Search

An 'active analog' approach to receptor mapping was used to identify a pharmacophore for a set of thymidine nucleoside analog inhibitors of HIV-1 reverse transcriptase. The preliminary results indicate that the O2, O4', and O5' atoms are capable of adopting a unique pharmacophoric pattern which may be the key to their recognition by reverse transcriptase.

Endotoxin (Lipopolysaccharide, LPS) is a part of the outer membrane of the cell wall of gram-negative bacteria. LPS induces activation of the coagulation cascade in humans. This procoagulant effect on citrated whole blood produces a shortened clotting time. Silver ion (Ag/sup +/) denatures the anticoagulant proteins and affects the intrinsic pathway of blood coagulation by producing a shortened clotting time. This in vitro study was performed by mixing human citrated whole blood (CWB) with LPS, silver nitrate (AgNO/sub 3/), and the combination of the two. The clotting time, rate of clot formation, and the maximum strength of the clot were determined. The results show that the combination of LPS and Ag/sup +/ significantly reduces the clotting time (p

The effect of copper ions on the blood coagulation time was determined. In the experiment that was performed in vitro, there were three different aliquots for each blood sample. The three aliquots were composed of the control, 0.05 mM CuSO/sub 4/, and 0.1 mM CuSO/sub 4/. Thirty two microliters of 0.1 M CaCl/sub 2/ was then added to each aliquot to initiate blood coagulation. When the copper ion concentration was increased, there was a significant increase in blood coagulation time.

Tissue factor (TF) is a transmembrane glycoprotein and the main triggering element for blood coagulation. Expression of TF on the cell surfaces and its appearance as a soluble molecule are characteristic features of acute and chronic inflammation in conditions such as arteriosclerosis leading to stroke and myocardial infection. A study was performed on human citrated whole blood, by separating plasma from the red blood cells. Ten microlitres of 25% tissue factor (TF) was added to both the plasma and packed red blood cells (RBC's), and the clotting time, rate of clot formation and the maximum strength of the clot determined. TF bearing samples clotted more rapidly and had greater clot strength when compared to that of control aliquots.

Clinically, the dissolution of pathologic blood clots through conventional therapeutics may alter patient coagulation profile and increase risk of thrombohaemorrhagic complications. We developed an in vitro model to determine the effect of soluble clotting factors on coagulation response. Blood clot solubles were added at an approximate 1:1000 dilution to matched human whole blood samples (n = 10). The clotting time and clot rate were measured using a Sonoclot/spl reg/ Coagulation Analyzer and compared with relevant controls. Two tailed paired t tests indicated a significant increase in clot rate and a significant decrease in clotting time between control and "spiked" groups (p

Silver ion, a potent antimicrobial and procoagulant, is hypothesized to achieve its haemostatic effect by binding anticoagulant proteins. We performed in vitro studies to gain more insight into its mechanism of action. 10 /spl mu/L of 5% AgNO/sub 3/ was added to 1 mL human plasma (n = 4), forming a precipitate. The precipitate was recovered through centrifugation and iteratively washed with saline. The supernatant(s) and precipitate were mixed with Coomassie blue stain and protein content was measured via spectrophotometric absorbance. An analysis of variance indicated significant (p

Protamine sulfate (protamine), a low molecular weight poly-cationic amine, has been used for some time on patients undergoing cardiac operations and procedures. It is particularly used on patients who have been treated with heparin (an anticoagulant), in order to neutralize the anticoagulant effects of heparin on the person's blood. In this in vitro study, various 500 /spl mu/L one-day old citrated whole human blood samples (n=18) have been subjected to different amounts of protamine of a single concentration (10 mg/mL in saline), using 0.9% saline added to blood as control. It is known that saline, by itself, has no effect on blood clotting. After thorough mixing and incubation for 10 min. at 37/spl deg/C, the time it takes for 200 /spl mu/L of each sample to clot, in presence of 20 /spl mu/L 0.1 M CaCl/sub 2/ was measured. The results show that protamine acts as an anticoagulant in the absence of heparin. Clotting time also increases with more protamine added.

