Low serum level of 1,25(OH)2 D is associated with chronic periodontitis.

BACKGROUND AND OBJECTIVES: Vitamin D has been studied primarily for its involvement in calcium and phosphate absorption and bone metabolism. The active form of vitamin D-1,25(OH)2 D-has also been investigated for its immune modulatory properties. We explored associations between serum levels of 25(OH)D and 1,25(OH)2 D and periodontal health. SUBJECTS AND METHODS: This case-control study included 55 subjects with chronic periodontitis (cases) and 30 periodontally healthy subjects (controls). Their serum levels of 25(OH)D, 1,25(OH)2 D, ultrasensitive C-reactive protein and high-density lipoprotein cholesterol were determined. Associations between vitamin D and periodontal health status were studied using logistic regression analysis. RESULTS: A statistically significant association was found between serum 1,25(OH)2 D level and periodontal health status; in that subjects with a low 1,25(OH)2 D were more likely to belong to the periodontitis group (OR = 0.97, 95% CI = 0.95-1.00). There was practically no association between 25(OH)D level and periodontal health status. CONCLUSION: In this case-control study low serum 1,25(OH)2 D level appeared to be associated with periodontitis, which was in line with the previously reported associations between serum 1,25(OH)2 D levels and other inflammatory diseases. Whether this association is causal in nature, remains to be confirmed in future studies.

Serum 25-hydroxyvitamin D is associated with major cardiovascular risk factors and cardiac structure and function in patients with coronary artery disease.

BACKGROUND AND AIMS: Vitamin D deficiency has been associated with increased risk for cardiovascular (CV) disease, but the possible effects of Vitamin D on cardiac structure and function are not well characterized. METHODS AND RESULTS: The correlation between 25-hydroxyvitamin D levels and metabolic and cardiac echocardiographic parameters was studied in ARTEMIS study population including 831diabetic and 659 non-diabetic patients with stable coronary artery disease (CAD). Low levels of Vitamin D were associated with high BMI (p < 0.001), high total and LDL cholesterol and triglyceride levels (p < 0.001 for all) in both diabetics and non-diabetics. Among non-diabetic patients, low Vitamin D was also associated independently with elevated systolic and diastolic blood pressure (p < 0.005). Low Vitamin D levels were independently associated with reduced left ventricular (LV) ejection fraction (p < 0.005) and increased left atrial diameter (p < 0.03) measured by cardiac ultrasound by 2-dimensional echo. In the non-diabetic group, low Vitamin D levels were associated with impaired LV filling (high E/E') (p < 0.03) and low E/A mitral flow pattern measured by Doppler echocardiography (p < 0.05). Among diabetics, low Vitamin D levels were also related to increased LV end-systolic diameter (p < 0.05) and right ventricular diameter (p < 0.005). The association between LV diastolic filling (E/E') and Vitamin D levels was significant (p < 0.01) after adjustment for the commonly recognized risk factors of diastolic dysfunction in linear regression analysis. CONCLUSIONS: Low Vitamin D is associated with several major cardiovascular risk factors and cardiac structural changes including impaired systolic and diastolic function, which together may explain the association of low Vitamin D to worse cardiovascular outcome.

Oral, transdermal and vaginal combined contraceptives induce an increase in markers of chronic inflammation and impair insulin sensitivity in young healthy normal-weight women: a randomized study.

