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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
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↗
PubMed2000

Dual role of plasma membrane electron transport systems in defense.

Because oxidative stress is one of the main sources of severe cellular damage, cells have different defense weapons against reactive oxygen species. Ubiquitous plasma membrane redox systems play a role in defense against oxidative stress damage. On the other hand, a tightly controlled and localized production of reactive oxygen species by a plasma membrane NADPH oxidase can be used as a potent microbicidal weapon. This dual, prooxidant and antioxidant role of plasma membrane electron transport systems in defense is studied and discussed.

Animals↗
PubMed2000

Methods for the determination of plasma total homocysteine: a review.

Total homocysteine is the sum of all homocysteine species present in plasma. This parameter is valuable for the diagnosis and follow up of cobalamine or folate deficiencies, and it has been accepted as an independent risk factor for premature cardiovascular disease. These reasons justify the introduction of total homocysteine assays in the routine clinical laboratory. In the present review, we discuss the procedures for sample collection, processing and storage, and review the methodologies for measuring total homocysteine. We compare their feasibility as routine methods in the clinical laboratory.

Chemistry, Clinical↗
PubMed1999

Histamine, polyamines, and cancer.

Mammalian ornithine decarboxylase and histidine decarboxylase present common structural and functional features, and their products also share pharmacological and physiological properties. Although accumulated evidence pointed for years to a direct involvement of polyamines and histamine in tumour growth, it has been only in the last few years that new molecular data have contributed to the clarification of this topic. The aim of this commentary is to review the molecular grounds of the role of histamine and polyamines in cancer and to point to possible directions for future research in emerging areas of interest.

Animals↗
PubMed1999

The pest regions containing C-termini of mammalian ornithine decarboxylase and histidine decarboxylase play different roles in protein degradation.

Proteasome 26S must recognize the PEST region-containing C-terminus of mammalian ornithine decarboxylase (ODC) monomer to proceed with degradation. We have detected PEST regions in both termini of mammalian histidine decarboxylase (HDC). In the present report, a chimaeric ODC/HDC was used to elucidate whether the PEST region-containing C-termini of ODC and HDC are exchangeable. Wild-type rat ODC had an expected antizyme and ATP-dependent degradation. This was not the case for both the chimaera and a C-terminus truncated rat ODC. Results suggest that the PEST region-containing C-terminus of rat HDC should have another role different to confering polypeptide availability to the proteasome.

Adenosine Triphosphate↗
PubMed1999

Glutamine, as a precursor of glutathione, and oxidative stress.

Oxidative stress is related to several pathologies and it is also associated with surgical operations. Reactive oxygen species generated during oxidative stress can induce severe damage to biomolecules. To prevent this damage, cells are endowed with both enzymatic and nonenzymatic defenses. One of the most important antioxidant molecules is glutathione. Since glutamine is a precursor of glutathione, its supplementation in the clinical diet can be used to maintain high levels of glutathione and to avoid oxidative stress damage. Here, recent literature concerning this recurrent topic is critically reviewed.

Glutamine↗
PubMed1999

A comparative study of the effects of genistein and 2-methoxyestradiol on the proteolytic balance and tumour cell proliferation.

The cytotoxicity of two compounds described as anti-angiogenic, the isoflavone genistein and the oestrogen metabolite 2-methoxyestradiol, has been studied in different human tumour cell lines. Since the degradation of the extracellular matrix is one of the essential steps in angiogenesis, the potential modulatory effects of both compounds on the proteolytic balance in media conditioned by different human tumour cells have been also investigated. The IC50 values for 2-methoxyestradiol were lower than those for genistein on all the cell lines tested. In all the cell lines expressing measurable amounts of active enzymes, genistein induced a shift towards antiproteolysis in both matrix metalloproteinase/tissue inhibitor of metalloproteinase and urokinase/plasminogen activator inhibitor proteolytic balances. On the other hand, 2-methoxyestradiol did not produce any clear net shift of the proteolytic balance, with the significant exception of the matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in WAC-2 cells, a neuroblastoma cell line with enhanced expression of the N-myc oncogene.

2-Methoxyestradiol↗
PubMed1998

Putrescine and chlorpheniramine inhibit Ehrlich ascites tumor cell plasma membrane ferricyanide reductase activity.

