Interleukin-18 promoter polymorphism associates with the occurrence of sudden cardiac death among Caucasian males: the Helsinki Sudden Death Study

ObjectiveThe increased plasma concentrations of pro-atherogenic and cardiomyocyte hypertrophic cytokine interleukin 18 (IL-18) predict mortality in patients with coronary heart disease (CHD) in addition to predicting the outcome of heart failure. The IL-18 gene has a functional ?137 G/C polymorphism (rs187238) in the promoter region. The C allele carriage is associated with attenuated IL-18 production. The effect of IL-18 genotype on SCD is unknown. We studied the association of the IL-18 gene ?137 G/C polymorphism with the occurrence of sudden cardiac death (SCD).MethodsUsing the TaqMan 5′ nuclease assay, we genotyped two independent consecutive and prospective autopsy series which were included in the Helsinki Sudden Death Study.ResultsOf the 663 men, 359 (54.1%) had the wild-type GG-genotype, 261 (39.4%) were heterozygotes (CG) and 43 (6.5%) were CC homozygotes. Compared to the GG homozygotes, the C allele carriers (i.e. subjects having CC or CG genotypes) had a lower adjusted risk for SCD from any cause (odds ratio [OR] 0.49; 95% confidence interval [CI], 0.31–0.77, p = 0.002), for SCD due to CHD (OR 0.51; 95% CI, 0.32–0.82, p = 0.005), and for SCD caused by non-coronary heart diseases (OR 0.34; 95% CI 0.13–0.90, p = 0.030).ConclusionIL-18 promoter ?137 G/C polymorphism, which regulates the expression of IL-18, is an important predictor of SCD from any cause as well as SCD in patients with and without underlying CHD.     

Echocardiographic Evaluation of Right Ventricular Function in Patients with Acute Pulmonary Embolism: A Study Using Tricuspid Annular Motion

Assessment of right ventricular (RV) function is a challenge due to complex anatomy. We studied systolic and diastolic tricuspid annular excursion and longitudinal RV fractional shortening as geometry‐independent measures in patients with acute pulmonary embolism (PE). Forty patients with PE were studied within 24 hours after admission and after 3 months, and compared to 23 healthy subjects used as controls. We recorded tricuspid annular plane systolic (TAPSE) and diastolic (TAPDE) excursion from the four‐chamber view and calculated RV fractional shortening as TAPSE/RV diastolic length. The diastolic RV function was defined as the ratio of the amplitude of tricuspid annular plane excursion during atrial systole to total tricuspid annular plane diastolic excursion (atrial/total TAPDE). In the acute stage, the TAPSE was decreased in PE compared to healthy subjects (19 ± 5 vs. 26 ± 4 mm, P < 0.001), with greater reduction in patients with increased, compared to normal, RV pressure (16.6 ± 5 vs. 20.5 ± 5 mm, P < 0.05). The atrial/total TAPDE was increased in patients compared to healthy subjects (47 ± 13% vs. 38 ± 7%, P < 0.001) and normalized during the follow‐up. Although the patients were asymptomatic after 3 months, the TAPSE recovered incompletely as compared to healthy subjects (21.4 ± 4 vs. 26 ± 4 mm, P < 0.001). Both systolic and diastolic RV function are impaired in acute PE. Diastolic function recovers faster than systolic; therefore, the atrial contribution to RV filling may be a useful measure to follow changes in diastolic function in PE. (Echocardiography 2010;27:286‐293)     

Meconium aspiration induces a concentration-dependent pulmonary hypertensive response in newborn piglets

To investigate the effects of aspirating different meconium concentrations on the pulmonary circulation in 10- to 12-day-old piglets, 30 catheterized animals were studied. The piglets received an intratracheal bolus of 3 ml/kg of a mixture of human meconium in saline with concentrations of 20 mg/ml (light, n = 7), 40 mg/ml (moderate, n = 6), or 65 mg/ml (thick, n = 10) meconium in saline. Control piglets (n = 7) received 3 ml/kg of intratracheal saline. Pulmonary and systemic pressures were measured and vascular resistances calculated at baseline and serially for 4 hours after instillation. Four of the piglets died early and were excluded from the study. In addition, 23 samples of human meconium-stained amniotic fluid were collected at delivery for determination of their meconium concentration. After an initial rise in pulmonary artery pressure and vascular resistance after meconium and saline instillation, pulmonary artery pressure and resistance increased progressively and concentration-dependently in the meconium groups, but returned to baseline in the control group. The saline and meconium-induced initial increases, and the subsequent meconium-stimulated progressive rise in vascular resistance occurred mainly in the postarterial segment. There were no significant changes in systemic hemodynamics. Mean airway pressure increased and oxygenation deteriorated after meconium instillation. The impairment of oxygenation depended on the meconium concentration in the instilled bolus and persisted throughout the study after moderate and thick meconium instillation. Similarly, the intrapulmonary shunt fraction increased initially and remained elevated in the moderate and thick meconium groups. Meconium concentrations in the human amniotic fluid samples were in the same range as concentrations used in the present experimental study. These results indicate that aspirated meconium at concentrations found in light to moderate meconium-stained human amniotic fluid has significant effects on pulmonary hemodynamic and oxygenation in newborn piglets. Pediatr. Pulmonol. 1998; 25:107–113. © 1998 Wiley-Liss, Inc.     

