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F Vargas

Publications and source records attributed to F Vargas.

At least 37 records · Page 2Linked to original sources

First evidence of transmission of Leishmania (Viannia) lainsoni in a Sub Andean region of Bolivia.

Using ubiquitous primers which amplify the variable parts of kDNA minicircle of all Leishmania spp, we obtained for Leishmania (viannia) lainsoni a major band of 605 bp (band 1) shared with L. V. braziliensis and a minor 524 bp band (band 2) specific of L. V. lainsoni. The specificity of the two bands was examined through Southern blot hybridization of kDNA PCR obtained from reference strains belonging to L. braziliensis, L. mexicana, L. donovani complexes with L. V. lainsoni species. Band 1 was not specific of L. V. lainsoni since it hybridized with some isolates belonging to L. braziliensis complex. In contrast, band 2 was L. V. lainsoni specific. PCR-based detection followed by hybridization with the new L. V. lainsoni probe (Band 2) and L. V. braziliensis probe (564 bp), was assayed using sample from a pool of 25 females of Lutzomiya nuneztovari anglesi, blood, skin and liver samples of 18 mammals, spinal cords of four mammals and blood and cutaneous ulcers aspirates from 95 patents from Sub Andean region of La Paz, Bolivia. We observed a ositive hybridization of four patients lesions and the pool of L. nuneztovari anglesi with the L. V. lainsoni probe. It is the first time that L. V. lainsoni is observed in a cycle of transmission in Bolivia. PCR products of three patients lesions and the pool of L. nuneztovari anglesi were also hybridized with the specific probe of L. V. braziliensis suggesting mixed infection in this focus.

Animals↗

In vitro culture and biochemical characterization of six trypanosome isolates from Peru and Brazil.

Six trypanosomatids isolated from different geographical areas from South America (Peru and Brazil) and different vectors and reservoir hosts (the triatomine Panstrongylus chinai [TP1], Triatoma infestans [TP2], Rhodnius ecuadorensis [TP3], R. prolixus [TB1], Didelphys marsupialis [TB2]), and one from a human asymptomatic patient [TB3], were characterized using lectin agglutination, isoenzyme profile, in vitro culture final metabolite patterns, and compared with a reference strain (Trypanosoma cruzi, Maracay strain [TC]). The different isolates were cultured in vitro in Grace's medium supplemented with 10% inactivated bovine foetal serum. According to our results and the statistical study, the isolate obtained from R. ecuadorensis should be designed as a Trypanosoma rangeli sp., showing all other isolates strong similarities to T. cruzi. Between them, two clusters could be identified, strongly correlating with the geographical origin. Cluster I grouped isolates from Peru and T. cruzi reference strain, and cluster II grouped the three Brazilian isolates.

Agglutination Tests↗

Studies on the photostability and phototoxicity of aloe-emodin, emodin and rhein.

Aloe-emodin (1), emodin (2) and rhein (3) were found to be photolabile by visible (390-500 nm) light under aerobic conditions. The drugs 1, 2 and 3 were phototoxic in vitro when examined by the photohemolysis test under both oxygen and argon atmospheres, although the photohemolysis rate was markedly lower under anaerobic conditions. The experiments were also carried out in the presence of butylated hydroxyanisole (BHA), reduced glutathione (GSH), sodium azide (NaN3) and superoxide dismutase (SOD). Based on the inhibition of this process on addition of BHA, GSH, SOD and NaN3, there would seem to be involvement of free radicals (type I mechanism) and singlet oxygen in the process (type II mechanism). The in vitro phototoxicity of this anthraquinone series was also verified in a lipid-photoperoxidation test with linoleic acid. In summary, this anthraquinone series is phototoxic in vitro. This behavior can be explained through the involvement of singlet oxygen and stable photoproducts.

Acetylcholinesterase↗

Anti-Trypanosoma activity of some natural stilbenoids and synthetic related heterocyclic compounds.

