Search PubMed⌕ Search

Biomedical subjects

R Vargas

Publications and source records attributed to R Vargas.

At least 55 records · Page 3Linked to original sources

Topological properties of two cubic phases of a phospholipid:cholesterol:diacylglycerol aqueous system and their possible implications in the phospholipase C-induced liposome fusion.

Water dispersions of phospholipid:cholesterol:diacylglycerol may, under certain conditions, originate either the lipid- and water-permeable Q224 cubic phase, or the lipid-permeable but water-impermeable Q227 cubic phase. These results are discussed within the framework of the phospholipase C-induced fusion of liposomes [Nieva et al. (1993) Biochemistry 32, 1054]. It is suggested that the cubic phases Q224 and Q227 represent two classes of lipid organization, one promoting, the other hindering the mixing of aqueous contents that is characteristic of membrane fusion. In this context, inverted micelles appear to be the end point of the fusion process, rather than fusion intermediates.

Bacillus cereus↗

Order-disorder phenomena in myelinated nerve sheaths: V. Effects of temperature on rat sciatic and optic nerves, and structural differences between the two types of nerve.

We describe in this work X-ray scattering and electron microscope studies of rat sciatic and optic nerves as a function of temperature. The scattering experiments were analyzed as described in the previous papers of this series: a variety of parameters were determined, some of which characterize the lattice disorder, others the structure of the motif. The main results are the following. All the parameters determined by the X-ray scattering study vary with temperature and the temperature-dependence is specific for the type of nerve (sciatic or optic). Most of the disorder-related parameters display a minimum or a maximum in the vicinity of physiological temperature (38 degrees C in rat); this observation, strongly supported by the electron microscope study, shows that the degree of organization of myelin is highest near physiological temperature. The structure of the motif, as revealed by the electron density profile, is fairly different in the two types of nerves (in contrast with the assumption made by previous workers); the structure also varies with temperature and the temperature-induced alterations are nerve-type specific. In the two types of nerve the thickness of the lipid bilayer varies with temperature as expected for a lipid-containing system with hydrocarbon chains in the disordered conformation. In sciatic nerve the thickness of the (thinner) cytoplasmic polar layer, which is also the layer most affected by lattice disorder in this type of nerve, decreases dramatically with increasing temperature. In optic nerve, in which lattice disorder predominantly affects the extracellular layer, the thickness of both the cytoplasmic and the extracellular layer is barely affected by temperature.

Algorithms↗

The interaction between endothelium-derived relaxing factor (EDRF) and eicosanoids in the regulation of the mesenteric microcirculation.

Locally produced eicosanoids and endothelium-derived factors are believed to be the mediators of vascular tone of various vascular beds including the mesentery. Using a small vessel isometric myograph which allows direct measurement of microvascular reactivity, the interaction of eicosanoids and endothelium-derived relaxing factor (EDRF) in regulating vascular tone of mesenteric microcirculation of the rat was characterized. The microvascular response to various vasoactive agents before and after inhibition of prostacyclin production with indomethacin (INDO, 5 microM) and inhibition of EDRF synthesis with N omega-nitro-L-arginine methyl ester (L-NAME, 50 microM) was compared. Analysis of dose-response curves for prostaglandin F2 alpha (PGF2 alpha), U46619, a stable thromboxane analog, and norepinephrine (NE) after pretreatment with INDO demonstrated that inhibition of endogenous eicosanoids significantly attenuated the vasoconstrictor response to PGF2 alpha and U46619 but not to NE. Inhibition of EDRF synthesis with L-NAME potentiated the vasoconstrictor response to PGF2 alpha, U46619, and NE. These results suggest that EDRF acts as the primary mediator of vasodilator tone in the mesenteric microcirculation rather than vasodilator cyclooxygenase products such as prostacyclin. It also appears that the vasoconstrictor action of PGF2 alpha and U46619 may be mediated by a release of an endogenous indomethacin-sensitive factor.

Animals↗

Deleterious effects of inhibition of the renin-angiotensin system in neonatal rats.

