Can blood pressure responses to tests unmask future blood pressure trends and the need for antihypertensive medication? Ten years of follow‐up

An exaggerated blood pressure (BP) response to test may unmask the subjects who have a high risk of developing hypertension. In this prospective 10 years of follow-up, we examined whether the predictive value of casual BP measurements on future BP level and need for antihypertensive medication could be improved by using BP responses to different physical tests. At baseline, BP was recorded by casual measurements and intra-arterial monitoring. During the intra-arterial BP recording, standardized postural and exercise tests were performed on 97 healthy, untreated men (34 normotensive, 29 borderline hypertensive, and 34 mild hypertensive). After 10 years of follow-up, 87 of them (90%) returned for casual and non-invasive 24-h BP measurements. At follow-up, 20 (23%) of the men had antihypertensive medication. The prediction of casual systolic blood pressure (SBP) was best improved by SBP at 10 min after the dynamic exercise test (adj. R2 = 0.448; adj. R2 = 0.356 for casual SBP alone). The prediction of casual diastolic blood pressure (DBP) was most improved by DBP at 10 min after the dynamic exercise test (adj. R2 = 0.282; adj. R = 0.259 for casual BP alone). SBP in the supine test best improved the prediction of 24-h SBP (adj. R2 = 0 448; adj. R2 = 0.275 for casual SBP alone). DBP in the standing test best improved the prediction of 24-h DBP (adj. R2 = 0.252; adj. R2 = 0.214 for casual DBP alone). Pre-exercise DBP and casual SBP were the best predictors of the need for antihypertensive medication (Cox-Snell R2 = 0.256; Cox-Snell R2 = 0.164 for casual SBP alone). In conclusion the prediction of future BP and need for antihypertensive medication can be improved by using BP measurements during postural and exercise tests. Future SBP is more predictable than DBP.     

Transfection of oocytes and other types of ovarian cells in rabbits after direct injection into uterine arteries of adenoviruses and plasmid/liposomes

Transfection of oocytes should be avoided in somatic gene therapy. However, several viral vectors including adenoviruses can transfect zona-pellucida-free eggs in vitro. During early stages of development, oocytes of postnatal ovaries lack the zona pellucida. Therefore, they may be susceptible to gene transfer and unintended toxic effects. The purpose of this study was to see whether the injection of adenoviruses (1 x 10(10) PFU) or plasmid (500 microg)/DOTMA:DOPE (1:2) liposomes directly into uterine arteries in pregnant rabbits leads to transfection of oocytes and other types of ovarian cells. LacZ and herpes simplex virus thymidine kinase (HSV-TK) were used as transgenes. It was found that both adenovirus and plasmid vectors transfected oocytes at the primordial and primary follicle stage when they were not protected by the zona pellucida, whereas no transfection was seen in oocytes surrounded by the zona pellucida. Efficient transfection of corpus luteum and granulosa cells was also detected by adenoviral and plasmid vectors. Transfection of oocytes and other ovarian cells was verified by X-gal staining and laser microdissection, followed by PCR analysis. HSV-TK gene transfer, followed by ganciclovir treatment, led to destruction of a significant number of oocytes, whereas HSV-TK gene transfer alone did not lead to toxic effects. It is concluded that the presence of a high concentration of adenovirus or plasmid vectors via the uterine artery may lead to transfection of zona-pellucida-free oocytes and other ovarian cells.     

Predictors of Long-Term Change in Adult Cognitive Performance: Systematic Review and Data from the Northern Finland Birth Cohort 1966

Objective: Several social life events and challenges have an impact on cognitive development. Our goal was to analyze the predictors of change in cognitive performance in early midlife in a general population sample. Additionally, systematic literature review was performed. Method: The study sample was drawn from the Northern Finland Birth Cohort 1966 at the ages of 34 and 43 years. Primary school performance, sociodemographic factors and body mass index (BMI) were used to predict change in cognitive performance measured by the California Verbal Learning Test, Visual Object Learning Test, and Abstraction Inhibition and Working Memory task. Analyses were weighted by gender and education, and p-values were corrected for multiple comparisons using Benjamini–Hochberg procedure (B–H). Results: Male gender predicted decrease in episodic memory. Poor school marks of practical subjects, having no children, and increase in BMI were associated with decrease in episodic memory, though non-significantly after B–H. Better school marks, and higher occupational class were associated with preserved performance in visual object learning. Higher vocational education predicted preserved performance in visual object learning test, though non-significantly after B-H. Likewise, having children predicted decreased performance in executive functioning but non-significantly after B-H. Conclusions: Adolescent cognitive ability, change in BMI and several sociodemographic factors appear to predict cognitive changes in early midlife. The key advantage of present study is the exploration of possible predictors of change in cognitive performance among general population in the early midlife, a developmental period that has been earlier overlooked.     