STUDY QUESTION: What is the effect of alternative administration routes of combined contraceptives (CCs) on androgen secretion, chronic inflammation, glucose tolerance and lipid profile? SUMMARY ANSWER: The use of oral, transdermal and vaginal CCs impairs glucose tolerance and induces chronic inflammation. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Oral CCs worsen insulin sensitivity and are associated with increased levels of circulating inflammatory markers, whereas the metabolic effects of transdermal and vaginal CCs have been reported to be minimal. This is the first study comparing three different administration routes of CCs on metabolic variables. STUDY DESIGN, SIZE AND DURATION: This randomized (computer-generated) open-label 9-week follow-up study was conducted at the Oulu University Hospital, Finland. Fasting blood samples were collected at baseline and thereafter at 5 and 9 weeks of treatment, and serum levels of 17-hydroxyprogesterone, androstenedione, testosterone, C-reactive protein (CRP), sex hormone-binding globulin (SHBG), glucose, insulin, C-peptide, total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were measured. Oral glucose tolerance tests were performed and plasma levels of pentraxin 3 (PTX-3) were measured at 0 and 9 weeks. The randomization list, with an allocation ratio of 1:1:1 and block size of six, was computer generated and constructed by a pharmacist at the Oulu University Hospital. The research nurse controlled the randomization list and assigned participants to their groups at the first visit. PARTICIPANTS AND SETTING: Forty-two of 54 healthy women who entered the study used oral contraceptive pills (n = 13), transdermal contraceptive patches (n = 15) or contraceptive vaginal rings (n = 14) continuously for 9 weeks. Inclusion criteria were regular menstrual cycles, at least a 2-month washout as regards hormonal contraceptives and no medication. MAIN RESULTS AND THE ROLE OF CHANCE: Serum levels of SHBG increased and consequently the free androgen index (FAI) decreased in all study groups from baseline to 9 weeks of treatment [FAI, oral: 1.3 (95% confidence interval, CI: 0.94; 1.62) to 0.40 (0.25; 0.54); transdermal: 1.2 (0.96; 1.4) to 0.36 (0.30; 0.43); vaginal: 1.6 (1.1; 2.1) to 0.43 (0.29; 0.58), P < 0.001 in all groups]. Insulin sensitivity was reduced at 9 weeks in all three groups according to the Matsuda index [oral: 7.3 (5.5; 9.0) to 5.6 (3.9; 7.3); transdermal: 9.1 (6.7; 11.4) to 6.6 (4.5; 8.8); vaginal: 7.7 (5.9; 9.5) to 5.4 (3.9; 7.0), P= 0.004-0.024]. Levels of HDL cholesterol, triglycerides and CRP rose in all three groups [CRP, oral: 0.70 (0.38; 1.0) to 5.4 (1.0; 9.9) mg/l; transdermal: 0.77 (0.45; 1.1) to 2.9 (1.4;4.4) mg/l; vaginal: 0.98 (0.52; 1.4) to 3.7 (-0.25; 7.7, a negative value due to skewed distribution to right) mg/l, P≤ 0.002 in all groups] and PTX-3 levels increased in the oral and transdermal study groups (P = 0.007 and P = 0.002). WIDER IMPLICATIONS OF THE FINDINGS: Although the long-term consequences of the present results remain undetermined, these findings emphasize the importance of monitoring glucose metabolism during the use of CCs, especially in women with known risks of type 2 diabetes or cardiovascular diseases. BIAS, LIMITATIONS, GENERALIZABILITY: The number of subjects was relatively low. Moreover, the 9-week exposure to CCs is too short to draw conclusions about the long-term health consequences. However, as the subjects were healthy, normal-weight young women, the possible alterations in the glucose and inflammatory profiles among women with known metabolic risks might be even greater. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the Academy of Finland, the Sigrid Jusélius Foundation, the Finnish Medical Foundation, the Research Foundation of Obstetrics and Gynecology, Oulu University Scholarship Foundation, the North Ostrobothnia Regional Fund of the Finnish Cultural Foundation, the Tyyni Tani Foundation of the University of Oulu and the Finnish-Norwegian Medical Foundation. No competing interests. TRIAL REGISTRATION NUMBER: NCT01087879.

Cardiac troponin-I as a screening tool for myocarditis in children hospitalized for viral infection.

