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C Carrasco

Publications and source records attributed to C Carrasco.

At least 19 recordsLinked to original sources
PubMed2002

Morpho-histochemical changes in the gills of turbot, Scophthalmus maximus L., induced by sodium dodecyl sulfate.

The present article reports the effect on survival as well as morpho-histochemical changes in the gills of juvenile turbot Scophthalmus maximus L., induced by acute action of the anionic surfactant sodium dodecyl sulfate (SDS). First, LC(50) at 96 h was found to be 7.5 mg/L of SDS. Second, lots with 20 individuals were exposed to SDS concentrations of 3, 5, 7, and 10 mg/L in order to obtain the exposure time required for 50% mortality of the specimens (384, 190, 12, and 4 h) and surface tension values (60.2, 56, 54.9, and 53.3 mN/m), respectively. Finally, histopathological lesions (clubbing and fusion of the secondary lamellae, hyperplasia and posterior rupture of the respiratory epithelium, destruction and shortening of gill filaments, and the presence of hemorrhagic foci) and histochemical alterations in the distribution of carbohydrates and proteins in the gills of treated specimens were noted. These morpho-histochemical changes in the gills provoked functional disorders (i.e. asphyxia and the loss of osmotic and ionic regulation) that may ultimately play an important role in the mortality of turbots exposed to SDS.

Animals↗
PubMed2002

Acute effects of sodium dodecyl sulphate on the survival and on morpho-histochemical characteristics of the trunk kidney of juvenile turbot Scophthalmus maximus L.

The present article reports the effect on survival as well as on the morpho-histochemical changes in the trunk kidney of juvenile turbot Scophthalmus maximus, L. induced by acute action of the anionic surfactant, sodium dodecyl sulphate (SDS). The LC50 of SDS at 96 hours was found to be 7.5 mg/l. Lots of 20 juvenile turbots were exposed to SDS concentrations of 3, 5, 7 and 10 mg/l: the exposure time required for 50% mortality of the specimens was 384,190,12 and 4 hours and surface tension values were 60.2, 56, 54.9, and 53.3 mN/m, respectively. It should be mentioned that there was a relatively high resistance to SDS of turbot compared to other teleost species, which may be related to its benthic habit. Histopathological lesions and histochemical changes that appeared in the trunk kidney of specimens exposed to the concentrations mentioned were examined. The abnormalities observed in this organ included vacuolation and desquamation of epithelial cells and degeneration of glomeruli and tubules. At the histochemical level, we appreciated some changes in the normal distribution of carbohydrates and proteins. Although the precise mechanism by which the renal tissue injury occurs is unknown, the function of this vital organ was seriously affected and this fact may ultimately play an important role in the mortality of turbots exposed to SDS.

Animals↗
PubMed2001

Evaluation of the influence of compound structure on stacked-dimer formation in the DNA minor groove.

The Human Genome Project as well as sequencing of the genomes of other organisms offers a wealth of DNA targets for both therapeutic and diagnostic applications, and it is important to develop additional DNA binding motifs to fully exploit the potential of this new information. We have recently found that an aromatic dication, DB293, with an amidine-phenyl-furan-benzimidazole-amidine structure can recognize specific sequences of DNA by binding in the minor groove as a dimer [Wang, L., Bailly, C., Kumar, A., Ding, D., Bajic, M., Boykin, D. W., and Wilson, W. D. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 12-16]. The dimer binding is strong, highly cooperative and, in contrast to many closely related heterocyclic dications, has both GC and AT base pairs in the minor groove binding site. The aromatic heterocycle stacked dimer is quite different in structure from the polyamide-lexitropsin type compounds, and it is a dication while all lexitropsin dimers are monocations. The heterocyclic dimer represents only the second small molecule class that can recognize mixed sequences of DNA. To test the structural limits on the new type of complex, it is important to probe the influence of compound charge, chemical groups, and structural features. The effects of these compound molecular variations on DNA complex formation with several DNA sequences were evaluated by DNase I footprinting, CD and UV spectroscopy, thermal melting, and quantitative analysis with surface plasmon resonance biosensor methods. Conversion of the amidines to guanidinium groups does permit the cooperative dimer to form but removal of one amidine or addition of an alkyl group to the amidine strongly inhibited dimer formation. Changing the phenyl of DB293 to a benzimidazole or the benzimidazole to a phenyl or benzofuran also inhibited dimer formation. The results show that formation of the minor groove stacked-dimer complex is very sensitive to compound structure. The discovery of the aromatic dimer mode offers new opportunities to enhance the specificity and expand the range of applications of the compounds that target DNA.

Amidines↗
PubMed2001

Effect of Salmonella-infected human monocytes on natural killer cell cytotoxicity. In vitro studies.

