s).)

Aims: Children with severe needle phobia find vaccination extremely distressing and can remain unvaccinated, which puts them at an increased risk of contracting and transmitting vaccine preventable disease. Referral to a specialist or hospital service may occur when they cannot be safely vaccinated in the community, but engagement of allied health services can be inconsistent. The aim of the study was to assess the impact of a multidisciplinary, consumer-oriented model of care on vaccinations for needle phobic children., Methods: Needle phobic children aged between 6 and 16 years attended multidisciplinary consultation, as part of a care package, to assess previous experiences and determine the level of intervention that was required to support vaccination. A multidisciplinary case meeting followed this appointment and an individualised plan formulated for each patient. The main outcome of the project was rate of successful vaccination., Results: The care package resulted in a successful vaccination rate of 83% (n = 20) with 69 vaccines administered across three clinics. Of those successful, 90% required multiple injections per visit. The majority of patients indicated moderate to high level of anxiety. Supportive care was escalated and de-escalated as tolerated., Conclusions: Results demonstrate the diversity of patients presenting with needle phobia and indicate an individualised, collaborative approach is preferable to a 'one size fits all' model of care. The study highlights a need for the development of guidelines that streamline the assessment and individualisation of procedural anxiety plans to meet patient needs and embed these processes into standard care., (© 2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Prostate cancer (PCa), an extremely common malignancy in males, is the most prevalent disease in several countries. Norcantharidin (NCTD) has antiproliferation, antimetastasis, apoptosis, and autophagy effects in various tumor cells. Nevertheless, the antitumor effect of NCTD combined with paclitaxel (PTX), a chemotherapeutic drug, in PCa remains unknown. The cell growth, proliferative rate, cell cycle distribution, and cell death were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, colony formation assay, PI staining, and Annexin V/PI staining by flow cytomertry, whereas the mitochondrial membrane potential (MMP) and endoplasmic reticulum (ER) stress was evaluated using the MitoPotential assay and ER-ID red assay. We also evaluated the protein and mRNA expression of SIRTs by Western blotting and qRTPCR assay. Overexpression effectivity was measured by DNA transfection assay. Our study showed that cell viability and proliferative PC3 and DU145 rates were effectively inhibited after NCTD-PTX combination. We also found that NCTD-PTX combination treatment significantly enhance G2/M phase arrest, induction of cell death and ER stress, loss of MMP, and ER- or apoptotic-related protein expression. Furthermore, NCTD-PTX combination treatment was significantly decreasing the protein and mRNA expression of SIRT7 in PCa cells. Combination therapy effectively reduced cell viability, ER stress-mediated apoptosis and p-eIF2α/ATF4/CHOP/cleaved-PARP expression inhibition in SIRT7 overexpression of PCa cells. These results indicate that NCTD combined with PTX induces ER stress-mediated apoptosis of PCa cells by regulating the SIRT7 expression axis. Moreover, combination therapy may become a potential therapeutic strategy against human PCa., (© 2021 Wiley Periodicals LLC.)

Introduction: Biologic disease-modifying anti-rheumatic drugs (bDMARDS) are increasingly used in clinical practice for a variety of conditions. Due to concerns surrounding persistence of drug levels and resulting immunosuppression, current case reports recommend against live vaccine administration in the first year of life for an infant exposed to perinatal bDMARDS. As a result, this significantly impacts receipt of rotavirus vaccination, a vaccine recommended in many countries' national immunization program. Area covered: We have reviewed all available published literature to explore the effect of peripartum bDMARDS exposure on infant immune responses, safety of live vaccines, and vaccine efficacy in the first year of life. Expert opinion: We recommend that otherwise healthy newborns with a history of perinatal exposure to bDMARDS should receive rotavirus vaccinations as per the recommended schedule. Bacille Calmette et Guerin vaccine should be withheld in the first year of life. No additional booster doses of inactivated vaccines are required as they appear to mount adequate immune responses to the routine schedule.

Colorectal cancer (CRC) is the third highest cause of cancer-related death and the main option for prolonged survival is chemotherapeutic intervention. There is increasing interest in dietary intervention using natural agents to enhance the sensitivity of such invasive chemical treatment. In this study, the chemotherapeutic efficacy of dihydromyricetin (DMY) intervention on treatments involving irinotecan (CPT-11) or gemcitabine (GM) was evaluated in an AOM/DSS-induced colitis-associated colon cancer model and a Min (Apc Min/+) mice model. Our data showed that DMY could promote the CPT-11 effect both in the mouse model of AOM/DSS and Apc Min/+ cancer and had no influence on the GM effect. In AOM/DSS cancer, tumors were sensitive to 100 mg kg-1 DMY chemotherapy under 100 mg kg-1 or 200 mg kg-1 CPT-11. DMY-driven CPT-11 chemotherapy induced enhanced IgG levels and the reduction of Fusobacterium abundance in the gut. In the Min model, CPT-11 with 20 mg kg-1 DMY prevented tumor formation but not with 100 mg kg-1 DMY. Mechanically, chloride ion-dependent CFTR, CLCN4, and CLIC4 signaling are not involved in DMY mediated chemotherapeutic colon tumorigenesis. These results suggested that a suitable dose of DMY could act as a coadjuvant to CPT-11 chemotherapy.

Colorectal cancer (CRC) is a disease involving a variety of genetic and environmental factors. Sirtuin-3 (Sirt3) is expressed at a low level in cancer tissues of CRC, but it is unclear how Sirt3 modulates colonic tumorigenesis. In this study, we found that gut microbiota play a central role in the resistance to CRC tumor formation in wild-type (WT) mice through APC (Adenomatous Polyposis Coli)-mutant mouse microbiota transfer via Wnt signaling. We also found that Sirt3-deficient mice were hypersusceptible to colonic inflammation and tumor development through altered intestinal integrity and p38 signaling, respectively. Furthermore, susceptibility to colorectal tumorigenesis was aggravated by initial commensal microbiota deletion via Wnt signaling. Mice with Sirt3-deficient microbiota transfer followed by chemically induced colon tumorigenesis had low Sirt3 expression compared to WT control microbiome transfer, mainly due to a decrease in Escherichia/Shigella, as well as an increase in Lactobacillus reuteri and Lactobacillus taiwanensis. Collectively, our data revealed that Sirt3 is an anti-inflammatory and tumor-suppressing gene that interacts with the gut microbiota during colon tumorigenesis.