AIM: The incidence of myocarditis in children is uncertain because patients with minor symptoms can remain undiagnosed. We hypothesized that screening all children who are hospitalized for an acute infection with troponin-I (TnI) would reveal myocarditis cases and performed a prospective screening study. METHODS: Between October 2005 and July 2008, a blood sample for TnI measurement was taken every time a sample for C-reactive protein measurement was drawn. If TnI value was above the screening limit (0.06 microg/L), electrocardiogram (ECG) and cardiac ultrasound were performed. TnI measurements were repeated until at normal level. RESULTS: Altogether, 1009 children were screened during the 33 months. TnI was above the screening limit (0.06 microg/L) in six children. None of them had any signs of myocarditis in ECG or cardiac ultrasound. Five of those six children were younger than 30 days. All had a respiratory infection as a cause for hospitalization, three of which was caused by RSV. In four children, all younger than 30 days, TnI levels remained high (>0.37 microg/L) for two months, but decreased after that to normal levels. CONCLUSION: The incidence of myocarditis during viral infections is low and a routine TnI screening for asymptomatic myocarditis is not useful.

High plasma leptin levels are associated with impaired diastolic function in patients with coronary artery disease.

BACKGROUND AND AIMS: Obese subjects have elevated leptin levels, which have been associated with increased risk of cardiovascular events. Because leptin has direct cellular effects on various tissues, we tested the hypothesis that leptin levels are associated with cardiac structure or function in patients with coronary artery disease (CAD). METHODS AND RESULTS: The study population consisted of 1 601 CAD patients, of whom 42% had type 2 diabetes mellitus. Plasma leptin was measured in fasted state and an echocardiography performed. Leptin levels were not related to LV dimensions or LV ejection fraction (NS for all), but higher leptin levels were associated with elevated E/E' (9.43 vs. 11.94 in the lowest and the highest leptin quartile, respectively; p=0.018 for trend). Correspondingly, a decreasing trend was observed in E/A (1.15 vs. 1.06; p=0.037). These associations were independent of obesity and other relevant confounding variables. CONCLUSION: We conclude that elevated plasma leptin levels are associated with impaired left ventricular diastolic function in patients with CAD independently of obesity and other confounding variables. Leptin may be one of the mechanistic links explaining the development of congestive heart failure in obese subjects.

Steroid-involved transcriptional regulation of human genes encoding prostatic acid phosphatase, prostate-specific antigen, and prostate-specific glandular kallikrein.

We have compared the steroid regulation of human genes encoding prostatic acid phosphatase (hPAP), prostate-specific antigen (hPSA), and prostate-specific glandular kallikrein (hK2) at the level of transcription. Reporter constructs of hPAP promoter covering the region -734/+467 were functional in both prostatic (LNCaP and PC-3) and nonprostatic (CV-1) cell lines in transient transfections. hPAP -231/+50 with eight identified transcription factor-binding sites showed the highest, and hPAP -734/+467 showed the lowest transcriptional activity in CV-1 cells. The hPAP promoter could not be induced with androgen, glucocorticoid, or progesterone, contrary to the hPSA (-620/+40) and hK2 (-493/+27) promoters in PC-3 cells cotransfected with the respective steroid receptor expression vector. Therefore, steroids cannot directly regulate hPAP gene expression via receptor binding to steroid response elements at -178 and +336, which have been shown to have androgen receptor-binding ability in vitro. Glucocorticoid was the most powerful activator of the hPSA construct at 10-nM steroid concentrations. On the contrary, glucocorticoid stimulation of the transcriptional activity of the hK2 construct was the weakest among the tested steroids. The results indicate that the steroid response elements in the proximal promoters of hPSA and hK2 genes are not androgen specific, offering the molecular basis for the expression of these genes outside the prostate in tissues containing steroid receptors.

Congestive heart failure in acute myocardial infarction. Treating the spectrum from mild failure to cardiogenic shock.

Congestive heart failure (CHF) accompanying acute myocardial infarction (MI) may have various manifestations, ranging from mild failure to cardiogenic shock. Initial treatment depends on the cause, which is usually determined through careful physical examination. The Forrester hemodynamic classification is useful in this determination. A practical working knowledge of the clinical correlates of left ventricular dysfunction in acute MI allows rational use of the several classes of drugs available to treat CHF. With severe CHF, invasive monitoring is usually required, and mechanical complications of MI need to be identified and managed appropriately.

Low Psychological General Well-Being (PGWB) is associated with deteriorated 10-year survival in men but not in women among the elderly.