The sedimentation rate (sed rate), also called, the Erythrocyte Sedimentation Rate (ESR) is a blood test for inflammation in the body. If it is elevated, then there is an inflammatory process in the body which can be monitored. The test is broad and non-specific; however, it may determine the effectiveness of therapy for the inflammatory condition. We performed studies on human citrated whole blood by adding 100 microlitres of 1% of MethylCellulose to each of glass and plastic tubes with the blood. The samples (n=12) were incubated at 37/spl deg/ for 10 minutes. Later, the blood from each of the tubes were placed in pipettes, sealed and left undisturbed for an hour. The ESR was measured, and it was found that the sedimentation rate of the blood in plastic settled at a higher rate than the one in glass.

The benefits of intensive insulin therapy for type 2 diabetics with cardiovascular disease (CVD) are highly controversial. We performed in vitro studies to determine whether insulin has any effect on whole blood coagulation and assess how insulin responds to monocyte membrane associated tissue factor (mmaTF) induced hypercoagulability. Mercuric ion (Hg/sup 2+/), which has been shown to increase mmaTF-dependent procoagulant activity in whole blood, was used to stimulate similar pathways in our experiment. We spiked human citrated whole blood with HgCl/sub 2/ and Humulin-N/sup /spl reg// (HN) at final concentrations of control, 0.02 U/mL HN, 0.004 U/mL HN, 0.002 U/mL HN, 0.005% HgCl/sub 2/, 0.02 U/mL HN:0.005% HgCl/sub 2/, 0.004 U/mL HN:0.005% HgCl/sub 2/, and 0.002 U/mL HN:0.005% HgCl/sub 2/. The samples (n=12) were incubated at 37/spl deg/C for 10 minutes and recalcified with CaCl/sub 2/ to initiate clotting. The clotting time (CT) was measured with an Amelung KC4A Micro. The results indicate that HN by itself has no effect on CT. However, each concentration of HN:HgCl/sub 2/ exhibited a shorter CT than either HN or HgCl/sub 2/ alone (p

Introduction of a lead ion in the form of lead nitrate has been found to induce coagulopathy in human blood. A marked toxic action on the normal hemocoagulative mechanism, under a background of lead intoxication, is manifested through an increase of clotting time for lead treated blood. The in vitro study carried out with citrated human blood samples (n=12) utilized celite as a procoagulant in both the control samples and the lead treated blood samples. Various 500 /spl mu/l samples of blood were treated with varying molar concentrations of lead nitrate. As a substitute for the lead nitrate solution, the control was treated with 0.1% saline solution. It should be noted that at this concentration, saline solution does not alter the coagulation time of blood. Following the incubation of the samples for 10 min. at 37/spl deg/C, 200 /spl mu/l of blood was taken from each sample and recalcified by 20 /spl mu/l of 0.1 M CaCl/sub 2/ to initiate clotting for measuring the coagulation time. Results thus obtained indicated a direct correlation between Pb(NO/sub 3/)/sub 2/ addition and coagulation time for each sample. Furthermore, anticoagulant activity was shown to increase with higher concentrations of Pb(NO/sub 3/)/sub 2/.

Endotoxin (lipopolysaccharide, LPS) is part of the outer wall of a Gram-negative bacterial cell. LPS is a powerful mediator that causes a number of pathophysiological changes such as inflammations, tissue destruction, respiratory distress, capillary damage, intravascular coagulation and hypotension. The effect of LPS on Erythrocyte Sedimentation Rate (ESR) determinations has not previously been investigated. We performed in vitro studies by mixing human citrated whole blood (CWB) with LPS at a concentration 5 ug/mL. The samples (n=11) and (n=5) were incubated at 37/spl deg/C for 10 minutes. The samples (n=11) were then refrigerated for 24 hours and incubated at 37/spl deg/C for 30 minutes. The samples (n=5) were incubated for 24 hours at 37/spl deg/C. The samples were allowed to settle for one hour and the ESR determined. The results indicate LPS treated blood had a significant reduction (p

Whether copper sulfate affects the sedimentation rate of erythrocytes in blood was investigated. We performed the experiment by placing by 1ml of blood in plastic vials. After that, we added 10/spl mu/l of 1% CuSO/sub 4/ solution to an aliquot. Then, we put 10/spl mu/l of 5% of CuSO/sub 4/ to 1ml of the same blood into different vial. Following this procedure, we incubated the blood with the various concentrations of CuSO/sub 4/ to 37 degrees Celcius for ten minutes. Then, we determined the sedimentation rates of the red blood cells (RBCs) for the control, the blood that contained .001% of CuSO/sub 4/, and the blood that contained .005% of CuSO/sub 4/. We repeated this experiment with fourteen (n=14) different samples of blood. The results indicate that there was a statistical significance (P