Inhibition of angiotensin-converting enzyme with quinapril (CI-906): investigation of antihypertensive mechanisms in spontaneously hypertensive rats

Treatment for 8 days with a new nonsulfhydryl angiotensin-converting enzyme inhibitor, quinapril (CI-906), produced a marked and progressive reduction in the blood pressure of spontaneously hypertensive rats. Quinapril was given p.o. in a dose of 20 or 40 mg/kg once daily. Both doses increased plasma renin activity and decreased the urinary excretion of aldosterone. These results, together with a marked decrease in serum angiotensin-converting enzyme activity, indicate that the drug produced a considerable fall in circulating angiotensin II. The urinary excretion of vasopressin was not altered by the smaller dose of quinapril but was reduced by the larger dose, which increased water intake and urine excretion. Quinapril did not affect plasma kininogen or the urinary excretion of kallikrein. The urinary excretion of neither the prostacyclin metabolite 6-keto-prostaglandin F1 alpha nor the thromboxane metabolite thromboxane B2 were altered by the drug. However, quinapril did produce a temporary decrease in the excretion of prostaglandin E2, the effect passing off with the continuation of the treatment. These data indicate that vasodilatory prostanoids do not contribute to the blood pressure lowering effect of quinapril in spontaneously hypertensive rats. The inhibition of the renin-angiotensin system is probably the principal mechanism of the drug's antihypertensive action, but these results do not rule out the possibility that an increase in vasodilatory kinins may also be involved.     

Trimethoprim pharmacokinetics in children with renal insufficiency

We studied the pharmacokinetics of trimethoprim in 14 children (two neonates) with renal insufficiency. They were 1 week to 16.4 years old and had glomerular filtration rates (GFR) between 10.8 to 72.3 ml/min/1.73 m2. The half-life (t1/2) of trimethoprim was inversely related to the GFR. The relation followed a power curve (correlation of t1/2 with GFR: r = -0.86; P less than 0.001). The slower elimination rate was mainly the result of lowered renal clearance of trimethoprim. The volume of distribution (Varea) was, in most patients, in the upper normal range for children. In some of the patients, chiefly infants with severe renal insufficiency, the Varea was larger than normal. In some individuals the pharmacokinetics of trimethoprim deviated from that to be expected from the GRF. We recommend reduced daily doses of trimethoprim if the GFR is less than 30 ml/min/1.73 m2. The reduction should be proportional to the reduction in GFR and primarily take the form of a prolonged dose interval.     

Effect of maternal age on uterine flow impedance

PURPOSE: This study was conducted to determine possible maternal age-related changes in uterine artery impedance in normal late pregnancy. PATIENTS AND METHODS: In a cross-sectional design study, Doppler velocimetry of the uterine vessels was performed in 884 pregnant women with normal, late, singleton pregnancies. We hypothesized that maternal age is associated with changes in uterine blood flow Doppler parameters. We tested for univariate associations and for an adjusted relationship between these factors using a multivariate model to control for confounders. RESULTS: We found a statistically significant, nonlinear relationship between mean uterine artery impedance (pulsatility index) and maternal age, with an increase of the pulsatility index in women above the age of 35. This association continued to be significant even when adjusted for gestational age and parity as confounders. CONCLUSIONS: In normal pregnancy, an increase in uterine artery impedance was noted in women above the age of 35. This finding may be related to the physiologic process of aging and may partly explain why pregnancies in older women are associated with diverse complications more often than those in younger women.     

Characterization of the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-provoked strong and rapid aversion to unfamiliar foodstuffs in rats

A conspicuous but scantly studied feature of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity is avoidance of unfamiliar foodstuffs, which seems to be one of the very few exquisitely sensitive behavioural effects in adult laboratory animals. Here we characterized this peculiar response further after low doses of TCDD. The time-course of the novelty avoidance, the role of nutriment form and dependence of the aversion on the time lag between TCDD exposure and the presentation of a novel food item was determined using rats with different sensitivities to lethality of TCDD. Rats were offered chocolate, liquid nutriment or familiar feed with an unfamiliar texture and the consumptions were measured for varying periods. Aversion to a novel food item (chocolate) emerged within 5.5h after TCDD exposure. A lag of a week or more between TCDD exposure and the presentation of chocolate abolished the avoidance whereas simultaneous presentation of chocolate with TCDD treatment rendered the rats oblivious to the chocolate's presence for over 40 days. Rats avoided also liquid nutriments when these were coupled with TCDD administration but this faded much sooner than chocolate aversion. Even a change in feed texture at the exposure was able to elicit the response. However, habituation was found to interfere with the aversion. These findings indicate that temporal proximity to TCDD exposure is a requisite for the avoidance response which emerges rapidly and may linger on for extended periods, but is not strictly confined to any specific food type. The molecular mechanisms of this tantalizing behavioural alteration remain to be determined.     