An optical method for continuous monitoring of the dissolution rate of pharmaceutical powders

Monitoring systems providing fast and reliable, even on-line data, from a distinct process stage or final product are needed in drug development, from the early stages of drug discovery until the drug product manufacturing procedures. This includes also processes involving solid particles, such as drug dissolution. However, the existing in vitro drug dissolution test methods suffer limitations, such as long sampling times of 30–60 s and thus the inability to be adapted to continuous monitoring, time consuming sample preparation and consumption of large amounts of reagents. In this study, an optical method for monitoring the dissolution rate of pharmaceutical powders was evaluated with model drugs having different dissolution rates. The measuring system consisted of a laser source, light detector, oscilloscope, magnetic stirrer and sample vessel. The intensity of laser light transmitted through the dissolution medium was recorded and displayed by the oscilloscope. Dissolution curves were produced by fitting the raw data with mathematical functions. The optical method was found to be resource-saving, reliable and capable of detecting differences in even rapid dissolution rates of drug compounds. This technique might have targets of application in real-time monitoring of processes in many different sectors, including the pharmaceutical industry.     

Time course of multisensory interactions during audiovisual speech perception in humans: a magnetoencephalographic study

During social interaction speech is perceived simultaneously by audition and vision. We studied interactions in the processing of auditory (A) and visual (V) speech signals in the human brain by comparing neuromagnetic responses to phonetically congruent audiovisual (AV) syllables with the arithmetic sum of responses to A and V syllables. Differences between AV and A+V responses were found bilaterally in the auditory cortices 150-200 ms and in the right superior temporal sulcus (STS) 250-600 ms after stimulus onset, showing that both sensory-specific and multisensory regions of the human temporal cortices are involved in AV speech processing. Importantly, our results suggest that AV interaction in the auditory cortex precedes that in the multisensory STS region.     

Dexamethasone-induced apoptosis and up-regulation of Bim is dependent on glycogen synthase kinase-3

Glucocorticoids are commonly used in the treatment of lymphoid malignancies. In this study, we show that apoptosis induced by dexamethasone (Dex), a synthetic glucocorticoid, was dependent on mitochondria, since overexpression of Bcl-X_L prevented Dex-induced apoptotic changes. Dominant negative (DN) caspase-9 also prevented Dex-induced apoptotic changes including the loss of mitochondrial membrane potential indicating that caspase-9 controls mitochondrial changes. In addition, we evaluated the role of glycogen synthase kinase (GSK3) in Dex-induced apoptosis. Inhibition of GSK3 attenuated Dex-induced up-regulation of Bim, loss of mitochondrial membrane potential, release of cyt c and DNA fragmentation. These results indicate that GSK3 contributes to Dex-induced apoptosis by controlling up-regulation of Bim.     

Maternal depression is associated with mother-infant interaction in preterm infants.

AIM: The purpose of this study was to assess the prevalence and the background factors of maternal depressive symptoms and their relation to the quality of mother-infant interaction in a group of preterm infants and their mothers. METHODS: The signs of maternal depression were evaluated in 125 mothers of very preterm infants (birth weight < or = 1500 g or < 32 gestational weeks) at 6 months of infant's corrected age using Edinburgh Postnatal Depression Scale (EPDS). The association between maternal depressive symptoms and the quality of mother-infant interaction as assessed by the parent child early relational assessment method (PCERA) method was studied at 6 and 12 months of corrected age in 32 preterm infants who were their mothers' firstborn infants and singletons. RESULTS: The prevalence of depression assessed by EPDS in mothers of very preterm infants was 12.6%. Most interestingly, the number of postnatal signs of depression associated negatively with the quality of the maternal interaction behaviour with their preterm infants. CONCLUSIONS: This study suggests that maternal depression may be a risk factor in the development of the mother-infant relationship between preterm infants and their mothers. Therefore, it would be important to identify signs of depression in mothers of preterm infants to offer early support.