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Biomedical subjects

M Vargas

Publications and source records attributed to M Vargas.

At least 19 recordsLinked to original sources
PubMed1998

Human lymphocyte heme oxygenase 1 as a response biomarker to inorganic arsenic.

We propose the use of human lymphocyte heme oxygenase 1 (HO1) as a biomarker of response to environmental arsenic exposure. We report the induction of HO1 in human lymphoblastoid cells (LBs) by arsenite in a dose-related manner. HO1 was identified by SDS-PAGE from its molecular weight and from its detection by Western blotting with anti-HO1. HO1 levels in LBs treated with arsenite increased by de novo synthesis as demonstrated by incorporation of 35S-methionine and by inhibition of HO1 synthesis by actinomycin D. The amount of HO1 in LBs was estimated by quantifying Western blots. HO1 was also induced by 10 microM cadmium or mercuric chloride. We suggest that circulating lymphocyte HO1 levels may be useful in assessing the biological activity of arsenic exposure in vivo under properly controlled conditions of simultaneous urinalysis for arsenic, cadmium, and mercury.

Arsenic↗
PubMed1998

Microbiological evidence for Fe(III) reduction on early Earth.

It is generally considered that sulphur reduction was one of the earliest forms of microbial respiration, because the known microorganisms that are most closely related to the last common ancestor of modern life are primarily anaerobic, sulphur-reducing hyperthermophiles. However, geochemical evidence indicates that Fe(III) is more likely than sulphur to have been the first external electron acceptor of global significance in microbial metabolism. Here we show that Archaea and Bacteria that are most closely related to the last common ancestor can reduce Fe(III) to Fe(II) and conserve energy to support growth from this respiration. Surprisingly, even Thermotoga maritima, previously considered to have only a fermentative metabolism, could grow as a respiratory organism when Fe(III) was provided as an electron acceptor. These results provide microbiological evidence that Fe(III) reduction could have been an important process on early Earth and suggest that microorganisms might contribute to Fe(III) reduction in modern hot biospheres. Furthermore, our discovery that hyperthermophiles that had previously been thought to require sulphur for cultivation can instead be grown without the production of toxic and corrosive sulphide, should aid biochemical investigations of these poorly understood organisms.

Earth, Planet↗
PubMed1998

Enteroaggregative Escherichia coli strains as a cause of traveler's diarrhea: a case-control study.

To elucidate the importance of enteroaggregative Escherichia coli (EAggEC) strains as a cause of traveler's diarrhea in Spanish travelers, a prospective case-control 1:1 study was done in a university hospital clinic for travelers. EAggEC strains were isolated from 23 of 165 case-patients and from 4 of 165 controls (P = .0003). In 16 patients, this was the only isolate recovered. Six of the EAggEC-positive isolates from the case-patients and 2 from the controls were positive for the enteroaggregative stable toxin type 1 gene. Other enteropathogens were also isolated. Shigella and enterotoxigenic E. coli strains showed significant differences between cases and controls (P = .0023 and P < .0001, respectively). Geographic distribution of the EAggEC strains was homogeneous, and the clinical symptom, secretory diarrhea, did not differ statistically with that for the enterotoxigenic E. coli strains. EAggEC strains are a cause of secretory diarrhea in Spaniards traveling to developing countries.

Case-Control Studies↗
PubMed1998

A case-control study of diarrhoea in children caused by Escherichia coli producing heat-stable enterotoxin (EAST-1).