We studied Psychological General Well-Being (PGWB) and its relation to 10-year survival in 75-year-olds from the general population. The PGWB global score (sum of six subscale scores) and the subscale scores were transformed to 0-100 scales. Ten-year survival in relation to PGWB global and subscale scores was studied in a cohort of 204 men and 213 women. Global PGWB score (median) was 83 in men and 79 in women (for difference p=0.001). Significantly higher male scores were found for most PGWB subscales. Global PGWB score was significantly related to better 10-year survival in men (relative risk per ten points of score was 0.80; p=0.001 and 0.85; p=0.022 adjusting for chronic diseases and living alone) but not in women (relative risk 0.94; p=0.478 unadjusted). Among 75-year-olds, PGWB score was significantly higher for men. A high PGWB score was significantly related to better survival in men but not in women.

Aging stability of complete blood count and white blood cell differential parameters analyzed by Abbott CELL-DYN Sapphire hematology analyzer.

This study presents the results of an aging stability study of complete blood count (CBC) and leukocyte differential parameters using the Abbott CELL-DYN Sapphire hematology analyzer. Stability studies showed no substantial change in CBC parameters up to 24-48 h at +23 +/- 2 degrees C (room temperature), except for optical platelet count (PLTo). For specimens aged over 24, the value of impedance platelet count yielded more reliable results than the routine PLTo. White blood cell (WBC) differential parameters, except eosinophils, were stable for up to 48 h at +23 +/- 2 degrees C. CBC parameters were stable for 72 h, except mean platelet volume, which slightly increased between 48 and 72 h, at +4 degrees C. WBC differentials were stable 48-72 h, with a slight decrease observed in absolute neutrophils and lymphocytes at +4 degrees C.

Augmented blood pressure response to exercise is associated with improved long-term survival in older people.

OBJECTIVE: Studies on the prognostic importance of the systolic blood pressure (SBP) response during exercise report ambiguous results. Most research focuses on younger and middle-aged selected patient groups and rarely includes women. We investigated the prognostic value of SBP response during exercise testing in 75-year-olds. DESIGN: Prospective observational cohort study. SETTING: A community-based random sample of 75-year-old men and women (n = 382). MAIN OUTCOME MEASURES: The prognostic value of SBP change from rest to peak exercise during a symptom-limited cycle test was evaluated for the endpoints all-cause mortality and cardiovascular mortality during long-term follow-up. RESULTS: After a median follow-up of 10.6 years, 140 (37%) of the participants had died, 64 (17%) from cardiovascular causes. The all-cause mortalities for exercise SBP changes of < or =30 mm Hg, 31-55 mm Hg and >55 mm Hg were 5.1, 4.2 and 2.6 per 100 person-years, respectively (logrank 9.6; p = 0.008). For every 10 mm Hg increase in SBP during exercise the relative hazard for all-cause mortality was reduced by 13% (p = 0.030) and for cardiovascular mortality by 26% (p = 0.004) after adjustment for sex, smoking, waist circumference, total/HDL cholesterol ratio, prevalent ischaemic heart disease, hypertension, diabetes, cardiovascular medication, pre-exercise SBP, exercise capacity, resting left ventricular ejection fraction and left ventricular mass index. CONCLUSIONS: Our findings suggest that an augmented SBP response during exercise is associated with an improved long-term survival among community-living 75-year-old individuals.

Performance evaluation of Abbott CELL-DYN Ruby for routine use.

CELL-DYN Ruby is a new automated hematology analyzer suitable for routine use in small laboratories and as a back-up or emergency analyzer in medium- to high-volume laboratories. The analyzer was evaluated by comparing the results from the CELL-DYN((R)) Ruby with the results obtained from CELL-DYN Sapphire . Precision, linearity, and carryover between patient samples were also assessed. Precision was good at all levels for the routine cell blood count (CBC) parameters, CV% being or= 0.98) with CELL-DYN Sapphire for the CBC parameters. For the absolute reticulocyte count, R(2) was 0.82. In the white blood cell (WBC) differentials, the between-days precision was good for all parameters (CV%: or= 0.97), and the correlation coefficient for absolute monocyte count and monocyte percentage were 0.91 and 0.87, respectively. For absolute basophil count and basophil percentage the correlations were weaker (R(2) = 0.46 and 0.34, respectively). Carryover was minimal for all the parameters studied. The linearities of WBC, red blood cell, PLTs, and hemoglobin were acceptable within the tested ranges. In conclusion, the results of the evaluation showed the performance of CELL-DYN Ruby to be good.