Parallel test paper generation is a biobjective distributed resource optimization problem, which aims to generate multiple similarly optimal test papers automatically according to multiple user-specified assessment criteria. Generating high-quality parallel test papers is challenging due to its NP-hardness in both of the collective objective functions. In this paper, we propose a submodular memetic approximation algorithm for solving this problem. The proposed algorithm is an adaptive memetic algorithm (MA), which exploits the submodular property of the collective objective functions to design greedy-based approximation algorithms for enhancing steps of the multiobjective MA. Synergizing the intensification of submodular local search mechanism with the diversification of the population-based submodular crossover operator, our algorithm can jointly optimize the total quality maximization objective and the fairness quality maximization objective. Our MA can achieve provable near-optimal solutions in a huge search space of large datasets in efficient polynomial runtime. Performance results on various datasets have shown that our algorithm has drastically outperformed the current techniques in terms of paper quality and runtime efficiency.

Background: Patients with adolescent idiopathic scoliosis (AIS) frequently receive x-ray imaging at diagnosis and subsequent follow monitoring. The ionizing radiation exposure has accumulated through their development stage and the effect of radiation to this young vulnerable group of patients is uncertain. To achieve the ALARA (as low as reasonably achievable) concept of radiation dose in medical imaging, a slot-scanning x-ray technique by the EOS system has been adopted and the radiation dose using micro-dose protocol was compared with the standard digital radiography on patients with AIS., Methods: Ninety-nine participants with AIS underwent micro-dose EOS and 33 underwent standard digital radiography (DR) for imaging of the whole spine. Entrance-skin dose was measured using thermoluminescent dosimeters (TLD) at three regions (i.e. dorsal sites at the level of sternal notch, nipple line, symphysis pubis). Effective dose and organ dose were calculated by simulation using PCXMC 2.0. Data from two x-ray systems were compared using independent-samples t-test and significance level at 0.05. All TLD measurements were conducted on PA projection only. Image quality was also assessed by two raters using Cobb angle measurement and a set of imaging parameters for optimization purposes., Results: Entrance-skin dose from micro-dose EOS system was 5.9-27.0 times lower at various regions compared with standard DR. The calculated effective dose was 2.6 ± 0.5 (μSv) and 67.5 ± 23.3 (μSv) from micro-dose and standard DR, respectively. The reduction in the micro-dose was approximately 26 times. Organ doses at thyroid, lung and gonad regions were significantly lower in micro-dose ( p  < 0.001). Data were further compared within the different gender groups. Females received significantly higher ( p  < 0.001) organ dose at ovaries compared to the testes in males. Patients with AIS received approximately 16-34 times lesser organ dose from micro-dose x-ray as compared with the standard DR. There was no significant difference in overall rating of imaging quality between EOS and DR. Micro-dose protocol provided enough quality to perform consistent measurement on Cobb angle., Conclusions: Entrance-skin dose, effective dose and organ dose were significantly reduced in micro-dose x-ray. The effective dose of a single micro-dose x-ray (2.6 μSv) was less than a day of background radiation. As AIS patients require periodic x-ray follow up for surveillance of curve progression, clinical use of micro-dose x-ray system is beneficial for these young patients to reduce the intake of ionizing radiation.

