Epidemiology of hypoxaemia in children with acute lower respiratory infection.
To determine the prevalence of hypoxaemia in children aged under 5 years suffering acute lower respiratory infections (ALRI), the risk factors for hypoxaemia in children under 5 years of age with ALRI, and the association of hypoxaemia with an increased risk of dying in children of the same age. Systematic review of the published literature. Out-patient clinics, emergency departments and hospitalisation wards in 23 health centres from 10 countries. Cohort studies reporting the frequency of hypoxaemia in children under 5 years of age with ALRI, and the association between hypoxaemia and the risk of dying. Prevalence of hypoxaemia measured in children with ARI and relative risks for the association between the severity of illness and the frequency of hypoxaemia, and between hypoxaemia and the risk of dying. Seventeen published studies were found that included 4,021 children under 5 with acute respiratory infections (ARI) and reported the prevalence of hypoxaemia. Out-patient children and those with a clinical diagnosis of upper ARI had a low risk of hypoxaemia (pooled estimate of 6% to 9%). The prevalence increased to 31% and to 43% in patients in emergency departments and in cases with clinical pneumonia, respectively, and it was even higher among hospitalised children (47%) and in those with radiographically confirmed pneumonia (72%). The cumulated data also suggest that hypoxaemia is more frequent in children living at high altitude. Three papers reported an association between hypoxaemia and death, with relative risks varying between 1.4 and 4.6. Papers describing predictors of hypoxaemia have focused on clinical signs for detecting hypoxaemia rather than on identifying risk factors for developing this complication. Hypoxaemia is a common and potentially lethal complication of ALRI in children under 5, particularly among those with severe disease and those living at high altitude. Given the observed high prevalence of hypoxaemia and its likely association with increased mortality, efforts should be made to improve the detection of hypoxaemia and to provide oxygen earlier to more children with severe ALRI.


Clinical signs of hypoxaemia in children with acute lower respiratory infection: indicators of oxygen therapy.
Hypoxaemia is a common complication of acute lower respiratory tract infections in children. In most developing countries, where the majority of deaths from pneumonia occur, facilities for early detection of hypoxaemia are lacking and oxygen is in short supply. This review examines the usefulness of different clinical signs and symptoms in the prediction of hypoxaemia associated with acute respiratory infections in children. Several respiratory signs were found to be associated with hypoxaemia. These include very fast breathing (with a respiratory rate of more than 60 or 70 breaths per minute), cyanosis, grunting, nasal flaring, chest retractions, head nodding and auscultatory signs, as well as signs of general depression of the child, such as inability to feed or lethargy. The sensitivity and specificity of these signs, as described in the reviewed studies, is presented, and combination rules are discussed. Through appropriate combination of several physical signs, which can be used by peripheral health workers and be taught to mothers, it is possible to predict hypoxaemia in children with acute respiratory tract infections with reasonable accuracy.


Hypoxaemia in children with severe pneumonia in Papua New Guinea.
To investigate the severity and duration of hypoxaemia in 703 children with severe or very severe pneumonia presenting to Goroka Hospital in the Papua New Guinea highlands; to study the predictive value of clinical signs for the severity of hypoxaemia, the predictive value of transcutaneous oxygen saturation (SpO2) and other variables for mortality. Prospective evaluation of children with severe or very severe pneumonia. SpO2 was measured at the time of presentation and every day until hypoxaemia resolved. Children with a SpO2 less than 85% received supplemental oxygen. By comparing with a retrospective control group for whom oxygen administration was guided by clinical signs, we evaluated whether there was a survival advantage from using a protocol for the administration of oxygen based on pulse oximetry. We determined normal values for oxygen saturation in children living in the highlands. In 151 well, normal highland children, the mean SpO2 was 95.7% (SD 2.7%). The median SpO2 among children with severe or very severe pneumonia was 70% (56-77); 376 (53.5%) had moderate hypoxaemia (SpO2 70-84%); 202 (28.7%) had severe hypoxaemia (SpO2 50-69%); and 125 (17.8%) had very severe hypoxaemia (SpO2 < 50%). Longer duration of cough or the presence of hepatomegaly or cyanosis predicted more severe degrees of hypoxaemia. After 10, 20 and 30 days from the beginning of treatment, respectively 102 (14.5%), 38 (5.4%) and 19 (2.7%) of children had persistent hypoxaemia; 46 children (6.5%) died. Predictors of death were low SpO2 on presentation, severe malnutrition, measles and history of cough for more than 7 days. The mortality risk ratio between the 703 children managed whose oxygen administration was guided by the use of pulse oximetry and the retrospective control group who received supplemental oxygen based on clinical signs was 0.65 (95%CI 0.41-1.02, two-sided Fisher's exact test, P = 0.07). There is a need to increase the availability of supplemental oxygen in smaller health facilities in developing countries, and to train health workers to recognise the clinical signs and risk factors for hypoxaemia. In moderate sized hospitals a protocol for the administration of oxygen based on pulse oximetry may improve survival.


Oxygen concentrators and cylinders.
A comparison is made between oxygen cylinders and oxygen concentrators as sources for clinical use. Oxygen cylinders are in widespread use, but costs and logistic factors favour the use of concentrators in many developing country situations, especially where cylinder supplies fail to penetrate.


Oxygen supply in rural africa: a personal experience.
Oxygen is one of the essential medical supplies in any hospital setting. However, in some rural African settings without regular electricity and with logistical problems in the transport of oxygen cylinders, the delivery of oxygen can be difficult. This paper compares the costs incurred using oxygen cylinders with a solar operated oxygen concentrator in a rural Gambian setting. The paper shows that a solar operated system has a high capital investment initially, but that running costs and maintenance are minimal. The system becomes cost effective if a rural hospital needs more than 6 treatment days (1 l/min) of oxygen per month and can be considered in a setting where 6 hours of sunlight per day can be guaranteed.


Oxygen delivery to children with hypoxaemia in small hospitals in developing countries.
Oxygen administration is one of the most important modalities of therapy for a patient with hypoxaemia to prevent death. This review summarises the methods of oxygen delivery applicable in small hospitals in developing countries, and evaluates information about their safety and efficacy. The following criteria were considered: cost and availability, efficiency/oxygen concentration achieved, tolerability/comfort of the method, requirement of humidification, demand for nursing care, and safety of the method and complications. In summary, it is concluded that all low-flow methods, i.e., nasopharyngeal catheters, nasal catheters and prongs, are effective in the oxygenation of sick children with severe pneumonia or bronchiolitis. Nasal prongs are the safest method of oxygen delivery, but nasopharyngeal catheters and nasal catheters are more easily available and less expensive. However, if they are used, they need close supervision to avoid serious complications. Nasal prongs are the method of choice for oxygen delivery in small hospitals in developing countries.


The early bactericidal activity of amikacin in pulmonary tuberculosis.
Stellenbosch University, a tertiary care hospital in Cape Town, South Africa. To determine the early bactericidal activity (EBA) of amikacin in dosages of 5 mg/kg, 10 mg/kg and 15 mg/kg body weight in comparison to that of isoniazid 6 mg/kg body weight or no drug. An open, randomised trial. Patients with previously untreated, sputum smear-positive pulmonary tuberculosis. Patients received amikacin 5 mg/kg (12 patients), 10 mg/kg (13 patients) or 15 mg/kg (15 patients), isoniazid 6 mg/kg (9 patients) or no drug (10 patients). The rate of decrease in log viable colony forming units of Mycobacterium tuberculosis per ml of sputum per day during the first 2 days of treatment with amikacin 5 mg/kg, 10 mg/kg and 15 mg/kg was 0.041 (SD 0.100), 0.045 (SD 0.144) and 0.052 (SD 0.096), respectively, 0.515 (SD 0.173) in the patients receiving isoniazid 6 mg/kg, and 0.041 (SD 0.113) in those receiving no drug. The EBA found in patients receiving amikacin did not differ significantly from that of the no drug group. However, as the EBA in the no drug group was the highest ever encountered at Stellenbosch University, the mean in patients receiving drug was tested against 0 and found to differ significantly (P = 0.03), suggesting minimal activity. Mean amikacin serum concentrations 1 hour after intramuscular drug administration were 13.5 microg/ml, 26.7 microg/ml and 39.2 microg/ml in the patients receiving 5 mg, 10 mg and 15 mg per kg body weight, respectively. Despite serum concentrations well in excess of the minimal inhibitory concentration of 2-4 microg/ml, the EBA of amikacin in patients with smear-positive pulmonary tuberculosis was only just detectable.


The relationship between the in vitro drug susceptibility of opportunist mycobacteria and their in vivo response to treatment.
It is generally accepted that qualitative drug susceptibility tests established and validated for Mycobacterium tuberculosis are not applicable to opportunist (non-tuberculous) mycobacteria. Previous studies have shown that in vitro antimicrobial susceptibilities for opportunist mycobacteria, performed by the method of modal resistance (MR), correlate poorly with clinical response. Minimum inhibitory concentration (MIC) determination may provide better correlation with predicted clinical response than the conventional MR results. To determine the relationship between quantitative in vitro sensitivity results for opportunist mycobacteria and their in vivo response to treatment. MICs were performed radiometrically with the Bactec TB-460 system; 35 M. avium complex isolates, 29 isolates of M. malmoense and 16 isolates of M. xenopi were tested. Susceptibility results were analysed in comparison with therapeutic outcome by Fisher's exact probability test. Only one significant association was found; in vitro resistance to ethambutol correlated with treatment failure for M. malmoense infections (P = 0.027). There were no other significant correlations between in vitro results and treatment outcome. Prediction of treatment outcome from in vitro susceptibility tests continues to be a problem in infections with opportunist mycobacteria.


Increased resistance to ciprofloxacin and ofloxacin in multidrug-resistant mycobacterium tuberculosis isolates from patients seen at a tertiary hospital in the Philippines.
A hospital-based study at the Makati Medical Center, Makati City, Philippines, a hyperendemic area for tuberculosis (TB). To determine the susceptibility of Mycobacterium tuberculosis to ciprofloxacin and ofloxacin. Retrospective analysis of drug susceptibility tests (DST) of M. tuberculosis isolated from 1995-2000. Resistance to ciprofloxacin was 26.8%, ofloxacin 35.3%, and multidrug resistance (MDR) was 17.2%. Of the MDR strains, 51.4% were resistant to ciprofloxacin and ofloxacin. Acquired resistance was significantly higher for all first-line drugs and for ciprofloxacin, but not for ofloxacin. A significant increase in resistance to ciprofloxacin and ofloxacin was noted compared to 1989-1994, while resistance to the firstline drugs was not significantly different. Ciprofloxacin and ofloxacin are now a significantly less effective alternative therapy in tuberculosis, particularly MDR-TB, due to a selection pressure from their widespread use in the treatment of TB and possibly other infections in the community, which is hyperendemic for tuberculosis.


