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Biomedical subjects

R García

Publications and source records attributed to R García.

At least 55 records · Page 3Linked to original sources
PubMed2001

Canines as sentinel species for assessing chronic exposures to air pollutants: part 1. Respiratory pathology.

A complex mixture of air pollutants is present in the ambient air in urban areas. People, animals, and vegetation are chronically and sequentially exposed to outdoor pollutants. The objective of this first of 2 studies is to evaluate by light and electron microscopy the lungs of Mexico City dogs and compare the results to those of 3 less polluted cities in MEXICO: One hundred fifty-two clinically healthy stray mongrel dogs (91 males/61 females), including 43 dogs from 3 less polluted cities, and 109 from southwest and northeast metropolitian Mexico City (SWMMC, NEMMC) were studied. Lungs of dogs living in Mexico City and Cuernavaca exhibited patchy chronic mononuclear cell infiltrates along with macrophages loaded with particulate matter (PM) surrounding the bronchiolar walls and extending into adjacent vascular structures; bronchiolar epithelial and smooth muscle hyperplasia, peribronchiolar fibrosis, microthrombi, and capillary and venule polymorphonuclear leukocytes (PMN) margination. Ultrafine PM was seen in alveolar type I and II cells, endothelial cells, interstitial macrophages (Mtheta), and intravascular Mtheta-like cells. Bronchoalveolar lavage showed significant numbers of alveolar macrophages undergoing proliferation. Exposure to complex mixtures of pollutants-predominantly particulate matter and ozone-is causing lung structural changes induced by the sustained inflammatory process and resulting in airway and vascular remodeling and altered repair. Cytokines released from both, circulating inflammatory and resident lung cells in response to endothelial and epithelial injury may be playing a role in the pathology described here. Deep concern exists for the potential of an increasing rise in lung diseases in child populations exposed to Mexico City's environment.

Age Distribution↗
PubMed2001

Canines as sentinel species for assessing chronic exposures to air pollutants: part 2. Cardiac pathology.

The principal objective of this study is to evaluate by light and electron microscopy (LM, EM) the heart tissues in stray southwest and northeast metropolitan Mexico City (SWMMC, NEMMC) dogs and compare their findings to those from 3 less polluted cities (Cuernavaca, Tlaxcala, and Tuxpam). Clinically healthy mongrel dogs, including 109 from highly polluted SWMMC and NEMMC, and 43 dogs from less polluted cities were studied. Dogs residing in cities with lower levels of pollutants showed little or no cardiac abnormalities. Mexico City and Cuernavaca dogs exhibited LM myocardial alterations including apoptotic myocytes, endothelial and immune effector cells, degranulated mast cells associated with scattered foci of mononuclear cells in left and right ventricles and interventricular septum, and clusters of adipocytes interspersed with mononuclear cells. Vascular changes included scattered polymorphonuclear leukocytes (PMN) margination and microthrombi in capillaries, and small venous and arteriolar blood vessels. Small veins exhibited smooth muscle cell hyperplasia, and arteriolar blood vessels showed deposition of particulate matter (PM) in the media and adventitia. Unmyelinated nerve fibers showed endoneural and epineural degranulated mast cells. EM examination of myocardial mast cells showed distended and abundant rough endoplasmic reticulum with few secretory granules. Myocardial capillaries exhibited fibrin deposition and their endothelial cells displayed increased luminal and abluminal pinocytic activity and the formation of anemone-like protrusions of the endothelium into the lumen. A close association between myocardial findings, lung epithelial and endothelial pathology, and chronic inflammatory lung changes was noted. The myocardial changes described in dogs exposed to ambient air pollutants may form the basis for developing hypothesis-driven mechanistic studies that might explain the epidemiological data of increased cardiovascular morbidity and mortality in people exposed to air pollutants.

Air Pollutants↗
PubMed2001

Inhibition of platelet activation in stroke-prone spontaneously hypertensive rats: comparison of losartan, candesartan, and valsartan.