Escherichia coli strains associated with diarrhoeal disease have been classified into several types according to the pathogenic mechanism. Among these, enteroaggregative E. coli strains (EAggEC) have been associated with persistent childhood diarrhoea. Some strains of EAggEC produce a heat-stable toxin (EAST-1) that differs from others described previously. The main goal of this case-control study was to determine the prevalence of EAggEC and EAST-1-producing E. coli strains as a cause of diarrhoea in children in Spain and to study their in-vitro susceptibility to 21 antimicrobial agents. In the case group (115 children) 22 (19%) isolates and four (3.5%) isolates were EAST-1-producing E. coli and EAggEC, respectively, whereas in the control group (79 children) four (5%) isolates produced EAST-1 (p = 0.005) and three (3.8%) isolates were EAggEC. The present study suggests that EAST-1-producing E. coli strains are associated with diarrhoeal diseases in Spanish children, whereas EAggEC strains are not. Moreover, EAST-1-producing E. coli strains showed a high susceptibility to all the antimicrobial agents tested except for ampicillin.

Anti-Bacterial Agents↗
PubMed1998

Antitrypanosomal activity of a new triazine derivative, SIPI 1029, In vitro and in model infections.

A recently developed diaminotriazine derivative [O,O'-bis(1, 2-dihydro-2,2-tetramethylene-4,6-diamino-S-triazin-1-yl)-1, 6-hexanediol dihydrochloride; T-46; SIPI 1029] was examined for activity against African trypanosomes in in vitro and in vivo model systems. In vitro, SIPI 1029 was 50% inhibitory for growth of bloodstream trypomastigotes of four strains of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense at 0.15 to 2.15 nM (50% inhibitory concentrations). In in vivo mouse laboratory models of T. b. rhodesiense clinical isolate infections, SIPI 1029 was curative for 12 of 13 isolates at </=10 mg/kg of body weight/day for 3 days. In eight infections, a single dose was >/=60% curative, and in six of these, a dose of </=5 mg/kg was sufficient for >/=60% cure rates. A number of these isolates were resistant to the standard trypanocide melarsoprol (Arsobal) and/or the diamidines diminazene aceturate (Berenil) and pentamidine. SIPI 1029 was also curative in combination with DL-alpha-difluoromethylornithine (Ornidyl) in a T. b. brucei central nervous system model infection. Some evidence of toxicity was found in dosage regimens of 10 mg/kg/day for 2 or 3 days in which deaths were observed in 6 of 65 animals given this dosage regimen. The activity of SIPI 1029 in this study indicates that this class of compounds (diaminotriazines) should be explored as leads for new human and veterinary trypanocides.

Acute Disease↗
PubMed1998

Similar hypoxic ventilatory responses in sea-level natives and high-altitude Andean natives living at sea level.

High-altitude (HA) natives have blunted ventilatory sensitivities to hypoxia, and it is uncertain whether this blunting is reversible on migration to sea level (SL). To study this, the ventilatory sensitivities to hypoxia of HA natives residing near SL were compared with those of SL natives. Two studies were performed. In study A, 24 HA subjects who had lived above 3,000 m for an average of 14 yr and had been resident at SL for an average of 23 yr were compared with 23 SL controls. In study B, 25 HA subjects who had lived above 3,500 m for at least 20 yr and had been resident at SL for no more than 5 yr were compared with 25 SL controls. Hypoxic sensitivities were assessed by breathing seven progressively more hypoxic gas mixtures that contained progressively more CO2 in an attempt to maintain isocapnia throughout. The ventilatory sensitivities to hypoxia (l . min-1 . %-1 . m-2) did not differ significantly (by analysis of variance) between HA and SL natives in either study A (-0.51 +/- 0.25, mean +/- SD) or study B (-0.34 +/- 0. 15), but the ventilatory sensitivities did differ significantly between the two studies for reasons which are not entirely clear. We conclude that HA natives residing at SL, even if previously at HA for >20 yr, do not maintain the severely blunted hypoxic responses that have been reported in such individuals.

Acclimatization↗
PubMed1998

Phase II-selective induction of hepatic drug-metabolizing enzymes by oltipraz -5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione-, 1,7-phenanthroline, and 2,2'-dipyridyl in rats is not accompanied by induction of intestinal enzymes.

