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Biomedical subjects

C Carrasco

Publications and source records attributed to C Carrasco.

36 records · Page 2Linked to original sources
PubMed1998

Syntheses and biological evaluation of indolocarbazoles, analogues of rebeccamycin, modified at the imide heterocycle.

A series of 10 indolocarbazole derivatives, analogues to the antitumor antibiotic rebeccamycin, bearing modifications at the imide heterocycle were synthesized. They bear an N-methyl imide, N-methyl amide, or anhydride function instead of the original imide. Their inhibitory potencies toward topoisomerase I were examined using a DNA relaxation assay and by analyzing the drug-induced cleavage of 32P-labeled DNA. Protein kinase C (PKC) inhibition and interaction with DNA were also studied together with the in vitro antiproliferative activities against B16 melanoma and P388 leukemia cells. The antimicrobial activities against two Gram-positive bacteria (Bacillus cereus and Streptomyces chartreusis), a Gram-negative bacterium (Escherichia coli), and a yeast (Candida albicans) were tested as well as their antiviral activities toward HIV-1. The efficiency of the anhydride compounds was compared to that of the parent compound rebeccamycin and its dechlorinated analogue. All the compounds studied were inactive against PKC. The structural requirements for PKC and topoisomerase I inhibition are markedly different. In sharp contrast with the structure-PKC inhibition relationships, we found that an anhydride function does not affect topoisomerase I inhibition, whereas a methyl group on the indole nitrogen prevents the poisoning of topoisomerase I. The compounds exhibiting a marked toxicity to P388 leukemia cells had little or no effect on the growth of P388CPT5 cells which are resistant to the topoisomerase I inhibitor camptothecin. This study reinforces the conclusion that the DNA-topoisomerase I cleavable complex is the primary cellular target of the indolocarbazoles and significantly contributes to their cytotoxicity and possibly to their weak but noticeable anti-HIV-1 activities. The structure-activity relationships are also discussed.

Aminoglycosides↗
PubMed1998

Substitution of 5-methylcytosines for cytosines enhances the stability of topoisomerase I-DNA complexes and modulates the sequence selectivity of camptothecin-induced DNA cleavage.

We have investigated the binding and cleavage of DNA by human topoisomerase I using a 160 bp restriction fragment containing either natural bases or 5-methylcytosine residues in place of cytosines. Experiments were performed in the presence and absence of the antitumour drug camptothecin which specifically inhibits topoisomerase I. Replacement of all cytosines with 5-methylcytosine residues (i) reinforces the enzyme-DNA interaction, (ii) enhances the stability of topoisomerase I-DNA complexes and (iii) modulates the sequence selectivity of camptothecin-induced DNA cleavage. The methyl group exposed in the major groove of the double helix is identified as a critical element for the interaction between topoisomerase I and DNA.

5-Methylcytosine↗
PubMed1998

Troponin-T is a calcium-binding protein in insect muscle: in vivo phosphorylation, muscle-specific isoforms and developmental profile in Drosophila melanogaster.

Two sets of muscle polypeptides showing calcium-binding capacity and intense labelling in vivo with 32P were purified and characterized from Drosophila melanogaster adult extracts. The polypeptides exhibit crossed immunoreactivity and share similar biochemical properties such as those involved in purification. They have been identified as isoforms of troponin-T (TnT) by sequence analysis of a cDNA clone isolated from an embryonic library. The two sets of TnT polypeptides correspond to the fibrillar and non-fibrillar muscle isoforms, respectively. The non-fibrillar muscle isoforms separate into two bands which are differentially expressed during development. Analysis of TnT isoforms in bee thoraces indicates that the expression of the fibrillar muscle isoform correlates with the acquisition of functional flight capability. In vivo labelling experiments reveal that the two TnT sets are readily phosphorylated. The Drosophila TnTs show calcium-binding properties by three different types of assays. Our results suggest that this property could be specific to insect TnTs and may be related to the long, extremely acidic polyglutamic carboxy-terminus present in these polypeptides, which does not occur in non-arthropod TnTs.