Aim: Varicella is a vaccine-preventable disease not notifiable in New Zealand (NZ), and varicella vaccine is not funded in the National Immunisation Schedule (NIS). Hospitalisations can occur because of bacterial secondary infection and other complications, which can result in long-term sequelae. Varicella may not be acknowledged in discharge coding when complications occur weeks after infection. Using the New Zealand Paediatric Surveillance Unit (NZPSU), the aim of this study was to document the hospitalisation burden of this disease., Methods: Cases (0-14 years) of varicella and post-varicella complications requiring hospitalisation, including stroke syndromes where varicella occurred in the preceding 6 months, were notified to NZPSU between 1 November 2011 and 31 October 2013. Herpes zoster cases were excluded. Questionnaires were used to capture demographics, clinical features, management and short-term outcomes., Results: One hundred seventy-eight notifications were received and 144 were confirmed cases. Overall incidence was 8.3/100,000 children per year. Fifty-two percent were women with a median age of 2.4 years. Māori and Pacific Island (PI) children accounted for 74% of hospitalisations, with incidence rate ratios compared with European children of 2.8 and 3.9, respectively (P < 0.01). Complications included: infection (75%), respiratory (11%), neurological (11%), electrolyte disturbance (6%) and haemorrhagic varicella (4%). Nine percent were immunocompromised. Median duration of hospital admission was 4 days with 9% requiring intensive care admission. There were no reported deaths; however, 19% had ongoing problems at discharge., Conclusion: Varicella has more associated morbidity than commonly perceived in immunocompetent children. Māori and PI children are more likely to have complications. This surveillance gives support for inclusion of universal varicella vaccine in the NZ NIS., (© 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Background Context: Existing prognostic factors for adolescent idiopathic scoliosis (AIS) patients have focused mainly on curve, maturity, and bone-related factors. Previous studies have shown significant associations between curve severity and morphological evidences of relative shorter spinal cord tethering in AIS, and increased prevalence of abnormal somatosensory cortical-evoked potentials and low-lying cerebellar tonsil in severe AIS. Earlier evidence suggests that there might be neural morphological predictors for curve progression., Purpose: The purpose of this study was to identify any morphological predictors associated with cord tethering, as measured by magnetic resonance imaging (MRI), for curve progression in AIS patients., Study Design/setting: This is a prospective cohort study., Patient Sample: A total of 81 female AIS subjects between 10 and 14 years were included, without surgical intervention during the follow-up period., Outcome Measures: Magnetic resonance imaging scans of hindbrain and whole spine and areal bone mineral density (BMD) at bilateral femoral necks were performed., Methods: All AIS patients were longitudinally followed up starting from initiation of bracing beyond skeletal maturity in 6-month intervals. Clinical and radiographic data were recorded at each clinic visit. Bone mineral density and MRI measurements including ratio of spinal cord to vertebral column length, ratio of anteroposterior (AP) and transverse (TS) diameter of cord, lateral cord space (LCS) ratio, cerebellar tonsil level, and conus medullaris position were obtained at baseline. Only compliant patients with a minimum 2-year follow-up were analyzed. Adolescent idiopathic scoliosis girls were assigned into three groups according to bracing outcome: Group A, nonprogression (curvature increase of less than or equal to 5°); Group B, progression (curvature increase of greater than or equal to 6°); Group C, progression with surgery indication (Cobb angle of greater than or equal to 50° after skeletal maturity despite bracing). The predictors for curve progression were evaluated using univariate analysis and multivariate ordinal regression model., Results: The average duration of follow-up was 3.4 (range, 2.0-5.6) years. There were 46 girls (57%) in Group A, 19 (23%) in Group B, and 16 (20%) in Group C. No significant intergroup differences were found in spinal cord length, tonsil level, and conus position. Group C had significantly longer vertebral column length, smaller cord-vertebral length ratio, and higher AP/TS cord ratio compared with Group A, whereas LCS ratio in Group C was significantly increased compared with both Group A and Group B. In regression model, five significant independent predictors including cord-vertebral length ratio (odds ratio [OR]: 1.993 [95% confidence interval {CI}: 1.053-3.771], p=.034), LCS ratio (OR: 2.639 [95% CI: 1.128-6.174], p=.025), initial Cobb angle (OR: 1.156 [95% CI: 1.043-1.281], p=.006), menarche age (OR: 1.688 [95% CI: 1.010-2.823], p=.046), and BMD (OR: 2.960 [95% CI: 1.301-6.731], p=.010) and a marginally significant predictor namely AP/TS cord ratio (OR: 1.463 [95% CI: 0.791-2.706], p=.096) were obtained., Conclusions: On baseline MRI measurement, cord-vertebral length ratio and LCS ratio are identified as new significant independent predictors for curve progression in AIS, whereas AP/TS cord ratio is suggested as a potential predictor requiring further validations. The earlier MRI parameters can be taken into accounts for prognostication of bracing outcome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Suspension exercise has been advocated as an effective means to improve core stability among healthy individuals and those with musculoskeletal complaints. However, the activity of core muscles during suspension exercises has not been reported. In this study, we investigated the level of activation of core muscles during suspension exercises within young and healthy adults., Design: The study was conducted in a controlled laboratory setting., Methods: Surface electromyographic (sEMG) activity of core muscles (rectus abdominis, external oblique, internal oblique/transversus abdominis, and superficial lumbar multifidus) during four suspension workouts (hip abduction in plank, hamstring curl, chest press, and 45° row) was investigated. Muscle activity during a 5-s hold period of the workouts was measured by sEMG and normalized to the individual's maximal voluntary isometric contraction (MVIC)., Results: Different levels of muscle activation were observed during the hip abduction in plank, hamstring curl, and chest press. Hip abduction in plank generated the highest activation of most abdominal muscles. The 45° row exercise generated the lowest muscle activation., Conclusions: Among the four workouts investigated, the hip abduction in plank with suspension was found to have the strongest potential strengthening effect on core muscles. Also, suspension training was found to generate relatively high levels of core muscle activation when compared with that among previous studies of core exercises on stable and unstable support surfaces., (Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Disturbed somatosensory evoked potentials have been demonstrated in patients with adolescent idiopathic scoliosis (but this functional delay was found to originate above the C5-6 level, while the lower cord level was unaffected). Together with MR imaging observation of tonsillar ectopia and a relatively tethered cord, we hypothesized that there is disturbed mean diffusivity integrity along the spinal cord. In this study, advanced DTI was used to evaluate whether there was underlying decreased WM integrity within the brain stem and spinal cord in adolescent idiopathic scoliosis and any relationship to cerebellar tonsillar ectopia. Clinical impact on balance testing was also correlated., Materials and Methods: Thirteen girls with adolescent idiopathic scoliosis with right thoracic curves were compared with 13 age-matched healthy girls. DTI of the brain and whole spinal cord was performed. ROIs were manually defined for the medulla oblongata and along each intervertebral segment of the cord. Mean values of fractional anisotropy and mean diffusivity were computed at the defined regions. Between-group comparisons were performed by 1-way ANOVA., Results: Significantly decreased fractional anisotropy values and increased mean diffusivity values were found at the medulla oblongata and C1-2, C2-3, C3-4, and C4-5 segments in patients with adolescent idiopathic scoliosis compared with healthy subjects. No significant difference was found in the lower cord levels. Significant correlation was found between the tonsillar level and fractional anisotropy value at the C4-5 level in patients with adolescent idiopathic scoliosis only., Conclusions: The findings from this study are in agreement with previous findings showing abnormal somatosensory evoked potential readings occurring only above the C5-6 level in patients with adolescent idiopathic scoliosis; these findings might partially explain the pathophysiology of the neural pathway involved., (© 2014 by American Journal of Neuroradiology.)

Aims: Varicella is now a vaccine-preventable disease but is generally considered benign, making it a low priority for a funded universal immunisation scheme. We aimed to increase the knowledge of the severity, morbidity and mortality caused by varicella, by a review of cases requiring paediatric intensive care in New Zealand where vaccine is available but not funded., Methods: This is a retrospective chart review of children admitted to the paediatric intensive care unit (PICU) over a 10-year period (July 2001-July 2011) identified from the PICU database with a primary or secondary code for varicella., Results: Thirty-four cases were identified and 26 cases were included. Of the 26 cases, 84.6% were Maori or Pacific Island ethnicity, 54% had no preceding medical condition and 23% were immunocompromised. Main PICU admission reasons were neurologic (38.5%), secondary bacterial sepsis or shock (26.9%), respiratory (15.4%), disseminated varicella (11.5%), or other causes (7.7%). Fifty per cent of children required inotropic support and 81% invasive ventilation. Four children died (15%), three of whom were immunocompromised. A further eight children (31%) had ongoing disability at hospital discharge., Conclusion: Varicella, or its secondary complications, requiring paediatric intensive care, carries high mortality, particularly for immunocompromised patients, and long-term morbidities, mostly affecting previously healthy children., (© 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

High quality segmentation of diffusion tensor images (DTI) is of key interest in biomedical research and clinical application. In previous studies, most efforts have been made to construct predefined metrics for different DTI segmentation tasks. These methods require adequate prior knowledge and tuning parameters. To overcome these disadvantages, we proposed to automatically learn an adaptive distance metric by a graph based semi-supervised learning model for DTI segmentation. An original discriminative distance vector was first formulated by combining both geometry and orientation distances derived from diffusion tensors. The kernel metric over the original distance and labels of all voxels were then simultaneously optimized in a graph based semi-supervised learning approach. Finally, the optimization task was efficiently solved with an iterative gradient descent method to achieve the optimal solution. With our approach, an adaptive distance metric could be available for each specific segmentation task. Experiments on synthetic and real brain DTI datasets were performed to demonstrate the effectiveness and robustness of the proposed distance metric learning approach. The performance of our approach was compared with three classical metrics in the graph based semi-supervised learning framework.

