Activation of muscarinic receptors elicits inotropic responses in ventricular muscle from rats with heart failure through myosin light chain phosphorylation

Background and purpose:

Muscarinic stimulation increases myofilament Ca²⁺ sensitivity with no apparent inotropic response in normal rat myocardium. Increased myofilament Ca²⁺ sensitivity is a molecular mechanism promoting increased contractility in failing cardiac tissue. Thus, muscarinic receptor activation could elicit inotropic responses in ventricular myocardium from rats with heart failure, through increasing phosphorylation of myosin light chain (MLC).

Experimental approach:

Contractile force was measured in left ventricular papillary muscles from male Wistar rats, 6 weeks after left coronary artery ligation or sham surgery. Muscles were also frozen, and MLC-2 phosphorylation level was quantified.

Key results:

Carbachol (10 µmol·L⁻¹) evoked a positive inotropic response only in muscles from rats with heart failure approximating 36% of that elicited by 1 µmol·L⁻¹ isoproterenol (20 ± 1.5% and 56 ± 6.1% above basal respectively). Carbachol-evoked inotropic responses did not correlate with infarction size but did correlate with increased left ventricular end diastolic pressure, heart weight/body weight ratio and lung weight, primary indicators of the severity of heart failure. Only muscarinic receptor antagonists selective for M₂ receptors antagonized carbachol-mediated inotropic effects with the expected potency. Carbachol-evoked inotropic responses and increase in phosphorylated MLC-2 were attenuated by MLC kinase (ML-9) and Rho-kinase inhibition (Y-27632), and inotropic responses were abolished by Pertussis toxin pretreatment.

Conclusion and implications:

In failing ventricular muscle, muscarinic receptor activation, most likely via M₂ receptors, provides inotropic support by increasing MLC phosphorylation and consequently, myofilament Ca²⁺ sensitivity. Enhancement of myofilament Ca²⁺ sensitivity, representing a less energy-demanding mechanism of inotropic support may be particularly advantageous in failing hearts.     

Purification and activity standardisation of a Ho solution

As part of a project to use the long-lived (T_1/2=1200a) ^166mHo as reference source in its reference ionisation chamber, IRA standardised a commercially acquired solution of this nuclide using the 4πβ–γ coincidence and 4πγ (NaI) methods. The ^166mHo solution supplied by Isotope Product Laboratories was measured to have about 5% Europium impurities (3% ¹⁵⁴Eu, 0.94% ¹⁵²Eu and 0.9% ¹⁵⁵Eu). Holmium had therefore to be separated from europium, and this was carried out by means of ion-exchange chromatography. The holmium fractions were collected without europium contamination: 162 h long HPGe gamma measurements indicated no europium impurity (detection limits of 0.01% for ¹⁵²Eu and ¹⁵⁴Eu, and 0.03% for ¹⁵⁵Eu). The primary measurement of the purified ^166mHo solution with the 4π (PC) β–γ coincidence technique was carried out at three gamma energy settings: a window around the 184.4 keV peak and gamma thresholds at 121.8 and 637.3 keV. The results show very good self-consistency, and the activity concentration of the solution was evaluated to be 45.640±0.098 kBq/g (0.21% with k=1). The activity concentration of this solution was also measured by integral counting with a well-type 5″×5″ NaI(Tl) detector and efficiencies computed by Monte Carlo simulations using the GEANT code. These measurements were mutually consistent, while the resulting weighted average of the 4π NaI(Tl) method was found to agree within 0.15% with the result of the 4πβ–γ coincidence technique. An ampoule of this solution and the measured value of the concentration were submitted to the BIPM as a contribution to the Système International de Référence.     

Association between breakfast composition and abdominal obesity in the Swiss adult population eating breakfast regularly

Background

Evidence from experimental and observational studies is limited regarding the most favorable breakfast composition to prevent abdominal fat accumulation. We explored the association between breakfast composition (a posteriori derived dietary patterns) and abdominal obesity among regular breakfast eaters from a Swiss population-based sample.

Methods

The cross-sectional survey assessed diet using two 24-h dietary recalls in a nationally representative sample of adults aged 18 to 75?years. We derived dietary patterns using principal component analysis based on the intake of 22 breakfast-specific food groups. All regular breakfast eaters were predicted an individual score for each identified pattern, and then classified into tertiles (T1, T2, T3). We defined abdominal obesity as waist-to-hip ratio (WHR) ≥ 0.9 in men and?≥?0.85 in women. Logistic models were adjusted for sociodemographic characteristics, relevant nutrition- and health-related behaviors, and diet quality during the rest of the day.

Results

Of the 2019 included survey participants, 1351 (67%) were regular breakfast eaters. Among them, we identified three breakfast types: 1) ‘traditional’???white bread, butter, sweet spread, 2) ‘prudent’???fruit, unprocessed and unsweetened cereal flakes, nuts/seeds, yogurt, and 3) ‘western’ – processed breakfast cereals, and milk. The ‘prudent’ breakfast was negatively associated with abdominal obesity. After full adjustment, including diet quality during the rest of the day, the association was weaker (T3 vs. T1: OR 0.72, 95% CI: 0.47 to 1.08). People taking a ‘prudent’ breakfast (in T3) had 1.2% lower WHR compared to people taking a breakfast distant from ‘prudent’ (in T1) (P?=?0.02, fully adjusted model with continuous log-WHR). We found no association between ‘traditional’ or ‘western’ breakfasts and WHR (OR 1.00, 95% CI: 0.67 to 1.50 and OR 1.16, 95% CI: 0.79 to 1.71, respectively). Findings were in the same directions for the three breakfast types when defining obesity with waist circumference, waist-to-height ratio, or body mass index (≥ 30?kg/m², for ‘prudent’ breakfast: OR 0.51, 95% CI: 0.31 to 0.85).

