Biomedical subjects

G Pacheco

Publications and source records attributed to G Pacheco.

At least 19 recordsLinked to original sources

PubMed1999

Effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and Nomega(6)-nitro-L-arginine methyl ester (NAME) on cyclic GMP levels during muscarinic activation of tracheal smooth muscle.

The effects of carbachol on the cyclic GMP (cGMP) content of bovine tracheal smooth muscle in the absence of phosphodiesterase inhibitors were evaluated. Carbachol (1 x 10(-5) M) induced two cGMP peaks, at 20 and 60 sec. Both cGMP signals were carbachol concentration-dependent (1 x 10(-11) to 1 x 10(-5) M), the first being higher than the second. The cGMP signal induction was studied using an inhibitor of the soluble guanylyl cyclase (GC), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and a nitric oxide (NO) synthase inhibitor, Nomega(6)-nitro-L-arginine methyl ester (NAME). ODQ (1 x 10(-7) M) did not affect the second cGMP peak but abolished the first peak, suggesting that a soluble GC may be involved. NAME (1 x 10(-4) M) did not affect the cGMP signals, but changed their 2:1 ratio and also induced a time-shift of the first peak to 10 sec and the second to 50 sec. These results indicate that the NO-soluble GC cascade is not responsible for these muscarinic effects on cGMP levels.

Animals↗

PubMed1998

IgA B and T cells in the intestinal Villi of immunodeficient rats orally treated with thymomodulin.

Previous studies on the effect of the oral administration of bacterial immunomodulators (1M-104 and RN-301) during the protein free diet period, have shown an increase on B and T cell gut repopulation, accompanied by IgA antibody production. The usefulness of oral administration of the immunomodulator thymomodulin (TmB) during the protein refeeding period was investigated. TmB allowed the recovery of a normal repopulation of gut lamina propria with IgA B and CD5 T cells and decreases to control values the number of activated intraepithelial lymphocytes (CD25+ T cell subset). Therefore, the oral administration of TmB may be useful as a therapeutic agent as it seems to improve the repopulation of intestinal villi with immunocompetent cells. Also, it seems to regulate the immunosurveillance at the epithelium level as it increases the CD5+ T cells but decreases the activated ones.

Adjuvants, Immunologic↗

PubMed1996

Biochemical characterization of a V-ATPase of tracheal smooth muscle plasma membrane fraction.

A biochemical characterization of a Mg(2+)-ATPase activity associated with a plasma membrane fraction isolated from airway (tracheal) smooth muscle was performed. This enzyme is an integral part of the membrane remaining tightly bound after 0.6 M KCl extraction. This enzyme activity showed a cold inactivation in the presence of ATP and Mg2+. Also, this Mg(2+)-ATPase was stimulated by monovalent anions being Cl-, the best anion for such stimulation, even though Br- and I- were good substitutes and F- was ineffective. This Cl--stimulated activity showed a powerful nucleosidetriphosphatase activity having the following divalent cation specificity: Mg2+ > Mn2+ > Ca2+, where Zn2+ and Fe2+ were ineffective. This ATPase activity was not inhibited by ouabain oligomycin C and vanadate indicating that neither P- or F-ATPases were associated with this enzyme activity. However, the existence of a V-ATPase was shown by the significant inhibition causes by bafilomycin A1. Additionally, this V-ATPase seems to be coupled to Cl- conductor because duramycin inhibited this ATPase activity. The presence of a H+ pump associated to this V-ATPase was shown indirectly, through the stimulatory effect produced by uncouplers such as FCCP and 1799, which were able to produce significant stimulation of this V-ATPase indicating the existence of a H(+)-ATPase. Finally, the immunodetection of a 72 kDa polypeptide using a specific antibody against the A subunit (72 kDa) of V-ATPase from chromaffin granule demonstrated the presence of a V-ATPase in this plasma membrane fraction.

Alkylation↗

PubMed1995

Cholinesterase inhibitors proposed for treating dementia in Alzheimer's disease: selectivity toward human brain acetylcholinesterase compared with butyrylcholinesterase.

One consistent finding in senile dementia of the Alzheimer's type is that the brain has reduced ability to synthesize acetylcholine. This has been related, in part, to memory dysfunctions. Although a cholinergic deficit is not singularly responsible for symptoms of dementia, treatment strategies have been designed to facilitate cholinergic activity by inhibiting acetylcholinesterase (AChE). To minimize toxicity, however, a cholinesterase inhibitor selective for only AChE would be an ideal treatment. The purpose of this study was to determine the selectivity of physostigmine, metrifonate, methanesulfonyl fluoride and tetrahydroaminoacridine (tacrine) toward AChE as compared with butyrylcholinesterase (BChE) in human cortex. The results show that methanesulfonyl fluoride is selective as an inhibitor of AChE as compared with BChE. Physostigmine inhibited AChE more than BChE. Metrifonate was found to inhibit BChE more than AChE. Tetrahydroaminoacridine inhibited both enzymes in a complex way.