The mercuric ion (Hg/sup 2+/) has been shown to have a procoagulant effect on citrated whole blood through its excitation of the extrinsic pathway. The silver ion (Ag/sup +/) affects the intrinsic pathway of blood coagulation also producing a shortened clotting time. This in vitro study involved mixing citrated whole blood (CWB) with mercuric nitrate Hg(NO/sub 3/)/sub 2/, silver nitrate AgNO/sub 3/, and the combination of the two. The eight samples were incubated for ten minutes at 37/spl deg/C and were analyzed by an Amelung KC 4A clot detector. The results show that the combination of Ag/sup +/ and Hg/sup 2+/ significantly reduces the clotting time (p

The hypochlorite ion (OCl/sup -/) is a powerful oxidant that participates in the pathogenesis of ischemia/reperfusion injury, inflammation, and atherosclerosis. Whether hypochlorite has any anticoagulative properties in blood has previously not been investigated. We performed in vitro studies by spiking human citrated whole blood (CWB) with sodium hypochlorite (NaOCl) at final concentrations of 0 /spl mu/g/mL (control), 9.5 FLg/mL, and 95 /spl mu/g/mL. The samples (n=12) were incubated at 37/spl deg/C for 10 minutes and recalcified with 0.1 M CaCl/sub 2/ to initiate clotting. The clotting or recalcification time (RT) was measured with a Sonoclot Coagulation Analyzer. The results indicate a significant prolongation (p

A rapid blood clotting test for monitoring the thrombin inhibiting activity of the drug hirudin is described. This test, a modified ecarin clotting time may enable the monitoring of a patient's hirudin dosage so that a safe, therapeutic level is achieved. The results show that there was an increase in clotting time with an increased level of hirudin. The data demonstrates a linear correlation between ecalin clotting time prolongation and hirudin content. Each clotting time is significantly prolonged (p

Summary form only given. An attempt has been made to construct a mathematical model of the cardiovascular system which will allow one to simulate the effects of changes in one or more hemodynamic parameters on myocardial oxygen supply and demand. The model used is a combination of several models which have been reported in the literature, along with the authors' own modifications. >

Summary form only given. The authors review the properties and functional characteristics of the H/sub 1/ receptor and postulate the nature of the ligand-receptor activation site using molecular modeling techniques. A model of the surface of the active site on the receptor was postulated and constructed using Sybyl software on a personal Iris workstation. The surface properties were inferred using the structure-activity relationships for the competitive antagonists which have been reported in the literature. >

A whole body thermal model simulating heat distribution and temperature regulation in rats during hemorrhagic shock and during post-shock microwave core rewarming period was developed. An electrical circuit was used to simulate the thermal system and PSpice was used to analyze the circuit. The blood pressure drop and cardiac output decrease were considered in the simulation, and the set point temperature was investigated in the model. Linear decrease and increase of the set point temperature were assumed during the simulation of the shock period and the post-shock rewarming period, respectively. General agreement between the simulation result and experimental data was obtained. >

A lung model for soluble gas exchange that will allow quantitative estimation of the pharmacokinetics of inhaled anesthetic agents is described. This lung model is coupled to a whole body hemodynamic model given by B. Pu/spl acute/ramic (M.S. thesis, New Jersey Inst. of Techn., 1992). The partial pressure of a soluble gas in the pulmonary artery (PPA), the integrated average pulmonary capillary pressure (PPC), and the partial pressure of gas in the pulmonary vein (PPV) system for one set of simulation values are shown. The partial pressures of the gas in the three lung capillary zones are also given. >

The authors take a pharmacophoric approach to the identification of a substrate/inhibitor binding site on HIV-1 RT. A pharmacophore is defined as the spatial arrangement of a set of atoms or groups in a ligand molecule while bound to a given receptor. The pharmacophore's usefulness is in the assumption that a single one exists for a series of compounds binding at the same receptor site. The superposition of a series of substrate and/or inhibitors along a pharmacophoric pattern provides an enzyme excluded volume, which represents a minimum volume requirement for substrate/inhibitors at the receptor binding site. The structure of HIV-1 RT complexed with dsDNA template-primer has been recently described at 7 /spl Aring/ resolution and is currently being extended to 3 /spl Aring/. The combination of crystallographic, pharmacophoric, and existing biochemical and genetic data regarding the substrate binding residues will help to generate an accurate structure of the substrate binding domain of HIV-1 RT and aid in the evaluation of new and specific RT inhibitors. >