Adolescent idiopathic scoliosis (AIS) is a multifactorial disease affecting approximately 1-4% of teenagers especially girls at the age of 10-16, but its etiopathogenesis remains uncertain. Previous study has revealed that the cortical thickness in AIS patients is different from that in normal controls. Cortical thickness measurements are known to be strongly correlated between regions that are axonally connected. Hence, a hypothesis is proposed to study the possibility to demonstrate abnormal structural network revealed by cortical thickness in AIS patients. The aim of the study is to investigate abnormalities in the organization of the brain cortical network in AIS patients. This study included 42 girls with severe idiopathic scoliosis (14.7±1.3 years old) and 41 age-matched normal controls (NC, 14.6±1.4 years old). The brain cortex was partitioned into 154 cortical regions based on gyral and sulcal structure. The interregional connectivity was measured as the statistical correlations between the regional mean thicknesses across the subjects. We employed the graph theoretic analysis to examine the alteration in interregional correlation, small-world efficiency, hub distribution, and regional nodal characteristics in AIS patients. We demonstrated that the cortical network of AIS patients fully preserved the small-world architecture and organization, and further verified the hemispheric asymmetry of AIS brain. Our results indicated increased central role of temporal and occipital cortex and decreased central role of limbic cortex in AIS patients compared with controls. Furthermore, decreased structural connectivity between hemispheres and increased connectivity in several cortical regions were observed. The findings of the study reveal the pattern of structural network alteration in AIS brain, and would help in understanding the mechanism and etiopathogenesis of AIS.

Background Context: Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformation that affects adolescents, especially girls. The etiopathogenesis of this disease remains uncertain, and studies have been carried out to understand its cause and related organs. Previous studies suggest that AIS is probably related to the cerebellum dysfunction, which could also be related to the abnormality in morphology of the cerebellum., Purpose: The purpose of the study is to investigate the relationship between AIS and the volume and morphology of cerebellum., Study Design/setting: The study design of the cerebellum segmentation and volume quantification involved the following four steps: whole-brain normalization, cerebellum isolation, mapping with the statistical cerebellum template, and cerebellum regional volume correction., Patient Sample: In particular, high-resolution T1-weighted magnetic resonance images of 50 AIS patients with the right-thoracic curves (ie, Cobb angle ≥20°) and 40 age-matched normal controls were acquired. The exclusion criteria included history of head injury, back injury, severe headache, weakness or numbness in any limbs, urinary incontinence, nocturnal enuresis, and any space-occupying lesion found on magnetic resonance (MR) images., Outcome Measures: The AIS subjects were all with moderate-to-severe curves (ie, Cobb angle ≥20°) (9 moderate and 41 severe; mean Cobb angle 48.7°, range 20°-90°)., Methods: The cerebellum was parcellated to 28 regions by mapping with a well-recognized probabilistic MR cerebellum atlas. Student t test of each cerebellar region and the correction for multiple comparisons were performed., Results: The volumes of four regions, namely right VIIIa, right VIIIb, left X, and right X, were significantly increased by approximately 7.43% to 8.25% in the AIS compared with the control group. Statistically, the results suggested that the cerebellar volume in AIS patients was larger compared with normal controls in the cerebellum regions of prepyramidal-prebiventer and intrabiventer fissures, intrabiventer and secondary fissures, and floccular-nodular (X)-posterolateral fissure to the inferior hemispheric margin., Conclusions: The functions of the affected regions involve motor control, somatosensory, working memory, language, and response to visual stimulation. We conclude that the volume difference could be compensatory consequences in the central nervous system because of the persistent effort in AIS patients to maintain the body balance given the asymmetric spine., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The aim of this review is to summarize the current magnetic resonance imaging (MRI) variants applied on the studies of Alzheimer's disease (AD). Experimental findings, advantages and disadvantages, and the prospect of every individual technique will be presented. MRI can be used to investigate the change of the brain in terms of volume, function, white matter track orientation and even mechanical properties and metabolic concentration.Results from volumetric and morphological analysis indicated that the hippocampus reduced by approximately 18%-24% or 3%-4% annually. Functional MRI (fMRI) detected the blood oxygen level dependent (BOLD) signaland suggested thatmedial temporal lobe (MTL) such as hippocampus and entorhinal cortex reduced at the early stage of AD, and frontal, temporal, and parietal cortices at the later stage. In diffusion tensor imaging (DTI), the white matter fiber track integrity is measured but the results are inconsistent. Besides,magnetic resonance spectroscopy (MRS), chemical shift imaging (CSI), arterial spin labeling (ASL), magnetic resonance elastography (MRE) and susceptibility weighted imaging (SWI) will also be included in this review.

Objective: Recently, much research has been proposed using nature inspired algorithms to perform complex machine learning tasks. Ant colony optimization (ACO) is one such algorithm based on swarm intelligence and is derived from a model inspired by the collective foraging behavior of ants. Taking advantage of the ACO in traits such as self-organization and robustness, this paper investigates ant-based algorithms for gene expression data clustering and associative classification., Methods and Material: An ant-based clustering (Ant-C) and an ant-based association rule mining (Ant-ARM) algorithms are proposed for gene expression data analysis. The proposed algorithms make use of the natural behavior of ants such as cooperation and adaptation to allow for a flexible robust search for a good candidate solution., Results: Ant-C has been tested on the three datasets selected from the Stanford Genomic Resource Database and achieved relatively high accuracy compared to other classical clustering methods. Ant-ARM has been tested on the acute lymphoblastic leukemia (ALL)/acute myeloid leukemia (AML) dataset and generated about 30 classification rules with high accuracy., Conclusions: Ant-C can generate optimal number of clusters without incorporating any other algorithms such as K-means or agglomerative hierarchical clustering. For associative classification, while a few of the well-known algorithms such as Apriori, FP-growth and Magnum Opus are unable to mine any association rules from the ALL/AML dataset within a reasonable period of time, Ant-ARM is able to extract associative classification rules.