Various chemicals, including some bacteria-derived components, modulate natural killer cell (NKC) activity. We have analyzed the effect of wild-type Ty2 and of mutant strain TYT1231 Salmonella typhi-infected monocytes (U937 cells and human autologous monocytes) on NKC cytotoxicity of peripheral blood mononuclear cell (PBMC) and highly purified NKC (HPNKC; CD16+/56+ > 95%; the rest corresponding to CD3+ T-cells). PBMC's co-culture with either S. typhi strain infected U937 cells (medium or non-infected U937 cells as controls) resulted in the induction of lymphocyte activated killer (LAK) cell activity showing cytotoxicity against target human NKC-resistant lymphoblastoid Daudi cell line. Comparable experiments using autologous monocytes gave similar results. Co-culture of HPNKC preparations with either S. typhi strain infected U937 cells resulted in increased LAK cell activity against target Daudi cells in each and everyone of the five samples tested; paired Student's t-test p < 0.01 for both times (20 and 40 h) tested. Similar to the results observed in the experiments using PBMC, we did not find significant differences in the ability between medium and non-infected cells, or between wild-type S. typhi Ty2 and mutant strain TYT1231 infected U937 cells, to induce LAK activity in HPNKC preparations. PBMC co-incubation with either S. typhi strain infected U937 cells or autologous monocytes resulted in significant increases in IL-12, TNF-alpha, and IFN-gamma secretion. In similar experiments using HPNKC samples instead, infected U937 cells significantly increased IL-12 and IFN-gamma, but not TNF-alpha secretion. PBMC co-incubation with non-infected U937 cells, but not with non-infected monocytes, significantly increased supernatant IL-12 and TNF-alpha levels (no significant changes in IFN-gamma were recorded). Secreted cytokines remained essentially unchanged after co-incubating HPNKC preparation with non-infected U-937 cells. Incubation of PBMC or HPNKC preparations with either S. typhi strain infected U937 cells failed to produce significant changes in the expression of NKC lineage (CD16+/56+) or activation (CD28+, CD69+ and CD95+) markers. The ability of infected monocytes to induce LAK activity, release NKC cytokines and upmodulate NKC's CD95+ marker expression was essentially the same for both infecting Salmonella strains used. These results suggest a role for NKC in the physiological defensive response against intracellularly infected monocytes representing, perhaps one of the earliest antimicrobial mechanisms of the innate immune system.

Acid Phosphatase↗
PubMed2001

Comparative study of the acute toxicity of anionic surfactans alkyl benzene sulphonate (ABS) and sodium dodecyl sulphate (SDS) on gilthead, Sparus aurata L., eggs.

In the present work we have evaluated the acute toxicity of two anionic surfactants, alkyl benzene sulphonate (ABS) and sodium dodecyl sulphate (SDS) to eggs of gilthead Sparus aurata. At each surfactant concentration, we determined the exposure time required for 50% mortality of the eggs (LT50), surface tension and volume of oil globule in gilthead eggs. Clear dose-response relationships for mortality of gilthead eggs was observed for both toxicants; at 30 mg/L 50% mortality took place at 45 minutes for ABS and 8 minutes for SDS. At this concentration, SDS was almost six times more toxic than ABS (LT50 is compared). However, at 0.3 mg/L 50% mortality occurred after exposures of 535 minutes to ABS and 425 minutes to SDS. Descriptively, our results showed SDS was more toxic than ABS at high concentrations whereas at low concentrations their toxicity was very similar. However, statistical analysis demonstrated there were no significant differences in the toxicity of both surfactants to gilthead eggs. Surface tension value at each concentration of both surfactants was also calculated. We found that these values decreased with increasing concentration of each surfactant, and this trend was more pronounced in solutions of SDS. We also found that the volume of the oil globule of exposed eggs was influenced by surfactants. After exposure, its volume clearly decreased in comparison to controls, mainly in eggs exposed to SDS.

Animals↗
PubMed2001

Acute toxicity of anionic surfactants sodium dodecyl sulphate (SDS) and linear alkylbenzene sulphonate (LAS) on the fertilizing capability of gilthead (Sparus aurata L.) sperm.

In the present work we have evaluated and compared the acute toxicity of two anionic surfactants, Sodium Dodecyl Sulphate (SDS) and Linear Alkylbenzene Sulphonate (LAS) on the fertilizing capability of gilthead Sparus aurata L. sperm. The criterion used to judge exposure effectiveness was fertilization success. Spawned eggs and sperms were collected from adult giltheads. Sperms were dosed separately with different concentrations of SDS and LAS for 60 minutes. After this period, sperms and eggs were combined for 20 minutes during which fertilization took place. Finally, the number of fertilized eggs were counted and recorded to estimate the percentage of fertilization. Exposure to SDS and LAS concentrations of 0.3, 0.6, 1.5, 3 and 6 mg/L for 60 minutes caused a significant inhibitory effect on fertilization success in gilthead Sparus aurata L.. In addition, the EC50 value for gilthead fertilization after sperm exposure was found to be 2.8 mg/L and in the case of LAS it was of 2.6 mg/L. The comparison of the results from SDS and LAS shows that the latter has a stronger negative effect on sperm viability than SDS.