We report the anti-Chagasic activity of the natural dihydrostilbenoid isonotholaenic acid and several simple derivatives, as well as that of some representative compounds of related synthetic series, with basic structures of benzalphthalides, dihydrostilbamides, isoindoles, phthalazin-1-ones, imidazo[2,1-a]isoindoles and pyrimido[2,1-a]isoindoles. The evaluation was performed in vitro on cultures of epimastigote and trypomastigote forms of Trypanosoma cruzi. Some of the tested compounds resulted to be as potent as benznidazole (epimastigotes), and others were shown to be more active than gentian violet (trypomastigotes), used as reference drugs.

Animals↗

Aminopeptidase activities after water deprivation in male and female rats.

Aminopeptidases (APs) play a major role in the metabolism of circulating and local peptides, such as angiotensins and vasopressin, substances involved in the control of blood pressure and water balance. In the present work, we studied the influence of dehydration on angiotensinases and vasopressin-degrading activity. Since sex differences may exist in the regulation of water balance by angiotensin II and differential sexual steroid modulation of vasopressin secretion, in response to osmotic stimulation have been reported, gonadotropin releasing hormone (GnRH)-degrading activity was also analysed in serum, neurohypophysis and adrenal glands of male and female rats. Our results did not suggest sex differences in the response to changes in osmolality. GnRH-degrading activity decreased in serum of dehydrated males and females, which suggests a longer action of the peptide under these conditions. In neurohypophysis, there was an increase in the activity of aminopeptidase A (APA), the enzyme responsible for the metabolism of angiotensin II to angiotensin III. This occurs with a decrease in alanyl aminopeptidase activity, which would lead to a prolonged action of angiotensin III by reduction of its metabolism. In adrenals of dehydrated animals, the results would imply a high degree of metabolism of angiotensin III and vasopressin.

Adrenal Glands↗

Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure.

BACKGROUND: Avoiding intubation is a major goal in the management of respiratory failure, particularly in immunosuppressed patients. Nevertheless, there are only limited data on the efficacy of noninvasive ventilation in these high-risk patients. METHODS: We conducted a prospective, randomized trial of intermittent noninvasive ventilation, as compared with standard treatment with supplemental oxygen and no ventilatory support, in 52 immunosuppressed patients with pulmonary infiltrates, fever, and an early stage of hypoxemic acute respiratory failure. Periods of noninvasive ventilation delivered through a face mask were alternated every three hours with periods of spontaneous breathing with supplemental oxygen. The ventilation periods lasted at least 45 minutes. Decisions to intubate were made according to standard, predetermined criteria. RESULTS: The base-line characteristics of the two groups were similar; each group of 26 patients included 15 patients with hematologic cancer and neutropenia. Fewer patients in the noninvasive-ventilation group than in the standard-treatment group required endotracheal intubation (12 vs. 20, P=0.03), had serious complications (13 vs. 21, P=0.02), died in the intensive care unit (10 vs. 18, P=0.03), or died in the hospital (13 vs. 21, P=0.02). CONCLUSIONS: In selected immunosuppressed patients with pneumonitis and acute respiratory failure, early initiation of noninvasive ventilation is associated with significant reductions in the rates of endotracheal intubation and serious complications and an improved likelihood of survival to hospital discharge.

Acute Disease↗

Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats.

1. The effects of an oral daily dose (10 mg kg(-1)) of the flavonoid quercetin for 5 weeks in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) were analysed. 2. Quercetin induced a significant reduction in systolic (-18%), diastolic (-23%) and mean (-21%) arterial blood pressure and heart rate (-12%) in SHR but not in WKY rats. 3. The left ventricular weight index and the kidney weight index in vehicle-treated SHR were significantly greater than in control WKY and these parameters were significantly reduced in quercetin-treated SHR in parallel with the reduction in systolic blood pressure. 4. Quercetin had no effect on the vasodilator responses to sodium nitroprusside or to the vasoconstrictor responses to noradrenaline or KCl but enhanced the endothelium-dependent relaxation to acetylcholine (E(max)=58+/-5% vs 78+/-5%, P<0.01) in isolated aortae. 5. The 24 h urinary isoprostane F(2 alpha) excretion and the plasma malonyldialdehyde (MDA) levels in SHR rats were increased as compared to WKY rats. However, in quercetin-treated SHR rats both parameters were similar to those of vehicle-treated WKY. 6. These data demonstrate that quercetin reduces the elevated blood pressure, the cardiac and renal hypertrophy and the functional vascular changes in SHR rats without effect on WKY. These effects were associated with a reduced oxidant status due to the antioxidant properties of the drug.