In vitro studies have suggested that losartan interacts with the thromboxane (TxA2)/ prostaglandin H2 (PGH2) receptor in human platelets, reducing TxA2-dependent platelet activation. The aim of this study was to evaluate the effect of different angiotensin II type 1 receptor antagonists in stroke-prone spontaneously hypertensive rats (SHRSP). The level of platelet activation was assessed by determining P-selectin expression in platelets by flow cytometry. The ex vivo adhesion of platelets was also analyzed. The number of platelets that expressed P-selectin in SPSHR was significantly increased (% P-selectin expression: WKY 4 +/- 0, 4%; SHRSP 15.5 +/- 0, 8% [n = 8], p < 0.05). In SHRSP receiving losartan (20 mg/kg body weight per day) the percentage of platelets expressing P-selectin fell to levels close to that observed in WKY. The number of platelets from SHRSP treated with valsartan and candesartan (20 mg/kg body weight per day for 14 days) that expressed P-selectin was not significantly different from those from untreated SPRHR. Only losartan treatment reduced ex vivo platelet adhesion to a synthetic surface. The antiplatelet effect of losartan does not appear to be related to the level of blood pressure reduction. In ex vivo experiments, losartan significantly reduced the binding of the radiolabeled TxA2 agonist U46619 to platelets obtained from SHRSP in a dose-dependent manner. Treatment with losartan reduced the number of activated platelets in SHRSP independently of its blood pressure effects. TxA2-receptor blockade is proposed as a mechanism by which losartan can prevent platelet activation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Dextranase (alpha-1,6 glucan-6-glucanohydrolase) from Penicillium minioluteum expressed in Pichia pastoris: two host cells with minor differences in N-glycosylation.

Differences in glycosylation between the natural alpha-1,6 glucan-6-glucanohydrolase from Penicillium minioluteum and the heterologous protein expressed in the yeast Pichia pastoris were analyzed. Glycosylation profiling was carried out using fluorophore-assisted carbohydrate electrophoresis and amine absorption high-performance liquid chromatography (NH(2)-HPLC) in combination with matrix-assisted laser desorption-time of flight-mass spectrometry. Both microorganisms produce only oligomannosidic type structures, but the oligosaccharide population differs in both enzymes. The native enzyme has mainly short oligosaccharide chains ranging from Man(5)GlcNAc(2) to Man(9)GlcNAc(2), of which Man(8)GlcNAc(2) was the most represented oligosaccharide. The oligosaccharides linked to the protein produced in P. pastoris range from Man(7)GlcNAc(2) up to Man(14)GlcNAc(2), with Man(8)GlcNAc(2) and Man(9)GlcNAc(2) being the most abundant structures. In both enzymes the first glycosylation site (Asn(5)) is always glycosylated. However, Asn(537) and Asn(540) are only partially glycosylated in an alternate manner.

Amino Acid Sequence↗
PubMed2001

Ultrastructural nasal pathology in children chronically and sequentially exposed to air pollutants.

Southwest Metropolitan Mexico City (SWMMC) children are repeatedly exposed to a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Nasal biopsies taken from these children exhibit a wide range of histopathologic alterations: marked changes in ciliated and goblet cell populations, basal cell hyperplasia, squamous metaplasia, and mild dysplasias. We studied the ultrastructural features of 15 nasal biopsies obtained from clinically healthy children 4 to 15 yr of age, growing up in SWMMC. The results were compared with nasal biopsies from 11 children growing up in Veracruz and exposed to low pollutant levels. Ultrathin sections of nasal biopsies revealed an unremarkable mucociliary epithelium in control children, whereas SWMMC children showed an epithelium comprised of variable numbers of basal, ciliated, goblet, and squamous metaplastic as well as intermediate cells. Nascent ciliated cells, as evidenced by the presence of migratory kinetosomes, were common, as were ciliary abnormalities, including absent central microtubules, supernumerary central and peripheral tubules, ciliary microtubular discontinuities, and compound cilia. Dyskinesia associated with these abnormal cilia was suggested by the altered orientation of the central microtubules in closely adjacent cilia. A transudate was evident between epithelial cells, suggesting potential deficiencies in epithelial junction integrity. Particulate matter was present in heterolysosomal bodies in epithelial cells and it was also deposited in intercellular spaces. The severe structural alteration of the nasal epithelium together with the prominent acquired ciliary defects are likely the result of chronic airway injury in which ozone, particulate matter, and aldehydes are thought to play a crucial role. The nasal epithelium in SWMMC children is fundamentally disordered, and their mucociliary defense mechanisms are no longer intact. A compromised nasal epithelium has less ability to protect the lower respiratory tract and may potentially leave the distal acinar airways more vulnerable to reactive gases. Impairment of mucociliary clearance has the potential to increase the contact time between deposited mutagenic particulate matter and the epithelial surface, thus increasing the risk for nasal carcinogenesis. Chronic exposures to air pollutants affect the whole respiratory tract; the nasal epithelium is an accessible and valuable sentinel to monitor exposures to toxic or carcinogenic substances.

Adolescent↗
PubMed2001

Tachyphylaxis following regular use of formoterol in exercise-induced bronchospasm.