Acetylcholinesterase↗

PubMed1993

[Role of H+ ATPases in plasma membranes of airway smooth muscle].

Protons generated inside the cells during metabolic activity have to be extruded through active mechanisms from the intracellular to the extracellular space. One of the systems involved in proton transport across membranes are the V-ATPases, which are oligomeric complexes that have been found in several subcellular organelles energizing such organelle through a proton gradient and a membrane potential. In this paper, a V-ATPase activity has been described at the plasma membranes fractions isolated from airway smooth muscle. This activity was measured as a Cl- stimulated Mg2+ ATPase. This Cl- activating effect was also shared by others halogens as I- and Br- but not F-. This Cl- stimulated ATPase is a nucleotide triphosphatase being unable to hydrolyze mono and dinucleotides. The divalent cations showed the following sequence of activation (Mg2+ > Mn2+ > Ca2+) of the Cl- activated Mg2+ ATPase. This Cl- stimulated Mg2+ ATPase was insensitive to ouabain, vanadate, sodium azide and rutamicina. NEM (N-ethylmaleimide) partially inhibited this activity but a complete inhibition was observed with p-CMB (p-chloromercurbenzoate ). Several specific proton transport inhibitors were employed to show the presence of a H+ pump activity. Thus, the strong inhibition induced by DCCD suggest the existence of hydrophobic subunits related to a proton channel. In addition, protonophores as 1799 and FCCP stimulated the Cl- stimulated ATPase indicating the presence of a H+ pump in these plasma membranes vesicles. The chloride requirement could be explained by the existence of a chloride conductor coupled to the proton pump (H+ ATPase-type V) due to the inhibitory effect of duramycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Anions↗

PubMed1991

The role of mannose in the receptor of the monocyte locomotion inhibitory factor produced by Entamoeba histolytica.

The effect of the monocyte locomotion inhibitory factor (MLIF) produced by Entamoeba histolytica is diminished, if not cancelled, when human monocytes are pre-exposed to concanavalin A or sodium periodate, respectively, but not when MLIF is pretreated with sodium periodate. When the MLIF-inhibited monocyte locomotion assays were performed in the presence of 12 different carbohydrates, only the runs containing D-mannose, 4-O-beta-galactosyl-mannoside or mannan revealed a significant reduction in the inhibitory effect. Finally, the MLIF activity was virtually absorbed out with mannan-coupled Sepharose 4B beads. This suggests that D-mannose constitutes an essential part of the receptor for MLIF on the human monocyte membrane.

Animals↗

PubMed1991

Coronary venous retroperfusion support during high risk angioplasty in patients with unstable angina: preliminary experience.

Synchronized coronary venous retroperfusion was used during coronary balloon angioplasty to support the ischemic myocardium of 20 patients with unstable angina and anatomy at high risk of a coronary event. Hemodynamics and left ventricular function were the major end points of the study. Coronary venous catheterization and retroperfusion were successfully performed in 15 patients. The target vessel was an unprotected left main artery in 2, left anterior descending artery in 10, left circumflex coronary artery in 1 and right coronary artery in 2 patients. A nonsupported balloon inflation (mean 44 +/- 13 s) was compared with a later retroperfusion-supported inflation (mean 145 +/- 21 s). Right anterior oblique left ventriculograms, aortic blood pressure, pulmonary artery pressure and thermodilution cardiac output were obtained before and during peak untreated and treated balloon inflations and on completion of angioplasty. All patients had either a baseline left ventricular ejection fraction less than 0.40 or greater than 40% of contracting myocardium estimated to be at risk for severe ischemia during angioplasty. The cardiac (liters/min per m2) and stroke work (g.m/m2) indexes decreased from mean baseline values of 2.5 +/- 0.52 and 52 +/- 15 to 1.7 +/- 0.47 and 27 +/- 12 (mean +/- SD), respectively, during nonsupported balloon inflations but decreased only to 2.1 +/- 0.52 (p less than 0.01 vs. nonsupported) and to 36 +/- 14 (p = 0.01 vs. nonsupported), respectively, during retroperfusion-supported inflations. Ejection fraction (n = 8) decreased from a baseline value of 55 +/- 13% to 27 +/- 7.3% during nonsupported inflations but only to 39 +/- 10% during retroperfusion-supported inflations (p = 0.01 vs. nonsupported). Regional wall motion (area change) in the ischemic (target) region was reduced from a baseline value of 49 +/- 17% to 11 +/- 16% during nonsupported inflations but only to 27 +/- 15% during retroperfusion-supported inflations (p less than 0.01 vs. nonsupported). All but two patients had a favorable hemodynamic response to retroperfusion. There were no serious adverse effects related to the procedures and no hospital deaths. It is concluded from this preliminary study that coronary venous retroperfusion appears to be safe, to provide hemodynamic support and to improve left ventricular function during angioplasty in patients with unstable angina and anatomy at high risk of a coronary event.

Angina, Unstable↗

PubMed1989