The induction of hepatic and intestinal cytochrome P450, NAD(P)H:quinone oxidoreductase (QOR), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UGT) activities by intragastric administration of 1,7-phenanthroline, 2,2'-dipyridyl, and oltipraz has been investigated in rats. In the liver, all three compounds induced phase II drug-metabolizing enzymes without inducing overall cytochrome P450 concentrations and, in a direct comparison, all agents induced the enzymes to a greater extent than did the same dose of tert-butyl-4-hydroxyanisole. With a 75 mg/kg daily, 3-day regimen, UGT, GST, and QOR activities were induced by all compounds. The changes in hepatic GST, QOR, and UGT activities induced by N-heterocyclic compounds were accompanied by increases in the amounts of mRNA for GST Ya (2-2.4-fold), QOR (1.6-2.8-fold), and the UGTs UGT2B1 (4-6-fold) and UGT1A6 (4-10-fold). Changes in the amounts of UGT2B1 mRNA and UGT1A6 mRNA were highly correlated (r = 0. 9), but there was no correlation between changes in either UGT2B1 or UGT1A6 mRNA and GST Ya mRNA. No significant mRNA changes were elicited by tert-butyl-4-hydroxyanisole. Neither GST nor UGT activities were induced in the small intestinal mucosa by any agent. QOR activity was slightly induced by oltipraz. The data suggest that requirements for induction of phase II enzymes in the intestine are markedly different from requirements in the liver.

2,2'-Dipyridyl↗
PubMed1997

Recent advances in genetic analyses of hyperthermophilic archaea and bacteria.

Hyperthermophilic Archaea and Bacteria are an extraordinarily important class of organisms for which genetic tools remain to be developed. Unique technological obstacles to this goal are posed by the thermophilic and, in some cases, strictly anaerobic nature of these organisms. However, recent advances in the cultivation of hyperthermophiles, in the discovery of genetic elements for vector development, and in the construction of genetic markers point toward the achievement of this goal in the near future. Transformation protocols have already been reported for Sulfolobus and Pyrococcus, and plasmid-mediated conjugation was recently found in Sulfolobus. Plasmids are available for Sulfolobus, Pyrococcus, and the bacterial hyperthermophile Thermotoga, and these provide the bases for vector construction in these hosts. A Desulfurococcus mobile intron may provide a novel means to introduce genes into a variety of archaeal hosts. With full genome sequences of several hyperthermophiles available soon, genetic tools will allow full exploitation of this information to study these organisms in depth and to utilize their unique properties in biotechnological applications.

Archaea↗
PubMed1997

Deletions and rearrangements of cyclin-dependent kinase 4 inhibitor gene p16 are associated with poor prognosis in B cell non-Hodgkin's lymphomas.

In the present study we examined by Southern blot analysis the presence of deletions and rearrangements of the p16 tumor-suppressor gene in B cell non-Hodgkin's lymphomas (NHLs) in order to determine whether or not these changes can be related to a particular histological subtype and the different clinico-biological and prognostic characteristics of the disease. 103 untreated patients were enrolled in the study. Seven cases displayed alterations in the p16 gene: four cases with homozygous deletions and three with gene rearrangement. The presence of these abnormalities did not correlate with any specific histological subtype: three cases were small lymphocytic lymphomas (two of them reclassified as mantle cell lymphoma on the basis of the REAL classification), two diffuse large cell lymphomas and two small non-cleaved cell lymphomas (one of them considered to be a Burkitt-like lymphoma according to the REAL). These seven cases showed a trend towards worse prognostic indicators than the remaining patients, and this was confirmed in the survival analysis, since the presence of p16 gene abnormalities was associated with a shorter survival (10 vs 81 months, P = 0.0006). In the multivariate analysis, p16 abnormalities were selected as an independent prognostic factor together with the LDH and beta2-microglobulin. These findings support a role for the p16 gene in the pathogenesis of B cell NHLs and suggest an association of p16 abnormalities with aggressive forms of the disease that could be useful to predict the prognosis of patients.