Our survey of 133 on-duty medical ward nurses showed that, during peak influenza season, 30 (23%) developed an influenza-like illness, despite wearing a mask at work. Suboptimal adherence to standard precautions, such as the use of a face shield (odds ratio, 3.56) during high-risk procedures, and failure to receive influenza vaccination (odds ratio, 4.82) were independent risk factors, adjusted for household contacts.

Traditional Chinese Medicine (TCM) has been actively researched through various approaches, including computational techniques. A review on basic elements of TCM is provided to illuminate various challenges and progresses in its study using computational methods. Information on various TCM formulations, in particular resources on databases of TCM formulations and their integration to Western medicine, are analyzed in several facets, such as TCM classifications, types of databases, and mining tools. Aspects of computational TCM diagnosis, namely inspection, auscultation, pulse analysis as well as TCM expert systems are reviewed in term of their benefits and drawbacks. Various approaches on exploring relationships among TCM components and finding genes/proteins relating to TCM symptom complex are also studied. This survey provides a summary on the advance of computational approaches for TCM and will be useful for future knowledge discovery in this area.

Berberine is the basic chemical component of a Chinese herb, Coptis chinensis Franch (coptis), considered to be useful in treating some diseases of the cardiovascular system, such as hypertension and chronic heart failure (CHF). In this study, we investigate the inhibitory effect of berberine on experimental cardiac hypertrophy, which is regarded as a risk factor of CHF and other heart diseases. Forty-two male SD rats were divided into four groups: age-matched control, aortic banding model, berberine-treated group and captopril-treated group. Cardiac hypertrophy was induced by suprarenal abdominal aorta constriction (banding). The drugs were orally administered for 8 weeks starting from 4 weeks after surgery at dosage of berberine 10 mg/kg and captopril 50 mg/kg. Blood pressure (BP) was measured four times during the period of the experiment, and hemodynamic parameters, cardiac index, cell size of left ventricular myocardium and total protein of left ventricular tissue were detected 8 weeks after treatment with drugs. The data from the present study showed that: (1) The BP of the aorta banded rats was increased compared with those of the normal (p < 0.001) and the age-matched control rats (p < 0.001), and berberine showed no significant effect on it. (2) After 8 weeks of treatment with berberine, the elevated left ventricular end diastolic pressure (LVEDP) was slightly decreased compared with the aortic banded rats. Meanwhile, the maximum rates of contraction and relaxation (+/- dp/dtmax) was increased (p < 0.05) and the time to reach the point of maximum rate from beginning of contraction (t-dp/dt) was shortened (p < 0.01), indicating that the functions of heart, both contraction and relaxation, were improved. (3) Cardiac growth was inhibited by treatment with berberine. Both whole heart and left ventricular weight were notably decreased compared with the banded rats (p < 0.05 and p < 0.01). (4) The cell size of left ventricular myocardium was significantly reduced (p < 0.001) and the total protein of left ventricular tissue was slightly down-regulated by treatment with berberine. These data suggest that berberine can improve abnormal cardiac function and can prevent the development of left ventricular hypertrophy induced by pressure-overload. This indicates that it may have therapeutic potential in the treatment of CHF.

The effects of tetrandrine, a Ca2+ antagonist of bis-benzylisoquinoline alkaloid origin, on endothelium-dependent and -independent vascular responsiveness were investigated in perfused rat mesenteric artery. In endothelium-intact preparations pre-contracted with 3 microM phenylephrine and fully relaxed by 0.3 microM acetylcholine tetrandrine caused a rapid transient contraction. In endothelium-denuded preparations, tetrandrine caused only vasorelaxation of phenylephrine-contraction. The biphasic effect of tetrandrine in acetylcholine-relaxed preparations could also be mimicked by sequential applications of atropine/tetrandrine or N(G)-nitro-L-arginine-methylester (L-NAME)/tetrandrine, but atropine or L-NAME alone caused only vasoconstriction. This tetrandrine-induced transient vasoconstriction was also observed in preparations relaxed with ATP, histamine or thapsigargin (TSG), but not those relaxed with A23187, sodium nitroprusside or nifedipine. The present results suggest that tetrandrine, in addition to its known inhibitory effects on vascular smooth muscle by virtue of its Ca2+ antagonistic actions, also inhibits NO production by the endothelial cells possibly by blockade of Ca2+ release-activated Ca2+ channels.

1. The effect of ondansetron, a selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist, was studied in morphine-addicted rats. Morphine-dependence and tolerance, induced by drinking increasing concentrations of morphine sulphate in 5% sucrose solution for 3 weeks, were demonstrated by the naloxone-precipitated withdrawal syndrome and tail flick response to a thermal noxious stimulus (water at 50 degrees C), respectively. 2. Morphine-dependence, assessed by naloxone precipitated withdrawal, was undetectable by the 6th day, when the animals drank only tap water for 7 days after the 3-week induction period. 3. When detoxified rats were offered sucrose and morphine solutions for 10 days, the recurrence of opiate solution preference with relapse to dependence and tolerance was observed. 4. Giving ondansetron (0.1 or 1 microgram kg-1; i.p.; twice daily) on the 14th day of, or 7 days prior to, the 3-week induction period reduced dependence and tolerance seen during the 3-week morphine induction and the 10-day drinking preference periods. 5. 5-Hydroxytryptamine2 (5-HT2) receptor antagonism by cyproheptadine (100 or 250 micrograms kg-1; i.p.; twice daily) did not influence morphine-dependence and tolerance. 6. These findings suggest that ondansetron may be useful for treating opiate addiction and lowering the recidivism rate.