Bioprosthetic heart valves have been tanned by conventional glutaraldehyde for many years. This comparative study investigates the merit of the Biocor No-React aldehyde detoxification process as an alternative biochemical modifier of renograft tissues. An in-vitro protease digestion study was performed by measuring the weight lost of tissue samples after incubated in a designed protease solution (pH=7.40) at 37/spl deg/C for 22 hours. The percentage weight lost of glutaraldehyde-treated and No-React treated bovine pericardial xenografts is 14.8/spl plusmn/0.8 and 10.4/spl plusmn/0.5 respectively (p

In the present study molecular modeling and molecular mechanics methods using the crystal structure coordinates for acetylcholinesterase (AChE) from Torpedo Californica were employed to demonstrate the behavior of key residues of the enzyme upon inhibition by both the P/sub R/ and P/sub S/ diastereomers of isopropylmethylphosphonofluoridate (sarin). Comparative studies between both the adducts of AChE with P/sub S/ and P/sub R/ sarin and with the native enzyme indicate the important role of the aromatic residues in the vicinity of the active site as well as that of His-440 which catalyzes both the C-O bond breaking in the dealkylation reaction and the reaction of bond breaking to the Ser /spl gamma/-O in reactivation. In contrast to previous studies, the role of Glu-199 in stabilizing the developing positive charge on the incipient carbonium ion in the dealkylation reaction was not verified in this study.

Reports research results on contour extraction from high voltage electron microscope (HVEM) images of thick cross section montages of small blood vessels. The previous work on this subject which was based on the conventional edge detection operations combined with edge linking, has proven inadequate to describe the inner structural compartments of microvessels. Here an active contour model (commonly referred to as "Snakes") has been applied to advance the previous work. Active contour models have proven themselves to be a powerful and flexible paradigm for many problems in image understanding, especially in contour extraction from medical images. With the developed energy functions, the active contour is attracted towards the edges under the action of internal forces (describing some elasticity properties of the contour), image forces and external forces by means of minimization of the energy functions. Based on this active model, an effective algorithm is implemented as a powerful tool for 2D contour extraction in the authors' problem for the first time. The results thus obtained turn out to be encouraging. >

For investigating the thrombus formation in a pneumatic diaphragm blood pump and the critical factors responsible for thrombus formation on smooth polyurethane blood contacting surfaces, four in vivo implanted blood pumps (implanted for 6 to 25 days) and four unused pumps were studied by scanning electron microscopy (SEM). The results demonstrate that one of the important reasons for thrombus formation in blood pumps is the morphology of the surface inside the blood chamber. Some surface defects were observed on the blood contacting surface. The defects could have been caused by material properties, the fabrication process, or excessive bending stress. The diaphragm and housing junction (DHJ) is a critical area where the thrombus formation of ten occurs. Marked reduction in thrombus formation for an improved pump is attributed to material pretreatment, stringent quality control, and reasonable redesign of the DHJ structure. >

A pharmacokinetic heterogeneous model was developed for the local anesthetic and antiarrhythmic drug lidocaine. It was assumed that transport and elimination of lidocaine and its metabolites are linear with concentration. Simulations were done using VisSim software on a 486 based personal computer. It was found that the rate of uptake and rate of breakdown were 0.48 min/sup -1/ and 0.49 min/sup -1/ respectively for lidocaine. Similar simulations were done for the lidocaine metabolites MEGX and 3-OHLID. Finally, a parameter sensitivity study was done for lidocaine and its metabolites,.

A systematic conformational search was performed on a set of H/sub 1/ histamine receptor antagonists in an effort to define a pharmacophore. This study suggests that the H/sub 1/ receptor may bind antihistamines with two acidic moieties located between 4.97A and 6.15A from one another. Disulfide bond formation is also possible for this class of antihistamines. This, however, would not explain reversible binding unless a thioesterase is involved.

Molecular modeling studies have been carried out to compare static, electronic and electrostatic properties of some Histamine HI receptor antagonists using SYBYL package. The present work does suggest a correlation between structure — function relationships of these molecules.

The rates of alkaline hydrolysis of seven acyclic and bridgehead esters of p-nitrophenyl carboxylic acids have been kinetically found to vary inversely with the size of the substituent R group. Computer assisted molecular modeling techniques were used to suggest a steric and electrostatic rationale for the effect of R group size upon the rate of hydrolysis.