Amino Acids↗
PubMed1997

Stimulation of the sympathetic perimesenteric arterial nerves releases neuropeptide Y potentiating the vasomotor activity of noradrenaline: involvement of neuropeptide Y-Y1 receptors.

Neuropeptide Y (NPY) appears to be involved in the sympathetic regulation of vascular tone. To assess the putative role of NPY in mesenteric circulation, the release and biological effect of NPY were examined after electrical stimulation of perimesenteric arterial nerves. Nerve stimulation with trains of 2-30 Hz increased the perfusion pressure of the arterially perfused rat mesenteric bed in a frequency- and time-dependent fashion. Trains of 15-30 Hz significantly displaced to the left, approximately threefold, the noradrenaline (NA)-induced pressor concentration-response curve, in addition to increasing significantly its efficacy. Perfusion with 10 nM exogenous NPY mimicked the electrical stimulation effect, causing a threefold leftward shift of the NA concentration-response curve and increasing the maximal NA response. These effects were antagonized by 100 nM BIBP 3226, indicating the activity of NPY-Y1 receptors. Electrical stimulation of the perimesenteric nerves released immunoreactive NPY (ir-NPY) in a frequency-dependent fashion; the ir-NPY coelutes with synthetic NPY as confirmed by HPLC. Both the electrically induced pressor response and the calcium-dependent release of NPY were obliterated in preparations perfused with 1 microM guanethidine or in rats pretreated intravenously for 48 h with 6-hydroxydopamine, thus revealing the sympathetic origin of these phenomena. Only a small proportion of the total NPY content in the perimesenteric arterial nerves is released after electrical stimulation. Chromatographic studies of the physiological sources of the ir-NPY support that NPY fragments are generated via peptidase degradation. The present findings demonstrate that NPY is released from the perimesenteric arterial sympathetic nerves and acts, via the activation of NPY-Y1 receptors, as the mediator responsible for the potentiation of NA's effect on perfusion pressure in the isolated rat mesenteric bed.

Animals↗
PubMed1997

A morphological study in the kidney and spleen of gilthead, Sparus aurata, L. caused by sodium dodecyl sulphate.

This paper reports the morphological changes in the kidney and spleen of gilthead (Sparus aurata, L), caused by acute action of the anionic detergent, sodium dodecyl sulphate (SDS). Twenty-five giltheads were exposed to SDS concentrations of 5, 8.5, 10 and 15 mg/l. Morphological changes depending on detergent concentrations and length of exposure were seen. Kidney shows loss of normal structure with tubular and renal corpuscle retraction; spleen shows tendency to damage the reticulae structure and a progressive increase of leucocytes and red cells infiltration.

Animals↗
PubMed1997

[Anal tuberculosis. Report of a case].

We report a 70 years old man presenting with malaise, anal pain and progressive defecation difficulty, with a decrease in stool caliber. The patient had no contact or past history of tuberculosis. On physical examination, there was an ulcerated anal lesion with purulent discharge, that produced an anal stenosis. The patient had an erythrocyte sedimentation rate of 108 mm/h, images of active tuberculosis in both apical pulmonary lobes and a chronic tuberculous inflammation with caseation and epithelioid tubercles was observed in a biopsy of the anal lesion. Treatment with antituberculous drugs produced a categorical remission of anal lesions and after five months of therapy the patient is well.

Aged↗
PubMed1995

Packing products for customers: an ergonomics evaluation of three supermarket checkouts.

The introduction of laser scanners at supermarket checkout areas has resulted in previous ergonomics studies focusing specifically on the scanning process and associated cumulative trauma disorders in the hands and arms. Few studies have evaluated the increased musculoskeletal load and exertion of checkout staff when they are also expected to pack the products into bags for the customers. This paper describes an ergonomics evaluation of three different designs of checkout workstation, which require the operator to stand when they scan the products, pack them into plastic bags and transfer the packed bags to the customer. Musculoskeletal load and exertion associated with the different checkouts were measured using OWAS, heart rate recordings and ratings of perceived exertion. In addition, subjective rankings of the workstations were obtained and the productivity associated with each design examined as part of the evaluation. Some of the variables measured showed significant differences in postural load between the workstations. The results of the evaluation formed the basis of recommendations for an improved workstation design. Some of the suggestions made to reduce postural load and increase productivity include positioning the weigh scale to the side and the bag frame beneath the scanner.