Aim: To examine the effects of tetrandrine (Tet) on the aggregation and ATP-release of rat washed platelets induced by several platelet activators., Methods: Gel-filtration (Sepharose 2B) was used to isolate washed platelets from adult rats and the platelet aggragation and ATP-release were measured simultaneously., Results: In the presence of Ca2+ 1 mmol.L-1, Tet 300 mumol.L-1 inhibited the aggregation induced by ADP (25 mumol.L-1), collagen (2.5 g.L-1), and thrombin (103 unit.L-1) by 62%, 60%, and 34%, respectively. It also inhibited arachidonic acid (1 mmol.L-1)-induced aggregation. Elevating intracellular Ca2+ concentration with the Ca2+ ionophore, calcimycin (30 mumol.L-1), or by blocking the intracellular calcium pump with cyclopiazonic acid (5 mumol.L-1) initiated platelet aggregation, which was also inhibited by Tet. In Ca(2+)-free medium, Tet still elicited an inhibitory effect on aggregation induced by ristocetin (2.5 g.L-1). Lower concentrations of Tet (30 nmol.L-1 to 3 mumol.L-1) failed to inhibit the aggregation (requiring Tet 10-300 mumol.L-1), but strongly suppressed ATP-release induced by ADP 10 mumol.L-1, both of which were measured simultaneously in a single sample., Conclusion: Tet elicits a nonselective inhibitory effect on platelet aggregation not solely due to its Ca2+ antagonism and may act on a final common pathway leading to platelet aggregation. Furthermore, Tet is a much potent inhibitor of the release of ATP in platelets.

Prazosin was injected i.v. at a dose of 50 micrograms/kg every 2 h for 8 h in conscious rats. Its hypotensive action significantly declined. A similar effect was also observed in rabbits pretreated with prazosin (40 micrograms/kg, i.v.) every 1 h for 4 h. In prazosin-treated rabbits, the total peripheral resistance became less responsive to phentolamine stimulation. Repeated prazosin administration abolished its ability to block receptors in a model of anococcygue muscle contraction after noradrenaline (NA) stimulation. The alpha-adrenoceptors in anococcygue muscle exhibited lower pD2 to NA and lower pA2 to prazosin in prazosin-treated rats. The results demonstrate that repeated prazosin administration reduces the effectiveness of alpha-adrenoceptors blockers.

The effects of tetrandrine (TET) on the contractile responses of rat aortic rings and perfused rat mesenteric arteries to phenylephrine (PE) were investigated. TET inhibited the maximal contraction to PE in a concentration-dependent manner. TET significantly inhibited the transient contraction in Ca(2+)-free medium presumably due to release of intracellular Ca2+ after activation of alpha 1-adrenoceptors. However, it caused a stronger inhibition of the sustained contraction in Ca(2+)-containing medium presumably the result of Ca2+ influx. TET has no inhibitory effect on caffeine-induced transient contraction. Radioligand receptor binding study using isolated dog aortic muscle membranes indicated that TET inhibited the binding of 3H-prazosin in a competitive manner, hence showing that TET interacted directly with the alpha 1-adrenoceptors. Thus, TET affected PE-induced aortic contractions by multiple mechanisms, inhibiting interaction of PE with alpha 1-adrenoceptors and interfering with PE-induced responses involving both Ca2+ entry and release.

This study was designed to evaluate the effects of small-volume infusion of 7.5% hypertonic saline/6% dextran-70 (HSD) on the cardiovascular function of traumatic-hemorrhagic shock rats at simulated high altitude. 32 rats were randomly divided into four groups: 1) normal saline (NS)-treated group, 2) .9% NaCl/6% dextran-70 (Dex)-treated group, 3) 7.5% hypertonic saline (HS)-treated group, and 4) 7.5% hypertonic saline/6% dextran-70 (HSD)-treated group. The rats were exposed to a simulated high altitude of 4,000 m in a hypobaric hypoxic chamber, and traumatic-hemorrhagic shock was inflicted through fracture of the shaft of the left femur and bleeding from femoral vein to reduce mean arterial pressure (MAP) to 6.00 +/- .67 kPa within 5 min. The MAP was kept at this level for 1 h, and then a bolus intravenous injection of 4 mL/kg NS, Dex, HS, or HSD were given to the rats, respectively. In the 5 h period after treatment, it was found that MAP, left ventricular systolic pressure, maximal rate of left ventricular pressure rise and drop (+/- dp/dtmax) were significantly higher in HSD group than in the NS, Dex and HS groups. It can be concluded that 1) HSD can improve the cardiovascular function and hemodynamics of traumatic-hemorrhagic shock rats at simulated high altitude and 2) HSD is more effective than HS.

NG-Nitro-L-arginine methyl ester (50 mg/kg s.c.), an inhibitor of nitric oxide (NO) synthase, has been reported to increase brain serotonin (5-hhydroxytryptamine, 5-HT) metabolism and induce hypophagia. Conversely, enhanced NO synthase activity is found to be accompanied by a decrease in 5-HT level. This negative correlation between NO and 5-HT in the regulation of food intake was further studied in mice. 5-HT depletion by p-chlorophenylalanine (250 mg/kg i.p., twice daily for 2 days) failed to antagonize the hypophagic effect of NG-nitro-L-arginine methyl ester. Similarly, treatment with the NO synthesis precursor, L-arginine (1000 mg/kg s.c.), did not reverse the anorexia induced by fenfluramine (10 mg/kg s.c.), a 5-HT releaser/uptake inhibitor. Pretreatment with (-)-pindolol, methylsergide and ritanserin had no effect on the hypophagic action of NG-nitro-L-arginine methyl ester, suggesting the lack of involvement of 5-HT1 and 5-HT2 receptors. The selective neuronal NO synthase inhibitor, 7-nitroindazole (12.5-50.0 mg/kg i.p.), however, did not exhibit any hypophagic effect whilst NG-nitro-L-arginine methyl ester increased gastric retention, which may subsequently induce satiety. Moreover, the hypophagic effect of NG-nitro-L-arginine methyl ester, which was unassociated with changes in water intake and malaise induction, was also unattenuated by cholecystokinin (CCK) receptor antagonists, devazepide (10 mg/kg i.p.) and PD 135,158 ([1S-[1 alpha,2 beta[S*(S*)],4 alpha ]]-4-[[2-[[3-(1 H-indol-3-yl)-2-methyl-1-oxo-2-[[[(1,7,7- trimethylbicyclo[2.2.1]hept-2-yl)oxy]carbonyl]amino]propyl]amino] -1-phenylethyl] amino]-4-oxo-butanoic acid N-methyl-D-glucamine salt; 1 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)

Ondansetron (0.08, 0.15 or 0.3 mg/kg) injected s.c., every 12 h with the fourth dose given 0.5 h before experiments, dose-dependently lessened gastric glandular mucosal ulceration produced by cold-restraint stress for 2 h. When given intracerebrally (i.c.) (0.1, 0.5 or 1 microgram), using the same treatment regimen, infusion of ondansetron 1 microgram into the nucleus amygdaloideus centralis decreased stress-evoked ulcers; in contrast, injection of the same dose into the nucleus accumbens intensified these lesions. The associated stress-induced stomach wall mast cell degranulation was unaffected by all s.c. or i.c. doses of ondansetron. Pretreatment with disodium cromoglycate i.p. alone, or concurrently with ondansetron s.c., prevented not only ulceration but also mast cell degranulation. 5-Hydroxytryptamine3 receptor antagonism appears to inhibit stress-evoked ulcers mainly by blocking the peripheral effects of the amine after its release from the gastric mucosal mast cells.

