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Biomedical subjects

M A Medina

Publications and source records attributed to M A Medina.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of the anti-angiogenic effect of aloe-emodin.

The present study identified aloe-emodin (AE, a hydroxyanthraquinone from Aloe vera and other plants) as a new anti-angiogenic compound with inhibitory effects in an in vivo angiogenesis assay and evaluates its effects on specific key steps of the angiogenic process. AE inhibits endothelial cell proliferation, but this effect is not cell specific, since AE also inhibits tumor cell proliferation. Cell migration and invasion are not remarkably affected by AE. On the other hand, AE has different effects on endothelial and tumor cell gelatinases. Two main targets of the pharmacological action of AE as an anti-angiogenic compound seem to be urokinase secretion and tubule formation of endothelial cells. Finally, AE produces a remarkable photocytotoxic effect on tumor cells. Taken together, our data indicate that AE can behave both as an anti-tumor and an anti-angiogenic compound and suggest that AE could be a candidate drug for photodynamic therapy.

Angiogenesis Inhibitors↗
PubMed2004

On the interpretation of Raman spectra of 1-aminooxy-spermine/DNA complexes.

By FT-Raman spectroscopy, we have investigated the effect of 1-aminooxy-spermine (AOSPM) on aggregation and stability of calf-thymus DNA and selected oligonucleotide chains. AOSPM is able to mimic spermine in some macromolecular interactions, but is unable to substitute polyamines to maintain cell proliferation, suggesting pharmacological applications. Raman spectra of solutions containing AOSPM and either genomic DNA or two 15mer oligodeoxyribonucleotides, with GC or AT sequences, were recorded. Precipitation was observed for calf-thymus DNA, aggregated structures and appearance of several Z marker bands were observed for the 15mer GC sequence, and no macromolecular changes were detected for the 15mer AT sequence. Specific binding sites between the aminooxy group and the base residues were also evidenced. Assignment of the AOSPM Raman bands was supported on a normal mode calculation for the molecule NH(2)-O-CH(3), as a model. The theoretical results, in combination with the analysis of the Raman bands, demonstrated that the aminooxy group played a relevant role in the AOSPM-DNA interaction. Preferential binding by the major groove was evidenced in the absence of macromolecular changes. When either precipitation or aggregation occurred, the interaction involved both the major and minor grooves. The specific interaction between AT/GC base pairs and the aminooxy group has also been theoretically investigated. The biological relevance of this work is discussed.

Animals↗
PubMed2003

Raman spectroscopy study of the interaction between biogenic polyamines and an alternating AT oligodeoxyribonucleotide.

The interaction between the 15-mer oligonucleotide d[A(TA)(7)].d[T(AT)(7)] and the three biogenic polyamines, putrescine, spermidine and spermine, under physiological conditions has been studied by Raman spectroscopy. Solutions containing 60 mM (phosphate) of the oligonucleotide and different polyamine concentrations ranging from 1 to 75 mM have been studied. Both natural and heavy water were used as solvents. Difference Raman spectra were computed by subtracting the sum of the separated component spectra from the experimental spectra of the complexes. The Raman data suggested that the interaction of biogenic polyamines with d[A(TA)(7)].d[T(AT)(7)] presents differences related with their sizes and electric charges. Preferential bindings through the oligonucleotide minor groove for putrescine and spermidine were proposed. Spermine would interact by both minor and major grooves, although interaction by the minor groove seems to be more favored. Main reactive sites were thymine-O2 and adenine-N3 atoms at the minor grooves and adenine-N7 and thymine-O4 at the major groove. Electrostatic attractions between the polyamine amino and oligonucleotide phosphodioxy groups were also proposed. Under our experimental conditions, no macromolecular effects on d[A(TA)(7)].d[T(AT)(7)] (changes on secondary or tertiary structures) were detected from Raman spectroscopy, contrary to what happened for GC sequences at the same experimental settings. This fact agrees with the role of the biogenic polyamines during the first steps of the macromolecular synthesis, which involve DNA opening in AT motifs.

Adenosine↗
PubMed2003

Homocysteine inhibits the proliferation and invasive potential of HT-1080 human fibrosarcoma cells.

The impairment of homocysteine metabolism has been related to several disorders and diseases. Recently, homocysteine has been shown to inhibit key steps of angiogenesis, including endothelial cell proliferation, invasion, and remodeling of the extracellular matrix. Since these are also key steps in tumor invasion and metastasis, it can be hypothesized that homocysteine can also interfere in these processes. Therefore, we studied the effects of homocysteine on tumor proliferation and invasion, as well as on urokinase, a key extracellular matrix-degrading protease, using a model human tumor cell line. This study demonstrates that, in fact, homocysteine inhibits HT-1080 proliferation and invasion, and is a potent inhibitor of tumor cell urokinase expression.