Acetylcholine↗

Effect of valsartan on angiotensin II- and vasopressin-degrading activities in the kidney of normotensive and hypertensive rats.

Valsartan, a selective antagonist of angiotensin II at the AT(1) receptor subtype, is an efficacious, orally active, blood pressure-lowering agent used in hypertensive patients. Given that aminopeptidases (APs) play a major role in the metabolism of local peptides involved in blood pressure control, studying them helped us to understand cardiovascular control. We studied the effect of valsartan on angiotensin II- (GluAP) and vasopressin- (CysAP) degrading activities in the kidney in the rat model of renovascular hypertension, Goldblatt two-kidney one-clip. GluAP and CysAP in renal cortex and medulla exhibited different responses to hypertension and valsartan treatment. In the renal cortex, GluAP decreased in clipped and non-clipped kidneys of hypertensive animals. However, while hypertension did not affect GluAP in the clipped kidney medulla, the non-clipped kidney exhibited an increase in soluble and a decrease in membrane-bound activity. Valsartan decreased soluble GluAP in the medulla of normotensive and hypertensive animals. In the renal cortex, CysAP activity was mainly downregulated following hypertension. Valsartan decreased soluble CysAP activity in sham-operated, but not in hypertensive animals. The renal medulla showed a significant valsartan-related decreased activity in clipped and non-clipped kidneys of both sham-operated and hypertensive animals. These results suggest a functional relationship between the AT(1) receptor and vasopressin-degrading activity.

Aminopeptidases↗

Bronchoscopy with bronchoalveolar lavage via the laryngeal mask airway in high-risk hypoxemic immunosuppressed patients.

OBJECTIVE: Fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) are major tools in the diagnosis of pulmonary complications in immunocompromised patients. Nevertheless, severe hypoxemia is an accepted contraindication to FOB in nonintubated patients. The purpose of this study was to evaluate the feasibility and safety of laryngeal mask airway (LMA)-supported FOB with BAL in immunosuppressed patients with suspected pneumonia and severe hypoxemia. DESIGN: Prospective, clinical investigation. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Forty-six immunosuppressed patients admitted to our intensive care unit with suspected pneumonia and Pao2/Fio2 < or = 125. INTERVENTIONS: After the administration of 0.3 mg x kg(-1) of etomidate, the patients were ventilated manually while receiving 1.0 Fio2. After the administration of 2.5 mg x kg(-1) of propofol, followed by an infusion of 9.1 +/- 2.3 mg x kg(-1) x hr(-1) of propofol, the LMA (size 3 or 4) was placed and connected to a bag-valve unit to allow manual ventilation with 1.0 Fio2. The FOB was introduced through a T-adapter attached to the LMA, and BAL was carried out with 150 mL of sterile 0.9% saline solution by sequential instillation and aspiration of 50-mL aliquots. MEASUREMENTS AND MAIN RESULTS: Three patients developed transient laryngospasm during passage of the bronchoscope via the LMA, which resolved with deepening of anesthesia. Changes in mean blood pressure, heart rate, Pao2/Fio2, and Paco2 values induced by the procedure did not reach significance. Seven patients (15%) presented hypotension (mean blood pressure, <60 mm Hg) maintained for 120 +/- 40 secs, which required plasma expanders in three cases. Oxygen desaturation to <90% occurred in six patients (13%) during BAL. Nevertheless, the lowest Sao2 during the procedure was significantly higher than the initial Sao2 (94% +/- 4% vs. 90% +/- 2%). No patient required tracheal intubation during the 8 hrs after the procedure. BAL had an overall diagnostic yield of 65%. Because of the results obtained by using the BAL analysis, treatment was modified in 33 (72%) cases. CONCLUSION: Application of the LMA appears to be a safe and effective alternative to intubation for accomplishing FOB with BAL in immunosuppressed patients with suspected pneumonia and severe hypoxemia.