The angiotensin I converting enzyme inhibitor (ACEI) perindopril (2 mg/kg body weight), the peripheral vasodilator dihydralazine (DHL) (25 mg/kg body weight) or distilled water was given daily from birth to day 14 to neonatal rats. Blood pressure, plasma creatinine, plasma renin activity (PRA), substrate (PRS) and concentration (PRC) and renin content of kidney tissue sections were evaluated on days 14 and 28. By day 14, a high mortality in the ACEI group was observed. ACEI, but not DHL, led to a significant fall (P < 0.01) in blood pressure, 57 +/- 11 versus 89 +/- 25 in the DHL group and 103 +/- 24 mmHg in controls, and to a dramatic increase in plasma creatinine. PRA and PRS were undetectable in ACEI-treated rats; in contrast, PRC and renal staining with anti-renin antibody were significantly increased in ACEI rats. On day 28, the blood pressure was normal in all groups and plasma creatinine returned to the normal range in ACEI rats. PRA, PRS and PRC were not significantly different in the ACEI group and controls. These results suggest that the renin-angiotensin system (RAS) plays a major postnatal role in the neonatal rat. Inhibition of the RAS during the first 2 weeks of life leads to high mortality, severe hypotension, reversible renal failure and a defect in circulating angiotensinogen.

Aging↗

Pretreatment of normal humans with monophosphoryl lipid A induces tolerance to endotoxin: a prospective, double-blind, randomized, controlled trial.

OBJECTIVES: Endotoxin is one of the principal mediators of Gram-negative septic shock. Pretreatment with monophosphoryl lipid A, a hydrolyzed derivative of endotoxin from Salmonella minnesota R595, induces endotoxin tolerance and nonspecific resistance to infection in experimental animals. The present clinical trial was undertaken to test the response to monophosphoryl lipid A in humans and the ability of monophosphoryl lipid A to attenuate the response of normal human volunteers to U.S. Reference Ec-5 endotoxin. DESIGN: Prospective, double-blind, randomized, controlled trial. SETTING: Clinical research center. PATIENTS: Forty-four healthy volunteers. INTERVENTIONS: In part 1 of the study, 29 volunteers were randomized in varying ratios to receive vehicle control or monophosphoryl lipid A intravenously in a double-blind dose escalation trial. In part 2 of the study, 12 volunteers were randomized to receive either monophosphoryl lipid A (20 micrograms/kg) or vehicle control and, 24 hrs later, all 12 volunteers were challenged with U.S. Reference Ec-5 endotoxin (20 units/kg intravenous, bolus injection). Systemic response to endotoxin challenge was evaluated and compared between the monophosphoryl lipid A and vehicle control-pretreated subjects. MEASUREMENTS AND MAIN RESULTS: In part 1 of the study, subjective effects and increases in cytokine levels were not observed until a dose of 10 micrograms/kg of monophosphoryl lipid A was administered. Six volunteers receiving a maximum dose of 20 micrograms/kg experienced mild-to-moderate symptoms that did not require therapy. Moderate increases in temperature, heart rate, and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 release were observed. IL-1 alpha and IL-1 beta were not detected but a significant increase in IL-1 receptor antagonist was observed. In part 2 of the study, monophosphoryl lipid A pretreatment reduced the number of volunteers who experienced one or more subjective complaints after endotoxin administration (3/6 vs. 6/6; p = .09). The febrile response and tachycardic response to endotoxin were significantly reduced by pretreatment with monophosphoryl lipid A. Monophosphoryl lipid A-pretreated volunteers demonstrated significantly reduced concentrations of TNF-alpha after endotoxin challenge, as compared with subjects treated with vehicle control (84 +/- 76 vs. 244 +/- 128 pg/mL; p < .05). IL-6 concentrations (100 +/- 91 vs. 268 +/- 171 pg/ml; p < .05) and IL-8 concentrations (136 +/- 86 vs. 632 +/- 323 pg/mL; p < .05) elicited by endotoxin challenge were also significantly reduced by monophosphoryl lipid A pretreatment. CONCLUSIONS: Data indicate that monophosphoryl lipid A, in a dose 10,000 times that of endotoxin, used in experimental pyrogenicity trials, is well tolerated in human volunteers. Pretreatment of normal human volunteers with monophosphoryl lipid A attenuated the systemic response to bacterial endotoxin. These data support further clinical testing of monophosphoryl lipid A for the prevention or amelioration of the severe sequelae of sepsis.

Adolescent↗

Effect of estradiol 17 beta on pressor responses of rat mesenteric bed to norepinephrine, K+, and U-46619.

