Comparing conformations at low temperature and at high viscosity

The influence of low temperature and high viscosity on the conformation of somatostatin and two of its analogues was investigated by ¹H NMR in solution. The conformation of native somatostatin, a cyclic octapeptide agonist DC13-116 and a linear octapeptide agonist were compared in ethylene glycol at 303 K and in methanol at low temperature. The first goal of this study was to investigate if either low temperature or high viscosity is the more important for the reduction of the conformational freedom. Secondly we wanted to compare the amount of information concerning the conformation present in both solvents. A larger amount of NOESY cross-peaks is observed in ethylene glycol at room temperature compared to methanol at low temperature. This indicates that the raising of the viscosity is a more important factor in reducing the flexibility of peptides than the lowering of the temperature.     

Acknowledgement to referees 2010

Acknowledgement to referees

Acknowledgement to referees 2010     

Comorbidity and metabolic context are crucial factors determining neurological sequelae of hypoglycaemia

Aim To determine risk factors for neurological sequelae following hypoglycemia. Method We analysed the neurological outcome in 164 patients (mean age 10y 10mo, SD 5.9) following hypoglycemia due to three diseases with various metabolic contexts, different ages at onset, and combinations with comorbidity (fever/infection, hypoxia/ischemia): glycogen storage disease type I (GSDI) (21 patients, mean age at first hypoglycemic episode 3.8mo, SD 3.5); fatty acid β‐oxidation defects (FAOD) (29 patients, mean age at first hypoglycemic episode 14.8mo, SD 12.6); and hyperinsulinism (HIns) (114 patients, mean age at first hypoglycemic episode 2.3mo, SD 4.7). Results Risk factors of poor neurological outcome were aetiology (p<0.006), comorbidity (p<0.001), and prolonged convulsions (p<0.001). Ordinal logistic regression showed that comorbidity (p<0.001) and status epilepticus (p=0.002) were the main determinants of sequelae. Asymptomatic hypoglycemia did not lead to sequelae, whatever the aetiology. Age was not correlated to sequelae, whatever the aetiology. The highest prevalence of hypoglycemic sequelae was found in FAOD and HIns combined with comorbidity, the lowest in GSDI (p<0.001) in which hypoglycemia is often asymptomatic, associated with increased plasma lactate, and rarely combined with comorbidity. Interpretation Hypoglycemia is severely deleterious for the brain in the context of fever/infection and/or hypoxia/ischemia, and status epilepticus. The metabolic context providing alternative fuels may improve neurological outcome.     

Topography of brain damage in metabolic hypoglycaemia is determined by age at which hypoglycaemia occurred

Aim Having previously shown that comorbidity is a major determinant of neurological sequelae in hypoglycaemia, our aim was to describe the neuroimaging patterns of brain damage in different hypoglycaemic situations and to elucidate the factors that determine lesion topography. Method We reviewed 50 patients (31 females, 19 males) with symptomatic hypoglycaemia (<2.8mmol/L) occurring between 1 day and 5 years of age (median 4d) who had undergone magnetic resonance imaging (MRI; at least axial T2‐weighted, sagittal T1‐weighted, and coronal fluid‐attenuated inversion recovery [FLAIR]‐weighted imaging). MRI was performed during the follow‐up examination at least 1 month after the occurrence of symptomatic hypoglycaemia, i.e. between 1 month and 5 years of age (median 3mo). Hypoglycaemia resulted from three inborn errors of metabolism: congenital hyperinsulinism (33 patients), fatty acid β‐oxidation disorders (13 patients), or glycogen storage disease type I (four patients). We selected the patients with clear MRI abnormalities and analysed their topography according to aetiology and age at occurrence of the lesion. Results The topography of the brain lesions depended on age: from the neonatal period to 6 months of age, lesions predominantly involved the posterior white matter; between 6 and 22 months the basal ganglia, and after 22 months the parietotemporal cortex (p=0.04). Interpretation The relationship between brain lesions and age could reflect the maturation sequence of the brain.     

