Ultrastructural localization of prostaglandin endoperoxide synthase (cyclooxygenase) to isolated, purified fractions of guinea pig peritoneal macrophage and line 10 hepatocarcinoma cell lipid bodies

The majority of equations used to predict values for basal metabolic rates (BMRs) are the result of indirect calorimetry measurements performed in the 1930s and 1950s. To assess the reliability of these equations in predicting the resting energy expenditure (REE) of the children in our community, indirect calorimetry was performed on 92 male and 107 female healthy children 2-3 h postprandial. Each individual was measured for a duration of 15-20 min. The data for analysis were obtained from 5-15 min steady-state periods. Subjects ranged in age from 5 to 16 years. The results were compared with BMRs calculated from the Harris-Benedict equation (Harris J, Benedict F. A biometric study of basal metabolism in man. Washington, DC: Carnegie Institute of Washington, publication no. 279, 1919.), the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU) equations, and the equations proposed by Schofield for use by the 1985 FAO/WHO/UNU Nutrition Committee. The values predicted by the FAO/WHO/UNU and Schofield equations were consistent with the measured resting values for all the children in the study population. Ninety-two children weighed between 90-110% of their ideal body weight. When the measured REE and estimated BMR were compared by gender and age in these children, the Schofield equations provided the best estimates. Ninety-four of the study subjects weighed > 110% of their ideal body weight. The predicted estimates by all equations were consistent with the measured values in this subgroup of the population. We conclude that the FAO/WHO/UNU and Schofield equations are reliable estimates of metabolic rate in healthy children when measurement of REE is not possible.     

Interaction of calcium channel antagonists with calcium: spectroscopic and modeling studies on diltiazem and its Ca2+ complex

Using spectral techniques, the solution conformation of diltiazem was studied in acetonitrile with special reference to the effect of Ca2+ on the drug structure. Complete assignment of the proton resonances in the 1H-NMR spectrum of the drug was made using one-and two-dimensional spectral analyses. A two-dimensional 1H-NOESY spectrum (in the phase-sensitive mode) was obtained to identify the interproton connectivities in the drug molecule. A molecular modeling program involving Monte Carlo simulation and energy minimization was employed to arrive at the structure of the drug. The program was run with and without the input of the interproton distances derived from the NOESY cross peaks. Both the protocols led to a structure of the drug which was generally similar to that reported from X-ray diffraction data on crystalline diltiazem hydrochloride (Kojic-Prodic, et al. Helv. Chim. Acta 1984, 67, 916-926). However, significant differences between the two structures were seen in the orientations of the substituent groups attached to the benzothiazepine ring. Substantial changes in the circular dichroic (CD) and 1H-NMR spectra of diltiazem were observed on addition of Ca2+ up to a mole ratio of 0.5 Ca2+ per drug. Relatively large changes were seen in 1H resonances of the N-methyl protons and the methylene protons attached to the heterocyclic nitrogen. Analysis of the binding isotherms from CD data at 22 +/- 1 degrees C indicated a 2:1 drug:Ca2+ "sandwich" complex with an estimated dissociation constant of 140 microM. One-dimensional difference NOE and two-dimensional NOESY spectra revealed interproton connectivities between two drug molecules that were compatible with the sandwich complex formation. The interproton distances derived from the volume integrals of the NOESY cross peaks were used as geometrical constraints in modeling the Ca(2+)-bound conformation of diltiazem. The minimum-energy conformation corresponded to the sandwich complex where Ca2+ was coordinated to three oxygens in each of the two drug molecules. Combined with our earlier data on the ability of diltiazem to translocate Ca2+ across the lipid bilayer in synthetic liposomes (Ananthanarayanan, V.S.; Taylor, L.; Pirritano, S.Biochem. Cell Biol. 1992, 70, 608-612), the structural data presented here point to a role for Ca2+ in the interaction of diltiazem with its membrane-bound receptor.     

Progression of asymptomatic carotid stenosis: a natural history study in 1004 patients

