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Biomedical subjects

R Otero

Publications and source records attributed to R Otero.

At least 37 records · Page 2Linked to original sources

Hexachlorocyclohexanes in human blood serum.

A simplified method allowing the determination of trace concentrations (ng/ml) of hexachlorocyclohexanes in human sera suitable for the analysis of large numbers of samples has been developed. Comparison of acid (conc. H2SO4,) and basic (5 M KOH) digestion has shown that good recoveries are obtained with the former when an internal standard, 1,2,4,5-tetrabromobenzene (TBB), is used to correct for volatilization losses. Good separation between alpha-, beta- and gamma-HCH isomers, TBB, hexachlorobenzene and some interfering compounds is obtained with DB-5 columns. The use of electron-capture detection (ECD) or negative ion chemical ionization mass spectrometry (NICI-MS) in the selected ion monitoring mode (m/z 71) provides sufficient sensitivity for quantitative determination. ECD is the most sensitive method for beta-HCH and NICI-MS for the other isomers. GC-NICI-MS is needed for the unambiguous determination of delta-HCH due to the coelution with one interfering compound. The method has been successfully applied to the analysis of a series of 625 samples collected in a population situated near the effluents of an organochlorinated solvent factory. The results have shown that beta-HCH is selectively accumulated in human sera and prompt to the preferential investigation of the toxic effects of this isomer in humans and mammals.

Gas Chromatography-Mass Spectrometry↗

Elastase contributes to antigen-induced mucociliary dysfunction in ovine airways.

Antigen-induced bronchoconstriction is associated with impairment of mucociliary clearance with a time course that is consistent with the initial influx of neutrophils into the airway. In this study we tested the hypothesis that elastase released from activated neutrophils contributes to the acute (0 to 6-hr) antigen-induced mucociliary dysfunction. Tracheal mucous velocity CTMV), an index of mucociliary function, was measured with a roentgenographic technique before and serially after airway challenge with Ascaris suum antigen alone, or after pretreatment with aerosolized alpha1-protease inhibitor (alpha1-PI, 10 mg) or the specific neutrophil elastase inhibitor ICI 200,355 (10 mg). Antigen alone significantly decreased TMV. Treatment with either alpha1-PI or ICI 200,355, given either at 30 min before antigen challenge or 1 h after challenge, significantly attenuated the antigen-induced reduction in TMV at 6 h after challenge, whereas sheep treated with inactivated alpha1-PI were not protected from this antigen-induced event. Inhalation of ovine elastase (obtained from stimulated neutrophils) significantly decreased TMV, and this effect was also blocked by pretreatment with alpha1-PI. Both alpha1-PI and ICI 200,355 inhibited the activity of elastase obtained from stimulated ovine neutrophils. To verify that the neutrophil numbers and elastase activity increased in sheep airways after antigen challenge, nine animals underwent bronchoalveolar lavage (BAL) at 2 h and 4 h after instillation of A. summ antigen. Four hours after challenge, the number of neutrophils had increased by 50-fold, and free elastase activity in lavage fluid had increased. These data indicate that the antigen-induced impairment of mucociliary clearance is partly dependent on increased elastase activity, and that elastase inhibitors may be useful in protecting against mucociliary dysfunction.

Allergens↗

Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population.

Serum and urine from 100 subjects of a general population highly exposed to airborne hexachlorobenzene (HCB) were analyzed to obtain new insights into the metabolism of this ubiquitous compound. HCB was detected in all serum samples with concentrations ranging between 1.1 and 953 ng/ml. The major known metabolites of HCB were investigated in urine collected over 24 hr. Pentachlorophenol (PCP) was detected in all urines with values ranging between 0.58 and 13.9 micrograms excreted in 24 hr [mean +/- standard deviation (SD), 2.52 +/- 2.05; geometric mean, 2.05]. A sulfur derivative that, after hydrolysis, yielded pentachlorobenzenethiol (PCBT) could also be identified and quantified in all the urines with values ranging between 0.18 and 84.0 micrograms of PCBT excreted in 24 hr (mean +/- SD, 3.47 +/- 10.8; geometric mean, 1.39). The sulfur derivative assessed as PCBT appeared to be the main metabolite, with urinary concentrations surpassing those of PCP in the subjects with higher HCB accumulation (HCB in serum > 32 ng/ml). PCBT concentration in urine collected over 24 hr showed a very strong association with HCB concentration in serum; the association was stronger in males than in females. An increase of 1 ng/ml of HCB in serum led to an increase of 2.12 micrograms of PCBT excreted in urine collected over 24 hr in males (95% CI, 1.82-2.44) and to an increase of 0.67 microgram of PCBT in females (CI, 0.33-1.09). A weaker association was found between PCP in urine and HCB in serum, which was only statistically significant in males (an increase of 1 ng/ml of HCB in serum led to an increase of 0.63 microgram of PCP excreted in urine collected over 24 hr; (CI, 0.34-0.95). These results show that the formation of the cysteine conjugate is a quantitatively more important metabolic pathway in humans than the formation of PCP. Moreover, the association found suggests that PCBT is a good urinary marker of HCB internal dose and glutathione-mediated metabolism.