The presence of putrescine or chlorpheniramine in the incubation medium of Ehrlich ascites tumor cells starved for 1 h significantly inhibits the rate of ferricyanide reduction by their plasma membrane redox system. Freshly harvested cells, without depletion of their intracellular pools of polyamines, and cells preincubated under conditions arranged to increase ornithine decarboxylase activity also reduced externally added ferricyanide at a lower rate than those cells starved for 1 h. All these data seems to indicate that the presence of putrescine is enough to significantly inhibit Ehrlich cell plasma membrane redox system activity.

Animals↗
PubMed1998

DNA-chlorpheniramine interaction studied by spectroscopic techniques.

It was previously studied that the antihistaminic chlorpheniramine elicits a biphasic response on cell growth and regulates polyamine metabolism, as described for polyamines. In part, polyamine effects on macromolecular synthesis and cell growth are attributed to nucleic acid:polyamine interactions. In this work, we have tested the hypothesis of a DNA:chlorpheniramine interaction, using fluorometry, FTIR and Raman spectroscopic techniques. The results indicate that DNA:chlorpheniramine interaction occurs inducing conformational changes in the macromolecule by affecting both phosphodiester bonds and bases. Results open new perspectives for characterization of action mechanisms of natural or synthetic diamines with pharmacological or physiological importance.

Chlorpheniramine↗
PubMed1998

Modulation of the proteolytic balance plasminogen activator/plasminogen activator inhibitor by enhanced N-myc oncogene expression or application of genistein.

The aim of this study was to determine whether enhanced expression of N-myc in a neuroblastoma cell line affects the balance of plasminogen activator/plasminogen activator inhibitor (PA/PAI), a shift towards proteolysis having been observed in other malignant tissues. Two transfected neuroblastoma cell lines with (WAC2 cells) or without (SH-EP007 cells) enhanced expression of the N-myc oncogene were examined by zymography and RNA extraction to determine UPA and PAI enzyme activity and uPA RNA and PAI RNA expression, respectively. The effect of genistein, an inhibitor of tyrosine protein kinase, on uPA/PAI was also investigated. Both the uPA/PAI-1 ratio at mRNA level and the PA/PAI ratio at protein activity level were higher in the more malignant, WAC2 cell line. Genistein attenuated uPA activity and stimulated PAI activity in both cell lines, leading to a decrease in the PA/PAI ratio. This effect was more pronounced in the more malignant, WAC2 cell line.

Cell Division↗
PubMed1997

Polyamine contents of human breast cancer cells treated with the cytotoxic agents chlorpheniramine and dehydrodidemnin B.

The cytotoxic agents chlorpheniramine and dehydrodidemnin B decreased the cell growth of estrogen receptor-negative human breast cancer cells MDA-MB231 and estrogen receptor-positive MCF-7, after 48 h treatment. Both agents reduced ornithine decarboxylase activity, but polyamine levels were increased in MDA-MB231 cells treated with dehydrodidemnin B. MCF-7 cells when treated with dehydrodidemnin B showed significant increases in spermidine and spermine contents. The results suggest that besides other effects, the cytotoxicity of DDB could be explained in part by the over-accumulation of spermidine and spermine.

Antineoplastic Agents↗
PubMed1997

Multifunctional plasma membrane redox systems.

All the biological membranes contain oxidoreduction systems actively involved in their bioenergetics. Plasma membrane redox systems seem to be ubiquitous and they have been related to several important functions, including not only their role in cell bioenergetics, but also in cell defense through the generation of reactive oxygen species, in iron uptake, in the control of cell growth and proliferation and in signal transduction. In the last few years, an increasing number of mechanistic and molecular studies have deeply widened our knowledge on the function of these plasma membrane redox systems. The aim of this review is to summarize what is currently known about the components and physiological roles of these systems.

Animals↗
PubMed1997

Identification of a Zn(2+)-sensitive component of Ehrlich cell plasma membrane redox system by CHAPS-agarose-polyacrylamide electrophoresis and in situ staining of activity.

A procedure based on CHAPS-agarose-polyacrylamide electrophoresis and in situ staining of activity was used to detect a Zn(2+)-sensitive component of Ehrlich cell plasma membrane redox system. The procedure is so powerful that it allows to use crude plasma membrane fractions and can be easily adapted for use in an electrophoretic approach to the purification of this protein.

Animals↗