Cell Division↗
PubMed2003

Green tea epigallocatechin-3-gallate is an inhibitor of mammalian histidine decarboxylase.

(-)-epigallocatechin-3-gallate, an antiproliferative and antiangiogenic component of green tea, has been reported to inhibit dopa decarboxylase. In this report,we show that this compound also inhibits histidine decarboxylase, the enzymic activity responsible for histamine biosynthesis. This inhibition was proved by a double approach, activity measurements and UV-Vis spectra of enzyme-bound pyridoxal-5'-phosphate. At 0.1 mM (-)-epi-gallocatechin-3-gallate, histidine decarboxylase activity was inhibited by more than 60% and the typical spectrum of the internal aldimine form shifted to a stable major maximum at 345 nm, suggesting that the compound causes a stable change in the structure of the holoenzyme. Since histamine release is one of the primary events in many inflammatory responses, a new potential application of (-)-epigallocatechin-3-gallate in prevention or treatment of inflammatory processes is suggested by these data.

Animals↗
PubMed2001

Raman study of the interaction between polyamines and a GC oligonucleotide.

The interaction between the oligonucleotide d[G(CG)(7)]. d[C(GC)(7)] and the three biogenic polyamines putrescine, spermidine, and spermine under physiological conditions has been studied by Raman spectroscopy. The results indicate the formation of highly ordered aggregated structures in solution, largely stabilized by electrostatic attractions, which have been described as cholesteric phases. Aggregation seems to be preceded by a partial B --> Z conformational transition for spermidine and spermine, which would allow for a deeper oligonucleotide-polyamine interaction. Interaction with the nucleic bases has also been evidenced for aggregates. At low polyamine concentrations the preferential binding sites are similar to those proposed for their interactions with ct-DNA. With increasing the polyamine concentration, the oligonucleotide-polyamine interactions involve both minor and major grooves, which is consistent with the formation of cholesteric phases.

Fourier Analysis↗
PubMed2001

Effects of phorbol ester and dexamethasone treatment on histidine decarboxylase and ornithine decarboxylase in basophilic cells.

Both histamine and polyamines are important for maintaining basophilic cell function and viability. The synthesis of these biogenic amines is regulated by histidine decarboxylase and ornithine decarboxylase, respectively. In other mammalian tissues, an interplay between histamine and polyamine metabolisms has been suspected. In this report, the interplay between histamine and ornithine-derived polyamines was studied in a non-transformed mouse mast cell line (C57.1) treated with phorbol ester and dexamethasone, a treatment previously used to increase histidine decarboxylase expression in mastocytoma and basophilic leukemia. Treatment with phorbol ester and dexamethasone increased histidine decarboxylase expression and intracellular histamine levels in C57.1 mast cells to a greater extent than those found for other transformed basophilic models. The treatment also induced a reduction in ornithine decarboxylase expression, intracellular polyamine contents, and cell proliferation. These results indicate that the treatment induces a co-ordinate response of polyamine metabolism and proliferation in mast cells and other immune-related cells. The decrease in the proliferative capacity of mast cells caused by phorbol ester and dexamethasone was simultaneous to an increase in histamine production. Our results, together with those reported by other groups working with polyamine-treated mast cells, indicate an antagonism between histamine and polyamines in basophilic cells.

Animals↗
PubMed2001

Agmatine uptake by cultured hamster kidney cells.

Agmatine, the product of arginine decarboxylation, has been recently found in a wide variety of animal tissues. In spite of the emergent interest on agmatine in animals, the mechanism of agmatine uptake in mammalian cells has been scarcely studied. An analysis of radiolabeled agmatine uptake was carried out by using a classical, kinetic approach with BHK-21 hamster kidney cells in culture. A high affinity, temperature- and energy-dependent agmatine transport system in BHK-21 kidney cells is here kinetically characterized which seems to be a "general" transporter shared by di- and triamines and different to a highly specific carrier for the tetraamine spermine.

Agmatine↗
PubMed2001

Characterization of spermine uptake by Ehrlich tumour cells in culture.