PURPOSE: The purpose of this study was to delineate the natural history of the progression of asymptomatic carotid stenosis. METHODS: In a 10-year period, 1701 carotid arteries in 1004 patients who were asymptomatic were studied with serial duplex scans (mean follow-up period, 28 months; mean number of scans, 2.9/patient). At each visit, stenoses of the internal carotid artery (ICA) and the external carotid artery (ECA) were categorized as none (0 to 14%), mild (15% to 49%), moderate (50% to 79%), severe (80% to 99%), preocclusive, or occluded. Progression was defined as an increase in ICA stenosis to >/=50% for carotid arteries with a baseline of <50% or as an increase to a higher category of stenosis if the baseline stenosis was >/=50%. The Cox proportional hazards model was used for data analysis. RESULTS: The risk of progression of ICA stenosis increased steadily with time (annualized risk of progression, 9.3%). With multivariate modeling, the four most important variables that affected the progression (P <.02) were baseline ipsilateral ICA stenosis >/=50% (relative risk [RR], 3.34), baseline ipsilateral ECA stenosis >/=50% (RR, 1.51), baseline contralateral ICA stenosis >/=50% (RR, 1.41), and systolic pressure more than 160 mm Hg (RR, 1. 37). Ipsilateral neurologic ischemic events (stroke/transient ischemic attack) occurred in association with 14.0% of the carotid arteries that were studied. The progression of ICA stenosis correlated with these events (P <.001), but baseline ICA stenosis was not a significant predictor. CONCLUSION: In contrast to recently published studies, we found that the risk of progression of carotid stenosis is substantial and increases steadily with time. Baseline ICA stenosis was the most important predictor of the progression, but baseline ECA stenosis also was identified as an important independent predictor. Contralateral ICA stenosis and systolic hypertension were additional significant predictors. We found further that the progression of ICA stenosis correlated with ischemic neurologic events but not baseline stenosis. The data provide justification for the use of serial duplex scans to follow carotid stenosis and suggest that different follow-up intervals may be appropriate for different patient subgroups.     

Folding pathway of a lattice model for proteins

The folding of a protein-like heteropolymer is studied by using direct simulation of a lattice model that folds rapidly to a well-defined "native" structure. The details of each molecular folding event depend on the random initial conformation as well as the random thermal fluctuations of the polymer. By analyzing the statistical properties of hundreds of folding events, a classical folding "pathway" for such a polymer is found that includes partially folded, on-pathway intermediates that are shown to be metastable equilibrium states of the polymer. These results are discussed in the context of the "classical" and "new" views of folding.     

Analysis of the quality of clinical diagnosis from generalized findings of the pathologoanatomic service

A statistical analysis of generalized data of the pathoanatomical service on quality of clinical diagnosis in curative-prophylactic institutions in 54 administrative territories of the RSFSR was carried out. The structure (extensive indices) and frequency (intensive indices)of erroneous clinical diagnoses referring to the most important classes of diseases were identified. As to the structure of indices and frequency of clinico-anatomic disparities the first place was occupied by oncological diseases (20.1+/-0.11 and 14.2+/-0.22%), the second--by infectious diseases (16.5+/-0.1 and 13.0+/-0.34%), the third--by diseases of the digestive system (14.6+/-0.09 and 13.0+/-0.33%), the forth--by diseases of the urogenital system (14.0+/-0.09 and 12.2+/-0.49%), the fifth--by disease of the respiratory system (12.7+/-0.09 and 10.6+/-0.24%), the sixth--by diseases of the cardiovascular system (11.1+/-0.08 and 8.0+/-0.14%). The recommendation is put forward to carry on annually a complex satistical analysis of extensive and intensive indices of erroneous clinical diagnoses demonstrating the quality of clinical diagnosis in therapeutic institutions of a given administrative territory.     

Social and medical rehabilitation of patients subjected to surgery on account of aneurysms of the anterior connecting artery

The report contains data concerning occupational and social rehabilitation of 46 patients operated on for aneurysma of the anterior communicative artery. It was established that the occupational prognosis depends upon the severity of the hemmorhage, character of surgical operation. Of significance are the conditions of work, time after the surgical operation. The authors mark that in 2/3 of the operated on patients the working capacity is being restored. A spontaneous restoration of diaturbed functions is slow and is not always sufficient. With this purpose it is expedient to repeat courses of a general tonic and special rehabilitative therapy. A favourable factor in the readaptation of patients is their early engagement in working activities. The authors give their recommendations for medical labour expert testimony for this category of patients.     

Resistance of Vigna unguiculata (cowpea) seeds to Callosobruchus maculatus is restricted to cotyledonary tissues

We have investigated the survival of Callosobruchus maculatus larvae when reared on resistant IT81D 1045 Vigna unguiculata seeds, whose resistance has been associated with variant forms of vicilins. Here, we present data which show that larvae of C. maculatus feeding on embryonic axis of resistant cowpea reach a mass of around 28 times higher than those feeding on cotyledonary tissues. Additionally, incorporation of 5–10% of embryonic axis flour on artificial seeds made of resistant flour restores toxicity of seeds to the bruchid. Vicilins purified from both susceptible and resistant embryonic axis had no deleterious effects either on insect development or on insect survival until a level of 4% of incorporation. In contrast, vicilins from resistant cotyledons show an LD₅₀ (50% lethal dose) and WD₅₀ (half weight dose) of 2%. Total vicilin contents of embryonic axes were around two times lower than in cotyledonary tissues, while proteolytic activities of all four proteinase classes were always higher in the former tissues. By 2D‐PAGE we visualized eight protein spots, which seem to be exclusively found on resistant cotyledons. Copyright © 2006 Society of Chemical Industry