Usefulness of electron beam tomography in adolescents and young adults with heterozygous familial hypercholesterolemia

BACKGROUND: Because of the success of secondary prevention of coronary events by intense risk factor modification, a more precise measure of atherosclerosis in youth would have great clinical value both in the design of clinical trials for the demonstration of the usefulness of coronary disease prevention early in life and in guiding therapy. Identification of calcium in coronary arteries by electron beam tomography has been associated with severity of atherosclerosis in adults. METHODS AND RESULTS: Twenty-nine youths 11 to 23 years old with familial hypercholesterolemia (average LDL cholesterol, 5.95 mmol/L) underwent electron beam tomography as well as comprehensive risk factor assessment with measurement of total cholesterol, triglycerides, HDL cholesterol, lipoprotein (a), apolipoprotein E phenotype, blood pressure, body mass index, and history of tobacco use. Significant coronary calcium was identified in 7 of 29 subjects. Increased body mass index was significantly associated with the presence of coronary calcium (25.3 versus 20.6 kg/m2, P<0.03). No other risk factors were associated with the presence of coronary calcium. CONCLUSIONS: Coronary calcium, uncommonly identified before the fourth decade, was found in a significant percentage of adolescents and young adults with familial hypercholesterolemia. Overweight may increase the likelihood of coronary calcium being present in individuals already at high risk.     

Sulfation of endogenous compounds and xenobiotics--interactions and function in health and disease

Sulfation is a major detoxication mechanism for endogenous compounds and xenobiotics performed by a family of sulfotransferase isoenzymes. Understanding the normal cellular functions of these different sulfotransferases and the way in which endogenous and exogenous factors are able to influence their activity and expression will provide us with the information necessary to develop novel therapeutic strategies for conditions where sulfation may be implicated. This concept is discussed and is illustrated by examples including adverse drug reactions, fetal development and cancer.     

Septic sacroiliitis

Two cases of septic sacroiliac (SI) joint arthritis are presented to illustrate the difficulty of diagnosing and treating this uncommon osteoarticular infection. The patients presented are a 68-year-old woman with septic sacroiliitis caused by Streptococcus agalactiae and a 20-year-old man with Salmonella infantis infection involving the SI joint. The recent literature is reviewed and compared with previously published series. Of the 177 cases we reviewed, 47 (27%) occurred in pediatric patients. The mean age was 20 years. Only six patients (3%) were older than 60 years of age. Magnetic resonance imaging (MRI) is most useful for defining extent of infection, osteomyelitis, and abscess formation in the SI joint. Computed tomography (CT) is valuable for defining the extent of bone involvement and for guidance of percutaneous needle arthrocentesis. Other imaging modalities are useful primarily in the initial evaluation of patients with a nonspecific presentation. Four to six weeks of intravenous (i.v.) antibiotic therapy is recommended. Indications for surgical intervention include abscess formation, osteomyelitis, sequestrum of necrotic bone, and failure to respond to i.v. antibiotic therapy.     

Reconstructive and plastic microsurgery in the treatment of combat trauma to the extremities

In the department of microsurgery of A.A. Vishnevsky Central Hospital the transplantation and transposition of the at the gunshot injuries of the extremities have begun to execute since 1990. For this time 94 surgical interventions have been conducted at 88 wounded: 57 transplantations and 37 transpositions of the bloody tissues. The transplantation and transposition of the vascularized complexes of tissues with application of microsurgical technique is the effective method of the treatment of the wounded in the extremities. In the conditions of the local armed conflicts it is necessary to provide deployment of the department of microsurgery at stages of the specialized medical care.     

Selective structure of the gene pool. III. Technology of determination from F(ST)-statistics using numerical resampling

The selection pressure on the ith gene was determined on the basis of the heterogeneity of interpopulation diversity FST(i), assumpting that the significant deviation of FST(i) (observed differentiation of the ith gene) from Fe (selectively neutral differentiation) indicates selection. A selectively neutral variation Fe was estimated from the mean FST, averaged over the total set of genes. Since the validity of the equation FST approximately Fe = (4NeMe + 1)-1 depends on the fulfillment of conditions of the theoretical model as well as on organization of sampling of genes and subpopulations rather than on statistical parameters of the gene sample, an additional correction by boot-strapping is suggested. Simulation of sampling of the gene pool using numerical resampling (10(6) samples from each of the 50 markers) allowed us to characterize the selective structure of the gene pool. This structure consists of the following: one class of selectively neutral genes, NEUTRAL (FST(i) approximately Fe); and two classes of selective genes, LOWER DIFF (FST(i) < Fe) and SUPER DIFF (FST(i) > Fe). Interclass regions N-LOWER and N-SUPER between the classes of neutral and selective genes were defined with the use of bootstrapping. The hypothesis on the presence or absence of selection cannot be formulated with regard to the genes included in the interclass regions. A general trend for all gene pools of the world was revealed: the ratio between the boundary values of selective classes and Fe is constant. On the basis of this, a rapid and simple technique for estimating selective values of genes was developed. The positions of more than 80 immunobiochemical gene markers in the selective structure of six gene pools of the world (Europe, Asia, Africa, Australia, America, and northeastern Eurasia) are presented. The selective structure of five subregions of northeastern Eurasia (Caucasus, Europe, Ural, Siberia, and Central Asia) are characterized as well.     