White blood cell counts associate more strongly to the metabolic syndrome in 75-year-old women than in men: a population based study.

BACKGROUND: A positive relation between the metabolic syndrome (MetS) and inflammatory activity has been reported. The purpose of this investigation was to study the relationships between 1) white blood cell (WBC) count and MetS, 2) WBC count and the individual components of MetS and 3) WBC count and insulin sensitivity in 75-year-old women and men from the general population. METHODS: The study included 200 women and 196 men comprising 64% of the 75-year old people from the city of Västerås in Sweden. MetS was defined according to the National Cholesterol Education Program (NCEP). RESULTS: WBC count (10(9)/L; median and interquartile range) was 5.7 (4.9-6.8) for women and 6.3 (5.4-7.2) for men, P < .001 for gender difference. For women with and without MetS, WBC count was 6.3 (5.3-7.3) and 5.4(4.7-6.3), respectively. For men the corresponding figures were 6.7 (5.9-7.6) and 6.1 (5.4-7.1).The difference in WBC count between individuals with and without MetS was significant (P < .001 for women; P = .014 for men). All individual components of MetS (with exception of blood pressure) were more strongly associated with WBC count for women than for men. Insulin sensitivity, measured as HOMA-IR (HOmeostasis Model Assessment-Insulin Resistance) index, was significantly associated with WBC count in women but not in men. CONCLUSIONS: In this elderly population, individuals with MetS had a higher WBC count than those without. Women had a lower WBC count and stronger relationship between WBC count and insulin sensitivity than did men.

QTc interval and survival in 75-year-old men and women from the general population.

AIMS: The study concerns the relationship of the corrected QT (QTc) interval to 6.4 years of survival and to measures of cardiac function, such as echocardiographic variables and plasma levels of brain natriuretic peptide (BNP), in 75-year-old people. METHODS AND RESULTS: QTc was measured in a 12-lead electrocardiogram (ECG) in 210 men and 223 women, comprising a randomly selected sample from the general population (70% participation rate). The Sicard 440/740 computer-analysis program, with Hodges' formula for heart rate-based QT correction, was used. The optimal cut-off point for predicting survival according to the receiver operating characteristic curve was found between 429 and 430 ms. Individuals with a QTc interval of > or =430 ms (n = 115) had decreased survival when compared with those with shorter QTc interval (n = 318); the relative risk was 2.4 (95% confidence interval 1.5-3.7). The predictive ability of QTc reflects an association between QTc and the following variables: BNP, left ventricular mass, and left ventricular ejection fraction (but not diastolic filling patterns). Both Hodges' and Bazett's formulae for heart rate correction of the QT interval were useful for predicting survival. The median QTc was 415 ms using Hodges' formula and 430 ms with Bazett's formula. The QRS component of QTc predicted survival better than the rest of the QTc interval and was approximately as useful as the QTc interval itself. CONCLUSION: The computer-derived QTc obtained from the ordinary 12-lead ECG identifies high-risk individuals among elderly people from the general population.

Evaluation of innotrac aio! Second-generation cardiac troponin I assay: the main characteristics for routine clinical use.

