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Biomedical subjects

C Pérez

Publications and source records attributed to C Pérez.

At least 19 recordsLinked to original sources
PubMed1999

Flavor preferences conditioned by intragastric nutrient infusions in rats fed chow or a cafeteria diet.

Numerous studies demonstrate that chow-fed rats learn to prefer flavors that are associated with the postingestive effects of nutrients. The rats>> limited dietary experience (i.e. only lab chow) may have facilitated preference learning because of the novelty of the training stimuli. This possibility was investigated by comparing nutrient conditioning in rats fed chow or a varied "cafeteria" diet. Rats in Experiment 1 were trained during alternate sessions (30 min/day) to drink two different flavors paired with concurrent intragastric infusions of 16% Polycose or water. Both diet groups displayed similarly strong preferences (89%) for and increased acceptance of the Polycose-paired flavor. A more demanding learning task was used in Experiment 2: new flavors were paired with delayed (15 min) infusions of Polycose or water. The chow and cafeteria groups both showed reduced, but comparable (78%, 77%) preferences for the Polycose-paired flavor. In Experiment 3, new flavors were paired with concurrent infusions of 7.1% corn oil or water. Again, the cafeteria and chow groups developed similar preferences for the nutrient-paired flavor (85%, 78%). Also, both groups preferred the Polycose-paired flavor of Experiment 1 to the oil-paired flavor of Experiment 3 (76%, 78%). These results indicate that dietary variety does not interfere with nutrient-conditioned flavor preference learning in rats.

Animals↗
PubMed1998

Abasic analogues of TSAO-T as the first sugar derivatives that specifically inhibit HIV-1 reverse transcriptase.

With the aim of assessing the role that the thymine base of TSAO-T may play in the interaction of TSAO compounds with HIV-1 reverse transcriptase (RT), we have designed, synthesized, and evaluated for their anti-HIV-1 activity a series of 3-spiro sugar derivatives substituted at the anomeric position with nonaromatic rings or with amine, amide, urea, or thiourea moieties that mimic parts or the whole thymine base of TSAO-T. Also, a dihydrouracil TSAO analogue and O-glycosyl 3-spiro sugar derivatives substituted at the anomeric position with methyloxy or benzyloxy groups have been prepared. Compounds substituted at the anomeric position with an azido, amino, or methoxy group, respectively, were devoid of marked antiviral activity (EC50: 10-200 microM). However, the substituted urea sugar derivatives led to an increase in antiviral potency (EC50: 0.35-4 microM), among them those urea derivatives that mimic most closely the intact TSAO-T molecule retained the highest antiviral activity. Also, the dihydrouracil TSAO derivative retained pronounced anti-HIV-1 activity. None of the compounds showed any anti-HIV-2 activity. The results described herein represent the first examples of sugar derivatives that interact in a specific manner with HIV-1 RT. Molecular modeling studies carried out with a prototype urea derivative indicate that a heteroaromatic ring is not an absolute requirement for a favorable interaction between TSAO-T and HIV-1 RT. Urea derivatives, which can mimic to a large extent both the shape and the electrostatic potential of a thymine ring, can effectively replace this nucleic acid base when incorporated into a TSAO molecular framework with only moderate loss of activity.

Animals↗
PubMed1998

Increased flavor acceptance and preference conditioned by the postingestive actions of glucose.

In Experiment 1, rats were given daily 2-h access to chow and water and 20-h access to flavored solutions (cherry or grape). On alternate days, one flavor (CS+) was paired with intragastric infusions of 16% glucose and another flavor (CS-) with IG water. In subsequent choice tests, the rats strongly preferred (95%) the CS+ to the CS-. CS+ intake also greatly exceeded CS- intake during one-bottle training sessions (71 vs. 18 g/20 h). This increased acceptance was due to both increased bout size and number. When CS+ was paired with IG water (extinction test), CS+ bout size declined to CS- levels, while CS+ bout number and total intake remained elevated. In Experiment 2, rats trained with sucrose octa acetate and citric acid solutions also showed increased CS+ acceptance and preference in one- and two-bottle tests, respectively. The rats also consumed more CS+ than CS- during short-term (30 min/day) one-bottle tests and intraoral intake tests under both deprived and ad lib. feeding conditions. These results demonstrate that the postingestive actions of glucose can condition substantial increases in flavor acceptance as well as flavor preference.

Animals↗
PubMed1998

Comparative binding energy analysis of HIV-1 protease inhibitors: incorporation of solvent effects and validation as a powerful tool in receptor-based drug design.