Familial outbreak of disseminated multidrug-resistant tuberculosis and meningitis.
Rapidly progressive multidrug-resistant tuberculosis (MDR-TB) is well documented in human immunodeficiency virus (HIV) positive subjects, but it is not fully recognised in HIV-negative subjects in the familial environment. We report three cases of MDR-TB in three young HIV-negative subjects from the same family. All the patients showed signs of meningitis during the course of their disease, and in two cases a resistant strain of Mycobacterium tuberculosis was isolated in cerebrospinal fluid. Two of the three subjects died from neurological complications; the other was successful treated utilising both systemic and intrathecal therapy for tuberculous meningitis. By a retrospective analysis of DNA obtained from Lowenstein-Jensen cultures, the strains were confirmed as M. tuberculosis resistant to rifampicin and isoniazid, and were closely related in the two cases where specimens were available for analysis. The resistance was acquired in two patients initially infected with a susceptible strain; in the other patient, the resistance was present on the first sensitivity test for which results were available. This report demonstrates the high risk of fatality from MDR-TB for HIV-negative subjects in the absence of reliable early diagnostic and preventive tools. It also reinforces the concept that genetic susceptibility to M. tuberculosis may be an important factor in the clinical presentation and outcome of MDR-TB.


Efficacy and safety of sparfloxacin in combination with kanamycin and ethionamide in multidrug-resistant pulmonary tuberculosis patients: preliminary results.
Department of tuberculosis and chest diseases of a tertiary referral tuberculosis institute in New Delhi, India. To study the efficacy and safety of sparfloxacin, in combination with kanamycin (for the initial 3-4 months) and ethionamide, in multidrug-resistant (MDR) pulmonary tuberculosis patients. Prospective, uncontrolled study of nine patients with pulmonary tuberculosis who had received adequate anti-tuberculosis treatment with first-line drugs, including supervised category II treatment regimen as per World Health Organization guidelines for 5 months, and were still sputum smear acid-fast bacilli positive. It was planned to give them kanamycin (initial 3-4 months), ethionamide and sparfloxacin for 2 years. All nine patients achieved sputum conversion within 6 months. Seven patients converted within 3.5 months, two of these within 1 month. All patients reported improvement in clinical symptoms, and chest X-ray improved in seven patients. Four patients developed mild to moderate phototoxicity. Eight patients have completed treatment for an average of 19 months (range 15-24 months), and are still under follow-up. One patient defaulted after 7 months of treatment. In MDR-TB patients, sparfloxacin, along with other anti-tuberculosis drugs, appears to be effective and safe. Mild to moderate phototoxicity is common. However, the long-term results, including relapses, are still awaited.


A population-based case-control study of the safety of oral anti-tuberculosis drug treatment during pregnancy.
To study the human teratogenic potential of isoniazid and other anti-tuberculosis drug treatment during pregnancy. Cases from a large population-based dataset at the Hungarian Case-Control Surveillance of Congenital Abnormalities, and controls from the National Birth Registry, between 1980 and 1996. Information on all oral anti-tuberculosis drug treatments during pregnancy was medically recorded. Women who had newborns or fetuses with congenital abnormalities (case group), and women who had babies with no congenital abnormality (control group). Congenital abnormalities in newborn infants and fetuses diagnosed prenatally during the second and third trimesters, and postnatally from birth to the age of one year. Of 38,151 controls, 29 (0.08%) were exposed to anti-tuberculosis drug treatment during pregnancy; the corresponding figures for cases were 22,865 and 11 (0.05%). The prevalence odds ratio was 0.6 (95%CI 0.3-1.3). Analysis of isoniazid and other oral antituberculosis drug use during the second and third months of gestation, i.e., in the critical period for most major congenital abnormalities, in case-control pairs did not indicate a teratogenic effect of these drugs in any group with congenital abnormality. Maternal exposure to oral anti-tuberculosis drugs during pregnancy did not show a detectable teratogenic risk to the fetus; however, the number of pregnant women who were treated with these drugs during the critical period of most major congenital abnormalities was limited (six cases vs. 21 controls).


Specificity of insertion sequence-based PCR assays for mycobacterium tuberculosis complex.
To determine the specificity of different insertion sequence-targeted polymerase chain reaction (PCR) tests for Mycobacterium tuberculosis complex. One M. bovis BCG strain, two M. tuberculosis strains and ten species of mycobacteria other than tuberculosis (MOTT) were tested by three PCR assays based on the repetitive elements IS6110, IS1081 and IS990 under variable amplification conditions (different temperatures of primer annealing and numbers of reaction cycles). DNA amplifications based on the three insertion sequences yielded fragments of expected sizes only in DNA from M. tuberculosis complex strains when the tests were conducted at high stringency (65 degrees C). At the annealing temperature of 60 degrees C the PCR assay with IS6110-specific primers yielded a 245 bp fragment also in nine MOTT strains tested. This could result from previously reported homology between non-tuberculous mycobacteria and a central region of IS6110. Amplification assays based on IS1081 and IS990 gave false-positive results in some MOTT isolates only under very low stringency (55 degrees C), which could be due to non-specific priming of the target DNA at that temperature. Repetitive elements IS1081 and IS990 may represent a more reliable alternative to the more widely used IS6110 PCR target for tuberculosis diagnosis.


A case series: initial outcome of persons with multidrug-resistant tuberculosis after treatment with the WHO standard retreatment regimen in Ho Chi Minh City, Vietnam.
Few data address the outcomes of patients who have multidrug-resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid and rifampin, and who receive a standard World Health Organization (WHO) recommended retreatment regimen after relapse or failure with initial treatment. In this case series, we examined treatment outcomes of a convenience sample of 42 relapse or failure patients who had documented MDR-TB and who had received a standard WHO retreatment regimen (2SHRZE/1HRZE/5H3R3E3). One patient died of tuberculosis in the last month of treatment; the remaining 41 patients completed retreatment. Of the 42, 14 (33%) were sputum smear-negative on completion of therapy. The proportion of patients cured of MDR-TB with the WHO retreatment regimen was similar to historic outcomes when no chemotherapy for TB was given.


Quantitative bacillary response to treatment in Mycobacterium tuberculosis infected and M. africanum infected adults with pulmonary tuberculosis.
Data regarding possible differences in microbiological response to therapy of disease caused by Mycobacterium tuberculosis and M. africanum are limited. Presenting clinical characteristics and sputum bacillary load during standard short-course chemotherapy in patients with newly-diagnosed pulmonary tuberculosis due to M. tuberculosis (n = 7) and M. africanum (n = 6) were compared. Changes in sputum bacillary load were measured using quantitative acid-fast bacilli smears, colony forming unit assay, and time until positive culture in the BACTEC radiometric system. Presentation and response to short course chemotherapy were comparable between patients infected with M. tuberculosis and those infected with M. africanum.


Tuberculous infection in student nurses in Madrid, Spain.
To determine the incidence of tuberculous infection in student nurses we performed a 3-year study in our hospital. Before training was initiated, 18.75% of males and 5.7% of females were Mantoux-positive (P = 0.09). During the following two years, 9.2% of the previously Mantoux-negative students became positive. No differences were found between males and females. We conclude that student nurses must be considered at risk for tuberculous infection in our hospital, and that stricter isolation procedures for tuberculous patients must be implemented.


High-resolution computed tomography classification of lung fibrosis for patients with asbestos-related disease.
This study tested a new high-resolution computed tomography (HRCT) scoring method for asbestos-induced parenchymal changes in the lung. HRCT scans of 602 asbestos-exposed workers and 49 referents were reviewed by 3 radiologists. Structured forms were filled out for a semiquantitative HRCT fibrosis score based on several specified parenchymal abnormalities scored separately. Observer agreement was studied with the use of the quadratic-weighted kappa (kappaqw). The HRCT fibrosis score (from 0 to V with definitions and index images given retrospectively) was compared with the radiographic classification of the International Labour Office (ILO) for the same patients. Receiver-operating characteristic (ROC) curves were computed to compare the tests for diagnosing asbestosis. Good inter- and intraobserver agreements were achieved (kappaqw = 0.64 and 0.72, respectively) as regards the HRCT fibrosis score. All the specified computed tomography findings explained 86% of the variance in the HRCT fibrosis score. Age and occupational group were significant predictors of fibrosis. The area under the ROC curve was significantly greater for the HRCT fibrosis score (0.89) than for the ILO radiographic classification (0.76). The sensitivity (70%) and specificity (91%) of the HRCT fibrosis score (classes I/II-V representing asbestosis) were better than those of the classification published by the International Labour Office (51% and 89%, respectively, score > or = 1/0 representing asbestosis). The examined HRCT scoring method proved to be a simple, reliable, and reproducible method for classifying lung fibrosis and diagnosing asbestosis also in large populations with occupational disease, and it would be possible to use it as a part of an international classification.


Cohort cancer incidence among pulp and paper mill workers in British Columbia.
A study was conducted to investigate cancer risks in a cohort of pulp and paper workers. All male workers with > or =1 years of employment in 14 pulp and paper mills in 1950-1992 were studied. Standardized incidence ratios (SIR) were used to compare the cancer incidence of the cohort with that of the Canadian male population. Record linkage with the National Cancer Registry was performed using the generalized iterative record linkage method. Altogether 1756 cancer cases were observed in the entire cohort. For > or =15 years of work, the entire cohort had significantly increased SIR values for pleural and prostate cancer and skin melanoma; there was also a significantly increased risk for skin melanoma among workers in the kraft process only, rectal cancer among workers in the sulfite process only, and stomach and prostate cancer and all leukemias combined among workers in both the kraft and sulfite processes. A separate analysis comparing workers in pulping and papermaking with those in the pulping process only did not reveal any difference in cancer risk and hence did not modify the results. The SIR values for skin melanoma were not significantly increased in a comparison using the British Columbia male population. Nine of 10 pleural cancers were mesotheliomas, which likely reflect past asbestos exposure. The results suggest that long-term work in the pulp and paper industry is associated with excess risks of prostate and stomach cancers and all leukemias for work in both kraft and sulfite processes and of rectal cancer for work in the sulfite process only.


