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Biomedical subjects

M C Theodorakis

Publications and source records attributed to M C Theodorakis.

18 recordsLinked to original sources
PubMed1985

Amino acid derived latent isocyanates: irreversible inactivation of porcine pancreatic elastase and human leukocyte elastase.

Several amino acid derived azolides (I) have been synthesized and investigated for their inhibitory activity toward human leukocyte elastase and porcine pancreatic elastase. The inhibitory activity was found to be dependent on the nature of the precursor amino acid ester. Thus, compounds derived from L-valine methyl ester 3, L-norvaline methyl ester 5, DL-norleucine methyl ester 9, and L-methionine methyl ester 10 were found to inhibit irreversibly both enzymes. Compound 10 was found to be a specific and selective inhibitor of human leukocyte elastase. In contrast to these, inhibitors derived from glycine methyl ester 1, D-valine methyl ester 4, and D-norvaline methyl ester 6 were found to be inactive. The results of the present study show that latent isocyanates derived from appropriate amino acids can serve as selective inhibitors of serine proteases and are of potential pharmacological value.

Amino Acids↗
PubMed1984

Synthesis and antitumor activity of some aromatic seleno lactones.

Several aromatic seleno lactones have been synthesized and shown to possess significant inhibitory activity against human colon tumor-8r cells in culture at concentrations lower than 1 mM. Although all of the compounds tested were found to be active, 5-hydroxy-3-[(phenylseleno)methyl]hydrocoumarinoctanoate (3d) and 5-hydroxy-3-[(phenylseleno)methyl]hydrocoumarindecanoate (3e) were found to be the most effective in inhibiting cell growth. In situ formation of the corresponding alpha-methylene lactones is postulated to account for the cytotoxic activity in this class of compounds.

Antineoplastic Agents↗
PubMed1983

External scintigraphy in monitoring the behavior of pharmaceutical formulations in vivo I: technique for acquiring high-resolution images of tablets.

A new method for monitoring tablet disintegration in vivo was developed. In this method, the tablets were labeled with a short-lived radionuclide, technetium 99m, and monitored by a gamma camera. Several innovations were introduced with this method. First, computer reconstruction algorithms were used to enhance the scintigraphic images of the disintegrating tablet in vivo. Second, the use of a four-pinhole collimator to acquire multiple views of the tablet resulted in high count rates and reduced acquisition times of the scintigraphic images. Third, the magnification of the scintigraphic images achieved by pinhole collimation led to significant improvement in resolution. Fourth, the radioinuclide was incorporated into the granulation so that the whole mass of the tablet was uniformly labeled with high levels of activity. This technique allowed the continuous monitoring of the disintegration process of tablets in vivo in experimental animals. Multiple pinhole collimation and the labeling process permitted the acquisition of quality scintigraphic images of the labeled tablet every 30 sec. The resolution of the method was tested in vitro and in vivo.

Computers↗
PubMed1982

Systemic and regional blood flow distribution in unanesthetized swine and swine anesthetized with halothane + nitrous oxide, halothane, or enflurane.

In order to study the distribution of cardiac output during various anesthetic regimens, we measured regional organ blood flow using 15 micrometers diameter radionuclide-labeled microspheres injected into the left atrium. Studies were carried out in nine pigs during resting unanesthetized state (control), during halothane (inspired concentration = 1.25 per cent) + nitrous oxide (50 per cent) anesthesia, during halothane (inspired concentration = 2.25 per cent) anesthesia, and during enflurane (inspired concentration = 4.0 per cent) anesthesia. The order of the last two treatments [halothane (2.25 per cent) and enflurane (4.0 per cent)] was randomized among the nine pigs. All anesthetic steps employed intermittent positive-pressure ventilation to maintain PaCO2 close to control values. Animals were allowed to recover towards the control state before changing to the next anesthetic regimen. Forty-five minutes were allowed for equilibration with each anesthetic regimen before hemodynamic measurements were made. In unanesthetized resting swine blood flow received by brain, cardiac ventricles, kidneys, liver (via hepatic artery), gastrointestinal tract, and skeletal muscle was 63.70 +/- 5.56, 128.56 +/- 14.92, 280.89 +/- 19.72, 21.95 +/- 3.25, 148.55 +/- 15.29 and 13.76 +/- 4.12 ml . min-1 . 100 g-1, respectively (mean +/- SEM). Corresponding values for the percentage of cardiac output received by the brain, cardiac ventricles, kidneys, liver (via hepatic artery), and gastrointestinal tract were 1.13 +/- .08, 3.04 +/- 0.13, 12.95 +/- 1.54, 4.27 +/- 0.76, and 18.71 +/- 0.91 per cent, respectively. Cardiac output and mean arterial blood pressure decreased significantly from control values with each of the three anesthetized steps. The decrease in cardiac output was greatest with the halothane anesthesia and least with halothane + N2O. Blood flow per unit weight of the cardiac, renal, and splanchnic tissues decreased significantly with each anesthetic regimen whereas brain blood flow and hepatic arterial blood flow were unaltered from control values. Thus, the per cent cardiac output received by the brain had increased with halothane (119 per cent) and enflurane (102 per cent) anesthesia while it was unaltered from the heart, renal, and splanchnic organs. Percentage of total cardiac output received by liver via the hepatic artery increased by 162 per cent during halothane anesthesia and 133 per cent during enflurane anesthesia, when compared to control values. During halothane + nitrous oxide anesthesia, the per cent of cardiac output going to the brain was not increased significantly. It is concluded that cardiac output as well as individual organ/tissue blood flow was better maintained during halothane + nitrous oxide anesthesia in comparison to halothane or enflurane anesthesia.