Air Pollutants↗

Endothelin-1 depresses tracheal mucus velocity in ovine airways via ET-A receptors.

Endothelin-1 (ET-1) is a potent constrictor of bronchial smooth muscle, but there is limited information on its actions on the airway mucociliary clearance in vivo. The purpose of this study was to determine (1) the effect of aerosolized ET-1 on tracheal mucus velocity (TMV), a marker of mucociliary clearance, in sheep and (2) if the ET-1-induced effects were mediated by ET-A or ET-B receptors. To measure TMV, radiopaque teflon particles were insufflated into six intubated, spontaneously breathing, adult sheep, and the velocity at which these particles traveled up the trachea was measured using a previously reported roentgenographic technique. After baseline TMV measurements, 50 breaths of either ET-1 (10(-7) M) or vehicle (phosphate-buffered saline) were aerosolized into the airways. TMV measurements were then obtained over a 2-h period. After exposure to ET-1, mean TMV decreased significantly as compared with vehicle, the effects being most marked within 30 min after administration (54%, p < 0.05). On subsequent days, animals were pretreated with an aerosolized ET-A receptor antagonist (BQ-123) or an ET-B receptor antagonist (BQ-788) before exposure to ET-1. When ET-1 was given after BQ-123, no significant drop in TMV was noted. In contrast, pretreatment with BQ-788 exhibited no protective effect on the decrease in TMV. The ET-1 effects were not influenced by pretreatment with either the cyclo-oxygenase inhibitor indomethacin or the leukotriene receptor antagonist MK-571, indicating that ET-1-induced depression in TMV does not involve the activation of prostanoids or peptide leukotrienes. Thus, exogenous ET-1 reduces TMV, an in vivo effect that is mediated through stimulation of ET-A receptors.

Aerosols↗

Ability of six Latin American antivenoms to neutralize the venom of mapaná equis (Bothrops atrox) from Antioquia and Chocó (Colombia).

This investigation compared the ability of six Latin American antivenoms (monovalent antibothropic INS, Santafé de Bogotá; polyvalent INS; polyvalent probiol, Santafé de Bogotá; antibothropic Instituto Butantan, IB, São Paulo, Brazil; polyvalent Instituto Clodomiro Picado, ICP, San José, Costa Rica; polyvalent MYN, Mexico) to neutralize various pharmacological and enzymatic effects of Bothrops atrox venom from Antioquia and Chocó, north-west of Colombia. Our results demonstrated conspicuous differences in the ability of the six antivenoms. In terms of neutralization of lethality, the highest efficacy was observed in the polyvalent INS and the lowest in the polyvalent MYN antivenom. All antivenoms were highly effective in the neutralization of hemorrhage, polyvalent INS and probiol being the highest. In the neutralization of edema-forming activity, the most effective antivenom was the polyvalent (ICP); monovalent (INS) and polyvalent (MYN) were the least effective. All antivenoms were effective in the neutralization of the myotoxic activity of B. atrox venom, the most effective being the polyvalent (INS) and antibothropic (IB). Defibrinating activity was neutralized by all antivenoms; polyvalent (MYN) showed the lowest efficiency. Polyvalent (ICP) antivenom had the highest neutralizing ability against the indirect hemolytic effect of B. atrox venom; polyvalent (MYN) did not neutralize this enzymatic activity. Overall, the polyvalent antivenom (INS) showed the highest neutralizing ability.

Animals↗

Physiological mechanisms regulating the conversion of selenite to elemental selenium by Bacillus subtilis.

We have demonstrated that the common soil bacterium, Bacillus subtilis, reduces selenite to an insoluble and much less toxic product--the red form of elemental selenium. Reduction was effected by an inducible system that appears to deposit elemental selenium between the cell wall and the plasma membrane. Glucose and sucrose supported selenite reduction. Although malate and citrate supported growth, no significant reduction of selenite occurred, indicating the importance of the redox state of the culture substrate. Selenite reduction in the millimolar concentration range (i.e., cultures supplemented with 1 mM selenite) was not affected by a ten-fold excess of nitrate or sulfate--compounds that serve as alternate electron acceptors and antagonize selenite reduction by anaerobic bacteria. Similarly, nitrite and sulfite did not significantly affect the rate or extent of selenite reduction. B.subtilis was able to grow and produce selenium (Se degree) at selenite concentrations ranging from 0.6 microM to 5 mM (50 ppb to 395 ppm selenium). At the lowest selenite concentration tested, 50 ppb selenium, B.subtilis removed 95% of the selenite from the liquid phase. The results suggest that selenite is reduced via an inducible detoxification system rather than dissimilatory electron transport. The findings establish the potential utility of B.subtilis for the bioremediation of selenite-polluted sites.