Chromosome aberrations in lymphocytes of persons exposed to an earthquake in Armenia.
This study attempted to determine the level of chromosome aberrations in lymphocytes of victims of the 1988 earthquake in Armenia. Chromosome aberrations were measured in blood samples taken from 41 victims of the earthquake that hit Armenia in 1988 and in samples of 47 reference blood donors. The victims suffered from severe psychoemotional stress but were otherwise healthy. All the samples were taken 2 to 3 weeks after the earthquake. All the subjects were lifetime nonsmokers. The cells were scored blind as to the exposure status. The subjects exposed to the earthquake had a higher proportion of cells with chromosome aberrations [3.1 (SD 2.1)%] than the referents [1.7 (SD 1.3)%, P-value for the difference 0.0009]. The difference persisted when the values were adjusted for age and gender [relative risk (RR) 1.9, 95% confidence interval (95% CI) 1.4-2.5]. The difference was present for double breaks (RR 4.1, 95% CI 2.6-6.4), but not for single breaks (RR 1.1, 95% CI 0.8-1.7). The exposed subjects also had a lower percentage of cells with 46 chromosomes (P=0.03) than the referents. This study suggests an increase in chromosome aberrations in the lymphocytes of victims of a severe earthquake as compared with the levels of referents. If not due to bias or confounding, the difference may reflect the effect of either environmental exposures related to the earthquake or severe psychogenic stress. The levels of chromosome aberrations found among the earthquake victims in this study are comparable with those found in prospective studies of long-term cancer risk.


Group-based measurement strategies in exposure assessment explored by bootstrapping.
The precision of mean exposure to pushing was examined in 2 occupational groups using various combinations of the number of workers and measurements per worker. The frequency and duration of pushing of the 2 occupational groups was assessed using onsite observation. All data were divided into successive periods of 30 minutes of observation. The precision of the group mean exposure to pushing was expressed by 90% confidence intervals obtained by bootstrapping. The effect on the confidence interval of varying numbers of workers and numbers of periods per worker was examined. For both occupational groups there was little precision to be gained when >10 workers were observed. Within the maximum number of workers used in the bootstrap simulations, it appeared that, beyond 10 workers, the confidence intervals decreased by <5% for every worker that was added, when each worker was observed at least 8 periods of 30 minutes. If workers were observed exactly 4 periods of 30 minutes per worker, an additional 4 workers were required to compensate for the loss of precision. An unbalanced strategy with approximately 8 periods of 30 minutes per worker hardly decreased the precision of the group mean, however. The precision of the group-based mean exposure to pushing is influenced by the number of workers observed and by the number of repeated measurements per worker. In the planning of measurement strategies, it is advisable to account for possible sources of variance in advance and to assess the exposure variability.


Total plasma protein adducts of allergenic hexahydrophthalic and methylhexahydrophthalic anhydrides as biomarkers of long-term exposure.
The aim of this study was to evaluate the applicability of total plasma protein adducts (TPPA) of 2 sensitizing low-molecular-weight allergens, hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydride (MHHPA), as biomarkers of long-term exposure. Urine samples from occupationally exposed workers were analyzed for the levels of urinary metabolites of HHPA and MHHPA, and the levels were used as the index of exposure. In addition, blood samples were obtained from the same persons, and the levels of TPPA were determined. Reversed solid phase extraction, derivatization using pentafluorobenzyl bromide, and gas chromatography-mass spectrometry analysis in the negative ion chemical ionization mode were used to quantify the exposure. To assess the suitability of TPPA as a biomarker of exposure to the anhydrides, the TPPA levels were correlated to urinary metabolite levels and hemoglobin (Hb) adducts. The toxicokinetics of TPPA were also studied to determine the elimination half-time of the adducts. The levels of TPPA correlated exceptionally well with the metabolite levels in the urine sampled repeatedly, giving r=0.97 for HHPA and r=0.92 for MHHPA. The TPPA of HHPA correlated highly with the Hb adducts with r=0.86. There were also good correlations between single urinary determinations and the TPPA levels (r(s)=0.71 and 0.81, respectively, for HHPA and MHHPA). The in vivo decay of TPPA gave an elimination half-time of 22 days for HHPA and 24 days for MHHPA. TPPA levels of HHPA and MHHPA are excellent biomarkers of long-term exposure to anhydrides.


Effects of electric field reduction in visual display units on skin symptoms.
This study investigated the facial skin complaints of office workers before and after the static electric fields of a visual display unit were reduced. On the basis of a screening survey of 4556 office workers in 11 companies, 120 of 227 subjects reporting facial skin complaints were randomly selected to this double blind intervention study. Antistatic measures were used to reduce the static electric fields of the visual display unit in the intervention group but not in the control group, which worked with a visual display unit resembling that of the intervention group. Electric fields, dust concentration, health complaints, and psychological behavior tests were recorded before and after the intervention. The intervention group reported statistically significantly fewer facial skin complaints than the control group. In the intervention group, among those with an office dust concentration of >58 microg/m3, a median reduction of 1.5 skin index points (scale 0-8) was achieved, whereas there was no change in the control group. In the regression model "group category" was still a significant variable after control for background factors. In addition, further linear regression analyses indicated that several static electric field parameters were predictors of the skin complaint reduction. This field trial indicates that removing static electric fields from visual display units can probably help reduce the facial skin complaints of workers in offices with high dust concentrations.


Association between job stress and depression among Japanese employees threatened by job loss in a comparison between two complementary job-stress models.
This study compared the separate effects produced by two complementary stress models--the job demand-control model and the effort-reward imbalance model--on depression among employees threatened by job loss. A cross-sectional analysis was conducted to examine these associations among 190 male and female employees who responded to a self-administered questionnaire in a small Japanese plant with economic hardship. The employees were engaged in 2 job types--direct assembly line and indirect supportive tasks--and the latter was threatened by job loss because of downsizing. Independent variables were measured by the Japanese versions of Karasek's demand-control questionnaire and Siegrist's effort-reward imbalance questionnaire. Depression was assessed by the Center for Epidemiologic Studies Depression Scale. The employees with indirect supportive tasks (target for downsizing) were more likely to have depressive symptoms than direct assembly-line workers. Job strain, a combination of high demand and low control at work, was more frequent among the latter, while the combination of high effort and low reward was more frequent among the former. After adjustment for work environment factors, low control [odds ratio (OR) 4.7], effort reward imbalance (OR 4.1), and overcommitment (the person characteristic included in the effort-reward imbalance model) (OR 2.6) were independently related to depression. There is some indication that these effects were particularly strong in the subgroup suffering from potential job loss. This study confirms that the 2 job stress models identify different aspects of stressful job conditions. Moreover, effort-reward imbalance and low control at work are both associated with symptoms of depression.


Association between pleural plaques and coronary heart disease.
The aim of this study was to verify a clinical impression that patients with coronary heart disease disproportionately frequently have calcified pleural plaques. Chest X-rays were collected from 148 patients referred consecutively to the Helsinki University Central Hospital for coronary angiography and from 100 consecutive lung cancer patients seen at the same hospital. The radiographs were analyzed for the presence of calcified pleural plaques according to the classification the International Labour Office. A generalized linear model with binomial distribution and log link was used to estimate the relative risks and their 95% confidence intervals (95% CI). The prevalence of calcified pleural plaques was 35% for the coronary patients and 19% for the lung cancer patients. Calcified pleural plaques were more common among the men than the women, and the risk increased with age. The relative risk of calcified pleural plaques, adjusted for age and gender, was 2.19 (95% CI 1.44-3.32) for the coronary patients as compared with the lung cancer patients. Further studies with better information on past exposure to asbestos and other potential risk factors are warranted to confirm the observations and to examine whether the association between coronary heart disease and calcified pleural plaques is related to an etiologic or an individual susceptibility factor common to both of these conditions.


Intervention in shift scheduling and changes in biomarkers of heart disease in hospital wards.
The effect of introducing regularity, few consecutive night shifts, more weekends off, and only 2 different types of shifts (day-evening or day-night) into shift scheduling on biomarkers of heart disease was studied. Ergonomic shift criteria were introduced in a quasi-experimental controlled intervention in 4 hospital wards. Six wards participated as controls. Altogether 101 nurses and nurses' aides were followed for 6 months with measurements of cholesterol and triglycerides. The intervention led to more regular schedules and more staff having 2 shifts in 2 of the intervention wards 1 year after the intervention. The schedules among the controls became less regular and less predictable. The number of consecutive night shifts remained unchanged. After 6 months the high-density lipoprotein (HDL) cholesterol level had increased in the intervention group, and the total cholesterol and low-density lipoprotein (LDL) cholesterol levels and the  cholesterol ratio had decreased. Regardless of the intervention, changes in regularity were associated with the triglyceride and HDL cholesterol levels and also with the  cholesterol ratio. More ergonomic changes were associated with lower LDL cholesterol levels, a lower  cholesterol ratio, and higher HDL cholesterol levels. Increased ergonomic scheduling was possible. Lipids and lipoproteins changed as predicted, both when the changes were assessed in respect to the changes in schedules that resulted from the intervention and the changes that occurred regardless of the intervention. The study suggests that scheduling based on ergonomic criteria is a possible means for reducing the risk of heart disease among shift workers.


Work environment of Danish shift and day workers.
Both shift work and other work environment factors have been shown to be related to heart disease. This study examined whether shift work is associated with other work environment factors related to heart disease in a random sample of the population. If so, shift work could be acting as a proxy for work environment differences. Data on 5940 employees in the Danish Work Environment Cohort Study from 1990 were reanalyzed. The information included work schedules [permanent day work, irregular workhours (including morning work), 2-shift or fixed evening and 3-shift or fixed night], length of workweek, physical factors (noise, heat, dust, passive smoking, walking, standing and monotonous repetitive tasks), and psychosocial factors (including demands and control dimensions, social support, conflicts and job insecurity). At least 1 group of shift workers had a higher prevalence of nearly every unfavorable work environment factor investigated. Exceptions were dust exposure and quantitative demands. Especially conflicts at work and low decision latitude were higher among all the groups of shift workers, and all-day walking or standing work and part-time jobs were more often found among female shift workers. The 3 different shiftwork groups were exposed to different parts of the work environment, and also men and women in shift work differed in relation to the work environment. Age and social class influenced the relationship, but not in any particular pattern. In a heterogenous population shift work was found to be associated with other work environment factors suspected to cause heart disease.