Animals↗
PubMed1982

Regional myocardial blood flow and coronary vascular reserve in unanesthetized young calves exposed to a simulated altitude of 3500 m for 8--10 weeks.

We determined regional myocardial blood flow (15-micrometer tracer microspheres) and hemodynamics in nine normal calves, seven calves with right ventricular (RV) hypertrophy induced by pulmonary artery banding (PAB) at sea level, and five calves exposed to simulated high altitude (HA) of 3,500 m (PB = 500 mm Hg) for 8--10 weeks. Progression of RV hypertrophy was very rapid in HA calves. RV weight:body weight ratio of 2.74 +/- 0.20 g/kg at 8--10 weeks of sojourn at HA significantly exceeded that in PAB calves (1.98 +/- 0.11 g/kg) 20 weeks post-banding. All calves were studied unanesthetized at sea level before (control) and during maximal coronary vasodilation (iv adenosine; 4 microM/kg per min). Normal and HA calves were also studied during acute hypoxemia (PaO2: 42 +/- 1 mm Hg) induced by administration of 12--13% O2 + N2 in the inhaled gas. RV myocardial blood flow was significantly increased only in PAB calves, whereas in HA calves it was similar to that in normal calves. Left ventricular (LV) mass and blood flow were identical in three groups of calves. Polycythemia did not occur in HA calves. Minimal coronary vascular resistance per unit weight of the hypertrophied RV was identical to that in the normal RV myocardium. This suggested that, despite very fast progression of RV hypertrophy in HA calves, functional cross-sectional area of the RV coronary vascular bed kept pace with the increase in cardiac mass. Minimal coronary vascular resistance per unit weight of the left ventricular myocardium was also identical in three groups of calves. This suggested that chronic hypoxemia by itself did not cause an increase in the functional cross-sectional area of the LV coronary vascular bed. Acute hypoxemia resulted in a significant increase in myocardial blood flow in all calves, but in HA calves, RV endo:epi perfusion ratio decreased below 1.00. Transmural RV myocardial blood flow and RV systolic pressure in HA calves during acute hypoxemia significantly exceeded that in normal calves.

Altitude Sickness↗
PubMed1982

Organ blood flow and distribution of cardiac output in nonanesthetized swine.

Organ blood flow and distribution of cardiac output (CO) were determined in awake resting swine, using radionuclide-labeled 15-micrometer diameter microspheres. Absolute values of blood flow (per 100-g basis) were determined for various organs and peripheral tissues. Internal organs of the swine, which constituted 8.25 +/- 0.79% of the total body mass, received 45.46 +/- 2.64% of the resting CO. The fraction of CO received by brain, heart, kidneys, liver (via hepatic artery), and gastrointestinal tract was 1.13%, 3.04%, 12.95%, 4.27%, and 18.71%, respectively.

Animals↗
PubMed1982

Tc-99m-labeled polystyrene and cellulose macromolecules: agents for gastrointestinal scintigraphy.