Alkanesulfonic Acids↗
PubMed2001

Morpho-histochemical changes in the liver and intestine of young giltheads (fish-nursery), Sparus aurata, L., induced by acute action of the anionic tensioactive alkylbenzene sulphonate.

In the present study we have assessed the effect on the survival and the morpho-histochemical changes in the liver and intestine of young giltheads (fish-nursery), Sparus aurata, L., induced by acute action of the anionic tensioactive, alkyl benzene sulphonate (ABS). Firstly, the LC50 of ABS at 96 hours was found to be 0.6 mg/L. Secondly, lots with 50 young giltheads (fish-nursery) were exposed to ABS concentrations of 0.5, 1, 3 and 5 mg/L, to obtain the surface tension value and exposure time required for 50% mortality of the specimens at each tested concentration. Exposure to ABS caused several forms of histopathological damage in the liver (the radial arrangement of hepatocytes was lost) and intestine (destruction of the structure of villi and increase in thickness of the other three layers). In addition, changes in bio-macromolecule components (proteins in general, siderophile proteins, neutral mucopolysaccharides, glycogen and acid mucopolysaccharides) were observed. The degree of these alterations was dependent upon the ABS concentration. These changes could have detrimental effects on the growth and survival of the species.

Alkanesulfonic Acids↗
PubMed2001

[Gestational hyperthyroidism: a case associated to molar pregnancy].

We report a 18 years old woman that was admitted with a history of four days of cardiac failure with acute pulmonary edema, high blood pressure, left ventricular dilatation and moderate to severe systolic dysfunction. Twenty four hours after admission she had a miscarriage, expelling a mole. The diagnosis of hyperthyroidism caused by a mole and early pre eclampsia was confirmed and the patient was managed with diuretics and dopamine. Symptoms abated, thyroid function tests, cardiac function and size returned to normal values and the patient was discharged asymptomatic, ten days after admission.

Adolescent↗
PubMed2000

Morpho-histochemical study of the biological effects of sodium dodecyl sulphate on the digestive gland of the Portuguese oyster.

In the present work we have studied the effects on survival as well as histopathological and histochemical alterations on the digestive gland of the Portuguese oyster (Crassostrea angulata, Lmk.) induced by acute action of the anionic tensioactive Sodium Dodecyl Sulphate (SDS) at different concentrations (50, 100, 200 and 400 mg/L). Firstly, the LC 50 at 96 h was found to be 136 mg/L SDS. Secondly we calculated the exposure time required for 50% mortality of the specimens exposed to different concentrations, and thirdly we examined histopathological alterations (degenerative processes ranging from inflammatory responses to extreme vacuolation) and histochemical changes in the distribution of carbohydrates and proteins that appeared at each employed concentration. The degree of these alterations and the effects on survival were dependent upon the SDS concentration. The above established modifications indicate that exposure to SDS has a detrimental effect on oyster digestive gland, perturbing metabolic and nutritional functions, what may have some influence on oyster survival.

Animals↗
PubMed2000

[Invasive hepatosplenic hyalohyphomycosis. Report of a case].

Invasive fungal infections are an increasingly common problem in patients with cancer and other vulnerable groups. We report a case of hepatosplenic hialohifomycosis probably by Aspergillus sp. In a patient with acute leukemia, and prolonged neutropenia, treated with corticosteroids and broad spectrum antibiotics. A review concerning diagnosis, clinical course and treatment of this condition is presented.

Acute Disease↗
PubMed2000

[Thyroid lymphoma. A case report].

Thyroid lymphoma represents less than 1% of malignant thyroid tumors and its diagnosis is difficult. We report a 25 years old woman, admitted with the diagnosis of diffuse euthyroid goiter and thyroid cancer. She was subjected to a subtotal thyroidectomy and the pathological study of the surgical piece showed a Hodgkin lymphoma, subtype nodular sclerosis. The patient was treated with three cycles of chemotherapy, using cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, blemycin, vinblastin and radiotherapy. She refused to continue treatment after the third cycle and after 3 years and 5 months of follow up, is well and free of disease.

Adult↗
PubMed1999

The camptothecin-resistant topoisomerase I mutant F361S is cross-resistant to antitumor rebeccamycin derivatives. A model for topoisomerase I inhibition by indolocarbazoles.