We reinvestigated the effect of estradiol 17 beta on the responses of adrenergic and nonadrenergic vasoconstrictors characterized it in terms of steroid specificity, time course, and the role of classic estrogen receptors. We evaluated the effect of estradiol 17 beta on the pressor responses of isolated perfused rat mesenteric vascular bed (McGregor's preparation). Estradiol 17 beta (7-700 nM) significantly increased the pressor response to bolus applications of norepinephrine (NE) (p < 0.05). However, estradiol 17 beta did not significantly increase the responses to endogenous NE release induced by electrical field stimulation. Other steroids, testosterone, and the 17 alpha isomer of estradiol (7 and 700 nM) were ineffective. Estradiol 17 beta (700 nM) also significantly increased the maximum pressor response of rat mesenteric preparation to both the prostaglandin endoperoxide analogue U-46619 and to K+. The potentiation by estradiol 17 beta of mesenteric vasoconstriction elicited by NE, K+, and U-46619 was rapid (2-8 min), suggesting that a nuclear receptor may not be involved. This notion received further support in that significant potentiation of the NE-induced pressor response was also observed with estradiol 17 beta conjugated to albumin (700 nM), but not when electrical field stimulation was used. The conjugate increased the effect of all NE concentrations. Its effect was also more consistent (p < 0.01) than that elicited by free estradiol 17 beta. The dose-response curve was shifted to the left, and the maximum effect was increased. These data suggest that estradiol 17 beta may possess rapid nongenomic actions unrelated to nuclear receptor binding and gene transcription.

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

Effect of testosterone treatment on vasoconstrictor response of left anterior descending coronary artery in male and female pigs.

Androgens may be risk factors in the pathogenesis of coronary artery disease by promoting coronary vasoconstriction. We studied the effect of testosterone treatment on coronary vascular reactivity of male and female domestic pigs treated for 2 weeks with either placebo or testosterone 10 mg/kg subcutaneous (s.c.) pellets. Vascular reactivity was studied in ring segments (4-5 mm) isolated from the left anterior descending coronary artery (LAD). No significant sex difference was noted in the response of LAD segments from placebo-treated male and female animals to KCl and prostaglandin F2 alpha (PGF2 alpha). Androgen treatment increased the maximum response (Tmax) of intact vessels to KCl from 3,647 +/- 689 mg in controls to 8,939 +/- 1,284 mg in testosterone-treated males (p < 0.01) and from 3,405 +/- 669 to 10,524 +/- 1,663 mg in testosterone-treated female pigs (p < 0.01). Testosterone similarly increased the response to PGF2 alpha 10(-6) M from a mean of 2,149 +/- 1,036 to 3,163 +/- 867 mg in males (p < 0.05) and from 2,076 +/- 810 to 3,565 +/- 578 mg in female segments (p < 0.05). Endothelial denudation significantly decreased the potentiating effect of testosterone treatment in males to both KCl and PGF2 alpha (p < 0.05), but not in segments from females. Our data show that testosterone treatment potentiates contractility of porcine LAD segments to both receptor- and nonreceptor-mediated agonists. In male pigs, this effect may be mediated by an effect on endothelium.

Animals↗

Pheocromocytoma and gastrointestinal bleeding.

A 46-year-old patient who presented with an abdominal mass and gastrointestinal bleeding associated with an extra-adrenal pheochromocytoma is discussed. He had no history of hypertension. An ill-defined mass was felt at the upper abdomen. CT and arteriography confirmed the presence of a large mass with calcifications in the right paravertebral region. Upper endoscopy revealed multiple varices at the third portion of the duodenum. Abdominal exploration revealed a huge tumor at the root of the small bowel mesentery with multiple arterial and venous vessels entering the third portions of the duodenum. The tumor was unresectable. Biopsy demonstrated a pheochromocytoma. The patient developed pulmonary edema in the immediate postoperative course. He recovered and was discharged home on Dibenzyline. He has been readmitted on various occasions with gastrointestinal bleeding and congestive heart failure. Presently he is working and feels relatively well 5 years after the operation. A review of the literature for gastrointestinal complications of pheochromocytomas was done. There is a scarcity of reports of gastrointestinal bleeding associated with pheochromocytomas.

Biopsy↗

[The evaluation of a monoclonal antibody panel for Lyssavirus typing in Mexico].

The purpose of this study was to evaluate the ability of a panel of eight antinucleocapsid monoclonal antibodies developed in Europe to identify different strains of rabies virus isolated from a variety of animal species from diverse geographic areas in Mexico. Fifty-one virus-positive samples of brain tissue from various animal species and humans were studied. Material from these samples was used to infect mice, whose brains were later tested by indirect immunofluorescence, using the monoclonal antibodies described above. Strains of the virus that showed antigenic variations were sent to the Pasteur Institute in Paris for confirmation of the results. No mouse brain sample showed a pattern of antigenic reactivity that indicated the presence of a Lyssavirus other than the classic rabies virus. However, four antigenic variations from serotype 1 of classic rabies were found. The panel of antibodies was judged to be useful for the rapid classification of rabies virus in Mexico. It is possible that autochthonous antigenic variations are appearing among strains circulating in that country, a scenario that could explain some of the failures observed with certain vaccines. For this reason, there is a need to produce antinucleocapsid monoclonal antibodies with strains of rabies virus indigenous to the area.