Bacillus subtilis↗

Internal fixation of ulnar fractures by locking nail.

Fractures and dislocations of the forearm are commonly observed in trauma clinics. With time, there will probably be significant increases in fractures of the forearm associated with traffic and sports. The efficacy of the treatment of ulnar fractures by a new locking nail, developed by Lefevre in Strasbourg, was tested in 20 patients. The fractures were severely displaced ulnae or both bones of the forearm. The minimum follow-up period was six months. The average age of the patients was 33.5 years (range, 14-77 years). The nail is placed into the ulna proximally. Locking is achieved by two screws placed at the proximal and distal end of the nail. The healing time for the fractures of both bones of the forearm ranged from 75 days to 20 weeks, with an average of 15 weeks. Healing time for the ulnar fractures ranged from eight to 20 weeks, with an average of ten weeks. The advantages of this nail were easy closed technique, compression effects at the fracture site, and enough stability so that an external support and tourniquet, in isolated ulnar fractures, were not necessary.

Adolescent↗

[An experimental evaluation of a splenic autograft in the greater omentum].

This report comprises a study of splenic autotransplantation in omental pouches in rats. Twenty six rats were operated. The spleen (50%) was transplanted after splenectomy in four different fragments. The animals were re-explored after periods between 3 and 5 1/2 months and the splenic implants retrieved for histological examination as well as size and weight evolution. In 25/26 animals a viable spleen was identified. The mean weight of the retrieved spleen fragments was 150 mg versus 525 mg weight of the implanted materials. In no case there was an increase in size of the implanted fragments. Fifty-two of the 104 implanted fragments were retrieved with weight increase in 8.65% of them.

Animals↗

[Inflammatory pseudotumor of the lung: presentation of 2 cases, one of them endobronchial].

Inflammatory pseudotumor (IP) is a rare pathological entity. Although, the pulmonary affection is the most frequent, any other organ can be involved. Its etiopathology is unknown. The disease is considered as a reactive process constituted by chronic inflammatory elements and a benign behavior. The lack of a specific clinical setting and the low profitability of the bloodless techniques makes mandatory the thoracostomy for a definitive diagnosis. We report two cases of pulmonary IP. One of them with an endobronchial localization which is a infrequent variety, scantily reported in the medical literature. We discuss the clinical and etiopathologic aspects of this rare pathological entity.

Adolescent↗

Isolation of basic myotoxins from Bothrops moojeni and Bothrops atrox snake venoms.

Three myotoxins, one from the venom of Bothrops atrox and two from the venom of B. moojeni, were isolated by ion-exchange chromatography on CM-Sephadex C-25. The three toxins are basic proteins with an estimated mol. wt of about 13,500, and similar amino acid compositions. When injected into the gastrocnemius muscle of mice, the three toxins induce drastic myonecrosis of rapid onset, as judged by histological observation and quantitation of plasma creatine kinase levels. B. atrox myotoxin also has phosphlipase A2 and anticoagulant activities, whereas B. moojeni myotoxins I and II lack these effects. The three toxins are antigenically similar to each other, and to previously isolated myotoxins I and II from the venom of B. asper, when tested by gel immunodiffusion against rabbit antiserum to B. asper myotoxin I. Two monoclonal antibodies against B. asper myotoxins were tested against the newly purified proteins. MAb-3 recognizes all of them, whereas MAb-4 recognizes only B. atrox myotoxin, by enzyme-immunoassay. B. atrox and B. moojeni myotoxins can be tentatively classified within a group of myotoxins having phospholipase A2 structure present in Bothrops venoms.

Amino Acids↗

[Pharmacologic and enzymatic effects of snake venoms from Antioquia and Choco (Colombia)].

We compared several pharmacological and enzymatic effects induced by 11 snake venoms from seven species, six of them from different geographic areas of Antioquia and Choco, north-west of Colombia, South America (Bothrops atrox, B. nasutus, B. schlegelii, B. punctatus, Lachesis muta, Micrurus mipartitus), and Crotalus durissus terrificus venom, from specimens captured in other provinces of the country (Tolima, Huila, Meta and Atlantico). Differences were observed in edema-forming, hemorrhage, defibrination, indirect hemolysis, myonecrosis, proteolysis and lethal activity between venoms from different genera or species, as well as according to the geographic area of origin in B. atrox and B. nasutus snake venoms. Bothrops venoms, in particular B. atrox and L. muta, produced major local effects. All of the venoms, including M. mipartitus, had myotoxic effects. The most defibrinating venoms were B. atrox, L. muta, B. punctatus and C. d. terrificus. All of the venoms had indirect hemolytic activity; the venom of M. mipartitus being greatest. The most lethal venoms were those of C. d. terrificus and M. mipartitus. Within Bothrops species, the venom of B. schlegelii was the least active in terms of local and systemic pathologic effects.

Animals↗