The availability of a simple, sensitive, and rapid test using whole blood to facilitate processing and to reduce the turnaround time could improve the management of patients presenting with chest pain. The aim of this study was an evaluation of the Innotrac Aio! second-generation cardiac troponin I (cTnI) assay. The Innotrac Aio! second-generation cTnI assay was compared with the Abbott AxSYM first-generation cTnI, Beckman Access AccuTnI, and Innotrac Aio! first-generation cTnI assays. We studied serum samples from 15 patients with positive rheumatoid factor but with no indication of myocardial infarction (MI). Additionally, the stability of the sample with different matrices and the influence of hemodialysis on the cTnI concentration were evaluated. Within-assay CVs were 3.2%-10.9%, and between-assay precision ranged from 4.0% to 17.2% for cTnI. The functional sensitivity (CV = 20 %) and the concentration giving CV of 10% were approximated to be 0.02 and 0.04, respectively. The assay was found to be linear within the tested range of 0.063-111.6 mu g/L. The correlations between the second-generation Innotrac Aio!, Access, and AxSYM cTnI assays were good (r coefficients 0.947-0.966), but involved differences in the measured concentrations, and the biases were highest with cTnI at low concentrations. The second-generation Innotrac Aio! cTnI assay was found to be superior to the first-generation assay with regard to precision in the low concentration range. The stability of the cTnI level was best in the serum, lithium-heparin plasma, and lithium-heparin whole blood samples (n = 10 , decrease < 10 % in 24 hours at +20( degrees )C and at +4( degrees )C. There was no remarkable influence of hemodialysis on the cTnI release. False-positive cTnI values occurred in the presence of very high rheumatoid factor values, that is, over 3000 U/L. The 99th percentile of the apparently healthy reference group was

Highly sensitive determination of C-reactive protein on the Innotrac Aio! immunoanalyzer.

C-reactive protein (CRP) is a widely recognized indicator of inflammation. Prospective studies have shown that CRP can be used to predict the risk of future cardiovascular events in apparently healthy subjects. Clinical and laboratory studies have also shown that inflammation has an important role in the inititation, progression and destabilization of atheromas, which makes high-sensitivity CRP determinations valuable in cardiovascular risk assessment. Innotrac Aio! is a fully automated random-access immunoanalyzer using a unique all-in-one (Aio!) dry reagent concept and time-resolved fluorometric detection. In this study, the analytic performance of the Innotrac Aio! ultrasensitive CRP assay (usCRP) was evaluated. The analytical detection limit was 0.003 mg/L, the limit of quantification was

Analytical performance of time-resolved fluorometry-based Innotrac Aio! cardiac marker immunoassays.

The results of an evaluation of the Innotrac Aio! cardiac markers are presented. This system is based on dry-chemistry, time-resolved fluorometry. All assay-specific reagents are dry-coated into assay-specific cups, and only the generic assay buffer is required. The levels of precision attained with pooled serum samples and control materials were acceptable for cTnI and CK-MB. Myoglobin assay showed higher CV, 5.6-9.5%. The linearity studies were performed in concentration ranges of 0.1-76 microg/L for cTnI, 0.7-450 microg/L for CK-MB and 0.6-1500 microg/L for myoglobin. The markers were found to be linear within the ranges tested. The correlation coefficient between the Aio! and AxSYM cTnI assays was 0.960, and the slope was 0.07. The correlation coefficients between the Aio! and AxSYM CK-MB and myoglobin assays were 0.995 and 0.971, respectively. They involved some differences in the measured concentrations (Aio! CK-MB was about 9% higher than AxSYM CK-MB, and Aio! myoglobin was 19% higher than AxSYM). Comparative studies with all the markers, using EDTA whole blood and lithium heparin plasma specimens and lithium heparin whole blood and plasma, yielded the following results: the slopes were close to 1.0 for all correlations, with the exception of that between CK-MB EDTA whole blood and lithium heparin (0.83). High correlation coefficients were obtained (> or = 0.97). The carryover results for all the cardiac markers were good, 0.0%, 0.0%, and 0.3% for cTnI, CK-MB, and myoglobin, respectively. The analytical detection limits were 0.01 microg/L for cTnI, 0.8 microg/L for CK-MB and 0.5 microg/L for myoglobin. The stability of the analytes in the lithium heparin samples at room temperature was also studied and was found to be decreased by from 10% (myoglobin and CK-MB) to 17% (cTnI) in 8 h. Innotrac Aio! provides a rapid and easy quantitative measurement of cardiac TnI, CK-MB, and myoglobin within < 18 min. This system is therefore suitable for use in emergency departments, coronary care units or central laboratory settings.

