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Biomedical subjects

R Alvarez

Publications and source records attributed to R Alvarez.

At least 217 records · Page 12Linked to original sources

Electrochemical evaluation of the interaction between ascorbic acid and the cardiotonic drug RS-82856.

The solution phase interaction between ascorbic acid and the cardiotonic drug N-cyclohexyl-N-methyl-4(7-oxy 1,2,3,5-tetrahydroimidazol[2,1-b] quinazolin-2-one butyramide (RS-82856) was evaluated using a differential pulse voltammetric technique. Shifts in the peak potential of ascorbic acid to higher energy as well as decreases in peak current values were monitored as a function of RS-82856 concentration. The electrochemical data were obtained under conditions where both the drug and the ascorbic acid concentrations exhibited linear relationships with peak current values. The methodology was extended to the study of two other structurally related phosphodiesterase inhibitors cilostamide and anagrelide. The complexation of these drugs with ascorbic acid were also characterized by decreases in the diffusion currents of ascorbic acid as well as by anodic shifts in the peak potential. The significance of these observations may be related to the inhibition of cyclic nucleotide phosphodiesterase activity by both the drugs tested and the ascorbic acid.

3',5'-Cyclic-AMP Phosphodiesterases↗

Changes in body composition and serum lipid fractions after four weeks of slimming treatment: results in nineteen obese male adolescents.

The changes in body composition and in serum levels of total cholesterol (T-chol), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), very low plus low density lipoprotein cholesterol (VLDL + LDL-C), the ratio T-chol/HDL-C and non esterified fatty acid (NEFA) were studied in nineteen obese male adolescents after 28 days of slimming treatment which consisted in hypoenergetic diet and exercise. Relative fat body weight (%BF) was calculated by Parizková and Roth's regression equations for five fatfolds and lean body weight was obtained as the difference between body weight and fat body weight. Significant reductions in %BF, T-chol and T-chol/HDL-C ratio were found. The decrease in TG was not significant but had a better correlation with the reduction of adiposity (delta %BF) than the previously mentioned two variables. The increase of lipolysis during the four weeks of study is expressed in the significant rise of NEFA and its correlation (r = -0.714) with delta %BF. A tendency to increase in HDL-C could be observed, and a significant inverse correlation (r = -.804) with delta %BF was found. The results obtained showed that the combination of diet and exercise for treating obesity in adolescents influences favourably the risk factors of ischaemic heart disease related to serum lipid and lipoprotein profiles and does not significantly affect lean body mass, at least up to four weeks.

Adolescent↗

The cerebellum of the dogfish, Scyliorhinus canicula: a quantitative study.

This quantitative study on neuron populations of the dogfish cerebellum reveals noticeable differences in cell size and density between its portions. A remarkable result was the large proportion of granule, Golgi and stellate cells as regards to the Purkinje cells, with some values higher than in many mammals. These results indicate that the complexity level of this Selachian cerebellum is not far from cerebella of some primitive mammals.

Animals↗

Prostanoid inhibition of canine parietal cells.

Cellular mechanisms underlying the anti-secretory actions of the prostaglandin E2 analogue enprostil were studied using enzyme-dispersed, elutriator-enriched canine parietal cells and the accumulation of the weak base 14C-labeled aminopyrine as a functional index. Enprostil inhibited the accumulation of aminopyrine stimulated by histamine and the phosphodiesterase inhibitor isobutylmethyl, but not by carbachol, gastrin, or dibutyryl cyclic adenosine monophosphate. Inhibition by enprostil was dose-dependent (0.1 nM to 1 microM), with maximal inhibition ranging from 65 to 95 percent. Over the same concentration range, enprostil inhibited the histamine-stimulated generation of cyclic adenosine monophosphate. This selective inhibition of histamine activation of parietal cell function was comparable to that found for prostaglandin E2. Forskolin, a diterpene that directly activates the catalytic subunit of adenylate cyclase, was also markedly inhibited by nanomolar concentrations of prostaglandin E2 and enprostil. We conclude that at least a component of the secretory inhibition by enprostil reflects direct interference with histamine stimulation of parietal cell adenylate cyclase.

1-Methyl-3-isobutylxanthine↗

External fixation of the foot and ankle.