Relationships among types of speech intelligibility in pediatric users of cochlear implants.
Twenty pediatric users of cochlear implants were administered three tests of speech intelligibility: (1) a test of contrast perception intelligibility, (2) a test of contrast production intelligibility, and (3) a test of production sentence intelligibility. Sixty adults with normal hearing served as listener judges for the two speech production tasks, and percent correct scores were generated for each of the three tasks. Correlational analyses showed significant correlations among overall scores for the three tasks. However, scores for individual feature classes from the contrast perception task were not correlated with their corresponding contrast production feature class scores, and only some of the feature class scores were correlated significantly with sentence intelligibility. We conclude that although these three types of intelligibility are related at a gross level, relationships are more tenuous at finer levels of analysis, suggesting that the separate skills may need to be addressed separately in remediation. As a result of this activity, the participant will be able to differentiate various methods for assessing speech intelligibility and describe the relationships among different types of speech intelligibility in pediatric users of cochlear implants.


Third person pronoun errors by children with and without language impairment.
Research findings have been mixed about pronoun case problems in the language-learning profile of children with specific language impairment (SLI). This study (N= 36) extended previous findings and located a number of error patterns using detailed error analyses. Results indicated that the children with expressive SLI produced more errors with third person singular (3Psg) pronouns than did their age-level peers, but they did not make more errors than their MLU-matched peers. Error patterns were similar in the children with SLI and their language-level peers. The most frequent type of error was the substitution of the objective case for the nominative case. More errors were made on the feminine pronoun, she, than on the masculine pronoun, he. Implications for theories and clinical practice were explored. As a result of this activity, the reader will (1) learn how children with SLI compare to their peers in producing third person pronouns, (2) learn the most common types of pronoun errors made by the children matched for mean length of utterance (MLU), and (3) evaluate how the findings relate to two current theories: one from typical language development and one from the area of SLI.


Family education seminars and social functioning of adults with chronic aphasia.
Aphasia affects functional activities and participation in social roles years after onset. Some group and individual programs have reported success in improving social activities and perceived wellness. These programs typically last several weeks or months. A short, 2-day seminar style program designed for adults with chronic aphasia and their families is described in this report. Six-month follow-up data from participant pairs demonstrates a significant improvement in functional activity level, improved knowledge of aphasia, and improved family relationships. Nonparticipant pairs did not demonstrate any changes over the same period. These findings replicate and extend those of a previous study on the same 2-day seminar [Top. Stroke Rehabil. 2 (1995) 53.]. The results of this study demonstrate the important outcomes of even a very brief program designed to address the long-term psychosocial needs of adults living with aphasia and their families. As a result of this activity, the participant will be able to: (1) describe a brief family education seminar for adults with chronic aphasia; (2) discuss outcomes in family adjustment, community reintegration, and activities of daily living associated with participation in a family education seminar; and (3) evaluate areas of programming and outcomes that should be addressed in future research.


Differentiating dialect from disorder: a comparison of two processing tasks and a standardized language test.
Previous research has indicated that norm-referenced language assessment protocols are often biased against dialectal speakers. Recently, the use of processing tasks has emerged as one possible means of reducing this bias in language testing. Processing tasks measure a child's ability to process and manipulate language rather than tap previous linguistic knowledge. The present study utilized 40 subjects between the ages of 7;0 and 7;3 in the following equal groupings: White normal language, White language impaired, African American normal language, African American language impaired. The subjects were administered the Test of Language Development-2P (TOLD-2P), the Nonword Repetition Task (NRT), and the Competing Language Processing Task (CLPT). Results indicated that all three measures differentiated normal-language and language-impaired subjects from one another. With regard to cultural group, confirmed speakers of African American English (AAE) with normal language scored significantly lower on the TOLD-2P compared to White normal-language subjects. Scores of the AAE-speaking subjects with normal language on the NRT and CLPT, however, did not differ significantly from the White normal-language subjects. These results suggest that AAE speakers with normally developing language (LN) may be at a disadvantage on tests of prior language knowledge and that processing tasks may be a useful tool in combination with other assessment measures to make less biased clinical decisions. As a result of this activity, the reader will (1) be able to determine the utility of processing tasks in culturally unbiased language assessment. (2) The reader will be able to discriminate the difference between the results of a standardized language test and processing tasks on speakers of AAE.


Low urethral pressure profile--clinical implications.
The clinical impact of urethral pressure profilometry (UPP) has been a main urological topic over the past three decades. Exaggerated expectations and differing techniques with incongruent results caused a controversial appearance. However, since the UPP is the only method to measure directly aspects of the urethral closure function, all types of sphincteric urinary incontinence represent indications for this measurement. Based on long-term experience this paper aims to discuss the various complexes regarding the urethral pressure profilometry. The significance of the urethral closure function for urinary continence and the urodynamic relevance of active and passive pressure transmission are described. In addition, clinical implications in terms of therapeutic strategies to treat urinary stress incontinence with regards to a low urethral pressure profile are presented.


Morphological and physiological characteristics of urethral circular and longitudinal smooth muscle.
The urethral wall contains circular and longitudinal smooth muscle. Both layers can develop spontaneous tone, and contract further or relax in response to excitatory or inhibitory stimuli. In the pig the cells do not generate action potentials, and the membranes possess L-type calcium channels and a variety of potassium channels which may modulate the membrane potential and tone. The importance of these layers in generating the urethral pressure is not well understood in the human, but it seems likely that the circular smooth muscle is involved in generating urethral pressure in the pig.


Neurotransmission and drug effects in urethral smooth muscle.
Urethral smooth muscle tension is one of the factors contributing to the maintenance of intraurethral pressure and to continence. This tension is controlled by nervous mechanisms involving a complex pattern of efferent and afferent signalling in parasympathetic, sympathetic, and somatic nerves, with resulting release of contraction- and relaxation-producing transmitters and mediators. Sympathetic activity, via release of NA and stimulation of urethral smooth muscle alpha1-ARs, is the main contraction-producing factor. Among the three high affinity alpha1-AR subtypes identified in molecular cloning and functional studies, the alpha1A subtype seems to predominate in both the male and female urethra. The physiological role of the urethral beta-adrenoceptors has not been established, and the importance of muscarinic receptors (and subtypes) for urethral function is presently unclear. Nitric oxide, produced by nitric oxide synthase within cholinergic nerves, seems to be the predominant inhibitory neurotransmitter, but there is good evidence for the existence of other, as yet unidentified, non-adrenergic, non-cholinergic inhibitory messengers. Vasoactive intestinal polypeptide, adenosine 5'-triphosphate, and carbon monoxide (CO) all relax urethral smooth muscle, and are potential candidates for the nonadrenergic, noncholinergic relaxation, but their roles for urethral function remain to be defined.


Neural control of the urethra.
Coordination between the urinary bladder and the urethra is mediated by multiple reflex pathways organized in the brain and spinal cord. Some reflexes promote urine storage; whereas other reflexes facilitate voiding. During bladder filling, activation of mechanoreceptor afferent nerves in the bladder wall triggers firing in the cholinergic efferent pathways to the external urethral sphincter (EUS) and in sympathetic adrenergic pathways to the urethral smooth muscle. These storage reflexes are dependent upon interneuronal circuitry in the spinal cord. During voiding the spinal storage reflexes are inhibited by supraspinal mechanisms which originate in the pontine micturition center. Glutamatergic, serotonergic and alpha, adrenergic excitatory transmission as well as GABAergic/glycinergic inhibitory transmission have been implicated in the central control of sphincter reflexes. During voiding, a parasympathetic nitrergic inhibitory input to the urethral smooth is activated. This reflex mechanism which is triggered by bladder afferents persists in paraplegic rats and therefore must be mediated at least in part by spinal interneuronal circuitry. In female rats, the parasympathetic nitrergic pathway is prominent; but in male rats it is obscured by a dominant parasympathetic cholinergic excitatory input to the urethral smooth muscle. The function of the cholinergic pathway in voiding is uncertain. Stimulation of urethral afferents can also influence bladder activity. Contraction of the external urethral sphincter activates afferents that inhibit reflex bladder contractions; whereas infusion of fluid through the urethra facilitates bladder contractions. These reflexes are also organized in the spinal cord and presumably play a role in urine storage and elimination. Alterations in primitive bladder-to-urethra and urethra-to-bladder reflex mechanisms may contribute to neurogenic bladder dysfunction.


Urethral pressure measurement--problems and clinical value.
Urethral pressure measurements are in use to assess urethral closure and voiding function. The lack of general agreement on an explicit definition of urethral pressure and standardisation of the methodology for measurement has limited the clinical utility of urethral pressure measurements.


The clinical value of ambulatory urethral pressure recording in women.
The value of ambulatory urethral pressure recording (AUPR) was evaluated by reviewing both data from 116 patients investigated and Ambulatory Urodynamic Monitoring (AUM) tracings. Typical tracings are shown from conditions where we find that AUPR is of value. (i) Stress incontinence where a patient who complains of stress incontinence does not leak during the stress test, but leaks while jumping on a trampoline. (ii) Mixed incontinence--in only 43% of patients complaining of both urge ands stress incontinence mixed incontinence was documented by AUM. Thirty-six per cent of patients complaining of both urge and stress incontinence were found to be stress incontinent and 21% were leaking due to an unstable detrusor. (iii) Urethral closure pressure of 20 cmH2O or less (low urethral closure pressure; LUCP). LUCP was found in 13% of the patients. Patients with LUCP may leak due to stress, unstable detrusor or unstable urethra. We conclude that ambulatory recording of both urethral and bladder pressures in addition to leakage may contribute to a more complete diagnosis and treatment in these conditions.


The innervation and properties of the urethral striated muscle.
The striated muscle forms an outer sleeve around the urethra and occupies about 80% of the wall. In humans more than 60% of the muscle consists of slow, fatigue resistant type I fibres whereas in male greyhounds only about 6% are type I. Most of the remainder (70% of fibres) are type IIa which are classified as fast but can contract for several hours with little decline in amplitude. Stimulation of pudendal but not pelvic nerves produces contraction of the striated muscle and a rapid increase in urethral pressure. Pelvic nerve branches enter the striated muscle sleeve but pass through it to supply the inner layer of smooth muscle. The striated muscles are well suited to maintain contraction necessary for continence.