DNA topoisomerase I is a major cellular target for antitumor indolocarbazole derivatives (IND) such as the antibiotic rebeccamycin and the synthetic analogue NB-506 which is undergoing phase I clinical trials. We have investigated the mechanism of topoisomerase I inhibition by a rebeccamycin analogue, R-3, using the wild-type human topoisomerase I and a well-characterized recombinant enzyme, F361S. The catalytic activity of this mutant remains fully intact, but the enzyme is resistant to inhibition by camptothecin (CPT). Here we show that the mutated enzyme is cross-resistant to the rebeccamycin analogue. Despite their profound structural differences, CPT and R-3 interfere similarly with the activity of the wild-type and mutant topoisomerase I enzymes, and the drug-induced cleavable complexes are equally sensitive to the NaCl concentration. CPT and IND likely recognize identical structural elements of the topoisomerase I-DNA covalent complex; however, differences do exist in terms of sequence-specificity of topoisomerase I-mediated DNA cleavage. For the first time, a molecular model showing that CPT and IND share common steric and electronic features is proposed. The model helps to identify a specific pharmacophore for topoisomerase I inhibitors.

Amino Acid Substitution↗
PubMed1999

Poisoning of topoisomerase I by an antitumor indolocarbazole drug: stabilization of topoisomerase I-DNA covalent complexes and specific inhibition of the protein kinase activity.

We have investigated the mechanism of topoisomerase I inhibition by an indolocarbazole derivative, R-3. The compound is cytotoxic to P388 leukemia cells, but not to P388CPT5 camptothecin-resistant cells having a deficient topoisomerase I. R-3 can behave both as a specific topoisomerase I inhibitor trapping the cleavable complexes and as a nonspecific inhibitor of a DNA-processing enzyme acting via DNA binding. In addition, the drug is a potent inhibitor of the kinase activity of topoisomerase I. Unlike camptothecin, R-3 completely inhibits the phosphorylation of SF2/ASF, a member of the SR protein family, in the absence of DNA. The inhibitory effect is also observed using mutant enzyme Y723F that lacks DNA cleavage/religation activity but does not affect phosphotransferase activity, indicating, therefore, that R-3 acts independently at both DNA cleavage and protein kinase sites. R-3 is the only compound known thus far that interferes specifically with the kinase activity of topoisomerase I and not with other kinases, such as protein kinase C and the cdc2 kinase. The study reinforces the view that topoisomerase I is a dual enzyme with a DNA cleavage site juxtaposed to a functionally independent kinase site and shows for the first time that indolocarbazole drugs can inhibit both the DNA cleavage/religation and kinase activities of the enzyme.

Animals↗
PubMed1999

Relationships between topoisomerase II inhibition, sequence-specificity and DNA binding mode of dicationic diphenylfuran derivatives.

Four diphenylfuran derivatives possessing different dicationic terminal side chains were used to investigate sequence-specific binding to DNA and poisoning of human topoisomerase II. Footprinting experiments with a range of DNA substrates attest that all four drugs bind selectively to AT-rich sequences in DNA. However, the quantitative analysis of the footprinting profiles reveals significant differences in terms of AT-selectivity according to the nature of the basic side chains. Furimidazoline (DB60) shows a reduced capacity to interact selectively with A.T tetrads compared with furamidine (DB75) and the 3-pentyl-substituted diamidine analogue DB226. DB244, for which the two amidine ends are substituted with a cyclopentyl group, exhibits the most pronounced AT specificity. It binds tightly to sites composed of at least four adjacent AT base pairs, such as 5'-TAAT, AATT and TTTT. At low concentrations (< 2 microM) DB60 is also capable of forming stable complexes with AT sites but at higher concentrations the binding becomes totally non-specific due to additional intercalation of drug molecules into GC-rich sequences. Nevertheless, DB60 is the only drug is the series which stabilizes DNA-topoisomerase II covalent complexes. This compound effectively promotes DNA cleavage by topoisomerase II whereas DB75, DB226 and DB244 have practically no effect. The topoisomerase II poisoning activity of DB60 correlates with its ability to intercalate into GC sites in DNA whereas the three other diphenylfurans essentially behave as typical AT-selective minor groove binders. The study suggests that the antimicrobial activity of the diphenylfurans, which are active against the Pneumocystis carinii pathogen (PCP), depends essentially on their capacity to recognize AT-rich DNA sequences rather than their ability to interfere with topoisomerase II. In contrast, the cytotoxicity of drugs like DB60 would be connected with the formation of intercalation complexes and the stimulation of DNA cleavage by human topoisomerase II.

Anti-Bacterial Agents↗
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↗