Journal Article↗
PubMed1995

Morphological and histochemical changes caused by sodium dodecyl sulphate in the gills of giltheads (Sparus aurata, L.).

An investigation was made into the biological effects of the anionic detergent sodium dodecyl sulphate (SDS), on the gills of giltheads (Sparus aurata, L.). The fish were exposed to concentrations of 5, 8.5, 10 and 15 mg/l SDS. The surface tension acquired at each concentration was determined and the LC50 calculated. Serious morphological damage to the gills and changes in protein and carbohydrate molecules (demonstrated by histochemical techniques) were observed. The degree of these alterations was dependent upon the SDS concentration and the length of time of exposure. It is suggested that changes in the gills lead to respiratory dysfunction and that this may be one of the major causes of death.

Animals↗
PubMed1991

A computerized system for measuring time perception in human subjects.

We describe an integrated computerized approach to the design, execution and recording of time perception experiments in human subjects. The program is menu driven and runs on an IBM-compatible microcomputer. The method is easy to use, non-obtrusive to the subjects, and flexible enough to allow the investigator to design studies with a wide range of experimental protocols and study parameters. The fact that the results do not depend on proctor bias or subject-proctor interactions are additional advantages. The technique was applied to study the effects of prompt positive feedback on the time perception of normal human subjects who undergo training. The results of this study are reported.

Adult↗
PubMed1990

Spider silkglands contain a tissue-specific alanine tRNA that accumulates in vitro in response to the stimulus for silk protein synthesis.

The large ampullate glands of the orb-web spider, Nephila clavipes provide massive amounts of fibroin throughout the lifetime of the adult female. We have developed methods to culture the glands and manipulate their biosynthetic activity. This has allowed us to monitor a series of molecular events that precede silk production in glands excised from appropriately stimulated animals. In this paper, we demonstrate that prior to the transient dramatic production of fibroin, such glands accumulate large amounts of tRNAs cognate to the abundant amino acids in spider silk. One of these, alanine tRNA, appears to consist of two isoaccepting forms--one constitutive, and the other silkgland specific. Moreover, the silkgland-specific form appears to accumulate preferentially in response to stimulation. This phenomenon of tissue-specific tRNA production appears similar to that found in the silkglands of Bombyx mori, but the spider system has the unique property of permitting manipulation in vitro. Thus, it provides an unusual opportunity to study the mechanism of regulated tRNA synthesis.

Animals↗
PubMed1987

Gastroduodenal mucosal injury during hepatic arterial infusion of chemotherapeutic agents. Lack of cytoprotection by prostaglandin E1 analogue.

Eighteen colorectal cancer patients with liver metastases receiving hepatic arterial infusion of chemotherapeutic agents (mitomycin-C + 5-FUDR) were randomized to receive misoprostol (a prostaglandin E1 analogue) or placebo as a mode of cytoprotection against inadvertent gastroduodenal mucosal injury. Four of 10 patients on misoprostol and 3 of 8 patients on placebo developed gastroduodenal mucosal injury (p greater than 0.1), which was confirmed by endoscopy. Significant tumor responses to chemotherapy were equally distributed between the two groups. Although our sample size was small and type II error (false-negative trial) cannot be excluded, these data strongly suggest that prophylaxis with misoprostol does not prevent the acute gastroduodenal mucosal injury associated with hepatic arterial infusion of chemotherapeutic agents.

Alprostadil↗
PubMed1985

[Sensory evaluation of quality and quality differences in slaughtered chickens].

A study was carried out with a trained panel for the purpose of determining if modifications produced in slaughtered chickens during the storage period, caused significant organoleptic differences, detectable by the consumer. The products examined corresponded to chickens slaughtered on three consecutive days, stored at 2 degrees C until their evaluation. Qualitative aspects in the raw product were investigated by a score test in which optimum quality is 13 points, as follows: for color (range 3), general appearance (range 5), and presence of defects (range 5). The values obtained were then analyzed through variance and Duncan multiple range test. Simultaneously, taste changes were estimated in fatty and meager meat by the triangular test. Homogeneity between judgements of panel members on both types of meat was statistically established (P = 0.05). The results obtained indicate that at the 0.1% level of significance, two products were identical; a third one proved to be different and of a significantly higher quality at the 5% level. The degree of difference, from slight to moderate, was due to flavor.