The clinical value of sonographic imaging of the urethrovesical anatomy.
Ultrasound is a complementary evaluation for the study of female urinary incontinence which allows functional-morphological documentation. With sonography dynamic images during coughing, Valsalva, pelvic floor contraction and micturition are provided. Ultrasonography of the urethrovesical anatomy improves our thinking of function and anatomy and will therefore have an important place in the diagnosis and treatment of urogynecologic disorders.


The clinical value of dynamic magnetic resonance imaging in normal and incontinent women--a preliminary study on micturition.
In this preliminary study in nine volunteers and nine women with genuine stress incontinence (GSI) dynamic magnetic resonance imaging (MRI) was used to study the voiding phase in the sitting position after physiological filling of the bladder by urine. The MRI technique has been documented as being useful for this purpose, but in this small group of women it was not possible to determine any specific difference in the voiding pattern between the volunteers and the G


Magnetic resonance imaging of the pelvic floor--possibilities and present status.
MRI has had both an increasing availability and fuctionality during the last 5-10 years. In diagnosing problems of the pelvic floor, it has been shown to have a potential, but is at present not to be considered a routine examination. Today's use of MRI of the pelvis includes anatomical/topographical images of high quality, but to make it a valuable diagnostic tool, functional imaging is mandatory. Functional MRI with a potential of simultaneously examining defecation, micturition, bladder motion and pelvic floor muscles, seems promising, but with having practical problems. The use of open MRI systems reduce the practical problems, but does not give the optimum image quality. In the future it is likely that MRI will have an increasing importance concerning diagnoses of the pelvic floor. However, clinical research is needed to evaluate the possible diagnostic gains, and maybe even open for more use of MRI.


Stress incontinence observed with real time sonography and dynamic fastscan magnetic resonance imaging--insights into pathophysiology.
Our concepts of pathophysiology of stress urinary continence have been greatly shaped by developments in radiographic imaging. Simple radiographs with and without contrast initially revealed the importance of urethral descent in pathogenesis. More recently, magnetic resonance imaging (MRI) and real time ultrasonography are showing soft tissue detail within both a global pelvic and a local urethral context. Careful examination of these studies can extend our concepts of pathophysiology and lead us beyond existing paradigms. We propose a unified theory of stress incontinence based on our dynamic fastscan MRI and real time ultrasonograms of stress incontinence, incorporating known details of pelvic anatomy, sphincteric location and function. The hypothesis introduces the concept of a continence threshold at which the urethra is subjected simultaneously to both shearing and explusive forces. If these forces are sufficient to overcome urethral coaptation at threshold, leakage results. The model proposes an anatomical sequence of changes through which the incontinent urethra cycles between periods of rest and increased abdominal pressure, and suggests a way in which repeated episodes of prolpase and urethral traction by shearing forces exerted by the vagina on the urethra may contribute to the development of intrinsic sphincteric deficiency.


Stenotherms at sub-zero temperatures: thermal dependence of swimming performance in Antarctic fish.
We examined the burst swimming performance of two Antarctic fishes, Trematomus bernacchii and T. centronotus, at five temperatures between -1 degrees C and 10 degrees C. As Antarctic fishes are considered one of the most cold specialised and stenothermal of all ectotherms, we predicted they would possess a narrow thermal performance breadth for burst swimming and a correlative decrease in performance at high temperatures. Burst swimming was assessed by videotaping swimming sequences with a 50-Hz video camera and analysing the sequences frame-by-frame to determine maximum velocity, the distance moved throughout the initial 200 ms, and the time taken to reach maximum velocity. In contrast to our prediction, we found both species possessed a wide thermal performance breadth for burst swimming. Although maximum swimming velocity for both T. bernacchii and T. centronotus was significantly highest at 6 degrees C, maximum velocity at all other test temperatures was less than 20% lower. Thus, it appears that specialisation to a highly stable and cold environment is not necessarily associated with a narrow thermal performance breadth for burst swimming in Antarctic fish. We also examined the ability of the Antarctic fish Pagothenia borchgrevinki to acclimate their burst-swimming performance to different temperatures. We exposed P. borchgrevinki to either -1 degrees C or 4 degrees C for 4 weeks and tested their burst-swimming performance at four temperatures between -1 degrees C and 10 degrees C. Burst-swimming performance of Pagothenia borchgrevinki was unaffected by exposure to either -1 degrees C or 4 degrees C for 4 weeks. Maximum swimming velocity of both acclimation groups was thermally independent over the total temperature range of 1 degrees C to 10 degrees C. Therefore, the loss of any capacity to restructure the phenotype and an inability to thermally acclimate swimming performance appears to be associated with inhabiting a highly stable thermal environment.


Ionic balance in the freshwater-adapted Chinese crab, Eriocheir sinensis.
Ionic regulation by the gills of the freshwater-adapted Chinese crab, Eriocheir sinensis, was examined. The balance of uptake and loss of NaCl in crabs living in freshwater was established. Urine production was measured directly by cannulating the nephropores. Daily urinary loss of Na+ is equivalent to 16% of the haemolymph Na+ content and is substantially higher than that based on data from indirect measurements reported in the literature. Weight and area of anterior and posterior gills are proportional to body weight. The role of the gills in compensating urinary loss by uptake was determined by analysing changes in Na+ and Cl- concentrations in the external medium in which isolated perfused gills were suspended. In posterior gills, salt loss is quantitatively balanced by NaCl net uptake from an external concentration of 1.3 mmol l(-1) NaCl upwards. The transport constant (Kt) for half maximum saturation of net uptake and saturation of NaCl uptake are 1.5 mmol l(-1) and 4 mmol l(-1), respectively. In contrast to previous studies in which tracer fluxes or transepithelial short-circuit currents were determined, our method of direct ion determination shows that no net uptake of Na+ or Cl- occurs in posterior gills in the absence of the respective counter ion, or when uptake of one ion is blocked by a specific inhibitor. Net uptake of Na+ and Cl- was about equal. We conclude that the uptake of the two ions is coupled. The properties of the branchial ion uptake of E. sinensis correlates with the distribution of this crab in river systems.


Lymph osmolality and rehydration from NaCl solutions by toads, Bufo marinus.
Toads, Bufo marinus, allowed to maintain an ad libitum state of hydration were dehydrated by 10 15% of their standard weight and allowed to rehydrate from either deionized water or from 10 or 50 mmol l(-1) NaCl solutions. Toads rehydrating from the dilute salt solutions recovered a larger fraction of their standard weight than did toads rehydrating from deionized water despite there being a reduced osmotic gradient. Amiloride did not reduce water gain from these solutions. Water uptake from 100 mmol l(-1) sucrose and 50 mmol l(-1) Na gluconate was reduced relative to deionized water by a fraction predicted from the osmotic gradient. Thus, the presence of both Na+ and Cl- are required for the augmentation of water gain from dilute salt solutions. Toads allowed to rehydrate from 120 mmol l(-1) NaCl for 180 min recovered nearly as much water as toads rehydrating from deionized water for 120 min and the lymph osmolality was not reduced relative to the dehydrated condition. The recovery of water from the salt solution was greater than that predicted from the reduced osmotic gradient and amiloride partially inhibited the rehydration from 120 mmol l(-1) NaCl. Solute coupled water transport can therefore be demonstrated in living animals but only from a NaCl solution that is nearly isoosmotic with the lymph. The mechanism for enhanced water gain from dilute salt solutions remains unresolved.


Differential catabolism of muscle protein in garden warblers (Sylvia borin): flight and leg muscle act as a protein source during long-distance migration.
Samples of flight and leg muscle tissue were taken from migratory garden warblers at three different stages of migration: (1) pre-flight: when birds face an extended flight phase within the next few days, (2) post-flight: when they have just completed an extended flight phase, and (3) recovery: when they are at the end of a stop-over period following an extended flight phase. The changes in body mass are closely related to the changes in flight (P<0.001) and leg muscle mass (P<0.001), suggesting that the skeletal muscles are involved in the protein metabolism associated with migratory flight. From pre- to post-flight, the flight and the leg muscle masses decrease by about 22%, but are restored to about 12% above the pre-flight masses during the recovery period. Biochemical analyses show that following flight a selective reduction occurred in the myofibrillar (contractile) component of the flight muscle (P<0.01). As this selective reduction accounts only for a minor part of the muscle mass changes, sarcoplasmic (non-contractile) and myofibrillar proteins of both the flight and leg muscle act as a protein source during long-distance migration. As a loss of leg muscle mass is additionally observed besides the loss in flight muscle mass, mass change seems not to be strictly associated with the mechanical power output requirements during flight. Whereas the specific content of sarcoplasmic proteins in the flight muscle is nearly twice as high as that in the leg muscle (P<0.001), the specific content of myofibrillar proteins differs only slightly (P < 0.05), being comparably low in both muscles. The ratio of non-contractile to contractile proteins in the flight muscle is one of the highest observed in muscles of a vertebrate.


A Na+-dependent electrogenic glutamate transporter current in voltage-clamped cells of corpora allata in the cricket Gryllus bimaculatus.
Application of L-glutamate (1 mM) to corpora allata cells of the adult male cricket Gryllus bimaculatus caused a membrane depolarization of 5.9+/-0.3 mV (mean +/- SE) from a resting potential of -62.2+/-1.3 mV (n=57). The underlying mechanism for this depolarization was studied by applying the two-electrode voltage-clamp technique. Application of L-glutamate (1 mM) elicited an inward current that peaked at 8.1+/-0.7 nA (n = 73) at a holding potential of-50 mV. Both L- and D-aspartate also induced an inward current of almost the same amplitude as L-glutamate, whereas D-glutamate failed to induce an inward current. Glutamate receptor agonists, such as kainate, quisqualate, alpha-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid, and N-methyl-D-aspartate, were ineffective in eliciting inward currents. The glutamate-induced inward current did not reverse even when the holding potential was set to +40 mV. The replacement of extracellular Na+ with choline+ eliminated the inward current. These results strongly suggest that the current induced by glutamate is mediated by a glutamate transporter rather than a glutamate receptor. We further examined the effects of 12 amino acid analogs which are known to be selective inhibitors of the mammalian excitatory amino acid transporters (EAATs) on the corpora allata transporter. From the effects of these inhibitors, we conclude that the glutamate transporter expressed in corpora allata cells of the cricket is similar to the high affinity glutamate transporters cloned from human brain, especially EAAT1 and EAAT3. Unlike mammalian transporters, however, serine-O-sulfate has the most potent action, suggesting the unique feature of the glutamate transporter expressed in the corpora allata.