Aged↗

Comparison of B-mode ultrasound and computed tomography in the diagnosis of maxillary sinusitis in mechanically ventilated patients.

OBJECTIVE: To compare B-mode ultrasound with sinus computed tomograph (CT) scan in the diagnosis of sinusitis in intubated patients undergoing mechanical ventilation. DESIGN: Prospective, clinical investigation. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Fifty patients undergoing intubation and mechanical ventilation more than 2 days, with a clinical suspicion of paranasal sinusitis with purulent nasal discharge. INTERVENTIONS: One hundred paranasal sinuses were examined. A paranasal CT scan and a B-mode ultrasound were performed the same day. Radiologic maxillary sinusitis (RMS) was defined as complete opacification of the sinus or as the presence of an air-fluid level. Absence of RMS was defined as normal sinus or as the presence of mucosal thickening. Important RMS was defined by total opacity or air-fluid level larger than half of the sinus area. Moderate RMS was defined by air-fluid level inferior than half of the sinus area. For ultrasonographic procedure, the image defined as normal was an acoustic shadow arising from the front wall. Two levels of positive echography were described: 1) a moderate lesion was defined as the visualization only of the hyperechogenic posterior wall of the sinus; 2) an important lesion was defined as the hyperechogenic visualization of posterior wall and the extension by the internal wall of the sinus outlining the hypoechogenic sinus cavity. MEASUREMENTS AND MAIN RESULTS: Sensibility, specificity, positive predictive value, and negative predictive value of B-mode ultrasound compared with CT were, respectively: 100% (95% confidence intervals [95% CI] = 94.9-100.0), 96.7% (95% CI = 82.8-99.9), 98.6% (95% CI = 92.4-99.9), and 100% (95% CI = 88.1-100). The concordance between a moderate B-mode ultrasound lesion and a moderate RMS on CT, and between an important B-mode ultrasound lesion and an important RMS on CT, assessed using kappa statistics was 93%. The concordance between B-mode ultrasound's results and CT's results assessed using weighted kappa statistics was 97%. CONCLUSION: B-mode ultrasound may be proposed first-line in a ventilated patient with suspicion of maxillary sinusitis.

Cross Infection↗

Engraftment of islets obtained by collagenase and Liberase in diabetic rats: a comparative study.

INTRODUCTION: Islet transplantation is an attractive solution for type I diabetes, but the results are at the present discouraging. Collagenase, the enzyme used to obtain islets for transplantation, presents interbatch variability and endotoxin contamination that induces inflammatory cytokine production. Liberase (Roche, Basel, Switzerland), a new mixture of purified enzymes, has the same composition in all batches and is endotoxin-free. AIMS: To compare the engraftment of islets obtained using either enzyme in streptozotocin-induced diabetic rats. METHODOLOGY: Collagenase- or Liberase-isolated islets were transplanted under the kidney capsule of diabetic rats. Collagenase islets restored glycemia and insulinemia in all animals at 24 hours, and both parameters were maintained in 45% of rats over 90 days; however, Liberase islets failed to reverse diabetes in all subjects. RESULTS: In vitro experiments showed that Liberase islets did not maintain active insulin secretion. Cytotoxicity assays showed toxicity of Liberase to islets; both enzymes induced inflammatory cytokine production by macrophages. CONCLUSION: In summary, in our model, Liberase is not a good substitute for collagenase as an islet-isolating reagent. A major effort and investment in developing enzymes for tissue dispersion is needed to improve the outcome of islet transplantation.

Animals↗

Isoenzyme profiles of Trypanosoma cruzi stocks from different areas of Paraguay.