A comparative binding energy (COMBINE) analysis (Ortiz et al. J. Med. Chem. 1995, 38, 2681-2691) has been performed on a training set of 33 HIV-1 protease inhibitors, and the resulting regression models have been validated using an additional external set of 16 inhibitors. This data set was originally reported by Holloway et al. (J. Med. Chem. 1995, 38, 305-317), who showed the usefulness of molecular mechanics interaction energies for predicting the activity of novel HIV-1 protease inhibitors within the framework of the MM2X force field and linear regression techniques. We first used the AMBER force field on the same set of three-dimensional structures to check up on any possible force-field dependencies. In agreement with the previous findings, the calculated raw ligand-receptor interaction energies were highly correlated with the inhibitory activities (r2 = 0.81), and the linear regression model relating both magnitudes had an acceptable predictive ability both in internal validation tests (q2 = 0.79, SDEPcv = 0.61) and when applied to the external set of 16 different inhibitors (SDEPex = 1.08). When the interaction energies were further analyzed using the COMBINE formalism, the resulting PLS model showed improved fitting properties (r2 = 0.89) and provided better estimations for the activity of the compounds in the external data set (SDEPex = 0.83). Computation of the electrostatic part of the ligand-receptor interactions by numerically solving the Poisson-Boltzmann equation did not improve the quality of the linear regression model. On the contrary, incorporation of the solvent-screened residue-based electrostatic interactions and two additional descriptors representing the electrostatic energy contributions to the partial desolvation of both the ligands and the receptor resulted in a COMBINE model that achieved a remarkable predictive ability, as assessed by both internal (q2 = 0.73, SDEPcv = 0.69) and external validation tests (SDEPex = 0.59). Finally, when all the inhibitors studied were merged into a single expanded set, a new model was obtained that explained 91% of the variance in biological activity (r2 = 0.91), with very high predictive ability (q2 = 0.81, SDEPcv = 0.66). In addition, the COMBINE analysis provided valuable information about the relative importance of the contributions to the activity of individual residues that can be fruitfully used to design better inhibitors. All in all, COMBINE analysis is validated as a powerful methodology for predicting binding affinities and pharmacological activities of congeneric ligands that bind to a common receptor.

Drug Design↗
PubMed1998

Devazepide, a CCK(A) antagonist, attenuates the satiating but not the preference conditioning effects of intestinal carbohydrate infusions in rats.

Endogenous cholecystokinin (CCK) is thought to participate in the satiating action of foods, and some data suggest that it may also mediate their postingestive reinforcing effects. This was investigated by determining if the CCK(A) receptor antagonist, devazepide, attenuates flavor preference conditioning by intraduodenal (I.D.) carbohydrate infusions. In Experiment 1, food-restricted female rats were trained 30 min/day to associate a cue flavor (CS+) with I.D. infusions of 8% Polycose and a different flavor (CS ) with I.D. water infusions. Half of the rats (DEV group) were pretreated with devazepide (300 microg/kg body weight) and the other half (CON group) with vehicle, 30 min prior to CS training sessions and choice tests. Both groups displayed similar CS+ preferences (CON: 68%; DEV: 69%). In contrast, devazepide blocked the feeding inhibitory effects of I.D. Polycose infusion and cholecystokinin octapeptide injection in Experiment 2. A higher dose of devazepide (1200 microg/kg) also failed to inhibit preference conditioning by I.D. Polycose in Experiment 3. These results indicate that, although CCK(A) mechanisms play a role in the satiating effect of I.D. carbohydrates, they do not mediate their reinforcing effect. The present study, along with other recent reports, indicate that different mechanisms mediate the satiating and reinforcing actions of nutrients.

Animals↗
PubMed1998

Hypoglycemic action of an oral fig-leaf decoction in type-I diabetic patients.

