Quantitative Structure - Activity Relationships for Microsomal Enzymatic System Modulants. Part I: Inhibitors

Pharmaceutical Chemistry Journal -     

The elimination of the retractility of the skin portion of the nasal septum]

The authors propose a method which decreases the traumatism of surgery for nasal septum repair and helps attain more stable cosmetic results. An open endonasal incision is made behind the alar cartilage pedicles and continued along the fold between the alar and triangular cartilages to the nostril wing base. Perpendicular to this incision and starting from its end, another incision is made, also through the mucosal and cartilagenous tissue to the site where lateral parts of alar cartilages are changed for median. The mucocartilaginous flap is thus cut from the external upper part of the lateral compartment of the alar cartilage. The same intervention is made from the other side. Then the flaps and wound edges are mobilized, the columella is rendered a proper position, and the detected hidden tissue defect is filled with mucocartilaginous flaps. This method is based on correct understanding of the deformation, detection of the latent defect of tissues, and its repair by means of the adjacent tissues making incisions from the nasal cavity. The modification differs favorably from the prototype method.     

Neurochemical Mechanisms of Consolidation of Associative Aversive Learning to Food in the Common Snail

Studies of the effects of the protein synthesis inhibitor cycloheximide and serotonin and NMDA glutamate receptor antagonists on the processes of consolidation of the associative skill of rejecting particular foodstuffs were performed in the common snail. The skill was not acquired when animals were trained on the background of cycloheximide. Repeated training of “amnestic” snails to reject the same foodstuff in the absence of the inhibitor also failed to produce learning. Training of snails on the background of the nonselective serotonin receptor antagonist methiothepin or the NMDA glutamate receptor antagonist MK-801 (dizocilpine maleate) did not result in the acquisition of the conditioned reflex to food. However, repeated training led to the rapid formation of the skill. These experiments provide the first evidence that interventions influencing different molecular mechanisms during a single type of training produce either reversible or irreversible impairment of the mechanisms of consolidation of long-term memory. It is suggested that the reversible effect is associated with suppression of reproduction processes, while irreversible impairment was associated with impairments to engram storage. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 8, pp. 860–870, August, 2008.     

A population-based study of the associations of stroke occurrence with weather parameters in Siberia, Russia (1982–92)

Previous studies have established a seasonal variation in stroke occurrence, but none have assessed the influence of inclement weather conditions on stroke incidence in a general population of Russia. We performed a stroke population-based study in the Oktiabrsky District of Novosibirsk, Siberia, Russia. Included in the analysis were 1929 patients with their first occurrence of ischemic stroke (IS), 215 patients with their first occurrence of intracerebral hemorrhage (ICH) and 64 patients with their first occurrence of subarachnoid hemorrhage (SAH): all patients were aged between 25 and 74 years. The cumulative daily occurrence of total strokes and stroke subtypes was evaluated in relation to aggregated daily mean values of ambient temperature, relative humidity and air pressure by means of Poisson regression analysis to estimate the rate ratio (RR) with corresponding confidence interval (CI) and to identify the weather parameters of most importance. In a multivariate analysis, with adjustment for the effects of season, solar and geomagnetic activity, and age of the patients, low ambient temperature (RR 1.32; 95% CI 1.05-1.66) and mean value of air pressure (RR 0.986; 95% CI 0.972-0.999) were important predictors of IS occurrence, while mild ambient temperature (RR 1.52; 95% CI 1. 04-2.22) was an important predictor of ICH occurrence. No relationship between SAH occurrence and any one of the weather parameters studied was revealed. There was no interaction between any meteorological variables that was statistically significant. Inclement weather conditions are associated with the occurrence of IS and ICH in Siberia, Russia. Among the meteorological parameters studied, low ambient temperature and mean air pressure are the most important predictors of IS occurrence, whereas the occurrence of ICH is associated with mild ambient temperature. There is no association between any one of the weather parameters studied and the occurrence of SAH.     

Lowering of resistance to oxidation of VLDL lipoproteins and some subfractions of LDL lipoproteins in patients with non-insulin-dependent diabetes mellitus]

AIM: To investigate composition of very low density lipoproteins (VLDLP) and some subfractions of low density lipoproteins (LDLP), and their resistance to oxidation in patients with non-insulin-dependent diabetes mellitus (NIDDM) varying in severity compared to healthy subjects. MATERIALS AND METHODS: 26 NIDDM patients and 16 healthy controls. VLDLP and subfractions of LDLP were isolated by ultracentrifugation. The lipoproteins were assayed for protein, cholesterol, initial products of lipid peroxidation (LPO). After autooxidation of lipoproteins, fluorimetry examined the degree of the oxidant modification. RESULTS: The initial level of LPO products was elevated in VLDLP and light subfractions of LDLP in severe and moderate NIDDM patients. Even in mild NIDDM, resistance to oxidation of dense LDLP subfractions was low and continued to decrease with aggravation of the disease. High ratio cholesterol/ protein occurred in VLDLP and subfractions of LDLP from patient with severe NIDDM. CONCLUSION: It is shown that subnormal resistance to oxidation of LDLP dense subfractions even in mild NIDDM is an informative diagnostic criterion of risk factor to develop atherosclerosis.     