1. The effects of the 5-HT3 receptor antagonists, ondansetron and tropisetron, on morphine consumption were studied in naive and morphine-dependent rats. 2. The administration of ondansetron (1 microgram kg-1, i.p. twice daily) 7 days prior to, and during a 21-day period of, morphine availability (increasing concentration from 0.1 to 0.4 mg ml-1) in 5% sucrose solution reduced opiate intake from the 9th day of morphine treatment. 3. The administration of ondansetron (0.1 microgram kg-1, i.p. twice daily) or tropisetron (0.1 microgram kg-1, i.p. twice daily) on the 14th day of the 21-day period of morphine treatment failed to reduce opiate consumption. Administration of the larger doses of tropisetron (1 microgram kg-1) or ondansetron (1 microgram kg-1) reduced morphine consumption. 4. After receiving 21 days of treatment with morphine alone or with the ondansetron or tropisetron regimens identified above, the sucrose solutions were substituted with tap water for 7 days. These detoxified rats were then allowed a free choice of sucrose or morphine for 10 days. Animals that had received concomitant treatment with ondansetron or tropisetron showed reduced morphine intake when compared with the controls treated with morphine only or with vehicle-treated controls. 5. The administration of cyproheptadine (100 or 250 micrograms kg-1, i.p. twice daily) on the 14th day of 21-day morphine treatment failed to modify morphine intake and also failed to influence the subsequent intake of the opiate in the free choice situation. 6. It is concluded that ondasetron and tropisetron can reduce morphine intake in both naive and morphine-dependent rats.

The endoperoxide analogues U46619 and U44069 when injected intravenously (i.v.), into the femoral artery or directly into the aortic arch in chloralose-anaesthetised rats, decreased arterial blood pressure dose-dependently. Treatment i.v. 30 min beforehand with indomethacin (8-15 mg/kg) or atropine (2 mg/kg) attenuated the hypotensive effect of U46619 or U44069, but methysergide (5 mg/kg) was ineffective. Combined pretreatment with indomethacin and atropine reduced further the hypotensive action of the endoperoxide analogues, but was unable to block the effect completely. However, pretreatment i.v. with AH23848, a specific thromboxane A2 (TXA2)-receptor antagonist, completely abolished the depressor responses to U46619 and U44069. Bilateral vagotomy did not change the hypotensive effect of both endoperoxide analogues. These findings suggest that the vasodepressor action of U46619 or U44069 is not a reflex mechanism, nor is it related to 5-hydroxytryptamine release. This effect appears to be mediated via TXA2-receptor stimulation, with the liberation of prostacyclin and/or acetylcholine or possibly an endothelium-derived relaxing factor (EDRF), all of which produce vasodilatation.

1. The changes in plasma levels of thromboxane-B2 (TXB2) and 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) were examined in rats given 5, 25, 50 or 100 micrograms/mL nicotine in drinking water for 10 days. 2. The effect of nicotine on prostacyclin (PGI2) synthesis from endogenous arachidonic acid by cultured rabbit aortic smooth muscle cells was also studied. 3. Plasma levels of TXB2 were increased dose-dependently by treatment for 10 day with nicotine. 4. 6-Keto-PGF1 alpha values were lowered dose-dependently, both in the plasma of nicotine-treated rats and in rabbit aortic smooth muscle cells incubated with the alkaloid. 5. The results suggest that endogenous synthesis of thromboxane-A2 and PGI2, as reflected by TXB2 and 6-keto-PGF1 alpha levels, respectively, is influenced by nicotine treatment. These findings may be related to cardiovascular diseases associated with cigarette smoking, but further studies are needed.

Chronic nicotine administration depresses the autonomic ganglia, but its effects on the muscarinic receptors at the neuroeffector sites remain unclear. The present study, using rats, examines the influence of chronic treatment with nicotine (25 micrograms/ml drinking water) for 10 or 15 days on muscarinic receptor responses, as reflected by bethanechol-evoked gastric secretion or by acetylcholine-induced decreases in mean blood pressure. Bethanechol, 0.4, 0.8, 1.6 or 3.2 mg/kg injected subcutaneously, dose-dependently increased the basal gastric secretory volume and acid output in pylorus-ligated control animals which normally drank tap water. Rats given nicotine in their drinking water for 10 or 15 days showed a further marked increase in both the volume of gastric secretion and acid output in response to bethanechol injections. Although bethanechol dose-dependently increased acid secretion, the ulcer index was very small and there was no significant difference between the control and nicotine-treated groups. The basal mean blood pressure remained normal after the 10-day nicotine treatment. Acetylcholine, 0.1, 0.3, 1 or 3 micrograms/kg given intravenously, decreased the mean blood pressure; this acetylcholine-evoked blood pressure fall was intensified by nicotine pretreatment. The findings suggest that the responses to muscarinic receptor stimulation are increased by chronic nicotine treatment for 10 or 15 days. These exaggerated effects are possibly the consequence of persistent autonomic ganglion blockade by chronic nicotine treatment.