Immediate and highly sensitive aversion response to a novel food item linked to AH receptor stimulation

Aversion to novel food items was studied in male rats and mice after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure using chocolate consumption as an indicator. The correlation of this phenomenon with susceptibility to acute toxicity and CYP1A1 induction was examined by determining the dose-response of chocolate aversion in differently dioxin-sensitive rat lines after TCDD (0.01-10 μg/kg). Furthermore, the dependence of this behavioral alteration on the AH receptor (AHR) was studied employing AHR-deficient and wild-type mice. We offered chocolate for both species as a novel food item immediately after the exposure, and it was available with standard rodent chow for 3 days. The ED₅₀ value for the extremely resistant rat line A (LD₅₀ value > 10,000 μg/kg) was 0.36 μg/kg, for the semi-resistant line B (LD₅₀ value 830 μg/kg) 1.07 μg/kg and for the TCDD-sensitive line C (LD₅₀ value 40 μg/kg) 0.34 μg/kg. Interestingly, the ED₅₀ values for chocolate aversion were very similar to those for CYP1A1 induction in these rat lines. Findings on AHR-deficient and wild-type mice implied the involvement of the AHR in this intriguing response, which may thus represent a mechanism to restrict exposure to potentially toxic dietary substances causing hepatic induction of drug-metabolizing enzymes.     

Relative contributions of Ebp Pili and the collagen adhesin ace to host extracellular matrix protein adherence and experimental urinary tract infection by Enterococcus faecalis OG1RF

Previous studies have demonstrated that the ebp operon and the ace gene of Enterococcus faecalis, encoding endocarditis- and biofilm-associated pili and an adhesin to collagen of E. faecalis, respectively, are both important in experimental urinary tract infections (UTI) and endocarditis. We have also shown that growth of E. faecalis in brain heart infusion (BHI) serum enhances Ebp pilus and Ace production and increases adherence to several host extracellular matrix proteins. Here, we report that deletion of ebpABC almost eliminated serum-elicited adherence to fibrinogen (P < 0.0001), resulted in moderate reduction in adherence to collagen (P < 0.05), and had no effect on fibronectin adherence relative to that of wild-type OG1RF. An OG1RFΔaceΔebpABC double mutant showed further reduced collagen adherence versus that of the OG1RFΔace or OG1RFΔebpABC mutants (P < 0.001). These results were corroborated by complementation and/or studies with native pilus-enriched surface extracts and a collagen-secreting 3T6 fibroblast cell line, as well as antibody inhibition. In the UTI model, both the OG1RFΔace and OG1RFΔaceΔebpABC mutants were found to be significantly attenuated compared to the wild type; however, no significant differences were observed between individual ace or ebp mutants and the OG1RFΔaceΔebpABC mutant. In summary, these data implicate the Ebp pili as having some role in collagen adherence, albeit less than that of Ace, and a very major role in fibrinogen adherence, which may explain in part the importance of these pili in experimental endocarditis. The OG1RFΔaceΔebpABC mutant was attenuated in the UTI model, although not significantly more so than the Δace or ΔebpABC mutants, suggesting involvement of other E. faecalis factors in urinary tract colonization or infection.     

Alexithymia and occupational burnout are strongly associated in working population

OBJECTIVE: The relationship between alexithymia and occupational burnout has not previously been studied. We investigated the association between alexithymia and occupational burnout in a representative nationwide population health study. METHODS: This study was a part of the Finnish Health 2000 Study. The nationally representative sample comprised 3322 employees aged 30-64 years. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20) and occupational burnout with the Maslach Burnout Inventory-General Survey. Sociodemographic and health-related variables including depression were treated as confounders in the logistic regression analyses, which were performed alternately with TAS-20 total score and the scores of the three TAS-20 factor scales as alexithymia variables. RESULTS: Alexithymia and its three facets were significantly associated with occupational burnout even when controlled for confounding factors. CONCLUSIONS: Even though both alexithymia and depression are associated with burnout, alexithymia may be an independent risk factor for occupational burnout.