Spermine is taken up by Ehrlich ascites tumour cells through a specific, saturable, temperature and energy-dependent transport system with a remarkably low affinity constant for spermine (around 1 microM). In the absence of a potassium ion gradient through the plasma membrane, spermine uptake remains saturable but the value of the Km for spermine is much higher (153 microM). Difluormethylornithine treatment (3 mM for 48h) induces significant increases in Vmax values (up to 9-fold) and changes in the Km values with scarce statistical significance. Among the biogenic amines tested, only spermidine and, partly, agmatine seem to share the same transport system with spermine. No difference is observed in the rate of spermine transport when assays are carried out in the presence of 50-fold excess of ornithine or calcium, or 100-fold excess of glutamine.

Agmatine↗
PubMed2001

Fourier transform Raman study of the structural specificities on the interaction between DNA and biogenic polyamines.

Biogenic polyamines putrescine, spermidine, and spermine are essential molecules for proliferation in all living organisms. Direct interaction of polyamines with nucleic acids has been proposed in the past based on a series of experimental evidences, such as precipitation, thermal denaturation, or protection. However, binding between polyamines and nucleic acids is not clearly explained. Several interaction models have also been proposed, although they do not always agree with one another. In the present work, we make use of the Raman spectroscopy to extend our knowledge about polyamine-DNA interaction. Raman spectra of highly polymerized calf-thymus DNA at different polyamine concentrations, ranging from 1 to 50 mM, have been studied for putrescine, spermidine, and spermine. Both natural and heavy water were used as solvents. Difference Raman spectra have been computed by subtracting the sum of the separated component spectra from the experimental spectra of the complexes. The analysis of the Raman data has supported the existence of structural specificities in the interactions, at least under our experimental conditions. These specificities lead to preferential bindings through the DNA minor groove for putrescine and spermidine, whereas spermine binds by the major groove. On the other hand, spermine and spermidine present interstrand interactions, whereas putrescine presents intrastrand interactions in addition to exo-groove interactions by phosphate moieties.

Animals↗
PubMed2001

Histamine prevents polyamine accumulation in mouse C57.1 mast cell cultures.

The effects of histamine on polyamine uptake and metabolism was studied in a mouse mast cell line (C57.1), as a cell model in which both biogenic amines are important for maintaining cell function and viability. Results obtained after incubations with exogenous histamine indicated that histamine prevents polyamine accumulation by affecting polyamine uptake. A plasma membrane transport system for polyamines has been also studied in mast cells. It seems to be a Na(+)-dependent uptake with high affinity for both spermine and spermidine and lower affinity for putrescine and agmatine. Polyamine uptake was reduced in both cells treated with exogenous histamine and histamine-preloaded cells. However, ornithine decarboxylase activity and cell proliferation were not affected by histamine. Incubation with histamine enhanced the spermidine/spermine acetyl transferase induction caused by N(1)-ethyl-N(11)-[(cyclopropyl)methyl]-4,8-diazaundecane, suggesting that polyamine acetylation could be another mechanism by which histamine prevents polyamine accumulation in C57.1 mast cells.

Acetyltransferases↗
PubMed2001

Glutamine and cancer.

Glutamine is the most abundant free amino acid in the human body; it is essential for the growth of normal and neoplastic cells and for the culture of many cell types. Cancer has been described as a nitrogen trap. The presence of a tumor produces great changes in host glutamine metabolism in such a way that host nitrogen metabolism is accommodated to the tumor-enhanced requirements of glutamine. To be used, glutamine must be transported into tumor mitochondria. Thus, an overview of the role of glutamine in cancer requires not only a discussion of host and tumor glutamine metabolism, but also its circulation and transport. Because glutamine depletion has adverse effects for the host, the effect of glutamine supplementation in the tumor-bearing state should also be studied. This communication reviews the state of knowledge of glutamine and cancer, including potential therapeutic implications.

Biological Transport↗
PubMed2000

[Factors associated with the occurrence of adverse reactions to drugs in patients who went to the emergency service of a general hospital: a case-control study].

OBJECTIVE: To describe adverse reactions to medicine (ARM) and analyse the factors associated with their presenting in patients attending a general hospital's emergency service. DESIGN: Case-control epidemiological study. SETTING: Emergency service of the San Cecilio University Hospital in Granada. PATIENTS: 654 patients over 15, men and women, who attended the emergency service between October and December 1997. 354 of them had an ARM (cases) and 300 did not (controls). MEASUREMENTS AND RESULTS: 60% of the cases were women, with an average age of 53 +/- 20. 68% of the ARM were type-A (expected). The most affected organs and systems were: digestive tract (41.8%) and skin (31.6%). Drug groups most associated with presentation of ARM were hypnosedatives and salicylates used as analgesics--antithermic drugs (28.2%), and beta-lactams and macrolides (22.6%). Most ARM were classified as probable (52%) and moderate (62%). Family practitioners were the main prescribers (49%) of medicines. 13% of patients were admitted to hospital because of a serious ARM and two people died (0.5%). According to the odds ratio, treatment with cytostatics, psychiatric drugs, NSAIDs, amoxycillin, digoxin, ACEIs and calcium antagonists, being a woman, self-medication, being under 65 and history of ARM were all associated with the presence of an ARM in our patients (cases). CONCLUSIONS: The type of medicine, being a woman, history of ARM, self-medication, and presenting digestive and dermatological symptoms were factors strongly linked to an ARM in patients attending the emergency service.