BACKGROUND: Formoterol is a highly effective therapeutic agent in the prevention of exercise-induced bronchospasm (EIB). Regular use of beta-adrenergic drugs may result in a reduction in the protective effect afforded by these bronchodilators against bronchoconstrictor stimuli. It is unknown whether this effect extends to formoterol and exercise. METHODS: We performed a randomized, double-blind, parallel clinical trial in 19 patients with EIB. Each patient received inhaled formoterol or placebo twice daily during 4 weeks. Patients performed two exercise tests in a cycle ergometer on the 1st, 14th, and 28th study days separated 3 hours from each other. A dose of formoterol was given 30 min prior to the 2nd test. RESULTS: There were significant differences in bronchoprotection between days 1 and 14 (p = .012) and between days 1 and 28 (p = .012) in the formoterol group. No differences were found in the placebo group. The evolution of the bronchoprotection index was also significantly different between the formoterol and the placebo group (p = .002) from day 1 to 28. CONCLUSIONS: Tachyphylaxis developed to the protective effect of formoterol against EIB after 4 weeks of regular dosing. Tolerance was already found on day 14, though not progressive. Formoterol should be recommended only as needed in EIB.

Adrenergic beta-Agonists↗
PubMed2001

[Activity of new fluoroquinolones against clinical isolates of Acinetobacter baumannii].

Acinetobacter baumannii is an opportunistic pathogen associated with numerous nosocomial infections. In recent years it has shown extraordinary ease in developing resistance to most antimicrobial agents, which is a serious problem as it makes these infections difficult to treat. We determined the in vitro activity of eight quinolones, five betalactam agents and colistin in 160 clinical isolates of A. baumannii. In general, we observed a high rate of resistance to the quinolones (90%), excluding clinafloxacin (25%), and to ampicillin-sulbactam (61.25%) and imipenem (50%). Colistin is the agent with least resistance (13.125%), although its toxicity limits its therapeutic use. Clinafloxacin may be a good option to treat A. baumannii infections, especially in cases of therapeutic failure with other antimicrobial agents.

Acinetobacter↗
PubMed2000

Binding of Escherichia coli lipopolysaccharide to fasciculata-reticularis and glomerulosa cells evaluated by flow cytometry.

Binding of Escherichia coli lipopolysaccharide (LPS) to the two cell types of the adrenal cortex: fasciculata-reticularis and glomerulosa cells has been studied by flow cytometry and using fluorescein-labeled lipopolysaccharide (FITC-LPS). The binding characteristics were different in relation to time course and number of binding sites. Both fasciculata-reticularis and glomerulosa cells bound LPS in a specific and saturable process. Fasciculata-reticularis cells showed a higher affinity for LPS binding than glomerulosa cells as deduced from Hill plots. Unlabeled LPS decreased FITC-LPS binding in both fasciculata-reticularis and glomerulosa cells, suggesting competition of both ligands for a limited number of binding sites. Lipid A seemed not to be essential for binding of LPS to fasciculata-reticularis cells. However, serum constituents inhibited FITC-LPS binding to both cell types, possibly due to cell interaction with HDL. The exposure of cells to LPS during cell culture did not modify the number of binding sites, but revealed cell size and surfaces structure changes.

Animals↗
PubMed2000

Improved capillary electrophoresis method for measuring rare-earth elements in synthetic geochemical standards.

An improved capillary electrophoresis (CE) method for quantifying rare-earth elements (REEs) in synthetic geochemical standards was developed. Synthetic standard solutions were obtained from high purity metal oxides. The separation of REE total group (lanthanum to lutetium) was defined as a primary objective. Special attention was also focused on the optimized separation of europium (Eu) and gadolinium (Gd) because in earlier applications they presented overlapping problems. Their separation and quantitative determinations are essential for geological applications. For the rapid separation of REEs in synthetic geochemical standards, the temperature of the separation device was optimized. An analysis temperature of 15 degrees C enabled both the rapid separation of REEs within 2 min and the overlapping problem of Eu-Gd to be resolved. The detection limits (<0.1 ng) and precision estimates (generally better than 5%) were found to be satisfactory for most geological applications.

Electrophoresis, Capillary↗
PubMed2000

Kinetic modelling of the synthesis of 2-hydroxy-5-hexenyl 2-chlorobutyrate ester by an immobilised lipase.