Free fatty acids digested from pollen and triolein in the honeybee (Apis mellifera carnica Pollmann) midgut.
Honey bees satisfy their lipid requirement by consuming pollen. The free fatty acid content of the midgut was used to quantify fat digestion. Midguts extracted from younger workers of known ages and from foragers were divided into three components: endoperitrophic region (peritrophic membrane with gut contents), extraperitrophic region and intestinal wall. Both the total amount of pollen and the amount of free fatty acids in the endoperitrophic region and in the intestinal wall depend on the bee's age. The amounts increase within the 1st 3 days of a honey bee's life, reach maxima around the age of 8 days and then decrease continuously to the lowest values, measured in forager bees. Forced feeding with triacylglycerol results in significantly higher levels of free fatty acids, especially in the endoperitrophic region, in 8-day-old bees and foragers. This indicates that lipolytic activity depends on age and that the free fatty acid content in 8-day-old bees is primarily limited by the amount and availability of lipids ingested. The results show further that fat digestion depends on the functional status of honey bees, as is the case for pollen consumption, speed of transport of pollen bolus through the alimentary canal and protein digestion.


Plasticity of myosin heavy chain expression with temperature acclimation is gradually acquired during ontogeny in the common carp (Cyprinus carpio L.).
Common carp (Cyprinus carpio L.) were reared from hatching until 61 mm total length (TL) at 21 degrees C. At 14 weeks and 20 weeks post-hatch, corresponding to initial lengths of 30 mm and 44 mm respectively, fish were acclimated to 10 degrees C using a rate of cooling of 1 degrees C per day. A statistical model was used to compare the time course in the change of white muscle myofibrillar ATPase activity with temperature acclimation. The myosin heavy chain (MHC) composition of white muscle myofibrils was investigated using peptide mapping. A significant increase in myofibrillar ATPase activity was observed after 2-3 weeks in the 44 mm group, but not until 4-5 weeks in the 30 mm group. when they had reached 37 mm TL. The MHC banding pattern of 120 mm TL fish acclimated to 10 degrees C or 21 degrees C for a minimum of 6 weeks were distinct from each other. The MHC peptide map characteristic of 10-degrees C-acclimated fish was not observed in individuals less than 37 mm length. We therefore conclude that the capacity to alter the composition and properties of myofibrils with cold acclimation is acquired in juvenile carp at around 37 mm TL.


Correlations of plasma lipid metabolites with hibernation and lactation in wild black bears Ursus americanus.
During the denning period, black bears (Ursus americanus) are capable of enduring several months without food. At the same time, female bears that are pregnant or lactating have an added metabolic stress. Based on laboratory studies, much of the energy required to support metabolism and lactation during denning in black bears comes from lipid reserves. These lipid reserves are mobilized and the most metabolically active lipid fraction in the blood are nonesterified fatty acids (NEFA). Therefore, we hypothesized that plasma NEFAs would be higher in denning relative to active bears and in lactating relative to non-lactating female bears. We further hypothesized that in bears with elevated plasma NEFA levels, other lipid-related parameters (e.g., ketone bodies, albumin, cholesterol, lipase) would also be elevated in the plasma. Denning bears had significantly increased NEFA levels in all classes (saturates, monoenes, and polyenes). A doubling of plasma NEFA levels and a 33% increase in albumin, the plasma fatty acid binding protein, in denning bears, resulted in NEFA/albumin ratios that were higher in denning bears (4:1) compared to those of active bears (3:1). Bears became relatively ketonemic with a 17-fold increase in D-beta-hydroxybutyrate levels during the denning period. Plasma cholesterol approximately doubled and lipase was ten-fold lower in denning relative to active bears. These findings indicate a strong correlation between plasma lipid metabolites and the denning period in a wild population of black bears.


Physiological responses to supercooling and hypoxia in the hatchling painted turtle, Chrysemys picta.
We investigated physiological responses to supercooling in hatchling painted turtles (Chrysemys picta) which remain in their natal nests over winter and therefore may become exposed to subzero temperatures. These turtles are freeze tolerant but also must rely on supercooling to survive exposure to the lower temperatures occurring in nests during winter. We compared whole-body concentrations of lactate, glucose, glycerol, and ATP in turtles chilled at 0 degrees C, -4 degrees C, or -6 degrees C for 5 days, or at 6 degrees C for 19 days. In a companion experiment, we measured metabolite concentrations in turtles exposed to a hypoxic environment for 1 day, 4 days, or 8 days. Supercooling and hypoxia exposure were both associated with an increase in concentrations of lactate and glucose and a decrease in glycerol concentrations (albeit no change in the ATP pool), suggesting that supercooling induces functional hypoxia. We conclude that hypoxia tolerance may be an important pre-adaptation for surviving exposure to subzero temperatures in hatchling C. picta.


The calibre of the foramen of Panizza in Crocodylus porosus is variable and under adrenergic control.
The foramen of Panizza is located within the outflow tract of the crocodilian heart, between the left and right aortas. It has been suggested that the foramen of Panizza has a variable calibre, which could explain the profound changes in the distribution of flows and pressure profiles recorded in the right and left aortas. We investigated this possibility using a modified in-situ perfused heart preparation in combination with isolated strip preparations from the outflow tract. In the perfused heart preparation, bolus injections of adrenaline increased the resistance in the foramen of Panizza, indicating a decrease in its diameter. Isolated strip preparations from the outflow tract showed a concentration-dependent increase in tension in response to adrenaline, while vasoactive intestinal polypeptide caused a relaxation in adrenaline pre-contracted strip preparations. We propose that an increase in the diameter of the foramen of Panizza may be important during pulmonary to systemic shunts to allow blood to flow from the left to right aorta (reverse foramen flow) in order to supply the carotid and coronary arteries. During non-shunting conditions, a constricted foramen may prevent excess flow from the right to left aorta during diastole.


Cytogenetic study of Callicebus hoffmannsii (Cebidae, Primates) and comparison with C. m. moloch.
Callicebus is a neotropical primate genus divided into four or five groups of species. Species of the moloch group are distributed in the tropical forests of the Amazon basin. The karyotype of Callicebus hoffmannsii (moloch group) was studied by means of G- and C-banding, Ag-NOR staining and in situ hybridization of telomeric probes. C. hoffmannsii had 2n = 50 chromosomes, with ten biarmed and fourteen acrocentric autosomal pairs. The X chromosome was submetacentric and the Y chromosome was a minor acrocentric. Constitutive heterochromatin was detected in the centromeric regions of all chromosomes; in pairs 7 and 10, it was found in the distal regions of the short arms, and distally in the long arm of the X chromosome. Size heteromorphism in C-bands was detected in pairs 7 and 10. Ag-NOR staining revealed a maximum of three nucleolar organizers. Telomeric probes hybridized only at the terminal regions of all chromosomes. Additionally, a comparison was carried out between C. hoffmannsii and C. m. moloch (2n = 48), as previously reported. Both species shared gross chromosomal similarities diverging by a single rearrangement of centric fusion/fission. A high similarity between C. hoffmannsii and C. donacophilus indicated a close association between the moloch and donacophilus groups.


Influence of hydrocortisone and microwave radiation on the mechanical characteristics of rat bone tissue.
This work deals with the mutual action of hydrocortisone and low intensity microwave radiation (MWR) on the bone tissue of rats. The bone density and velocity of ultrasound was measured in order to evaluate the Young's modulus of the femur. The results show a stimulating effect of the low-intensity MWR field on regeneration of the bone tissue of rats. The MWR, during a long application of hydrocortisone, may be a characteristic protective factor for the bone tissue.


Microscopical aspects of accessory air breathing through a modified stomach in the armoured catfish Liposarcus anisitsi (Siluriformes, Loricariidae).
The presence of an accessory air breathing mechanism as verified by several authors, is widespread among Loricariidae, where modified parts of the digestive tract act primarily as oxygen-exchange organs. An anatomical and histological analysis was carried out on the stomach and intestine of the armoured catfish Liposarcus anisitsi. The data support the assumption that the modified stomach is responsible for holding air and allows blood oxygenation under hypoxia. Experiments demonstrating survival of air breathing Liposarcus in severely hypoxic water support the hypothesis and are discussed.


Analysis of the distribution pattern of sister chromatid exchanges in mitotic chromosomes of human T-lymphocytes.
Band locations of 344 sister chromatid exchanges (SCE), observed in chromosome preparations of peripheral T-lymphocyte cultures, were identified using a sequential Q-banding-sister chromatid differentiation staining protocol. A comparison between expected Poisson, expected negative binomial distributions and observed SCE patterns, revealed that the negative binomial distribution provided a better fit to our SCE data. The aggregated pattern of SCE distribution indicated that some bands were more prone to undergo these events. Genetic markers assigned to those bands recording a significant number of exchanges seemed to correspond with the transcriptionally active genes. The results confirm that SCE are induced at the early S-phase of the cell cycle involving the early replicating genes in these events. Potential applications of cytogenetic techniques employed in the present study are proposed.


Cytophotometric estimation of in situ DNA content in several species of Araceae.
A wide variation in the in situ 4C DNA content, ranging from 15.02 pg to 54.09 pg was found in thirteen genera of the family Araceae. The obligate perennial species showed greater 4C DNA values compared with the facultative perennials and annuals. A remarkable heterogeneity in 4C nuclear DNA amounts was noted among obligate perennials. Intraspecific constancy in the amount of 4C DNA was recorded. The nuclear DNA content correlated positively with chromosome size, duration of the mitotic cycle, and annual to perennial growth forms. Despite an extensive variation in DNA content among the aroids investigated, each species was distinctly characterized by its specific nuclear DNA value, indicating its usefulness in taxonomic characterization and comparison of different aroids.


Antihyperlipidaemic and antihypercholesterolaemic effects of Anethum graveolens leaves after the removal of furocoumarins.
Serum triacylglycerides and total cholesterol levels in rats, with hyperlipidaemia induced by diet, were determined after oral adminstration of a water extract of Anethum graveolens leaves before and after the extraction of the furocoumarin content of the leaves. Administration of the extracts consecutively for 14 days reduced the triacylglycerides and total cholesterol levels by almost 50 and 20%, respectively. Chloroform extraction of furocoumarins from the aqueous extracts did not reduce the antihyperlipidaemic potential of the extracts to a significant degree. Oral administration of the essential oil of A. graveolens seeds, at two different doses, also reduced the triacylglyceride levels by almost 42%. The total cholesterol level was not reduced by the same doses of the essential oil.