The use of Hoffmann external fixation in the treatment of ankle and foot trauma in 26 patients is reviewed. There were 21 males and five females, ranging in age from 14 to 56 years. There were 22 fresh fractures and four arthrodeses. Fourteen of the 22 injuries were open fractures. Eight of 22 involved foot joint disruptions. This form of treatment required a complete set of external fixation equipment, sound knowledge of foot and ankle anatomy, and technical skill in frame construction and application. This fixateur allowed three plane stabilization of complex fractures, mobilization of unaffected joints, and access to wounds for soft tissue care. Follow-up evaluations from 24 to 48 months demonstrated good clinical results. The fractures healed and soft tissue and joint function were preserved. The arthrodeses fused. There were no neurovascular complications, pin tract infections, or equipment breakage. Foot trauma frequently combines soft tissue injury and complex skeletal instability, which makes external fixation particularly attractive. Although ideal indications for the use of this technique have not yet been determined, the theoretical advantages and initial results are encouraging. External fixation is a useful addition to the treatment armamentarium of the foot surgeon.

Adolescent↗

A potent and selective inhibitor of cyclic AMP phosphodiesterase with potential cardiotonic and antithrombotic properties.

Some biochemical and pharmacological properties of a novel, potent inhibitor of cyclic AMP phosphodiesterase, N-cyclohexyl-N-methyl-4-(7-oxy-1,2,3,5-tetrahydroimidazo[2,1-b] quinazolin-2-one) butyramide (RS-82856), were investigated. RS-82856 selectively inhibits the high affinity form of cyclic AMP phosphodiesterase (type IV) isolated from human platelets (Ki = 0.5 nM) with only weak effects on both the nonspecific and cyclic GMP-sensitive phosphodiesterases. The inhibitor reduces both maximum velocity and substrate affinity of the type IV enzyme. This mixed pattern of partial competitive and noncompetitive inhibition was also obtained with one of the two high affinity forms of phosphodiesterase found in dog heart (Ki = 0.75 nM). Of several human and dog tissues examined, RS-82856 exhibits marked selectively for the platelet high affinity enzyme. It also has significant inhibitory effects on cardiac membrane-bound phosphodiesterase. RS-82856 inhibits the aggregation of human platelets in response to adenosine 5'-diphosphate (IC50 = 0.11 microM) in vitro and is active ex vivo for at least 2 hr following oral administration (10 mg/kg) to rhesus monkeys. Administration of RS-82856 to instrumented, anesthetized dogs by either intravenous or intraduodenal routes increases cardiac contractile force and reduces afterload. These data suggest that RS-82856 may be useful as an agent to increase cardiac output in the treatment of congestive heart failure.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Not Available].

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France↗

On the identification and biological properties of prostaglandin J2.

Prostaglandin D2 spontaneously decomposes at physiological pH and temperature to 9-deoxy-delta 9-PGD2 (designated PGJ2). We developed a TLC procedure for the isolation of PGJ2 which was identified by both proton-NMR and mass spectrometry. Freshly prepared PGJ2 was active in inhibiting aggregation induced by ADP in citrated human platelet rich plasma. As reported by Fukushima et al. (1). PGJ2 was less active (x 0.1-0.25) than PGD2 as an inhibitor. Concentrations of PGJ2 that markedly inhibited aggregation of human platelets were generally incapable of inhibiting aggregation of rat or guinea pig platelets. Using a heterologous system of human platelets mixed with guinea pig plasma samples (2), it was shown that the ability of PGJ2 to inhibit platelet aggregation was lost immediately following intravenous injection in anesthetized guinea pigs. This apparent rapid uptake and/or degradation of PGJ2 might also explain why PGJ2 had no effect on blood pressure of anesthetized guinea pigs. PGJ2 was potent in inhibiting proliferation of cultured vascular smooth muscle cells, mouse melanoma cells and mouse fibroblasts. Less potent anti-proliferative effects were seen with two other degradation products of PGD2, one of which was the delta 12 metabolite reported (3,4) to be formed from PGJ2 in a reaction catalyzed by serum albumin.

Adenosine Diphosphate↗

An implementation of dual energy CT scanning.

We have described a prereconstruction method for dual energy (PREDECT) analysis of CT scans. In theory, this method can (a) eliminate beam hardening and produce an accuracy comparable with monoenergetic scans and (b) provide the effective atomic number and electron density of any voxel scanned. Our implementation proves these statements and eliminates some of the objectionable noise. We constructed a phantom with a cylindrical sleeve-like compartment containing known amounts of high atomic number material simulating a removable skull. Conventional scans, with and without this beam hardener, were done of a water bath containing tubes of high electron and high atomic number material. Dual energy scans were then done for PREDECT. To increase the effective separation of the low and high energy beams by using more appropriate tube filtration, we fabricated a beam filter changer containing erbium, tungsten, aluminum, and steel. We used erbium, tungsten, and steel at high energy and aluminum, steel, and erbium at low energy for data acquisition. The reconstructions were compared visually and numerically for noise levels with the original steel only filtration. We found a decrease in noise down to approximately one-half the prior level when erbium/aluminum or tungsten/aluminum replaced the steel/steel filter. Erbium and tungsten were equally effective. Steel/erbium and steel/aluminum also significantly reduced image noise. The noise in the photoelectric (P) and Compton (C) images is negatively correlated. At any pixel, if the noise is positive in the P image, it is most probably negative in the C. Using this fact, the noise was reduced by postreconstruction processing.