Innovations in pathogenetic therapy for peripheral affection of the cranial nerves in otorhinolaryngology

A total of 150 patients with peripheral affection of the facialnerve, 100 patients with acute neurosensory hypoacusis, 50 patients with affection of the reciprocal nerve were treated by the method using reciprocal interaction between M- and H-cholinergic mechanisms. Treatment outcomes showed that anticholinesterase therapy raises the efficacy of rehabilitation in patients with peripheral affection of the cranial nerves.     

The International Database of Ambulatory Blood Pressure in relation to Cardiovascular Outcome (IDACO): protocol and research perspectives

OBJECTIVES: The International Database on Ambulatory Blood Pressure Monitoring (1993-1994) lacked a prospective dimension. We are constructing a new resource of longitudinal population studies to investigate with great precision to what extent the ambulatory blood pressure improves risk stratification. METHODS: The acronym IDACO refers to the new International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome. Eligible studies are population based, have fatal as well as nonfatal outcomes available for analysis, comply with ethical standards, and have been previously published in peer-reviewed journals. In a meta-analysis based on individual patient data, composite and cause-specific cardiovascular events will be related to various indexes derived by ambulatory blood pressure monitoring. The analyses will be stratified by cohort and adjusted for the conventional blood pressure and other cardiovascular risk factors. RESULTS: To date, the international database includes 7609 patients from four cohorts recruited in Copenhagen, Denmark (n=2311), Noorderkempen, Belgium (n=2542), Ohasama, Japan (n=1535), and Uppsala, Sweden (n=1221). In these four cohorts, during a total of 69,295 person-years of follow-up (median 9.3 years), 1026 patients died and 929 participants experienced a fatal or nonfatal cardiovascular event. Follow-up in five other eligible cohorts, involving a total of 4027 participants, is still in progress. We expect that this follow-up will be completed by the end of 2007. CONCLUSION: The international database of ambulatory blood pressure in relation to cardiovascular outcome will provide a shared resource to investigate risk stratification by ambulatory blood pressure monitoring to an extent not possible in any earlier individual study.     

Hyperhomocysteinemia in men of Novosibirsk

Prevalence of hyperhomocysteinemia (HHC) in a sample of male population (n=84, age 50-64 year) of Novosibirsk assessed in the framework of the international project "Determinants of cardio-vascular diseases in the Eastern Europe: multicentral cohort research" during winter-spring period of vitamin deficiency was 50%. In 90.5% of cases HHC was moderate (15-30 micromol/l) and in 9.5% of cases -- medium (30-100 micromol/l). No correlations or independent associations were found between homocysteine blood level and CHD, as well as main risk factors (hyperlipidemia, hypertension, smoking and excessive body weight). No cases of CHD were registered among men with medium HHC. Homocysteinemia correlated positively with age, history of stroke, and negatively -- with alpha-tocopherol concentration in LDL. Men with medium HHC compared with those with normohomocysteinemia had higher systolic and diastolic blood pressure and 29% lower alpha-tocopherol concentration in LDL.     

Regulation of Tentacle Length in Snails by Odor Concentration

The upper tentacle of the snail, bearing the olfactory organ, produces complex movements when the snail explores a new environment. Tentacle trajectories were reconstructed in the presence and absence of odors using two simultaneous video recordings. Reconstructions showed that in the absence of odor, snails constantly scanned the surrounding space with the extended tentacles. Presentation of an odor elicited rapid flexion, independent of the odor concentration, accompanied by concentration-dependent tentacle contractions. Activation of identified motoneuron MtC3 is known to elicit tentacle contraction. Recordings made in semi-intact preparations showed that the dynamics and duration of the spike activity of MtC3 produced in response to odors correlated with the degree of tentacle contraction in response to odors. These data suggest that the central motoneuron MtC3, which triggers tentacle contraction, is involved in controlling the margins of the scanning field. Slow contraction or extension of the tentacle, associated with the level of MtC3 activity, may operate to tune the snail's investigative behavior to the conditions of the sensory environment. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 54, No. 5, pp. 655–665, September–October, 2004.