Local angiotensin II-generating system in vascular tissues: the roles of chymase.
Roles of each angiotensin II producing enzymes of each of the angiotensin II-producing enzymes were reviewed based on experimental models. In vascular tissues, angiotensin II is potentially cleaved from angiotensin I by angiotensin converting enzyme (ACE) and chymase. It has been confirmed that vascular tissues of humans, monkeys, dogs and hamsters have a chymase-dependent angiotensin II-forming pathway. Much like other hypertensive models, hamster hypertensive models show high levels of vascular ACE activity, but not chymase activity. In hypertensive hamsters, administration of either an ACE inhibitor or an angiotensin II type 1 (AT1) receptor antagonist resulted in similar reductions in blood pressure, suggesting that chymase is not involved in the maintenance of high blood pressure in this model. In monkeys fed a high-cholesterol diet, ACE activity was increased in the atherosclerotic lesions, and an ACE inhibitor and an AT1 receptor antagonist prevented atherosclerosis to a similar degree, suggesting that ACE may be mainly involved in the development of atherosclerosis. After balloon injury in dog vessels, both ACE and chymase activities were locally increased about 3-fold in the injured arteries, and an AT1 receptor antagonist was effective in preventing the intimal formation, but an ACE inhibitor was ineffective. In dog grafted veins, the activities of chymase were increased 15-fold, but those of ACE were increased only 2-fold, and the intimal formation was suppressed by either an AT1 receptor antagonist or a chymase inhibitor. In the normal vascular tissues, ACE plays a crucial role for angiotensin II production, whereas chymase is stored in mast cells in an inactive form. Chymase acquires the ability to form angiotensin II following mast cells activation followed by mast cells activation by a strong stimulus such as occurs in catheter-injury or grafting. Together, these results indicate that chymase plays a major role in the vascular angiotensin II-generating system, particularly in cases of vascular injury.


Diurnal variation of hemodynamic indices in non-dipper hypertensive patients.
The purpose of this study was to elucidate the underlying mechanisms of blunted nocturnal blood pressure reduction in non-dipper hypertensive patients. We studied the diurnal variations in systemic hemodynamic indices and baroreflex sensitivity. In 45 subjects with essential hypertension (24 men; mean age, 49+/-1 years), intra-arterial pressure was monitored telemetrically. Non-dippers were defined as those with a nocturnal reduction of systolic blood pressure of less than 10% of daytime systolic blood pressure. Stroke volume was determined using Wesseling's pulse contour method, calibrated with indocyanine green dilution. Baroreflex sensitivity was calculated as deltapulse interval/deltasystolic blood pressure on spontaneous variations. The mean values of the hemodynamic parameters were calculated every 30 min. Twenty-six subjects were classified as non-dippers. Daytime blood pressure was not significantly different between dippers (149+/-4/87+/-3 mmHg) and non-dippers (147+/-3/82+/-2 mmHg), while the nighttime blood pressure was significantly reduced in dippers (131+/-3/77+/-2 mmHg) but not in non-dippers (145+/-3/80+/-2 mmHg). Nocturnal decreases in both cardiac index and stroke index were smaller in non-dippers (-12.0+/-1.2% and 1.5+/-1.0%) than in dippers (-17.5+/-1.4% and -2.2+/-1.1%). Baroreflex sensitivity significantly increased at nighttime both in dippers (6.5+/-0.6 to 8.0+/-0.7 ms/mmHg) and in non-dippers (5.1+/-0.3 to 6.4+/-0.4 ms/mmHg). Neither daytime nor nighttime baroreflex sensitivity was significantly different between the groups. We conclude that the hemodynamics of non-dipper essential hypertension are characterized by an inadequate nocturnal decrease in cardiac index and stroke index, suggestive of relative volume expansion or malsuppressed sympathetic activity.


Profiles of patients who control the doses of their antihypertensive drugs by self-monitoring of home blood pressure.
The present study profiled patients who control doses of antihypertensive drugs by themselves based on self-monitoring of their blood pressure (self-controllers). A total of 1,028 consecutive outpatients who were taking antihypertensive drugs and who were attending the cardiovascular outpatient clinic of our institute responded to a questionnaire in 1998. They were asked how often they measured their blood pressure, how often they missed taking their medication, and whether or not they had a chance to adjust the doses of antihypertensive drugs by themselves based on self-monitored blood pressure. The frequency of self-controlling of antihypertensive drugs was also examined in 918 patients on antihypertensive drugs in 1997. In 1997, 23 of 918 patients (2.5%) were self-controllers, and 26 of 1,028 patients (2.5%) were self-controllers in 1998. The frequency of home blood-pressure measurement was significantly greater in self-controllers than in the remaining patients (non self-controllers) (p<0.01). The prevalence of proteinuria was significantly less in the former than in the latter. Prior to the start of antihypertensive drugs, blood pressure was significantly lower for the self-controllers (154.4+/-3.8/96.4+/-1.4 mmHg) than for the non self-controllers (169.3+/-0.7/101.7+/-0.4 mmHg) (p<0.001). Clinically measured blood pressures did not differ significantly between the self-controllers and non self-controllers. Thus, about 2.5% of patients on antihypertensive drugs controlled their drug doses by themselves based on self-monitoring of their blood pressure. These patients were characterized by having a milder form of hypertension and by more frequent home blood-pressure measurement than non self-controllers.


Cardiovascular and sympathetic responses to dental surgery with local anesthesia.
We investigated changes in blood pressure and blood variables, including plasma catecholamines, serum glucose and insulin concentrations, during dental surgery. The study included 11 normotensive patients (age, 22.5+/-0.7 years) who underwent tooth extraction at Kyushu Dental College Hospital. Three to 7 days prior to dental surgery, blood pressure, pulse rate, and heart rate variability were measured every 30 min over 24 h. The low frequency (LF: 0.05 to 0.15 Hz) and high frequency (HF: 0.15 to 0.40 Hz) powers were calculated, and the ratio of LF to HF (LF/HF) and HF were used as indexes of sympathetic and parasympathetic activities, respectively. Lidocaine, 2% with epinephrine (1:80,000), was used as the local anesthetic for all patients. Systolic blood pressures significantly increased during dental surgery (+10.8+/-3.5 mmHg); however, this increase failed to correlate not only with baseline systolic blood pressure but with 24-h averaged blood pressures, LF/HF or HF. On the other hand, plasma epinephrine and norepinephrine concentrations increased during dental surgery, and peak values of these variables were obtained after local anesthesia and during tooth extraction, respectively. Serum glucose level increased after local anesthesia (control vs. local anesthesia: 5.16+/-0.11 vs. 5.62+/-0.10 mmol/l; p<0.01); however, plasma insulin concentrations did not change significantly. These results suggest that 1) ambulatory measurements of blood pressure and heart rate variability over 24 h cannot predict the responses of blood pressure during dental surgery, and that 2) administration of local anesthetic and tooth extraction activate sympathoadrenal outflow, resulting in an increase in serum glucose level in normotensive subjects.


Non-Linear trends in the blood pressure of Japanese adults.
Hypertension is one of the risk factors for the development of coronary artery disease as well as stroke. The National Nutrition Survey shows that the systolic and diastolic blood pressures of Japanese adults have decreased over time. These trends have plateaued during the last decade. We investigated national trends in blood pressure (BP) levels during these 10 years by plotting the relation between the mean BP levels during year t, BP(t), and those of the following year, BP(t+1). When we plotted the systolic BP levels of Japanese men and women aged 15 to 80 years, the trace revolved clockwise, with cycles of 4 to 5 years. The approximate center of the circular trace corresponding to data for 1985 through 1990 was at 134 mmHg in men and 129 mmHg in women, and the approximate center of a smaller circle was at 135 mmHg in men and 130 mmHg in women, respectively. In addition, with respect to the data for Japanese men in their 60s, the mean systolic BP level decreased linearly from 1982 to 1986, whereas it seemed to generate 4 circles after 1986. The approximate center of the first circle was 146 mmHg in the men. The center of the second circle was 145 mmHg and that of the third circle was 144 mmHg. Plotting of the data for Japanese women of the same age group yielded the same number of circles as the data for men. Our method of documenting changes in the mean BP levels in Japanese adults provided information about a chaotic oscillation that occurred in the populations we studied. The centers of Lorenz-plotted circles may thus provide essential information about trends in the BP levels in these populations.


Structure and function of the left ventricle and carotid artery in hemodialysis patients.
Hemodialysis patients frequently show associated hypertension, which can lead to a number of cardiovascular complications. The aim of this study was to assess the effects of hypertension on the structure and function of the carotid artery and left ventricle (LV) in hemodialysis patients. In addition, we investigated the contribution of hemodialysis and other risk factors. Fifty-two hemodialysis patients, 71 hypertensive patients (HT group) and 30 normotensive subjects (NT group) were included in this study. Hemodialysis patients were divided into two groups: 35 patients with hypertension (HDHT group), and 17 patients without hypertension (HDNT group). We measured intima-media thickness (IMT), plaque score, end-diastolic diameter, and stiffness index beta of the carotid artery by ultrasonography, and LV mass index (LVMi), endocardial fractional shortening (FS), and midwall FS (MWS) by echocardiography. A multiple stepwise regression analysis including hemodialysis, hypertension, diabetes mellitus, and other risk factors was also performed. IMT was significantly higher in the HT and HDHT groups than in the NT group. Plaque score and diameter of the carotid artery were higher in the HDHT group than in the other three groups. The stiffness index beta was higher in the HDHT group than in the non-hemodialysis groups. In multivariate analysis, IMT was independently correlated with age and hypertension. Plaque score and stiffness index beta were independently associated with age, hypertension, and hemodialysis. LVMi was higher in HT and hemodialysis-patients groups than in the NT group. Hypertension and hemodialysis were strong and independent predictors of LVMi. FS showed no significant differences among the four groups, but MWS was significantly lower among the hemodialysis patients than in the NT group. MWS was independently correlated with hemodialysis and diabetes. In conclusion, hemodialysis per se advanced both atherosclerosis and arteriosclerosis of the carotid artery. Moreover, it increased LVMi and caused cardiac dysfunction. Associated hypertension might thus accelerate the progression of atherosclerosis and arteriosclerosis of the carotid artery and the increase of LVMi.