The protective action of tocopherol acetate in simultaneous administration with nitrobenzene and its chloro derivatives]

In this article the results of the study of regularities in the development of outbreak morbidity in shigellosis, caused by S.flexneri 2a, in hospitals are presented. The study was carried out with the use of the method of typing by the plasmid profile. The study showed the continuity of the epidemic process in the foci which appeared at intervals considerably exceeding the incubation period. The fact of the interhospital spread of S.flexneri 2a was established. The strain causing the disease was identified by the characteristic set of plasmids and their size. The possibility of reinfection of patients with S.flexneri 2a under hospital conditions was confirmed. The possibility of changes in the main transmission routes in the course of the spread of S.flexneri 2a infection in closed groups was pointed out.     

A P-loop-like motif in a widespread ATP pyrophosphatase domain: implications for the evolution of sequence motifs and enzyme activity

A conserved amino acid sequence motif was identified in four distinct groups of enzymes that catalyze the hydrolysis of the alpha-beta phosphate bond of ATP, namely GMP synthetases, argininosuccinate synthetases, asparagine synthetases, and ATP sulfurylases. The motif is also present in Rhodobacter capsulata AdgA, Escherichia coli NtrL, and Bacillus subtilis OutB, for which no enzymatic activities are currently known. The observed pattern of amino acid residue conservation and predicted secondary structures suggest that this motif may be a modified version of the P-loop of nucleotide binding domains, and that it is likely to be involved in phosphate binding. We call it PP-motif, since it appears to be a part of a previously uncharacterized ATP pyrophophatase domain. ATP sulfurylases, NtrL, and OutB consist of this domain alone. In other proteins, the pyrophosphatase domain is associated with amidotransferase domains (type I or type II), a putative citrulline-aspartate ligase domain or a nitrilase/amidase domain. Unexpectedly, statistically significant overall sequence similarity was found between ATP sulfurylase and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) reductase, another protein of the sulfate activation pathway. The PP-motif is strongly modified in PAPS reductases, but they share with ATP sulfurylases another conserved motif which might be involved in sulfate binding. We propose that PAPS reductases may have evolved from ATP sulfurylases; the evolution of the new enzymatic function appears to be accompanied by a switch of the strongest functional constraint from the PP-motif to the putative sulfate-binding motif.     

Optimal electrical stimulation for latissimus dorsi muscle after cardiomyoplasty

A new property of the presequence of the mitochondrial precursor protein cytochrome oxidase subunit IV is presented. This mitochondrial presequence induces interbilayer contacts between large unilamellar vesicles consisting of phosphatidylcholine and cardiolipin. The presequence-vesicle aggregates can be dissociated by applying a membrane potential across the bilayers (negative inside). These effects require the presence of cardiolipin and are not observed for other negatively charged phospholipids. We propose a role for the presequence in the formation and dissociation of mitochondrial contact sites.     

Correlation between pharmacokinetic parameters of rifampicin and its biologically active metabolite as related to estimation of the relative bioavailability of the antibiotic

In the bioavailability studies with drugs biotransformed to biologically active metabolities only the concentrations of the parent drug (PD) are usually taken into account even when the pharmacokinetic data on the metabolite(s) (M) are available. However, such data may be useful as an alternative source for the bioavailability determination. Moreover, the clinical outcomes often depend on both the PD and M concentrations. The aim of the study performed with two rifampicin formulations, tablets and dragee, was to correlate the pharmacokinetic parameters of the PD and 25-O-deacetylrifampicin, a microbiologically active M of rifampicin, and to examine whether the bioavailability parameters based on the PD and M concentrations were compatible. The serum concentrations of the PD and M were determined in 8 healthy volunteers by HPLC. Despite different patterns of the PD and M pharmacokinetic profiles the PD peak concentration (Cmax) and especially the AUC correlated with Cmax or the AUC of the M (r = 0.76 and 0.92 respectively). Moreover, the extent of the absorption expressed as the AUC ratio for the PD correlated with the AUC ratio for the M (r = 0.86). However, neither the time to reach the maximum (tmax), nor the Cmax/AUC ratio, a measure of the absorption rate, based on the PD pharmacokinetic data correlated with the respective parameters calculated with using the M concentrations. Thus, only the estimates of the extent of the absorption and not of the absorption rate based on the PD and M data may be considered as compatible.     

D-Glyceraldehyde-3-phosphate dehydrogenase: structural basis and functional role of the acyl transfer reactions

The catalytic mechanism of D-glyceraldehyde-3-phosphate dehydrogenase is considered in the light of the available structural information. The design features of the enzyme molecule determining the pathway of the acyl transfer, i.e., the transfer of the acyl group produced in the oxidative step of the reaction to one of the two acceptors, inorganic phosphate or water, are discussed. The properties of enzyme forms possessing cysteine residues oxidized to sulfenic acid derivatives are described. The participation of these residues in the acyl transfer to water is considered.