Development of analytical methods for hydrochloride salts of cardiocyclide,a new Russian class III antiarrhythmic

Cardiocyclide, a new Russian class III antiarrhythmic agent, was developed at the State V. V. Zakusov Science Research Institute Pharmacology, Russian Academy of Medical Sciences. The aims of the present work were to study the physicochemical properties of the hydrochloride salt of this agent (N¹-(3-diethylaminopropyl)-N¹-(p-nitrobenzoyl)aminoacetic acid N,N-dicyclohexylamide HCl) and to develop an analytical method for this compound. IR, ¹H NMR, and UV spectra were obtained for cardiocyclide; its solubility was studied; its melting temperature, weight loss on drying and the transparency, color, and pH of its solutions were determined. The purity of material containing compound I was determined by thin-layer chromatography; quantitative cardiocyclide contents were estimated by non-aqueous titration. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 8, pp. 42–45, August, 2007.     

The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?

The substitution of leucine for valine at amino acid position 34 of the factor XIII gene is commonly referred to as FXIII Val34Leu polymorphism. The homozygous leucine/leucine genotype has been reported to confer protection against venous thromboembolism, but previous studies have not evaluated a population limited to those with idiopathic venous thromboembolism. The primary objective of the study was to determine whether the FXIII Val34Leu polymorphism is independently associated with the occurrence of idiopathic venous thromboembolism. We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic venous thromboembolism. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. All participants were tested for the FXIII Val34Leu polymorphism in addition to several well-known thrombophilias. Data from 309 cases and 306 controls were analyzed. The FXIII leucine/leucine genotype was present in 4.9% of cases and 6.5% of controls. An adjusted odds ratio of 0.59 (95% confidence interval, 0.25-1.38) was found for the recessive model and 0.69 (95% confidence interval, 0.46-1.02) for the dominant model. Our results do not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our Caucasian Canadian study population.     

The association between seated immobility and local lower-limb venous coagulability in healthy adult volunteers: a simulation of prolonged travel immobility.

This is the first study to examine the hypothesis that prolonged sitting is associated with procoagulant changes in the local lower-limb venous system. A comparison was made with upper-limb venous changes. Changes in markers of thrombin generation, fibrinolysis, endothelial perturbation and haemoconcentration were analysed as 10 healthy adult male participants sat for 8 h. The change in foot volume was estimated. Subjective venous thromboembolism assessment was undertaken hourly, along with 2-week and 4-week safety follow-up for clinical events.Expected increases in median prothrombin fragments 1 and 2, thrombin-antithrombin complex and D-dimer were not observed in either limb. An increase greater than 45% in the median tissue plasminogen activator and plasminogen activator-1 molar ratio (t-PA/PAI-1), and a decrease greater than 15% in median soluble thrombomodulin were noted in both limbs. Median haematocrit decreased minimally (1%) in the lower limbs, while the foot volume increased by 4%. Subjects experienced vague symptoms after 6 h of sitting, but none developed symptomatic venous thromboembolism. Upper and lower-limb changes in biomarkers did not correlate, except those in t-PA/PAI-1 ratio and plasminogen activator-1. Significant correlation was found between changes in the lower-limb t-PA/PAI-1 ratio and right foot volume.This study originally reveals that even in the lower limbs, prolonged daytime cramped sitting is not associated with significant procoagulant changes in healthy adult male volunteers, and confirms a previous observation that local lower-limb venous changes are not identically reflected in the upper limbs.     

Human dignity in the Nazi era: implications for contemporary bioethics

Background  

The justification for Nazi programs involving involuntary euthanasia, forced sterilisation, eugenics and human experimentation were strongly influenced by views about human dignity. The historical development of these views should be examined today because discussions of human worth and value are integral to medical ethics and bioethics. We should learn lessons from how human dignity came to be so distorted to avoid repetition of similar distortions.     

Surgical treatment of extensive hemangiomas of the liver

The results of treatment of 7 patients with extensive hepatic hemangiomas are analysed. In 6 patients the diagnosis was established before the operation. The liver was resected in 4 patients. One patients with malignant degeneration of the hemangioma was inoperable, in another the hemangioma was not removed because of his old age, and still in another because the process had spread. The authors conclude that in large hemangiomas of the liver in young and middle-aged patients resection of the organ is indicated, especially if there is a destruction cavity and a rapid growth of hemangioma. The operation is not indicated in capillary, surface hemangiomas of a small size, old age of the patient, extension of the process in to the main vascular structures of the other hepatic lobe.     

Invasion of visual cortex by the auditory system in the naturally blind mole rat.

Previously we have shown that the dorsal lateral geniculate body (LGB), which is strictly visual in sighted mammals, receives a strong auditory input in the naturally blind mole rat (Spalax ehrenbergi). Here we show with the 2-deoxyglucose technique and with single-unit recordings that in this species the initially non-degenerated visual cortex, as defined by its connection with LGB, is also activated by the auditory modality. These findings suggest that cross-modal compensation may occur as a natural consequence of the degeneration of a sense organ.