The effect of a decoction of fig leaves (Ficus carica), as a supplement to breakfast, on diabetes control was studied in insulin-dependent diabetes mellitus (IDDM) patients (six men, four women, age 22-38 years, body mass index (BMI): 20.8 +/- 3.0 kg/m2, HbA1c 7.6 +/- 0.9% with a mean duration of diabetes of 9 +/- 6.3 years). The patients were managed with their usual diabetes diet and their twice-daily insulin injection. During the first month, patients were given a decoction of fig leaves (FC) and during the next month a non-sweet commercial tea (TC). The patients were divided into two groups (n = 5) with random allocation and cross-over design. A standard breakfast was given at the beginning and end of each month-run. C-peptide, 2 h pre- and post-prandial glycemia, HbA1c, cholesterol, lipid fractions and hematology data, were analyzed during each visit. Glycemic profiles (7/day per week) were recorded by patients. Only two patients had intolerance dropout. Post-prandial glycemia was significantly lower during supplementation with FC 156.6 +/- 75.9 mg/dl versus TC 293.7 +/- 45.0 mg/dl (P < 0.001) without pre-prandial differences 145.0 +/- 41.5 and 196.6 +/- 43.2 mg/dl, respectively. Medium average capillary profiles were also lower in the two sub-groups of patients during FC 166.7 +/- 23.6 mg/dl, P < 0.05 and 157.1 +/- 17.0 mg/dl versus TC 245.8 +/- 14.2 mg/dl and 221.4 +/- 27.3 mg/dl. Average insulin dose was 12% lower during FC in the total group. The addition of FC to diet in IDDM could be of help to control postprandial glycemia.

Administration, Oral↗
PubMed1998

Antidiarrhoeal activity of Waltheria americana, Commelina coelestis and Alternanthera repens.

The antidiarrhoeal activity of the hexane, chloroform, methanol and aqueous extracts of Waltheria americana, Commelina coelestis and Alternathera repens, was tested on mice with diarrhoea induced by castor oil and MgSO4. The methanol extract of C. coelestis and A. repens and aqueous extract of A. repens, presented antidiarrhoeal effect, monitored by number of liquid feces defecated and intestinal transit of a suspension of graphite with castor oil in Wistar rats.

Administration, Oral↗
PubMed1998

Regiospecific synthesis and anti-human immunodeficiency virus activity of novel 5-substituted N-alkylcarbamoyl and N,N-dialkylcarbamoyl 1,2,3-triazole-TSAO analogues.

Several 5-N-alkyl and 5-N,N-dialkylcarbamoyl substituted analogues of the anti-human immunodeficiency virus (HIV) type 1 lead compound [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-5- (N,N-dimethylcarbamoyl)-1,2,3-triazole]-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"-dioxide) have been prepared and evaluated as inhibitors of HIV-1 replication. A new regiospecific synthetic procedure is described. The compounds were prepared by cycloaddition of the appropriate glycosylazide to 2-oxoalkylidentriphenyl-phosphoranes, followed by treatment with primary or secondary amines, to yield, exclusively, 5-substituted 1,2,3-triazole-TSAO analogues. Several 5-substituted 1,2,3-triazole-TSAO derivatives proved to be potent inhibitors of HIV-1 replication with higher antiviral selectivity than that of the parent TSAO prototype.

Anti-HIV Agents↗
PubMed1998

cAMP increasing agents attenuate the generation of apoptosis by etoposide in promonocytic leukemia cells.

Treatment of U-937 promonocytic cells with the DNA topoisomerase II inhibitor etoposide rapidly caused death by apoptosis, as determined by changes in chromatin structure, production of DNA breaks, nucleosome-sized DNA degradation, decrease in mitochondrial membrane potential and phosphatidyl serine translocation in the plasma membrane, and at the same time induced intracellular acidification. Both the execution of the apoptotic process and the intracellular acidification were reduced by the addition of forskolin plus theophylline or other cAMP increasing agents. These agents also attenuated the induction of apoptosis by camptothecin, heat-shock, cadmium chloride and X-radiation. Although etoposide slightly increased the production of reactive oxygen intermediates, this increase was not prevented by forskolin plus theophylline, and the addition of antioxidant agents failed to inhibit apoptosis. Etoposide caused a great increase in NF-(kappa)B binding activity, which was not prevented by forskolin plus theophylline, while AP-1 binding was little affected by the topoisomerase inhibitor. The treatments did not significantly alter the levels of Bcl-2 and Bax. By contrast, the expression of c-myc, which was very high in untreated U-937 cells and only partially inhibited by etoposide, was rapidly and almost totally abolished by the cAMP increasing agents. Finally, it was observed that etoposide caused a transient dephosphorylation of retinoblastoma (Rb), which was associated with cleavage of poly(ADP-ribose) polymerase (PARP). Both Rb dephosphorylation and PARP cleavage were inhibited by forskolin plus theophylline. The inhibition of Rb (type I) phosphatase and ICE/CED-3-like protease activities, and the abrogation of c-myc expression, are mechanisms which could explain the anti-apoptotic action of cAMP increasing agents in myeloid cells.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Treatment of chronic Chagas' disease with itraconazole and allopurinol.