Adult↗
PubMed1997

Intestinal UDP-glucuronosyltransferase activities in rat and rabbit.

1. Tissues other than the liver can contribute significantly to the drug-metabolizing capacity of an animal. In the current study, the glucuronidation of several aglycones in microsomes from the small intestinal mucosa of rat and rabbit has been investigated and compared with glucuronidation in liver microsomes. 2. UDP-glucuronosyltransferase activities in intestinal microsomes were generally higher in rabbit when compared with rat, ranging from 200 to 300% for 1-naphthol, 2-naphthol, 4-methylumbelliferone, 2-hydroxybiphenyl and 4-hydroxybiphenyl. 3. In contrast, hepatic activities were much higher in rat than in rabbit, ranging from 300 to 400% for 1-naphthol, 2-naphthol, 4-methylumbelliferone, 2-hydroxybiphenyl and testosterone; and from 150 to 250% for 4-nitrophenol and diclofenac. 4. In rabbit, activities in the small intestinal mucosa were comparable (70-100%) with hepatic activities for most aglycones. In rat, intestinal mucosa activities were much lower than in liver, with activities toward 1-naphthol, 2-naphthol, 4-nitrophenol, 4-methylumbelliferone, 2-hydroxybiphenyl and 4-hydroxybiphenyl in the small intestine representing 5-15% of hepatic activities. 5. With a higher intestine:liver activity ratio, intestinal UDP-glucuronosyltransferases could be anticipated to contribute more to overall drug glucuronidation in rabbit as compared with rat, thereby contributing more to reducing drug bioavailability.

Animals↗
PubMed1997

In vivo efficacies of 5'-methylthioadenosine analogs as trypanocides.

5'-Deoxy-5'-(methylthio)adenosine (MTA), a key by-product of polyamine biosynthesis, is cleaved by MTA phosphorylase and is salvaged as adenine and, through conversion of the ribose moiety, methionine. An analog of MTA, 5'-deoxy-5'-(hydroxyethylthio)adenosine (HETA), is a substrate for trypanosome MTA phosphorylase and is active in vitro and in vivo against Trypanosoma brucei brucei, an agent of bovine trypanosomiasis. In this study, HETA and three O-acylated HETA derivatives were examined for their activities against model infections of T. b. brucei and Trypanosoma brucei rhodesiense, the agent of East African sleeping sickness. HETA was curative (>60%) for infections caused by 5 of 11 clinical isolates of T. b. rhodesiense when it was given to mice at 200 mg/kg of body weight for 7 days as a continuous infusion in osmotic pumps. HETA at 150 to 200 mg/kg also extended the life spans of the mice infected with four additional isolates two- to fivefold. Di- and tri-O-acetylated derivatives of HETA also proved curative for the infections, while a tri-O-propionyl derivative, although also curative, was not as effective. This study indicates that substrate analogs of MTA should be given important consideration for development as novel chemotherapies against African trypanosomiasis.

Animals↗
PubMed1997

Isolation of verotoxin-producing Escherichia coli O-rough:K1:H7 from two patients with traveler's diarrhea.

Two Escherichia coli O-rough:K1:H7 strains producing verotoxin 1 that were isolated from stool samples of two travelers with diarrhea who consulted our clinic after trips to the Indian Subcontinent and Central America were characterized. Both strains were sorbitol negative, the same phenotype presented by E. coli O157:H7, but in contrast they were beta-glucuronidase positive. Low-frequency restriction analysis of chromosomal DNA and pulsed-field gel electrophoresis and repetitive extragenic palindrome-PCR showed that both strains were epidemiologically related. The illness was self-limited in both cases but involved long-duration, watery diarrhea (10 to 50 days) accompanied by abdominal cramps and flatulence. This serotype should be taken into account as a possible cause of traveler's diarrhea.

Adult↗
PubMed1997

Molecular characterization of myosin IB from the lower eukaryote Entamoeba histolytica, a human parasite.