Animals↗

[Technical innovations in total extracardiac cavo-pulmonary connection in Fontan-type operation. An experimental study and first 2 operated clinical cases with excellent immediate results].

INTRODUCTION: Three technical modalities are presented with total extracardiac cava-pulmonary connection, with bidirectional Glenn, as coverage of this type of extracardiac connection for all types of cardiopathies suitable for Fontan type correction. METHODS: Development of an experimental protocol for the perfecting of the three technical variants tested: "Tunnel from inferior cava to right pulmonary artery by means of right atrial wall and vascularized pericardium", "Tunnel from inferior cava to the trunk of the pulmonary artery with or without pulmonary valve with P.T.F.E. hemiconduit" and "Tunnel from inferior cava to the pulmonary graft as a artery with P.T.F.E. graft as a hemiconduit". RESULTS: The first two clinical cases operated on using the third technical variant are presented. Both cases evolved during immediate postoperative period with a very favourable hemodynamic response, with pressures at conduit and P.A. level of 10-12 mmHg, normal cardiac output and sinus rhythm. The later clinical evolution in both cases is very satisfactory. The five cases published by Laschinger with this same technique showed a very favourable evolution during the immediate postoperative period and later. CONCLUSION: The technical facility of its performance, the slight traumatism of this surgery, the important technical advantages with respect to the total cava-pulmonary intraauricular connection and the good initial hemodynamic results make us consider the total extracardiac cava-pulmonary connection as an important contribution in this type of surgery. It is clear that time and greater clinical experience with this type of connection is required for the correct evaluation of all and each one of the numerous theoretical advantages shown and in order to detect possible disadvantages.

Adolescent↗

Evaluation of the antipyretic effect of ketorolac, acetaminophen, and placebo in endotoxin-induced fever.

The authors studied the antipyretic effect of three intramuscular doses of ketorolac (15, 30, and 60 mg), acetaminophen 650 mg PO, and placebo in healthy male volunteers using an endotoxin-induced fever model. In this double-blind, double-dummy, parallel study, subjects were assigned randomly with equal probability to one of the above treatment groups. Thirty minutes after study medication administration, a 20 unit per kilogram dose of reference standard endotoxin (RSE) was administered intravenously, and temperature was determined every 15 minutes for an 8-hour period. Compared with placebo, all active treatment groups demonstrated a statistically significant reduction in both adjusted area under the temperature-by-time curve (AAUC) and the maximum increase over baseline temperature (dTmax). Furthermore, the 30 mg intramuscular dose of ketorolac demonstrated approximately the same antipyretic activity as the 650 mg oral dose of acetaminophen, and there was a statistically significant dose response across the three ketorolac doses studied (P < .0001). The majority of side effects reported during this study were symptoms associated with fever, including chills, headache, myalgia, and dizziness, all of which are effects of RSE. The frequency of side effects tended to be less in the treatment groups with the greatest antipyretic activity.

Acetaminophen↗

Inhibitory activity of 3-methylenhydroxy-5-methoxy-2,4-dihydroxy tetrahydrofurane isolated from Selaginella lepidophyla on smooth muscle of Wistar rat.

A new compound, 3-methylenhydroxy-5-methoxy-2,4-dihydroxy tetrahydrofurane, has been isolated from a methanol extract of Selaginella lepidophyla. The structure is based on 1H-NMR, 13C-NMR and MS analysis. The compound was tested on uterus (oestrus), ileum and duodenum of Wistar rats. It proved to have a slight inhibitory effect on the contraction response of the uterus, but it did not have any effect on the two other muscles.

Animals↗

Epidemic cholera in the Amazon: the role of produce in disease risk and prevention.