Influence of serotonin on total intravascular capacity in the anaesthetized dog.

The influence of serotonin on intravascular volume in the total capacitance circulation has not previously been examined. Thus, blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that total intravascular volume changes could be recorded as the inverse of changes in reservoir volume in 31 anaesthetized dogs. Serotonin (588 +/- 47 micrograms) in the left atrium was associated with an initial decrease in intravascular volume of 39 +/- 12 ml (P less than 0.01) followed by an increase of 129 +/- 31 ml (P less than 0.01) above control at 20 min. Mean arterial pressure increased from a control of 74 +/- 4 mmHg to 99 +/- 7 mmHg (P less than 0.01) initially and then decreased to 64 +/- 5 mmHg (P less than 0.05) at 20 min. Following ganglionic blockade with mecamylamine, serotonin caused only a decrease in intravascular volume, which was 73 +/- 12 ml (P less than 0.01) at 20 min. 5-HT2 and alpha-adrenergic blockade with ketanserin did not attenuate the early decrease in intravascular volume. 5-Carboxamidotryptamine (82 +/- 39 micrograms), a 5-HT1 agonist, was associated with only an increase in intravascular volume, which was 82 +/- 13 ml (P less than 0.01) at 20 min and which was abolished after ganglionic blockade. Thus, serotonin causes a biphasic change in total intravascular volume. The initial decrease in intravascular volume is not mediated by a reflex or by 5-HT1, 5-HT2, or alpha-adrenergic receptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of antiarrhythmic drugs on the chronic pacing threshold and the endocardial R wave amplitude in the conscious dog.

To determine the effects of antiarrhythmic drugs on the chronic pacing threshold and the endocardial R wave amplitude, we tested seven drugs (representative of Vaughn Williams' antiarrhythmic class-I-IV) on four to six dogs after the implanted ventricular endocardial bipolar leads had reached chronic stable thresholds. The seven antiarrhythmic drugs tested were procainamide (oral [p.o.] and intravenous [IV], class IA), lidocaine (IV, class IB), tocainide (p.o., class IB), flecainide (p.o. and IV, class IC), propranolol (p.o. and IV, class II), amiodarone (p.o. and IV, class III), and verapamil (p.o. and IV, class IC), propranolol (p.o. and IV, class II), amiodarone (p.o. and IV, class III), and verapamil (p.o. and IV, class IV). The drugs were administered in sufficient doses to achieve plasma levels associated with antiarrhythmic efficacy in humans. All oral drugs were given for sufficient time to achieve expected steady state levels. The pacing thresholds, both voltage and current, and the endocardial R wave amplitude were measured in the conscious dog with a Medtronic pacing system analyzer at a pulse width of 0.1, 0.5, 1.0, and 2.0 ms at intervals following IV or p.o. administration of each antiarrhythmic drug. We found that there were no significant effects of the tested seven antiarrhythmic drugs on the chronic pacing threshold and the endocardial R wave amplitude at any of the pulse widths. We conclude that in the healthy dog antiarrhythmic drugs do not alter the pacing threshold and the endocardial R wave amplitude.

Enterococcus faecalis pheromone binding protein, PrgZ, recruits a chromosomal oligopeptide permease system to import sex pheromone cCF10 for induction of conjugation.

Conjugative transfer of the plasmid pCF10 by Enterococcus faecalis donor cells occurs in response to a peptide sex pheromone, cCF10, secreted by recipients. The plasmid-encoded cCF10 binding protein, PrgZ, is similar in sequence to binding proteins (OppAs) encoded by oligopeptide permease (opp) operons. Mutation of prgZ decreased the sensitivity of donor cells to pheromone, whereas inactivation of the chromosomal E. faecalis opp operon abolished response at physiological concentrations of pheromone. Affinity chromatography experiments demonstrated the interaction of the pheromone with several putative intracellular regulatory molecules, including an RNA molecule required for positive regulation of conjugation functions. These data suggest that processing of the pheromone signal involves recruitment of a chromosomal Opp system by PrgZ and that signaling occurs by direct interaction of internalized pheromone with intracellular effectors.