An esterification process was developed for the direct synthesis of 2-hydroxy-5-hexenyl 2-chlorobutyrate ester from 2-chlorobutyric acid by using the epoxide 1,2-epoxy-5-hexene and Mucor miehei immobilised lipase as the biocatalyst in a batch reactor. The effect of temperature, catalyst concentration, and substrate and product concentration has been studied. An ordered Bi Uni enzymatic mechanism with competitive inhibition by the epoxide and acid has been proposed. The corresponding kinetic parameters were calculated by non-linear regression. Activation energy shows a value of 8.04kcal/mol. The thermodynamic parameters of the process, enthalpy and entropy, were 15.4kcal/mol and 45cal/mol, respectively.

Journal Article↗
PubMed2000

Neuregulin found in cultured-sciatic nerve conditioned medium causes neuronal differentiation of PC12 cells.

The present work deals with the search and identification of the molecule or combination of molecules, present in a medium conditioned by cultured rat-sciatic nerves (CM), able to cause neuronal differentiation of PC12 cells. The molecular mass range of the active fraction, as well as the thermostability and heparin affinity of the active component found in previous work, all characteristics shared with neuregulin (NRG) family members, led us to search for a NRG protein in the CM. Nerves were previously cultured for 8 days and the CM collected every 24 h, the following 3 days. The CM was concentrated (30,000 NMWL) and fractionated by quaternary ammonium chromatography and Cibacron blue affinity chromatography. The most active fraction B1.2 was further characterized by heparin affinity chromatography, size exclusion HPLC, Western blotting and immunoprecipitation. Results reveal abundance of NRG mRNA in the cultured nerves, presence of a 54 kDa NRG protein in the CM that increases along fractionation, and progressive diminution of fraction B1.2 differentiation activity on PC12 cells by gradual removal of the NRG protein by immunoprecipitation. The abundance of Schwann cells and the lack of axons in the cultured nerves suggest Schwann cells as the main NRG source, to which fibroblasts and perineurial cells might contribute.

Animals↗
PubMed2000

Renal Doppler sonographic and histologic findings in post-transplant primary cytomegalovirus disease.

Cytomegalovirus (CMV) infections frequently develop in renal transplant patients. The transplanted kidney may be not only the source of infection but also the target for it. We report a case of primary CMV infection in a seronegative patient who received a graft from a seropositive cadaveric donor. The onset of CMV was clinically apparent on post-transplant day 22. Interestingly, soon after transplantation, the patient developed a long-lasting graft dysfunction episode for which diffuse endothelial-cell swelling was the most relevant finding at biopsy. On sonography, renal graft vascular impedance deteriorated and improved repeatedly during the follow-up period. We postulate that the patient had CMV-induced immunogenic-mediated endothelial-cell injury.

Adult↗
PubMed2000

Synthesis of a series of 3-cyanopropionamides and 4-imino-gamma-butyrolactams and evaluation of their function as modulators of multidrug resistance.

The synthesis of the 3-cyanopropionamides 3a and 3b, of the 2,2-dimethyl-3-cyanopropionamides 4a-4c and of the 4-imino-gamma-butyrolactams 5a and 5b (cyclic functional isomers of 3-cyanopropionamides) is described. The amides 3a and 3b were obtained by aminolysis of the corresponding acid chlorides, which are accessible via hydrolysis of the ethyl esters to the acids. This methodology was not used for the synthesis of the amides 4a-4c owing to steric hindrance to hydrolysis in the corresponding ethyl esters. These nonreactive esters, accessible by alkylation of 1-cyano carbanions with ethyl bromodimethylacetate, could be directly converted into the amides 4a-4c by aminolysis with the lithium amide of 3,4-dimethoxy-N-methylphenethylamine. Instead of open-chain amides, the lactams 5a and 5b are obtained when the lithium amide of 3,4-dimethoxyphenethylamine (i.e., of a primary rather than secondary amine) is used for the aminolysis. The synthesized compounds were tested for their ability to decrease the resistance to vincristine in a multidrug-resistant subline of murine leukemic lymphoblasts that are 300-fold resistant to the antiproliferative drug. The amides 4a and 4c, and lactam 5a, all of which have a highly branched carbon backbone, were active. Lactam 5a reduced the vincristine resistance by 90% at a 2-microM concentration.

Amides↗
PubMed2000

High-resolution imaging of antibodies by tapping-mode atomic force microscopy: attractive and repulsive tip-sample interaction regimes.