Conclusions

Regular breakfast consumers had less abdominal obesity if their breakfast was composed of fruit, natural cereal flakes, nuts/seeds and yogurt. This association was partly explained by their healthier diet during the rest of the day.

Trial registration

ISRCTN16778734.

     

Intercomparison of activity measurements for beta-emitters in Swiss nuclear medicine laboratories

OBJECTIVE: The activity of injected radiopharmaceuticals in nuclear medicine, including beta-emitters used for pain palliation, has to be monitored systematically. The objective of the present work was to evaluate the situation and precision of activity monitoring for beta-emitters in Swiss nuclear medicine laboratories. METHODS: A questionnaire about the monitoring methods used was sent to 50 centers. On the basis of the questionnaire results, an intercomparison of activity measurements with 90Y and 169Er sources was organized. RESULTS: This study showed that most laboratories check beta-emitter activity with a dose calibrator measurement in the original vial provided by the producer or in the injection syringe. They therefore need to have calibration factors for the corresponding measurement geometries. The results of the intercomparison were disappointing overall. Sixteen of 27 90Y measurements and 17 of 22 169Er measurements in the original vial deviated from the reference activity by more than 20%. The situation was similar for the syringe. These discrepancies did not stem from the intrinsic limitation of the measuring method but were mainly attributable to the poor quality of the calibration factors provided by the manufacturers, in addition to lack of follow-up and incorrect background subtraction, particularly for 169Er, by the nuclear medicine laboratories. Manufacturers are being contacted to discuss possible improvements for the situation. CONCLUSION: This study showed that commercial dose calibrators are generally adequate for measurement of the activities of beta-emitters. However, in some cases, the measurement of 90Y can lead to errors reaching +/-50%. For 169Er, with its much lower beta-energy, the situation is even worse; the observed differences can be higher than 1 order of magnitude.     

Predictors of maternal mortality in institutional deliveries in Nigeria

Background

Maternal mortality in poor countries reflects the under-development in these societies. Global recognition of the burden of maternal mortality and the urgency for a reversal of the trend underpin the Millenium Development Goals (MDGs).

Objective

To determine risk factors for maternal mortality in institutional births in Nigeria.

Method

Twenty one health facilities in three states were selected using stratified multi-stage cluster sampling strategy. Information on all delivered mothers and their newborn infants within a three-month period was culled from medical records.

Results

A total of 9 208 deliveries were recorded. About one-fifth (20.5%) of women had no antenatal care while 79.5% had at least one antenatal visit during pregnancy. Four-fifths (80.5%) of all deliveries were normal deliveries. Elective and emergency caesarean section rates were 3.1% and 11.5% respectively. There were 79 maternal deaths and 8 526 live births, giving a maternal mortality ratio of 927 maternal deaths per 100 000 live births. No antenatal care, parity, level of education, and mode of delivery were significantly associated with maternal mortality. Low maternal education, high parity, emergency caesarean delivery, and high risk patients risk independently predicted maternal mortality.

Conclusion

Meeting goal five of the MDGs remains a major challenge in Nigeria. Multi-sectoral approaches and focused political will are needed to revert the high maternal mortality.     

Estimation of the noisy component of anatomical backgrounds.

The knowledge of the relationship that links radiation dose and image quality is a prerequisite to any optimization of medical diagnostic radiology. Image quality depends, on the one hand, on the physical parameters such as contrast, resolution, and noise, and on the other hand, on characteristics of the observer that assesses the image. While the role of contrast and resolution is precisely defined and recognized, the influence of image noise is not yet fully understood. Its measurement is often based on imaging uniform test objects, even though real images contain anatomical backgrounds whose statistical nature is much different from test objects used to assess system noise. The goal of this study was to demonstrate the importance of variations in background anatomy by quantifying its effect on a series of detection tasks. Several types of mammographic backgrounds and signals were examined by psychophysical experiments in a two-alternative forced-choice detection task. According to hypotheses concerning the strategy used by the human observers, their signal to noise ratio was determined. This variable was also computed for a mathematical model based on the statistical decision theory. By comparing theoretical model and experimental results, the way that anatomical structure is perceived has been analyzed. Experiments showed that the observer's behavior was highly dependent upon both system noise and the anatomical background. The anatomy partly acts as a signal recognizable as such and partly as a pure noise that disturbs the detection process. This dual nature of the anatomy is quantified. It is shown that its effect varies according to its amplitude and the profile of the object being detected. The importance of the noisy part of the anatomy is, in some situations, much greater than the system noise. Hence, reducing the system noise by increasing the dose will not improve task performance. This observation indicates that the tradeoff between dose and image quality might be optimized by accepting a higher system noise. This could lead to a better resolution, more contrast, or less dose.     

Impact of a nurse vaccination program on hepatitis B immunity in a Swiss HIV clinic

We evaluated the impact of a nurse program for hepatitis B virus vaccination in a center from the Swiss HIV Cohort Study. Immunity (anti-HBs >10 IU/mL) increased from 32% to 76% in the intervention center (n = 238) where vaccine management was endorsed by nurses, but only from 33% to 39% in control centers (n = 2712, P < 0.001) where management remained in charge of physicians. Immunity against HBV in the HIV population is insufficient in Switzerland. Specific nurse vaccination program may efficiently improve health care.