Combination of Sotalol and Quinidine in a Canine Model of Torsades de Pointes

Sotalol Plus Quinidine and Torsades de Pointes. Introduction: Clinical treatment with a combination of Class IA and III antiarrhythmic drugs is not recommended, as they both favor bradycardia-dependent proarrhythmic events such as torsades de pointes (TdP). However, this theoretical additive effect on ventricular repolarization has never heen demonstrated and could be questioned as other Class I drugs, such as mexiletine, a Class IB drug, limit the number of sotalol-induced TdP in dogs with AV block, suggesting the possibility of an antagonistic action of Class I properties against Class III effects. Methods and Results: We compared the electrophysiologic and proarrhythmic effects of sotalol (Class III) alone and combined with quiuidine (Class IA) in a canine model of acquired long QT syndrome. Seven hypokalemic (K*: 3 ± 0.1 mEq/L) dogs with chronic AV block had a demand pacemaker implanted and set at a rate of 25 beats/min. They were submitted to two (sotatol-alone and sotalol-plus-quinidine) experiments 48 bours apart usiug a randomized cross-over protocol. They were pretreated with quinidine (10 mg/kg + 1.8 mg/kg per hour) or saline infused throughout the experiment, aud given sotalol (4.5 mg/kg + 1.5 mg/kg per hour) for 2 hours, 30 minutes after the beginning of the pretreatment infusion during both experiments. Ventricular and atrial cycle lengths were similarly increased by sotalol after quinidine or saline. The sotalol-induced prolongation of the QT interval was significantly shorter in quinidine-pretreated dogs (24 ± 7 msec after quinidine vs 40 ± 8 msec after saline). Fewer dogs developed TdP: significantly during the first hour of infusion (1/7 sotalol-plus-quinidine vs 6/7 sotalol-alone dogs, P < 0.05) but nonsignificantly during the second hour (3/7 vs 6/7). Conclusion: In this model, the sotalol-plus-quinidine combination is at least no more arrhythmogenic than either of the drugs given alone.     

Detection of Stent Underdeployment by StentBoost Imaging

Objective

To evaluate the additional value of StentBoost® (SB), a motion‐corrected X‐ray technique that enhances stent visualization, for the assessment of stent deployment and procedure optimization during routine percutaneous coronary interventions (PCI).

Background

Underdeployment and malapposition of stents during PCI may lead to in‐stent thrombosis and restenosis. Coronary angiography (CA) is of limited value for the assessment of stent deployment. Intravascular ultrasound and optical imaging techniques are the gold standard, but are used in <10% of routine PCIs.

Methods

We retrospectively analyzed 260 coronary lesions treated by stent implantation and assessed by SB during 168 consecutive PCI procedures. The immediate results of SB analysis and CA were assessed by 2 independent interventional cardiologists and compared.

Results

A total of 275 stents were implanted; 45% were drug‐eluting stents (DES). Direct stenting was performed in 78%. Results of SB and angiography were concordant for 210 lesions: 194 stents were correctly deployed (75%) and 16 were underdeployed (6%), shown by both techniques. In 47 patients (18%), SB detected an underdeployment of the stent whereas the angiographic result was good. Postdilatation was performed on the basis of SB in 89% of these cases. The additional contribution of SB was higher for left main lesions and for DES, and was not affected by coronary calcifications.

Conclusions

This study confirmed the usefulness of the stent visualization enhancement technique StentBoost® in current PCI practice. SB revealed about 20% underdeployed stents not detected by CA, and allowed for optimizing PCI by ad hoc effective postdilatation. (J Interven Cardiol 2013;26:444‐453)

     

Comparative efficacy of house dust mite extermination products

The acaricidal efficacy of nine marketed products, i.e. Acardust, Acarosan (foam and powder), Actelic 50, Artilin 3A (spirit and water base), liquid nitrogen, Paragerm AK, and Tymasil, and of intensive vacuum-cleaning have been compared on four different test surfaces: mattress, tufted carpet, gypsum board and rough wooden board, all covered with artificial house dust. They were inoculated with the house dust mite, Dermatophagoides pteronyssinus or the house-dust fungus Aspergillus repens for evaluation of the fungistatic claims of some products. The acaricidal activity of Tymasil did not surpass that of vacuuming; its fungistatic effect was not apparent. The other products showed complete to almost complete eradication on at least one of the substrates tested. Taking into account the results of acaricidal efficacy as well as the data on safety and practicality acquired earlier, Acarosan powder was considered first choice for carpet treatment. Acarosan and liquid nitrogen, were found to be effective in the treatment of mattress, pillow, upholstered furniture and heavy curtains. On wooden surfaces Acarosan was found to be both effective and safe, while Acardust, Actelic 50, Artilin 3A (both fungistatic as well as acaricidal), liquid nitrogen and Paragerm also passed the efficiency test.