Differential effects among thiazolidinediones on the transcription of thromboxane receptor and angiotensin II type 1 receptor genes.
Peroxisome proliferator-activated receptor (PPAR)-gamma ligands thiazolidinediones (TZDs) have recently been reported to be anti-hypertensive and anti-atherosclerotic. We have previously shown that one of the TZDs troglitazone significantly suppressed the transcription of both thromboxane receptor (TXR) and angiotensin II type 1 receptor (AT1R) genes in vascular smooth muscle cells (VSMCs) by activating PPAR-gamma. In the present study, we compared the effects of troglitazone and other TZDs on the transcription of these genes. TXR and AT1R mRNAs in rat VSMCs were determined by semi-quantitative RT-PCR. Luciferase chimeric constructs containing either the 989-bp rat TXR gene promoter or the 1,969-bp rat AT1R gene promoter were transiently transfected into VSMCs. The cells were incubated with troglitazone, RS-1455 (a derivative of troglitazone which does not contain the hindered phenol resembling alpha-tocopherol), pioglitazone, or rosiglitazone for 12 h before harvesting. mRNA expression levels of TXR and AT1R were significantly decreased by troglitazone in contrast to rosiglitazone. TXR gene and AT1R gene transcription was significantly suppressed by troglitazone in a dose-dependent manner, while RS-1455 was less potent. Pioglitazone and rosiglitazone weakly suppressed the transcription of both genes in a manner almost similar to RS-1455. We have shown that troglitazone suppresses transcription of both the TXR and AT1R genes more potently than other TZDs. The structure of troglitazone and RS-1455 is identical except the hindered phenol, which is recently recognized to function as an antioxidant. Moreover, we have shown that the potency for activating PPAR-gamma is almost identical between troglitazone and RS-1455. We therefore speculate that the strong transcriptional suppression of the TXR and AT1R genes by troglitazone may be mediated in part by its antioxidant effect.


Benidipine inhibits expression of ET-1 and TGF-beta1 in Dahl salt-sensitive hypertensive rats.
Endothelin and growth factors such as transforming growth factor (TGF)-beta1 are important regulators of the cardiovascular system. Although increased production of endothelin-1 (ET-1) and TGF-beta1 have been reported in left ventricular hypertrophy, the detailed roles of these substances in hypertrophy remain to be determined. To elucidate the cardioprotective effects of calcium antagonists in left ventricular hypertrophy, we evaluated the effects of long-term treatment with benidipine, a long-acting calcium antagonist, on preproET-1, ET(A) receptor (ETAR) and TGF-beta1 expression in the left ventricle and evaluated the relations between these effects and myocardial remodeling in Dahl salt-sensitive hypertensive (DS) rats fed a high-salt diet. After 5 weeks of feeding an 8% NaCl diet to 6-week-old DS rats (i.e., at 11 weeks of age), a distinct stage of concentric left ventricular hypertrophy (DSLVH) was noted. Benidipine (DSLVH-B group, n= 8; 1 mg/kg/day, subdepressor dose) or vehicle (DSLVH-V group, n=8) was administered to 6-week-old DS rats for 5 weeks, or until the onset of DSLVH stage, and age-matched (11-week-old) Dahl salt-resistant rats fed the same diet served as a control group (DR-C, n=8). Blood pressure was similar between the DSLVH-B and DSLVH-V groups, but was significantly lower in DR-C rats. The preproET-1, ETAR and TGF-beta1 expressions in the left ventricle were significantly higher in DSLVH-V than in DR-C rats, and significantly lower in DSLVH-B than in DSLVH-V. Benidipine administration resulted in significant improvements in the wall-to-lumen ratio and perivascular fibrosis in the coronary arterioles, and in myocardial fibrosis. We therefore concluded that myocardial remodeling and left ventricular hypertrophy in DS hypertensive rats fed a high-salt diet were significantly ameliorated by a subdepressor dose of benidipine, and that this amelioration was partly due to decreases in the expression of ET-1 and TGF-beta1 in the left ventricle.


Antioxidants inhibit JNK and p38 MAPK activation but not ERK 1/2 activation by angiotensin II in rat aortic smooth muscle cells.
Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) hypertrophy, which results in several cardiovascular diseases. Ang II-induced cellular events have been mediated, in part, by reactive oxygen species (ROS) which also involve activation of mitogen-activated protein (MAP) kinases. Although it has been proposed that the therapeutic administration of antioxidants is useful for vascular diseases, the precise mechanisms which regulate ROS-sensitive signaling events have not been well characterized. Thus, we hypothesized that antioxidants may affect ROS-mediated MAP kinases activation induced by Ang II. The present findings showed that Ang II stimulated rapid and significant activation of ERK 1/2, JNK and p38 MAPK in cultured rat aortic smooth muscle cells (RASMC). Ang II-induced ERK 1/2 activation was not affected by all antioxidants examined, whereas JNK was sensitive to all antioxidants. In contrast, p38 MAPK activation was inhibited by DPI and ascorbic acid concentration-dependently, but by NAC only at high concentration. DETC and Trolox C had no effects on p38 MAPK activation by Ang II. We further examined the effects of antioxidants on Ang II-induced increases in oxygen consumption as an index of ROS generation in RASMC. DPI strongly inhibited Ang II-induced increases in oxygen consumption. DETC also inhibited Ang II-induced oxygen consumption, whereas ascorbic acid markedly augmented it. These findings suggest that the inhibitory effects of antioxidants on MAP kinases activation in VSMC are attributable, in part, to their modulating effects on ROS generation by Ang II in VSMC. Thus, inhibition of MAP kinases by antioxidants may imply their usefulness for relief of cardiovascular diseases.


Estriol improves membrane fluidity of erythrocytes by the nitric oxide-dependent mechanism: an electron paramagnetic resonance study.
The present in vitro study was performed to investigate the effects of estriol (E3) on membrane fluidity of erythrocytes by means of an electron paramagnetic resonance (EPR) and spin-labeling method. E3 was shown to significantly decrease the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS obtained from EPR spectra of erythrocyte membranes. This finding indicated that E3 might increase the membrane fluidity of erythrocytes. The effect of E3 was significantly potentiated by the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), and a cyclic guanosine 3',5'-monophosphate (cGMP) analog, 8-bromo-cGMP. In contrast, the change in the membrane fluidity induced by E3 was antagonized by the NO synthase inhibitor, L-NG-nitroarginine-methyl-ester (L-NAME), and asymmetric dimethyl-L-arginine (ADMA). The results of the present study showed that E3 significantly increased the membrane fluidity and improved the microviscosity of erythrocyte membranes, partially mediated by an NO- and cGMP-dependent pathway. Furthermore, the data might be consistent with the hypothesis that E3 could have a beneficial effect on the rheological behavior of erythrocytes and may play a crucial role in the regulation of microcirculation.


Calcium buffering of resting, voltage-dependent Ca2+ influx by sarcoplasmic reticulum in femoral arteries from spontaneously hypertensive rats at prehypertensive stage.
We examined the Ca2+-buffering function of the sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) at a prehypertensive stage. Differences in the effects of cyclopiazonic acid (CPA) and thapsigargin, agents that inhibit SR Ca2+-ATPase, and of ryanodine, which depletes SR Ca2+, on tension and cellular Ca2+ level were assessed in endothelium-denuded strips of femoral arteries from 4-week-old SHR and normotensive Wistar-Kyoto rats (WKY). Addition of CPA, thapsigargin or ryanodine to the resting state of the strips caused an elevation of cytosolic Ca2+ level and a contraction in both WKY and SHR. These responses were larger in SHR than in WKY. The contractions were inhibited strongly by 100 nM nifedipine or 3 microM verapamil and were abolished by Ca2+-free solution. Nifedipine, verapamil or Ca2+-free solution itself caused a relaxation from the resting state of SHR strips, but not from that of WKY strips. The resting Ca2+ influx in arteries measured by a 5-min incubation with 45Ca was significantly larger in SHR than in WKY. This influx was decreased by 10 microM CPA or 10 microM ryanodine in both WKY and SHR. These results suggest that in the resting state of the femoral artery from 4-week-old SHR, the greater part of the increased Ca2+ influx via L-type Ca2+ channels is buffered by Ca2+ uptake into the SR, while some Ca2+ reaches the myofilaments, resulting in the maintenance of resting tone.


Intravascular ultrasound detects coarctation of the renal artery in a patient with Moyamoya disease.
A 19-year-old man with moyamoya disease was diagnosed as having renovascular hypertension, based on stenosis of the proximal portion of the right renal artery with elevated plasma renin activity. Intravascular ultrasound (IVUS) imaging at the renal artery lesion revealed focal narrowing of the renal artery without vascular wall thickening (i.e., coarctation). The coarctation of the renal artery was adequately dilated by stent implantation after suboptimal balloon angioplasty. After the procedure, the patient's hypertension improved. The findings of the present case suggest that IVUS-guided renal angioplasty is an effective therapeutic procedure for correcting coarctation of the renal artery in patients with moyamoya disease.


Lack of correlation between Mbo I restriction fragment length polymorphism of renin gene and essential hypertension in Japanese.
Predisposition to essential hypertension is associated with gene polymorphisms of the renin angiotensin system (RAS). Gene polymorphisms of the angiotensinogen and angiotensin converting enzyme genes are known to be risk factors for hypertension, while few studies concerning the renin gene polymorphism have been published. In the present investigation, we carried out a case control study using a Japanese population to examine the genetic influence of the renin gene on the predisposition to hypertension. Patients (n=235) recruited from outpatients at Osaka University Hospital and diagnosed with essential hypertension or receiving long-term antihypertensive medication participated in the study. Normotensive control subjects (n=510) without a history of hypertension and without diabetes mellitus were recruited from the same population, and were sex-matched with experimental subjects. A polymorphism in intron 9 of the human renin gene was determined as the Mbo I restriction fragment length polymorphism (Mbo I-RFLP). There was no significant association between Mbo I-RFLP of the renin gene and predisposition to essential hypertension in Japanese (p>0.05, chi2=2.1). These results suggest that the Mbo I (+) allele of the renin gene does not increase the risk for hypertension in Japanese.