Twenty one Trypanosoma cruzi stocks from humans, domiciliary triatomines and one sylvatic animal of different areas of Paraguay were subjected to isoenzyme analysis. Thirteen enzyme systems (15 loci in total) were studied. MN cl2 (clonets 39) and SO34 cl4 (clonets 20) were used as references. Relationships between stocks were depicted by an UPGMA dendrogram constructed using the Jaccard's distances matrix. Among the Paraguayan stocks 14 zymodemes were identified (Par1 to Par14), Par 5 being the most frequent. Polymorphism rate and clonal diversity were 0.73 and 0.93, respectively. Average number of alleles per polymorphic locus was 2.5 (range 2-4). These measurements show a high diversity, which is confirmed by the dendrogram topology. All stocks belong to the same lineage, as MN cl2 reference strain (T. cruzi II). Moreover three distinct subgroups were identified and two of them correspond to Brazilian and Bolivian zymodemes, respectively. The third subgroup, the most common in Paraguay, is related to Tulahuen stock. The large geographical distribution of some zymodemes agrees with the hypothesis of clonality for T. cruzi populations. However sample size was not adequate to detect genetic recombination in any single locality.

Alleles↗

Photosensitizing activity of thiocolchicoside: photochemical and in vitro phototoxicity studies.

The phototoxic drug thiocolchicoside (2-dimethoxy-2-glucosidoxythiocolchicine, 1), is photolabile under irradiation with UV-A light from TL 100 W-P Philips bulbs (at lambda max 355 nm) light and also with a N2 laser (at 337 nm) in aerobic and anaerobic conditions. Irradiation of a methanol solution of 1 produces two photoproducts without a glucoside group. One of these lost the methylthio-group, while the other is oxidized (only under aerobic conditions) to sulfoxide. The formation of singlet oxygen by photolysis of 1 was evidenced by trapping with 2,5-dimethylfuran (GC-MS), furfuryl alcohol, 1,3-cyclohexadiene-1,4-diethanoate (HPLC) and by the histidine test as 1O2 scavengers. Thiocolchicoside has been shown to photosensitize the reduction of nitro blue tetrazolium by direct electron transfer mechanism, when irradiated under the same conditions as for photolysis. Oxygen may also be involved in this electron transfer reaction to form the superoxide anion radical. Thiocolchicoside was screened in vitro in different concentrations for UV-Vis-induced phototoxic effects in a photohemolysis test, in the presence and absence of different radical scavengers, singlet oxygen and superoxide radical quenchers. In addition, 1 photosensitized the peroxidation of linoleic acid, monitored by the UV-detection of dienic hydroperoxides. Studies on peripheral blood mononuclear cells (lymphocytes) demonstrated phototoxic effects on them. Protection by GSH, DABCO, sodium azide and SOD are indicative of both Type I and II photosensitization pathways mediated by free radicals and singlet molecular oxygen.

Colchicine↗

[Usefulness of brain stem auditory evoked potentials].

The neonates, children under 4 years and patients with central nervous system pathology are a population that need a screening test to estimate the hearing threshold. ABR-test (auditory brainstem response) is a viable and effective tool for identification a hearing impairment.

Central Nervous System Diseases↗

Inhibitors of tripeptidyl peptidase II. 2. Generation of the first novel lead inhibitor of cholecystokinin-8-inactivating peptidase: a strategy for the design of peptidase inhibitors.

The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase which has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO(3)H)-Met-OH + Gly-Trp-Met-Asp-Phe-NH(2). In seeking a reversible inhibitor of this peptidase, the enzymatic binding subsites were characterized using a fluorimetric assay based on the hydrolysis of the artificial substrate Ala-Ala-Phe-amidomethylcoumarin. A series of di- and tripeptides having various alkyl or aryl side chains was studied to determine the accessible volume for binding and to probe the potential for hydrophobic interactions. From this initial study the tripeptides Ile-Pro-Ile-OH (K(i) = 1 microM) and Ala-Pro-Ala-OH (K(i) = 3 microM) and dipeptide amide Val-Nvl-NHBu (K(i) = 3 microM) emerged as leads. Comparison of these structures led to the synthesis of Val-Pro-NHBu (K(i) = 0.57 microM) which served for later optimization in the design of butabindide, a potent reversible competitive and selective inhibitor of the CCK-8-inactivating peptidase. The strategy for this work is explicitly described since it illustrates a possible general approach for peptidase inhibitor design.

Aminopeptidases↗