Several polystyrene resin and cellulose derivatives were evaluated for potential use as Tc-99m-labeled particulate markers for studies of gastric emptying and intestinal transit time, and for imaging segments of the gastrointestinal tract. The polyamine and quaternary ammonium polystyrene resins bound pertechnetate (Tc--99m) anions effectively; the labeling efficiency was over 95% at physiological pH values. In-vitro stability studies of Tc-99m-labeled resins in simulated gastric and intestinal fluid showed that less than 8% of the label was released after 24 h. The commercial resins dowex 2-XB, AG 1-X2, and Bio-Rex 9, labeled with Tc-99m, may be used as particulate markers of solid digesta in external scintigraphic studies of the gastrointestinal tract. Dowex 2-X8 showed relatively more extensive uptake of pertechnetate and greater stability in simulated gastric and intestinal fluids.

Cellulose↗
PubMed1982

Liver scintigraphy in ponies.

Six derivatives of ethylenediamine-N,N'-bis (alpha-2-hydroxy phenyl) acetic acid labeled with technetium 99m were prepared and their imaging qualities evaluated in ponies. The 6 agents produced good scintigraphic images of certain structures of the liver in the pony. For each agent, 13 different scans were taken. Dorsal views of the left lateral, right lateral, and quadrate lobe were obtained with dorsal scans. Left lateral and left lateral oblique (45 degrees) scans provided a left lateral view of the left lobe and a medial view of the right lateral lobe. Right lateral scans revealed the right lateral and quadrate lobes. Administration of 99mTc-labeled colloids which are commonly used in other species for liver scintigraphy resulted in extensive lung uptake in the pony.

Animals↗
PubMed1980

Rate and pattern of gastric emptying in humans using 99mTc-labeled triethylenetetraamine-polystyrene resin.

The preparation and application of a new radiopharmaceutical used in the investigation of the rate and pattern of gastric emptying by external scintigraphy are described. Triethylenetetraamine was bound covalently to cross-linked chloromethylated polystyrene. The triethylenetetraamine-polystyrene resin tenaciously and rapidly bound technetium 99m. The gastric emptying rate was evaluated in normal adult volunteers and patients by serially recording the gastric radioactivity after ingestion of a test meal mixed with 99mTc-labeled triethylenetetraamine-polystyrene resin. The data indicated that 99mTc-labeled triethylenetetraamine-polystyrene resin was an ideal agent for assessing the rate and pattern of gastric emptying in humans. The gastric emptying half-time (t 1/2 GE) in normal subjects ranged from 25 to 75 min.

Ethylenediamines↗
PubMed1980

Localization of technetium 99m-ethylenediamine-N,N'-bis(alpha-2-hydroxy-5-bromophenyl)acetic acid and technetium 99m-N-(2-mercapto-1-oxopropyl)glycine in hepatobiliary system.

Two radiopharmaceuticals, technetium 99m-N-(2-mercapto-1-oxopropyl)glycine (99mTc-I) and technetium 99m-ethylenediamine-N,N'-bis(alpha-2-hydroxy-5-bromophenyl)acetic acid (99MTc-II), were prepared and evaluated in dogs, rabbits, and rats. Both agents gave good scintigraphic images of the liver and gallbladder in dogs. The cumulative amount of 99mTc-I and 99mTc-II excreted in the bile of dogs and the physiological disposition data in rats revealed slight, inconclusive differences in their distributions. However, the scintigraphic images and physiological disposition data in rabbits revealed gross differences in the distribution pattern of the two agents. The observed similarities in the biliary excretion of both agents in dogs and rats were attributed to the fact that these species are relatively good biliary excretors, and both agents therefore were excreted extensively. However, rabbits, which are poor biliary excretors relative to dogs and rats, excreted 99mTc-II more extensively than 99mTc-I because of the favorable molecular characteristics of 99mTc-II.

Amino Acids, Sulfur↗
PubMed1980

External scintigraphy in measuring rate of gastric emptying in beagles.

The application of external scintigraphy and preparation of a new radiopharmaceutical agent for the investigation of the rate and pattern of gastric emptying in beagles and for the visualization of segments of the intestines have been described. 99mTc-labeled triethylenetetramine-polystyrene resin was mixed in a test meal and was administered to the animal. The gastric emptying rate of the beagle was evaluated by serially recording the gastric radioactivity by means of a scintillation camera, The experimental data indicate that the pattern of gastric emptying of beagles during the first 60 min was monoexponential and the gastric emptying half time was 1.3 h. The usefulness of external scintigraphy as a noninvasive method for determining the gastric emptying rates and for visualizing segments of GI tract in animals has been demonstrated.

Animals↗