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Biomedical subjects

Mario H Vargas

Publications and source records attributed to Mario H Vargas.

8 recordsLinked to original sources
PubMed2004

LTD4 induces hyperresponsiveness to histamine in bovine airway smooth muscle: role of SR-ATPase Ca2+ pump and tyrosine kinase.

Airway hyperresponsiveness is a key feature of asthma, but its mechanisms remain poorly understood. Leukotriene D(4) (LTD(4)) is one of the few molecules capable of producing airway hyperresponsiveness. In this study, LTD(4), but not leukotriene C(4) (LTC(4)), produced a leftward displacement of the concentration-response curve to histamine in bovine airway smooth muscle strips. Neither LTC(4) nor LTD(4) modified the concentration-response curve to carbachol. In simultaneous measurements of intracellular Ca(2+) ([Ca(2+)](i)) and contraction, histamine or carbachol produced a transient Ca(2+) peak followed by a plateau, along with a contraction. LTD(4) increased the histamine-induced transient Ca(2+) peak and contraction but did not modify responses to carbachol. Enhanced responses to histamine induced by LTD(4) were not modified by staurosporine or chelerythrine but were abolished by genistein. Western blot showed that carbachol, but not histamine, caused intense phosphorylation of extracellular signal-regulated kinase 1/2 and that LTD(4) significantly enhanced the phosphorylation induced by histamine, but not by carbachol. L-type Ca(2+) channel participation in the hyperresponsiveness to histamine was discarded because LTD(4) did not modify the [Ca(2+)](i) changes induced by KCl. In tracheal myocytes, LTD(4) enhanced the transient Ca(2+) peak induced by histamine (but not by carbachol) and the sarcoplasmic reticulum (SR) Ca(2+) refilling. Genistein abolished this last LTD(4) effect. Partial blockade of the SR-ATPase Ca(2+) pump with cyclopiazonic acid reduced the Ca(2+) transient peak induced by histamine but not by carbachol. These results suggested that LTD(4) induces hyperresponsiveness to histamine through activation of the tyrosine kinase pathway and an increasing SR-ATPase Ca(2+) pump activity. L-type Ca(2+) channels seemed not to be involved in this phenomenon.

Animals↗
PubMed2004

Possible role of substance P in the ischemia-reperfusion injury in the isolated rabbit lung.

The origin of the endothelial damage leading to the ischemia-reperfusion injury after lung transplantation has not been elucidated. We postulated that neurotransmitters released during the preservation of the donor lung might explain this vascular derangement. Thus, in isolated rabbit lungs preserved over 24 hours, we evaluated the release of acetylcholine (ACh) and substance P (SP), the activity of their major degrading enzymes, acetylcholinesterase (AChE) and neutral endopeptidase (NEP), and changes in the capillary permeability. Both neurotransmitters showed the highest release rate in the first 15 minutes, followed by a sharp exponential decrement at 1, 6, 12 and 24 hours. AChE and NEP activities showed no variation at these time intervals. Basal capillary permeability significantly increased (P<0.01) after 24 hours preservation with saline. This increased permeability was avoided (P<0.01) by the SP fragment 4-11 (an SP receptors antagonist), but not by atropine. These results suggest for the first time a pathogenic role of SP in the ischemia-reperfusion injury, and thus the potential usefulness of SP antagonists as additives in the lung preservation solutions should be explored.

Animals↗
PubMed2004

Spontaneous changes in guinea-pig respiratory pattern during barometric plethysmography: role of catecholamines and nitric oxide.

Barometric plethysmography for unrestrained animals is a non-invasive method that allows repetitive measurements of pulmonary function, but habituation of the conscious animal to this technique has not been explored. Respiratory frequency (f(R)) and 'enhanced pause' (P(enh)) were measured by barometric plethysmography for a period of 8 h in guinea-pigs. Compared with basal values, during the first hour of recording a progressive increase in P(enh) (up to 25-50%) and a corresponding decrease in f(R) were recorded, followed by a relative plateau in each for up to 8 h. These changes were avoided by a 30-min pretreatment with propranolol and l-NAME (nitric oxide synthase inhibitor), with P(enh) values as high as this plateau phase since the beginning of recording. Atropine, salbutamol or budesonide did not modify the progressive increment in P(enh). We concluded that catecholamines and nitric oxide are released when guinea-pigs are introduced into the plethysmographic chamber, leading to initial low P(enh) values. These mediators probably diminish owing to habituation of the animal to the new environment, with an apparent progressive increment in P(enh). These spontaneous changes in P(enh) and f(R) must be taken into account during barometric plethysmography in order to avoid misinterpretation of the results.

Animals↗
PubMed2004

Trends of asthma in Mexico: an 11-year analysis in a nationwide institution.

STUDY OBJECTIVES: Asthma prevalence is increasing in many countries. Some recent articles, however, claim that this tendency is ending. Our aim was to investigate asthma trends in Mexico. DESIGN: Annual data on health services provided to asthmatic patients were retrospectively analyzed from 1991 to 2001. SETTING: The Instituto Mexicano del Seguro Social, the largest nationwide medical institution in Mexico (approximately 24 to 32 million insured subjects). PARTICIPANTS: Health services provided to subjects of any age. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Asthma-associated health services, either expressed as absolute number or as rate per insured subjects, progressively increased until 1997 in family physician office visits (FPOVs) [newly diagnosed cases only], emergency department visits (ERVs), and hospital discharges (HDs). From that year onward, the number and rates of asthma-associated health services decreased. The same trends were observed for age groups 0 to 4 years, 5 to 14 years, 15 to 44 years, and 45 to 64 years. Using a different approach, asthma was diagnosed each year in approximately 0.4% of all FPOVs, but a decrease in this percentage was observed from 1997 onward. Likewise, asthma caused increasing percentages of all ERVs and HDs until 1997, followed by a sharp decline thereafter. CONCLUSIONS: A decline in absolute and relative numbers of asthma-associated health services occurred over recent years in all medical settings, suggesting that the epidemic of new asthma cases is ending and/or that better control of the disease has been achieved.