Ondansetron, a specific 5-hydroxytryptamine3 (5-HT3)-blocker, injected s.c. (0.038, 0.075, 0.15 or 0.3 mg/kg) every 12 h with the fourth dose given 0.5 h before restraint at 4 degrees C (stress) or oral administration (p.o.) of 1 ml 80% ethanol, dose-dependently prevented gastric mucosal damage in female Sprague-Dawley rats (160-180 g); the animals were killed 2 or 1 h after stress or ethanol p.o., respectively. A similar pretreatment regimen with cyproheptadine (0.1, 0.25 or 0.5 mg/kg) or ketanserin (15, 30, or 75 micrograms/kg), both being 5HT2-receptor antagonists, also dose-dependently lowered the severity of stress- or ethanol-induced mucosal lesions. Only the higher doses of phenobarbitone (25 or 50 mg/kg given s.c. in a single dose 0.5 h beforehand) inhibited stress-induced gastric ulcers; however, even the lowest non-antinuclear dose (12.5 mg/kg), effectively produced CNS depression. These preliminary findings suggest that 5HT3-receptor blockade not only can antagonise stress- or ethanol-evoked gastric mucosal damage, but also may act through a peripheral mechanism.

The depressor responses to intravenous injections of arachidonic acid, prostacyclin (PGI2), prostaglandin E2 (PGE2) and sodium nitroprusside were studied in chronically nicotine-treated rats. Arachidonic acid, PGI2, PGE2 and sodium nitroprusside decreased the diastolic blood pressure dose-dependently in the control animals. The vasodepressor effect of arachidonic acid was significantly enhanced in rats given nicotine 5 and 25 micrograms/ml in their drinking water for 10 days but remained unchanged in the animals treated with 1 microgram/ml nicotine for 10 days or given 1 mg/kg i.v. nicotine 10 min before administration of arachidonic acid. Indometacin abolished arachidonic-acid-induced depressor responses in both the control and nicotine-treated rats. Hypotension induced by PGI2, PGE2 and sodium nitroprusside was of similar magnitude in the control and nicotine-treated animals. It is suggested that the enhancement by chronic nicotine treatment of depressor responses to arachidonic acid could be due to changes in the formation and/or removal of its vaso-active metabolites (i.e. prostacyclin and/or thromboxane A2).

In chloralose anaesthetized rats, intravenous administration of captopril, SQ 20881, SA 446 or MK 421 (0.5 mg/kg) potentiated the depressor responses to arachidonic acid 3 mg/kg given intravenously. Same doses of the above angiotensin converting enzyme inhibitors caused an approximately 100-fold decrease in sensitivity to the pressor effects of angiotensin I, with a concomitant similar increase in sensitivity to the depressor effects of bradykinin. Depressor responses to arachidonic acid, both before and after administering the converting enzyme inhibitors, were abolished by intravenous indomethacin (5 mg/kg). These results suggest that increased synthesis of prostaglandins in the circulation may contribute to the hypotensive effect of the angiotensin converting enzyme inhibitors, a group of newly developed antihypertensive agents.

The vasodepressor responses to intravenous injections of arachidonic acid, and the formation of its metabolites, were studied in rats made diabetic 1 or 2 weeks after a 1-dose alloxan treatment. Arachidonic acid dose-dependently decreased the diastolic blood pressure in normal animals, but this hypotensive effect was significantly weaker in 2-week postalloxan-treated rats. Indometacin abolished arachidonic-acid-induced depressor responses in both normal and diabetic animals. Hypotension induced by sodium nitroprusside was of the same magnitude in non-diabetic and insulin deficient rats. Plasma levels of thromboxane B2 were significantly increased in both the 1- and 2-week diabetic rats, being greater in the latter group; those of 6-keto-PGF1 alpha remained unchanged during the 2-week diabetic period. It is concluded that the attenuation by diabetes of depressor responses to arachidonic acid could be due to changes in the thromboxane/prostacyclin balance, with thromboxane formation being elevated whereas prostacyclin generation remains unaffected.

The mechanisms underlying potentiation by captopril of the depressor responses to arachidonic acid were studied in chloralose-anaesthetized rats. Captopril, in a dose (0.5 mg/kg, i.v.) which inhibited the pressor responses to angiotensin I (0.03-1 microgram/kg, i.v.), enhanced the depressor responses to bradykinin (3-300 micrograms/kg, i.v.) and potentiated the hypotensive action of arachidonic acid (3 mg/kg, intravenously). This phenomenon was observed not only when captopril and arachidonic acid were administered intravenously, but also when these compounds were injected directly into the aortic arch. The enhancement of arachidonic acid-induced hypotension by captopril was not significantly affected by pretreatment with a low dose of aprotinin (3 mg/kg, i.v.), but was abolished by bilateral nephrectomy or by pretreatment with a higher dose of aprotinin (6 mg/kg, i.v.). It is suggested that captopril augments the depressor responses to arachidonic acid by inhibiting angiotensin converting enzyme. This results in accumulation of bradykinin which in turn increases release of vasodilator prostaglandins, originating most probably, from the kidneys. The possibility that blockade of angiotensin II formation by captopril may leave the vasodilator action of prostaglandin unopposed cannot be excluded.

1. In cats, under chloralose anaesthesia, captopril (0.1-0.3 mg/kg i.v.) inhibited the potentiation of the pressor effects of the ganglion stimulant McNeil-A-343 caused by intravenous infusion of angiotensin I (0.1 microgram/min). 2. In both cats and rats under chloralose anaesthesia captopril (0.01-1.0 mg/kg i.v.) depressed pressor responses to McNeil-A-343 whilst not modifying those to bilateral occlusion of the carotid arteries, or intravenous injection of the ganglion stimulant dimethylphenylpiperazinium or adrenaline. 3. It is concluded that in the cat and rat captopril depresses cardiovascular responses to sympathetic postganglionic nerve activation, both in the presence and absence of exogenous angiotensin I by an action which is proximal to the terminal synapse.

Studies have been made of the effects of prior exposure to cigarette smoke on cardiovascular responses of the anaesthetized rat to arachidonic acid, prostaglandin E2 (PGE2), PGF2 alpha and PGI2. When compared with a control group, falls in systolic and diastolic blood pressure and tachycardia following intravenous PGI2 were significantly reduced in those animals exposed to smoke 1 and 24 h previously. Responses 48 h after exposure were not significantly different. Pressor effects of PGF2 alpha and depressor responses to arachidonic acid and PGE2 were not significantly affected these times. It is suggested that the specific and long lasting attenuation of the effects of PGI2 which occurs following cigarette smoke inhalation could contribute to both acute cardiovascular changes and the circulatory diseases associated with smoking.