1. 1. The kinetics of the reaction of iodoacetamide with poly- l -lysine, α-acetyllysine, and e-acetyllysine has been investigated over the pH range 7.4–11.2. 2. 2. The reactivities correlated with the respective basicities of the various nucleophiles. 3. 3. The reactivity of the polylysine was resolved into two parts; one associated with the amines of the helical regions, the other associated with the amines of the coil regions.

One aim of this in vitro investigation was to determine the effect of substituting four phenols and two methacrylates with vinyl functions on the dentin bond strengths of several new experimental dentin bonding agents. Another objective was to determine the effect of postextraction age and dentin level within the tooth on tensile bond strengths of these toluene diisocyanate-derived adhesives. Extracted third molars were divided into postextraction age groups and sectioned into three slices approximately 400 microns thick. The four substituted phenols were: eugenol, o-methoxyphenol, o-chlorophenol, and p-cresol. Substituted methacrylates with vinyl ligands were 2-hydroxyethyl methacrylate (HEMA) and 6-hydroxyhexyl methacrylate (HHMA). Results showed that adhesives made with o-chlorophenol, p-cresol, and methoxyphenol with HEMA were the best, while those made with eugenol and HHMA were the worst. The post extraction age of the tooth and the dentin depth had no consistent effect on most adhesive bond strengths which were generally around 10.3 MPa (1500 psi).

Les vitesses d'hydrolyse basique d'esters bi- et tricycliques tete-de-pont substitues varient a l'inverse de la taille du pont

Whole human blood was recently established as a thixotropic fluid whose apparent viscosity depends on the shear rate as well as the duration of the shear. The rheograms which characterize a thixo tropic fluid, the hysteresis loop and the torque-decay curve, were observed in whole human blood samples. These rheograms can be represented by a rheological equation developed by Huang. The thixo tropic parameters of the equation can be used to calculate the apparent viscosity of a whole human blood sample under different flow conditions.In addition, they supply certain unique information which can’t be obtained by conventional viscosity measurement of blood. This information includes the relative amount of erythrocytes in rouleaux formation, the rate constant of breakdown of rouleaux into individual red cells induced by a shear stress, the initial stress to start the blood flow, the Newtonian and non-Newtonian contribution of viscosity, etc. In this communication, we report the temperature dependency of these thixotropic parameters of blood samples taken from apparently healthy human subject. The temperature ranged from 22.8 to 41°C. Rheograms were measured of each whole blood sample via a Weissenberg Rheogoniometer modified with an electronic continuous drive system. Thixotropic parameters of the sample were calculated by a digital computer via a non-linear regression analysis program. Our results show the following original findings which will be of interest to biorheologists as well as physiologists. When these thixotropic parameters were plotted against the reciprocal absolute temperature, it was found that the yield stress, the Newtonian contribution of viscosity, the relative amount of rouleaux, the apparent viscosity and the non-Newtonian contribution of viscosity are all at a minimum value at 37°C. The rate constant of rouleaux breakdown to individual red cells has a linear relationship with a negative slope, from which, the activ ation energy of the rouleaux breakdown reaction can be evaluated. It is also found that the mechanicism of rouleaux breakdown reaction is independent of temperature.

Les vitesses d'hydrolyse basique d'esters bi- et tricycliques tete-de-pont substitues varient a l'inverse de la taille du pont

Research on human immunodeficiency virus (HIV) infection and opportunistic infections (OIs) that accompany acquired immunodeficiency syndrome (AIDS) requires various resources, including biomedical instrumentation, data acquisition programs using high- or low-level languages and database technology. The viral serology laboratory uses various testing methodologies to study the interrelationships of HIV with cytomegalovirus (CMV) and the protein /spl betasub 2/-microglobulin (/spl betasub 2/-M) for various research and clinical protocols. Among other instrumentation, this laboratory uses Abbott's IMx system to detect the concentration or presence of analytes in patient specimens. The IMx system software and hardware provide facilities for data acquisition. This study focuses on the automation of data capture and storage mechanisms following specimen testing involving CMV and /spl betasub 2/-M immunoassays using Abbott's IMx system. >

Many students feel that typical chemistry exams do not accurately reflect their comprehension of subject matter. These authors look at possible alternatives in providing more accurate evaluations.

There is widespread ambiguity concerning the theoretical definitions and everyday practical applications involving the terms: triple point, melting point, freezing point, and freezing point depression.