Four hundred four patients with chronic Chagas' disease were treated with itraconazole (6 mg/kg of body weight/day for 120 days), allopurinol (8.5 mg/kg of body weight/day for 60 days), or with a placebo of pure starch. Patients were monitored over a period of four years by clinical examination, serology, xenodiagnosis, hemoculture, and electrocardiogram. Drug tolerance was good, with only four treatments discontinued due to side effects that subsided after suspension of treatment. Parasitologic cure was evident in 44% of the those treated with allopurinol and 53% of those treated with itraconazole, and the electrocardiographic evaluation showed normalization in 36.5% and 48.2%, respectively, of patients with chronic or recent cardiopathy.

Adolescent↗
PubMed1998

[Resistance of human immunodeficiency virus (HIV) to zidovudine. Genotypic analysis in strains isolated from Chilean patients].

BACKGROUND: Resistance of HIV to AZT is the result of mutations in the pol gene that codifies the enzyme reverse transcriptase. AIM: To assess the resistance to antiretroviral drugs in Chilean patients infected with HIV. MATERIAL AND METHODS: The presence of mutations was searched in 22 patients infected with HIV. The emergence or persistence of these mutations was studied in sequential samples of 19 patients. The presence of the mutation that confers resistance to didanosine (DDI) was studied in those subjects exposed to the drug. Polymerase chain reaction techniques were used to analyze mutations in codons 41, 70 and 215 of the pol gene (resistance to AZT) and the mutation in codon 71 (resistance to DDI). RESULTS: On admission, none of the patients without previous exposure to AZT had drug resistance mutations. Seven of 12 patients (58.3%) that had received AZT had mutations in codon 215. In two, they were associated to a mutation in codon 41 and in two, a mutation in codon 70. After a mean follow up of 14 months, 13 of 15 patients (86%) that received AZT had viral strains genotypically resistant to the drug. In nine of these, the resistance was associated with disease progression. None of the 10 patients that received DDI had the mutation in codon 74 that confers resistance to the drug. However, in one of these patients, that never received AZT, a virus with a mutation in codon 215 was detected. CONCLUSIONS: A high percentage of patients that have received monotherapy with AZT have genotypic resistance to the drug. This resistance is associated with clinical and immunological derangement in 70% of these subjects.

Anti-HIV Agents↗
PubMed1998

[Variability of the Boston test for the diagnosis of aphasia in active working adults].

INTRODUCTION: The aim of this study was to analyze the influence of age, gender, socioeconomic status (SES), academic achievement (education), and type of occupation, on the performance of the Boston Diagnostic Aphasia Examination (BDAE) Spanish version. MATERIAL AND METHODS: The BDAE was administered to a group of 156, 19 to 60 years old, occupationally active normal subjects. RESULTS: A descriptive analysis showed that some subjects (1 to 3%) scored in the pathological range of the centiles and profiles of the BDAE. A MANOVA (p < 0.05) demonstrated a significant effect of education over most of the BDAE subtests. Females outperformed males on some reading and writing subtests. SES had an effect over body part identification and naming. Significant differences were observed between younger and middle age groups in confrontation naming, oral and word picture reading. The older group scored significantly lower than the younger group in serial writing and sentences to dictation. No differences were observed between the older and the middle groups. Only oral spelling was affected by the type of occupation but a significant interaction of occupation and level of education was found. CONCLUSIONS: Language tests are influenced by demographic variables, particularly education. Normal variability on the BDAE should be considered when dealing with clinical populations.

Adolescent↗
PubMed1998

[Antibody radiolabeling with technetium-99m].

Nowadays, labelled polyclonal and monoclonal antibodies are widely used for immunoscintigraphic diagnosis of different diseases. Technetium-99m is often considered to be the label of choice for radioimmunodiagnosis for reasons of cost, availability and imaging properties, in spite of its relatively short physical half-life (6.01 h). The existing labelling methods may be classified into two types: direct approaches, in which disulphide bridges within are reduced to generate endogenous sulfhydryl groups able to efficiently bind technetium due to their strong chelating capacity and indirect methods, in which an exogenous chelator is covalently attached to the protein to serve as the binding site. All these procedures have their advantages and drawbacks. There is no consensus among the authors about which of the methods is the best. The employed approach depends on the particular situation. The aim of the present work is to show an update about the available procedures for 99mTc-labelling of antibodies and its fragments.

Antibodies↗
PubMed1998

The health of northern residents.