The complete amino acid sequence of the Entamoeba histolytica unconventional myosin IB (Eh-myosin IB) is reported. Sequencing of overlapping cDNA fragments reveals a single open reading frame which predicts a 130 kDa protein of 1049 aa. Eh-myosin IB presents the three characteristics domains of myosins I subclass 1. This protein presents homology with myosins IB from other amoebae, but striking homologies with vertebrate unconventional myosins were also observed. The predicted actin and ATP-binding sites are located in the head domain. The heavy chain phosphorylation region is homologous to metazoan myosins I with an acidic residue present at the phosphorylation site. In the neck domain, an IQ motif indicates potential binding of calmodulin to the myosin I heavy chain. In the tail of Eh-myosin IB the three characteristic regions of myosin I are found. A putative membrane binding domain a very short domain rich in alanine and proline we demonstrate to be functional for actin binding, and the src-homology 3 domain. The Entamoeba histolytica myosin IB is the first unconventional myosin so far described in a lower eukaryote.

Actins↗
PubMed1997

[Evaluation of the efficacy of image-guided drainage in the treatment of abdominal fluid collections].

In this paper the Authors report their experience in the diagnosis and management of abdominal fluid collections either primary or secondary to surgery. Sixty-eight patients with abdominal fluid collections were considered: in 28 cases an imaging guided percutaneous drainage was performed, while in 40 cases patients were treated with medical or surgical therapy. The Authors describe the different techniques, the approaches and the types of catheter used on the basis of the localization of the collections. The results show the efficacy of drainage procedures in 89% of the patients treated, without any major complication. Some considerations comparing patients treated with percutaneous drainage and patients who underwent different therapy as well as a review of the international literature are also reported. In conclusion the Authors affirm that percutaneous imaging guided drainage is the treatment of choice for abdominal fluid collections anatomically accessible, for the high effectiveness, good tolerability, low cost and minimal incidence of major complications.

Abdomen↗
PubMed1997

In vitro comparison of restoration wear and tensile strength following extended brushing with Sonicare and a manual toothbrush.

The purpose of this study was to compare the wear, cement margin breakdown and bond strength of restorations following 6 to 12 months of simulated use in vitro of the Sonicare and a manual toothbrush. Extracted molar teeth with Class V hybrid composite resin restorations (n = 21) or with Class V gold inlays cemented with zinc phosphate cement were tested for wear and marginal integrity following brushing for a period that simulated 6 months of typical use. One-third of the molars in each group were brushed with the Sonicare and one-third were brushed with the manual brush. The remaining third served as non-treated controls. Toothbrushing was performed under a standardized load using a piston-action brushing machine. After brushing, the enamel, dentin/cementum and restorations were examined by light and scanning electron microscopy. There was no apparent wear of tooth structure or of restorative materials with either the Sonicare or the manual brush. There was a small loss of cement from the margins of the gold inlays following toothbrushing, which was similar and not significantly different between the sonic and manual brush. To test brushing effects on crown retention, four identical metal dies were prepared to simulate premolar crown preparations. Thirty cast copings, prepared to fit the dies, were cemented with zinc phosphate cement. Toothbrushing with Sonicare or the manual toothbrush was performed as before (n = 15 for each brush), but the simulated time was extended to the equivalent of 1 year of brushing. The dislodgement force of cemented crowns was not significantly different (t-test, p > 0.10) between the manual (207 +/- 69 N) and Sonicare (221 +/- 61 N) groups. These results demonstrate that despite its high frequency bristle motion, Sonicare exerts no detrimental effects on cement margin integrity, crown bond strength or surface wear of dental and restorative materials.

Analysis of Variance↗
PubMed1996

Relationship between parathion and paraoxon toxicokinetics, lung metabolic activity, and cholinesterase inhibition in guinea pig and rabbit lungs.