Humans↗

[Not Available].

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Genetics↗

[Differentiation among species of the genus Azospirillum].

To replace the Spirillum lipoferum denomination (2) for the nitrogen fixing group of soil spirilla, the Azospirillum genus has been created in recent years (12), which includes two species: A. lipoferum and A. brasilense. Both of them are nitrogen fixing bacteria able to induce a specific infection of grass roots (1, 6). Consequently it is important to differentiate correctly the species when plant-bacteria relationships must be studied or inoculation assays must be carried out. For this reason the response of 20 strains of Azospirillum to the classification tests will be described. Microorganisms were isolated from washed plant roots (Table 1) by similar methods to those described by Döbereiner et al. (5). NFb medium was used replacing the micronutrients with 0.05 g/l of yeast extract, which gave better results. For easily identification of Azospirillum colonies, Congo Red was added to the medium (11). Morphology, motility and type of colonies were typical of Azospirillum (1, 3, 4). Nitrogenase activity ranging from 7 to 57 nM C2H2/ml of culture medium/h, according to strain, was detected in all strains pure cultures, by a colorimetric ethylene determination (8). Differentiation tests were performed by Tarrand et al. method (12) (Table 2). Four strains were classified as A. lipoferum and 9 as A. brasilense. Five were A. brasilense-like organisms unable to grow in, a biotin-free medium. As these five strains have been isolated in a medium containing biotin (yeast extract), they might be A. brasilense mutants which have lost the biotin synthesizing capacity. The last two organisms could not be classified and a DNA study should be done to determine whether they belong to any of the Azospirillum species known (7, 10, 13). The results obtained show that to achieve a correct classification of Azospirillum strains (6, 9), all known tests should be performed.

Bacterial Proteins↗

[Isolation of atmospheric-nitrogen-fixing spirilla from the waters of the Paraná delta and other rivers].

Seventeen strains of Spirillum-like organisms (2) were isolated from the Parana Delta and other rivers (Table 1), using the following medium: 0.5% malic acid; 0.4% KOH; 0.5% K2HPO4; 0.005% yeast extract; pH was adjusted to 7 with KOH and 0.15% agar. The organisms produced a white, dense and sub-superficial pellicle in this medium, and streaking them on plates, single colonies could be isolated. They were easily recognized thanks to the Congo red added to the medium, because the bacteria, as it happens with Azospirillum species (6) (Spirillum lipoferum) (1), concentrated the strain. Using a colorimetric determination for ethylene (5), nitrogenase activity was detected in all the strains and in the NFb and potato-agar media the colonies were typical of Azospirillum (3). In PSS-semisolid and solid media, the growth was similar to that observed with Azospirillum strains. The isolated organisms developed in this medium better at 28 degrees C than at 37 degrees C, and the same was observed with 8 strains of Azospirillum isolated from plan roots of different species obtained from temperate regions. Some physiological tests were performed to identify the isolated organisms (Table 2). None of the isolated strains could be classified as a known species of Spirillum (4, 7), according to these tests. As thirteen strains showed properties in common with the terrestrial species A. brasilense and the others with A. lipoferum (8) they were tentatively identified as members of these species. Further studies are needed to ensure the classification of these strains and to determine the importance of these bacteria in the nitrogen balance of the waters from where they were isolated.

Argentina↗

Radiosensitization by derivatives of isoindole-4,7-dione.

New derivatives of isoindole -4,7-dione have been synthesized and their radiation sensitization and chemical behavior have been studied. One-electron reduction potentials have been determined by pulse radiolysis and found to be in the range of -0.45 to -0.36 V vs NHE . Radiosensitization effects were tested in vivo using soft tissue sarcoma transplanted in mice. All the isoindole -4,7-diones tested were found to exert considerable radiosensitization, approaching that of misonidazole tested under comparable conditions. The derivatives which contain a carbethoxy group on the pyrrolic ring were found to have more positive reduction potentials and to act as more efficient sensitizers. Further development of this class of radiosensitizers is underway.

Animals↗