OBJECTIVES: This article examines differences in health status and health determinants between residents of the North (Yukon and Northwest Territories) and of the provinces, and between Aboriginal and non-Aboriginal territorial residents. The use of health services and medications is also analyzed. DATA SOURCE: The data are from the 1994/95 National Population Health Survey (NPHS), both the territorial and provincial components. The population analyzed consists of household residents aged 12 and older. MAIN RESULTS: Compared with non-Aboriginal Northerners, Aboriginal people in the territories more frequently rated their health poorly. However, they reported fewer injuries and diagnosed chronic conditions. The prevalence of alcohol consumption was lower among Aboriginal people, while the proportion of smokers was substantially higher. A lower proportion of Aboriginal territorial residents had consulted a general practitioner in the previous year, and a higher proportion had consulted a nurse. Aboriginal people also had a low rate of medication use.

Adolescent↗
PubMed1998

Chronic hepatitis C: treatment comparison between 3 and 5 million units of interferon alpha-2b.

Interferon (IFN) is the only drug that has been approved by the FDA for therapy of chronic hepatitis C. However, optimal dose and duration of therapy are still controversial. This study compares the effectiveness of treatment of chronic hepatitis C patients with 3 vs. 5 million units (MU) of recombinant alpha-interferon 2-b three times per week. We also evaluated the relapse rate with a shorter 12 week-course of therapy in those patients who had normalization of aminotransferases by week 12. Seventy-five patients were randomized to receive either 3 vs. 5 MU of IFN; seventy-two completed the study. A complete response was seen in 11/35 (31%) of those treated with 5 MU vs. 13/37 (35%) in the 3 MU dose (p = 0.74). Patients were followed after IFN was withdrawn and only 2 had persistently normal aminotransferases. Analysis of multiple variables was done to predict response to IFN and only elevations of GGT, ferritin and alkaline phosphatase were found to be predictors of a poor response. Therefore, we recommend initial therapy with 3 MU of IFN for a longer period than 12 weeks in patients who show a response.

Adult↗
PubMed1998

Attitudes toward smoking.

OBJECTIVES: This article examines socio-demographic variations in attitudes about the health effects of smoking, second-hand smoke, and the importance of smoke-free environments. DATA SOURCE: The data are from the Health file of the 1996/97 cross-sectional provincial household component of the National Population Health Survey, conducted by Statistics Canada. The sample consists of 60,260 respondents aged 12 or older. ANALYTICAL TECHNIQUES: Three smoking attitudes scores were derived. Multivariate analyses were used to study how age, sex, educational attainment, province and smoking status were associated with attitude scores. MAIN RESULTS: Smokers placed less emphasis than non-smokers on the health risks associated with smoking. Older Canadians, particularly smokers aged 65 and older, tended to have more lenient attitudes toward smoking, compared with younger age groups. Respondents with high school education or less held more lenient attitudes, compared with those with a university degree. Quebec residents were more tolerant of tobacco use than were residents of other provinces.

Adolescent↗
PubMed1997

Rearrangement of interstrand cross-links into intrastrand cross-links in cis-diamminedichloroplatinum(II)-modified DNA.

In the reaction of the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP) with DNA, bifunctional intrastrand and interstrand cross-links are formed. In this work, we show that at 37 degrees C interstrand cross-links (ICL) are labile and rearrange into intrastrand cross-links. The ICL instability was first studied with a 10 base pairs (bp) double-stranded oligonucleotide containing a unique site-specific ICL resulting from chelation of the N7 position of two guanine residues on the opposite strands of DNA at the d(GC/GC) site by a cis-diammineplatinum(II) residue. The bonds between the platinum and the N7 of guanine residues within the interstrand adduct are cleaved. In 50 mM NaCl or NaClO4, this cleavage results in the formation of monofunctional adducts which subsequently form intrastrand cross-links. One cleavage reaction takes place per cross-linked duplex in either of both DNA strands. Whereas the starting cross-linked 10 bp duplex is hydrogen bonded, the two complementary DNA strands separate after the cleavage of the ICL. Under these conditions, the cleavage reaction is irreversible allowing its rate measurement (t1/2= 29+/-2 h) and closure of monofunctional adducts to intrastrand cross-links occurs within single-stranded DNA. Within a longer cross-linked oligonucleotide (20 bp), ICL are apparently more stable (t1/2= 120+/-12 h) as a consequense of monofunctional adducts closure back to ICL. We propose that the ICL cleavage is reversible in DNA and that these adducts rearrange finally into intrastrand cross-links. Our results could explain an 'ICL unhooking' in previously reported in vivo repair studies [Zhenet al. (1993)Carcinogenesis14, 919-924].

Antineoplastic Agents↗