A force microscope operated with an amplitude modulation feedback (usually known as tapping-mode atomic force microscope) has two tip-sample interaction regimes, attractive and repulsive. We have studied the performance of those regimes to imaging single antibody molecules. The attractive interaction regime allows determination of the basic morphologies of the antibodies on the support. More importantly, this regime is able to resolve the characteristic Y-shaped domain structure of antibodies and the hinge region between domains. Imaging in the repulsive interaction regime is associated with the irreversible deformation of the molecules. This causes a significant loss in resolution and contrast. Two major physical differences distinguish the repulsive interaction regime from the attractive interaction regime: the existence of tip-sample contact and the strength of the forces involved.

Aluminum Silicates↗
PubMed2000

In vivo estrogen bioactivities and in vitro estrogen receptor binding and transcriptional activities of anticoagulant synthetic 17beta-aminoestrogens.

Estrogenic activities of the two 17beta-aminoestrogen (AE) derivatives, prolame and butolame, were studied upon coagulation, serum luteinizing hormone (LH) and uterine weight, including endometrial morphology in castrated female rats. We have also investigated the ability of these two compounds, as well as another AE pentolame, to activate transcription through the estrogen receptor alpha (ERalpha) and the estrogen receptor beta (ERbeta). Administration of prolame and butolame to castrated animals increased significantly (P < 0.01) the mean clotting time when compared with that obtained in the group of control animals. Butolame was a more potent anticoagulant than prolame (P < 0.01), as judged by their corresponding IC(50) (5.4 +/- 0.65 and 66.6 +/- 2.57 micro;g/animal, respectively). In contrast, estradiol significantly shortened blood clotting times (P < 0.005). Both prolame and butolame caused a significant inhibition of serum LH levels (EC(50) 8.10 +/- 0.79 and 17 +/- 64 microg/animal, respectively), and restored castration-induced reduction in uterine weight of ovariectomized rats (EC(50) 4.14 +/- 1.57 and 17.0 +/- 1.78 microg/animal, respectively). In terms of the effects of prolame, butolame and pentolame in transient transfection assays, all the three AE activated ER dependent reporter gene expression, however, only at high concentrations. Prolame had the highest activity followed by butolame and pentolame. Induction of transcription by these compounds was preferentially mediated through the ERalpha, especially in the case of pentolame where little, if any, activation occurred through the ERbeta. None of the compounds showed antagonistic activities through either ER subtype. The overall data suggest that modifications in the structure and length of the amino-alcohol side-chain at C-17 might have an impact on the affinity and estrogenic intrinsic properties of AE at the level of diverse target tissues.

Amino Alcohols↗
PubMed2000

Cytotoxic constituents of the roots of Ekmanianthe longiflora.

Bioactivity-directed fractionation of the CHCl(3) extract of the roots of Ekmanianthe longiflora resulted in the isolation of three new natural products, (2R,3R,4R)-3,4-dihydro-3, 4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone (1), (2S,3R, 4R)-3,4-dihydro-3, 4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone (2), and (2R, 3aR,9R,9aR)-9-hydroxy-2-(1-hydroxy-1-methylethyl)-2,3,3a,4,9 , 9a-hexahydro-naphtho[2,3-b]furan-4-one (3), together with the known compounds 2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-quinone (4), 2-acetylnaphtho[2,3-b]furan-4,9-quinone (5), dehydro-iso-alpha-lapachone (6), alpha-lapachone (7), catalponol, and epi-catalponol. The structures of 1-3 were determined using a combination of NMR spectroscopic techniques, and the absolute configurations of compounds 1 and 2 were obtained using Mosher ester methodology. Compounds 4-6 showed significant cytotoxicity in a panel of human cancer cells. alpha-Lapachone (7) exhibited only marginal activity, and catalponol and epi-catalponol were inactive in this regard. When tested at 72 mg/kg/injection in an in vivo mouse P-388 leukemia system, compound 4 was inactive (110% T/C).

Animals↗
PubMed2000

Allogeneic peripheral stem cell transplantation in a case of hereditary sideroblastic anaemia.

We report on a case of pyridoxine refractory hereditary sideroblastic anaemia (HSA) in a 19-year-old man who underwent peripheral blood stem cell transplantation (PBSCT) from his HLA-identical brother. By using short tandem repeat polymorphism, 100% donor cells were observed in peripheral blood on day +21; bone marrow showed mixed chimaerism from day +21 to day +221, when 100% cells of donor origin were observed. The patient developed extensive chronic graft-versus-host disease with favourable response to treatment. When the haemoglobin range was normal, a programme of phlebotomies reduced serum ferritin levels. Three years after transplantation, the patient has an ECOG rating of 0, with completely normal haemoglobin values (15 g/dl). To our knowledge, this is the first PBSCT reported in a case of hereditary sideroblastic anaemia.

Adult↗