Kinetic parameters of parathion and paraoxon uptake were determined in isolated and perfused rabbit and guinea pig lungs. They were related to organophosphate-induced lung cholinesterase inhibition. A single pass procedure was used to perfuse the lungs with an artificial medium perfusate containing paraoxon or parathion. The paraoxon and parathion concentrations were determined in the effluents collected at chosen intervals over an 18-min period beginning at the start of perfusion. Three inflowing concentrations (1 nmol/ml, 10 nmol/ml, and 20 nmol/ml) were tested in guinea pig lungs and one (10 nmol/ml) in rabbit lungs. Cholinesterase activity was determined at time 0 and at the end of the experiment. The lungs abundantly extracted paraoxon and parathion over the perfusion period. The extraction ratio was consistently greater in guinea pig than in rabbit lungs. The uptake velocity varied biexponentially in time, suggesting the existence of two compartments. Initial uptake velocities (A, B) and slopes (alpha and beta) were calculated for both compartments. In guinea pigs, A, B and A + B increased proportionally to the supply rate of paraoxon and parathion while a and b remained constant. No significant difference was observed between parathion and paraoxon uptake kinetics. Parameter B was the only one to differ significantly between the two species (rabbits: 8.19 +/- 1.53 for parathion and 6.85 +/- 1.26 for paraoxon; guinea pigs: 12.75 +/- 0.88 for parathion and 15.02 +/- 3.84 for paraoxon). In the lungs of both species, there was a linear relation between y, the percentage of cholinesterase inhibition induced by either organophosphate, and X, the total amount of drug taken up by the lung tissue (in nmol/g/18 min). The following equations were obtained: y = 0.128 x + 0.979 (R2 = 0.89, p < 0.001 for paraoxon); y = 0.120 x - 6.57 (R2 = 0.82, p < 0.005 for parathion). No difference was observed between the two organophosphates. After treatment with the cytochrome P450 inhibitor piperonyl butoxide, the above relations ceased to apply, but this treatment did not influence the kinetics of paraoxon and parathion uptake. The IC50 value calculated for paraoxon, i.e., the paraoxon concentration required to produce 50% inhibition of lung cholinesterase activity, was similar for guinea pigs (2.22 10(-7) +/- 0.22 M) and rabbits (2.36 10(-7) +/- 0.24 M). In conclusion, the biexponential evolution of the velocity of paraoxon and parathion uptake by the lungs thus demonstrates the presence of two pools. The lower extraction ratios calculated for rabbit lungs reflect the lower initial uptake velocity of the second compartment. In the range of concentrations investigated in guinea pigs, no saturable mechanism could be demonstrated for paraoxon and parathion. Cytochrome P450-related lung metabolic activity, through which parathion is converted to paraoxon, appears as a major step in parathion-induced lung cholinesterase inhibition, although it does not appear to affect parathion toxicokinetics.

Animals↗
PubMed1996

Identification and cellular localization of the actin-binding protein ABP-120 from Entamoeba histolytica.

Several actin-binding proteins participate in the morphological changes that occur during amoeboid movement. The gene encoding one of these proteins, the gelation factor ABP-120, was identified and characterized from trophozoites of Entamoeba histolytica. The sequence contains 2574 nucleotides, with an open reading frame of 858 amino acids, giving a protein of 93 kDa belonging to the spectrin family. The N-terminal domain of ABP-120 from E. histolytica revealed a consensus site for actin binding homologous to the actin-binding sites of ABP-120 of Dictyostelium discoideum, alpha-actinin and spectrin. Analysis of the central domain revealed the presence of four repeats of a 73-amino-acid motif constituting 31% of the protein. In addition, a stretch of 105 amino acids was highly divergent when compared with the C-terminal domain of D. discoideum ABP-120. This sequence showed short motifs that are homologous to microtubule-binding domains. We found that ABP-120 from E. histolytica binds to F-actin. In addition, upon motility of the parasite, this protein localized in the pseudopod and the uroid region, implying a role for ABP-120 in movement and capping of surface receptors in E. histolytica.

Actins↗