Adolescent↗
PubMed2003

Acetylcholine and tachykinins involvement in the caffeine-induced biphasic change in intracellular Ca2+ in bovine airway smooth muscle.

1. Caffeine has been widely used as a pharmacological tool to evaluate Ca(2+) release from the sarcoplasmic reticulum in isolated smooth muscle cells. However, in nervous tissue this drug also causes neurotransmitters release, which might cause additional effects when smooth muscle strips are evaluated. To assess this last possibility, simultaneous measurements of contraction and cytosolic Ca(2+) concentration (using Fura-2/AM) were carried out in bovine airway smooth muscle strips during caffeine stimulation. 2. A first stimulation (S1, n=11) with caffeine (10 mM) induced a biphasic change in cytosolic Ca(2+), which consisted of a transient Ca(2+) peak (254+/-40 nM, X+/-SEM) followed by a plateau (92+/-13 nM), and a transient contraction (204.72+/-31.56 mg tension mg tissue(-1)). A second caffeine stimulation (S2) produced a similar response but these parameters had a different magnitude. The S2/S1 ratios for these parameters were 0.69+/-0.02, 0.83+/-0.06 and 1.01+/-0.03, respectively. Addition of omega-conotoxin GVIA (1 micro M) and tetrodotoxin (3.1 micro M) before S2 significantly diminished these S2/S1 ratios (0.26+/-0.05, 0.26+/-0.09 and 0.64+/-0.11, respectively, n=5, P<0.05), implicating the neurotransmitters release involvement in the response to caffeine. A similar effect (P<0.01) was observed with atropine (1 micro M, n=4), the fragment 4-11 of substance P (SP) (an SP receptor antagonist, 10 micro M, n=5), and with both substances (n=4). 3. We discarded a direct effect of omega-conotoxin GVIA (1 micro M) plus tetrodotoxin (3.1 micro M) or of atropine (1 micro M) plus SP fragment 4-11 on smooth muscle cells because they did not modify caffeine responses in isolated tracheal myocytes. 4. We confirmed by HPLC that caffeine increased the release of acetylcholine (from 0.43+/-0.19 to 2.07+/-0.56 nM mg tissue(-1), P<0.02) in bovine airway smooth muscle strips. Detection of substance P by ELISA was not statistically different after caffeine stimulation (geometric means before and after caffeine, 0.69 vs. 1.97 pg ml(-1) mg tissue(-1), respectively, P=0.053). 5. We concluded that acetylcholine and tachykinins release are involved in the caffeine-induced biphasic changes in cytosolic Ca(2+) concentration.

Acetylcholine↗
PubMedDate not supplied

Spirometric changes in fire-eating subjects in Mexico City.

BACKGROUND: Fire-eating is an activity mainly carried out by inner-city poorest subjects as a way to obtain money. Scant information has been reported concerning the consequences of this activity on lung function. METHODS: This study was accomplished in the streets of Mexico City by performing spirometric studies on 30 fire-eaters prior to and after their daily activity; in 16 of these subjects these studies were also conducted after salbutamol inhalation. RESULTS: All fire-eaters were males, 27.9 +/- 1.1 years of age (mean +/- standard error of the mean). Up to two thirds showed abnormalities in baseline spirometry (11 with an obstructive pattern and 9 with mixed pattern) not related to a smoking habit or drug abuse. Number of years in the fire-eating activity was inversely correlated with FEF50 (r=-0.46, p<0.01) and FEF75 (r=-0.33, p<0.05). Likewise, body mass index was inversely correlated with FEF25 and FEF50. These results were corroborated with multiple regression analysis. At the end of daily fire-eating activity, further diminution of FEF75 was observed (-7.6 +/- 1.4%, p<0.01). Aerosolized salbutamol caused statistically significant increment (p<0.05 to p<0.01) in nearly all spirometric variables, although on an individual basis only 10 of 16 (63%) had positive bronchodilation response. CONCLUSIONS: Fire-eaters showed a mild decrease of airflows, which partially correlated with number of years spent in this activity. After a 1-day fire-eating activity, further airflow limitation increased. Up to 63% of subjects tested improved some spirometric airflow value after salbutamol inhalation.

Adult↗
PubMedDate not supplied

Effect of acute ozone exposure on pregnant rat uterus contractile responses.

Pulmonary effects of ozone (O(3)) inhalation have been comprehensively studied, but little is known about its extrapulmonary consequences, particularly in the reproductive tract. Thus, the effects of an acute O(3) exposure on the contractile response of the pregnant rat uterus were evaluated. Nonpregnant and pregnant (5, 10, and 18 days of gestation) rats were exposed to air or O(3) (3 ppm) for1 h, and uterine strips isolated from these animals were studied 16-18 h later. Contractile responses to acetylcholine (ACh) and oxytocin (OT) were evaluated with respect to three parameters (area under the curve, amplitude, and frequency). O(3) did not modify the sensitivity (-logEC(50)) to either agonist at any pregnancy stage, but induced a statistically significant increase in all maximum responses to OT at gestational day 5, and increased the maximum response (area under the curve) to ACh at pregnancy days 5 and 10. Our results suggest that O(3) inhalation can produce abnormal contractility in the pregnant uterus, and identify the need for further investigation of this issue.

Acetylcholine↗