Animals↗
PubMed1976

The electro-oculogram in diffuse (familial) drusen.

Twelve patients with diffuse drusen of Bruch membrane had their condition evaluated by electro-oculography (EOG). All had normal EOG light-peak/dark-trough ratios, which suggests that the disease does not involve a diffuse functional abnormality of the retinal pigment epithelium. This finding is in contrast to the abnormal EOG ratios reported in patients with fundus flavimaculatus. Categorizing these two diseases along with fundus albipunctatus as flecked retina syndrome should be continued on the basis of the somewhat similar morphologic appearance of the lesions, rather than because of similar results on functional testing.

Adult↗
PubMedDate not supplied

Molecular recognition of quadruplex DNA by quinacridine derivatives.

The interaction of monomeric and dimeric quinacridines with quadruplex DNA has been investigated using a variety of biophysical methods. Both series of compounds were shown to exhibit a high affinity for the G4 conformation with two equivalent binding sites. As shown from the SPR and dialysis experiments the macrocyclic dimer appears more selective than its monomeric counterpart.

Base Sequence↗
PubMedDate not supplied

DNA binding properties of the indolocarbazole antitumor drug NB-506.

Indolocarbazoles derived from the antibiotic rebeccamycin represent an important group of antitumor agents. Several indolocarbazoles are currently undergoing clinical trials. These compounds inhibit topoisomerase 1 to produce DNA breaks that are responsible for cell death. Unlike classical topoisomerase I poisons like camptothecin, glycosyl indolocarbazoles can form stable complexes with DNA even in the absence of topoisomerase I. At least in part, their mode of action is reminiscent of that of the anthracyclines, which also bind to nucleic acids and interfere with topoisomerase II. The lead synthetic compound in the series is the uncharged drug NB-506, which bears a glucose residue attached to the indolocarbazole chromophore substituted with two hydroxyl groups at positions 1 and 11. Here we report a detailed biophysical study aimed at characterizing the DNA binding properties of NB-506. Molecular modeling was used to compare the conformation and electronic properties of NB-506 and its analogue ED-571 bearing the two hydroxyl groups at positions 2 and 10. Surface plasmon resonance experiments, performed with DNA hairpin oligomers, indicate that NB-506 binds almost equally well to both AT and GC base pairs, and the binding affinity (K = 10(5) M(-1)) is similar to that of certain classical intercalators such as amsacrine and bisantrene. Isothermal titration calorimetry experiments show that the binding of NB-506 is enthalpy-driven (deltaH = -7.2 kcal/mol). The binding enthalpy measured for NB-506 is similar to that obtained with doxorubicin but the DNA interaction processes for the two drugs differ markedly in terms of entropy and deltaG. The free energy of NB-506 binding to DNA is considerably less favorable than that of doxorubicin. These biophysical data help us to understand further how rebeccamycin-type anticancer drugs interact with DNA.

Algorithms↗
PubMedDate not supplied

Anthropometrical analysis of the hand as a Repetitive Strain Injury (RSI) predictive method in pianists.

In the present work we have studied the anthropometrical characteristics of the pianists hands to predict their potential vulnerability to suffer from Repetitive Strain Injury (RSI). To get this goal we studied the size and morphotype of the hands of pianists affected by RSI. Firstly we observed that 222 individuals from 341 studied pianists (65.1% of the total) presented RSI. Secondly we appreciated that affected hands were mostly small sized (60% of the affected hands) and classifiable in a distinct morphotype named B (68% of the affected hands). This fact suggest they both were the most vulnerable to RSI. Finally we may conclude anthropometrical analysis of pianists hands may be used to reduce the high incidence of this illness given that it may predict performers potential vulnerability to RSI. It also has to be remarked that further studies in this knowledge field are required to reduce the incidence of playing-related medical problems in general, and RSI in particular, in pianist population.

Adolescent↗