Case-Control Studies↗
PubMed2000

Rat histidine decarboxylase is a substrate for m-calpain in vitro.

We have followed the in vitro degradation of rat histidine decarboxylase in a reconstituted system, containing only rat histidine decarboxylase (obtained by in vitro transcription and translation), calcium ions in the millimolar range of concentrations, and m-calpain. Under the experimental conditions used, m-calpain quickly and efficiently degraded rat histidine decarboxylase, giving rise to a major proteolytic band of 29 kDa. In a conventional in vitro degradation system containing rabbit reticulocytes supplemented with calcium ions, there was also an intense proteolysis of rat histidine decarboxylase, strongly inhibited in the presence of calpeptin, a highly specific calpain inhibitor.

Animals↗
PubMed2000

Determination of a cAMP-dependent protein kinase phosphorylation site in the C-terminal region of human endothelial actin-binding protein.

Three different C-terminal regions of human endothelial actin-binding protein-280 (ABP-280 or ABP; nonmuscle filamin) were subcloned and efficiently expressed in the Escherichia coli BL21 (DE3) system as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. As predicted by the aminoacid sequence one of the fragments, a 109-kDa peptide (residues 1671-2647), contained a calpain cleavage site and two potential cAMP-dependent protein kinase (PKA) phosphorylation sites (serine 2152 and threonine 2336). A second fragment, a 74-kDa peptide (residues 1671-2331), contained a calpain cleavage site and one of the three presumptive PKA phosphorylation sites (serine 2152). The third fragment, a 48-kDa peptide (residues 2223-2647), contained only one of the PKA sites (threonine 2336). Phosphorylation of these truncated peptides indicated that only the fragments containing serine 2152 incorporated phosphate after PKA treatment. Site-directed mutagenesis analysis confirmed that serine 2152 is the unique substrate for PKA in the C-terminal region of ABP. The functional significance of phosphorylation of this residue, which belongs to a serine-proline motif, is discussed.

Amino Acid Motifs↗
PubMed2000

Homocysteine: an emergent cardiovascular risk factor?

Cardiovascular disease is the leading cause of mortality and disability in the western world. In the last years, the accumulation of evidence coming from both retrospective and prospective clinical studies has led to an increased interest in the potential role of mild hyperhomocysteinemia as a major, independent risk factor for cardiovascular disease. The present paper reviews the position of homocysteine in metabolism to understand the pathogenesis of hyperhomocysteinemia, as well as the clinical data pointing to its proposed role as an independent cardiovascular disease risk factor.

Cardiovascular Diseases↗
PubMed2000

In vitro study of proteolytic degradation of rat histidine decarboxylase.

Mammalian ornithine decarboxylase (ODC) is a very unstable protein which is degraded in an ATP-dependent manner by proteasome 26S, after making contact with the regulatory protein antizyme. PEST regions are sequences described as signals for protein degradation. The C-terminal PEST region of mammalian ODC is essential for its degradation by proteasome 26S. Mammalian histidine decarboxylase (HDC) is also a short-lived protein. The full primary sequence of mammalian HDC contains PEST-regions at both the N- and C-termini. Rat ODC and different truncated and full versions of rat HDC were expressed in vitro. In vitro degradation of rat ODC and rat 1-512 HDC were compared. Like ODC, rat 1-512 HDC is degraded mainly by an ATP-dependent mechanism. However, antizyme has no effect on the degradation of 1-512 HDC. The use of the inhibitors MG-132 and lactacystine significantly inhibited the degradation of 1-512 HDC, suggesting that a ubiquitin-dependent, proteasome 26S proteolytic pathway is involved. Results obtained with the different modifications of rat HDC containing all three PEST regions (full version, 1-656 HDC), only the N-terminal PEST region (1-512 HDC), or no PEST region (69-512 HDC), indicate that the N-terminal (1-69) fragment, but not the C-terminal fragment, determines that the HDC protein is a proteasome substrate in vitro.

Adenosine Triphosphate↗