Epidemic cholera struck Peru in January 1991 and spread within a month to the Amazon headwaters. A case-control study was done in the Amazonian city of Iquitos, Peru. Cholera-like illness was associated with eating unwashed fruits and vegetables (odds ratio [OR] = 8.0; 95% confidence limits [CL] = 2.2, 28.9) and drinking untreated water (OR = 2.9; 95% CL = 1.3, 6.4). Consumption of a drink made from toronja, a citrus fruit, was protective against illness (OR = 0.4; 95% CL = 0.2, 0.7). Illness was inversely associated with the quantity of toronja drink consumed (P < .01). Produce has not previously been convincingly documented as a risk factor for cholera; this study underscores the importance of washing produce before eating it. Acidic juices, such as toronja drink (pH 4.1), inhibit vibrio growth and may make contaminated water safer. Wild citrus fruits such as toronja are abundant, cheap, and popular in the Amazon region. Promoting the consumption of toronja drink may be a useful cholera prevention strategy in this region.

Adult↗

Parental prompting of smoking among adolescents in Tijuana, Mexico.

Latino adolescents in the United States and Mexico may have higher rates of tobacco experimentation than other ethnic groups, possibly due to cultural factors and parental influences. This study examined three parental behaviors that may prompt smoking in children in Grades 3, 5, 7, and 9 in Tijuana. Mexico. Surveys were administered to 758 students in randomly selected classes in randomly selected schools in Tijuana. The most frequent prompt was the smoking parent asking the child to buy cigarettes (about two thirds), whereas about 60% asked the child to light the parent's cigarette, and about 20% of smoking parents asked the child to place the cigarette in his or her mouth to light it. Rates of prompting were very low among third graders but increased by Grade 5. Mother's smoking was associated with higher rates of all three types of parental prompting.

Journal Article↗

Epidemic cholera in Trujillo, Peru 1992: utility of a clinical case definition and shift in Vibrio cholerae O1 serotype.

Epidemic cholera continues in Peru. Since 1991, cholera surveillance in Peru has been based mainly on clinical recognition. To determine the proportion of reported cholera patients who actually have cholera and to evaluate the clinical case definition used in surveillance, we cultured rectal swabs from patients presenting with acute diarrhea in March 1992 in Trujillo, Peru. Of 197 patients meeting the clinical case definition, 174 (88%) had confirmed Vibrio cholerae O1 infection. In this epidemic setting, watery diarrhea of sudden onset in a person of any age presenting for treatment is highly predictive of cholera. Of note, 90% of the current V. cholerae O1 El Tor isolates were of serotype Ogawa, while a year earlier, all were of serotype Inaba.

Acute Disease↗

[Natural killer cytolytic activity in renal and prostatic cancer].

Natural killer cytolytic activity, the basis of cancer immunotherapy that uses cytolytic cells, may be impaired in cancer. The aim of this work was to study in vitro the natural killer cytolytic activity and its response to the immunomodulators interleukin-2, interferon and phytohemagglutinin stimulated lymphocyte proliferation in a group of 9 patients with renal cell cancer and 6 with prostatic cancer. The results were compared with those of 20 normal volunteers. Twelve patients were operated and were studied twice 48 h and 14 days after surgery. Natural killer cytolytic activity was significantly lower in renal cell and prostatic cancer patients than controls (3.3 +/- 1.6, 4.9 +/- 2.2 and 20.6 +/- 3.7% of specific lysis respectively). This activity was not modified in cancer patients by interleukin-2 50 UI/ml or interferon 3000 UI/ml and did not differ in the two postoperative periods. Phytohemagglutinin stimulated lymphocyte proliferation was also lower in cancer patients, compared to controls (stimulation index of 18 +/- 3 and 26.5 +/- 5 respectively). It is concluded that these patients have a low immunological level and that this study is the first step towards an immunological characterization of cancer patients that are candidate to adoptive immunotherapy.

Adult↗

Cubic phases of lipid-containing systems. A translational diffusion study by fluorescence recovery after photobleaching.

The lateral diffusion coefficient of fluorescent lipid analogues incorporated in four cubic phases of lipid-water systems was determined by the modulated fringe pattern photobleaching technique. In two of the phases, Q230 and Q224, whose structure is bicontinuous, the diffusion is almost as fast as in the fluid lipid bilayers, and is essentially independent of the chemical nature of the probe. In the other two phases, whose structure consists of disjointed hydrocarbon micelles embedded in a water matrix (phase Q223, type I) and of water-containing micelles embedded in a hydrocarbon matrix (phase Q227, type II), the diffusion coefficient is strongly dependent on the chemical structure of the probe and on the topological type (I or II) of the structure. The conclusion is drawn that in the micellar phases the apparent diffusion mirrors the ability of the probe to hop from micelle to micelle.

Diffusion↗