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Biomedical subjects

M Martínez

Publications and source records attributed to M Martínez.

At least 19 recordsLinked to original sources
PubMed2002

Heterogeneous mechanisms of azole resistance in Candida albicans clinical isolates from an HIV-infected patient on continuous fluconazole therapy for oropharyngeal candidosis.

Molecular mechanisms of azole resistance in Candida albicans include alterations in the target enzyme and increased efflux of drug, but the impact of specific treatment regimens on resistance has not been established. A patient with advanced AIDS was enrolled in a longitudinal study to receive continuous oral fluconazole (FLU) 200 mg/day for the treatment of oropharyngeal candidosis (OPC). Oral cultures were obtained at time of enrollment, during episodes of OPC and quarterly for surveillance. The patient had five symptomatic relapses on continuous FLU during 43 months. All OPC episodes were successfully treated with increasing doses of FLU although increased FLU MICs were detected for C. albicans isolates with progression of time. DNA-typing techniques demonstrated that resistance developed in a persistent strain of C. albicans. Both FLU-resistant and isogenic isolates with reduced susceptibility were detected in the same clinical samples through multiple episodes. Analysis of molecular mechanisms of resistance revealed overexpression of MDR and CDR genes encoding efflux pumps (but not ERG11) in isolates with decreased FLU susceptibility. In addition, the presence of the G464S amino acid substitution in their lanosterol demethylase, affecting its affinity for FLU, was also detected. However, other isogenic, but FLU-susceptible isolates recovered from the same samples did not harbour the mutation, indicating microevolution of yeast populations within the oral cavity. In this patient, the continuous antifungal pressure exerted by FLU resulted in development of resistance of multifactorial nature. Despite their clonal origin, different subpopulations of C. albicans demonstrated distinct resistance mechanisms, including concomitant presence and absence of functional point mutations in ERG11 genes.

AIDS-Related Opportunistic Infections↗
PubMed2001

Increased cAMP immunostaining in cerebral vessels in Alzheimer's disease.

Increasing evidence suggests that up-regulation of the cAMP-second messenger system is implicated in Alzheimer's disease neurodegeneration. Since previous studies reported an increased level of cAMP in microvessels of Alzheimer's patients compared with those from non-demented elderly controls, we have carried out an immunohistochemical study to compare cAMP immunostaining in brain vessels from patients with dementia and neuropathological criteria of Alzheimer's disease (n=5) with those of age-matched patients (n=10). We have also included a control group of adult patients (n=5) to evaluate the role of aging separate from the effects of dementia. Our results demonstrated an increased cAMP immunostaining in cerebral cortical and meningeal vessels from Alzheimer's patients compared to nondemented elderly and adult controls. Vascular cAMP immunostaining was mainly observed in frontal and temporal cortex, the hippocampus being the region that showed the more intense and widespread vascular cAMP immunostaining. We also observed a conspicuous vascular beta-amyloid immunostaining specifically in those vessels that showed the highest cAMP immunostaining. We suggest that increased vascular cAMP immunostaining is mainly localised in the selectively vulnerable targets of neurodegeneration that characterise AD. Moreover, the co-immunolocalisation of cAMP and beta-amyloid protein in cerebral vessels of patients with AD suggests a possible role of cAMP up-regulation in the accumulation of those amyloidogenic peptides.

Aged↗
PubMed2001

A comparative study of the effect of pH and inorganic carbon resources on the photosynthesis of three floating macroalgae species of a Mediterranean coastal lagoon.

This study examines the effect of pH changes on photosynthetic characteristics and the role of dissolved inorganic carbon (DIC) in determining the dominance of three species of macroalgae Chaetomorpha linum (O.F. Müller) Kützing, Gracilaria verrucosa (Hudson) Papenfuss and Ulva sp. in a Mediterranean coastal lagoon. Fluctuations of pH were measured in the lagoon in summer. Water column CO(2) and HCO(3)(-) concentrations inside the algal mat showed significant diurnal fluctuations, from a morning peak to an afternoon low, decreasing 96 and 40%, respectively. The response of photosynthesis to increased pH was examined in laboratory conditions in spring (May) and summer (July). The photosynthetic rate declined rapidly at pH above 8.5 and below 6.5. G. verrucosa responded differently in spring and summer showing acclimation to higher pH in summer than in spring. In Ulva sp. incubations, we observed optimum photosynthesis between pH 6 and 7.5. The decrease in photosynthetic rate below pH 6 was lower (12.30%) than above pH 8 (81.03%). This difference may be related to the origin of the macroalgae, suggesting acclimation to the original pH of the environment. Results from instantaneous photosynthesis measurements indicate that low DIC-availability limits the photosynthetic capacity of G. verrucosa, C. linum and Ulva sp. in spring and of C. linum at high irradiances in summer. Our results also show that G. verrucosa has a higher efficiency at low CO(2) concentrations than C. linum and Ulva sp. It is suggested that G. verrucosa may be better adapted to maintain higher photosynthetic rates than other macroalgae in conditions of tissue N sufficiency and low water DIC concentrations which are typical of shallow coastal environments in summer.

Journal Article↗
PubMed2001

[Colonoscopic follow-up of patients undergoing curative resection of colorectal cancer].

AIM: To investigate the role of colonoscopy in the follow-up of patients undergoing curative resection of colorectal cancer. MATERIAL AND METHODS: A prospective study was performed of 102 patients with colorectal cancer who underwent surgery with curative intention. Postoperative colonoscopic follow-up was a minimum of 5 years. RESULTS: There were 62 males and 40 females. The mean duration of follow-up was 73.4 months. Synchronous polyps were found in 44.1% (114 in 45 patients) and metachronous polyps in 33.4% (64 in 34 patients). Synchronous carcinoma was detected in 7.8% (9 in 8 patients), metachronous carcinoma in 1.9% (2 in 2 patients) and suture recurrence in 4.9% (5 in 5 patients). Metachronous polyps developed in 55.5% of the patients with synchronous polyps and in only 15.8% of those with no synchronous polyps (p < 0.00005); the odds ratio was 6.67. Colonoscopy diagnosed 92 synchronous polyps and 64 metachronous polyps; of these, 34 were found to be significant(in 22 patients). Colonoscopy diagnosed 5 synchronous carcinomas; in 3 of these (polyps with non-invasive carcinoma) polypectomy constituted definitive therapy and in the remaining 2, curative resection was achieved. Colonoscopy diagnosed 2 stage C2 metachronous carcinomas at 63 and 94 months. Curative resection was achieved in both cases. Colonoscopic follow-up diagnosed 2 suture recurrences and resection was potentially curative. CONCLUSIONS: Colonoscopy was found to play an essential role in 30% of the patients. The technique allowed the early diagnosis of synchronous carcinomas and curative treatment of metachronous carcinomas and demonstrated that the presence of synchronous polyps increases the risk of developing metachronous polyps.

Adenomatous Polyps↗
PubMed2001

Allergy to grape: a case report.

We report a case of a 5-year-old child who suffered an oral allergy syndrome and lip angiedema after eating grapes. We obtained a positive prick test with commercial grape extract and a positive prick-by-prick test with pulp and peel of fresh white grape (Moscatel variety) and pulp and peel of blue grape. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by immunoblotting revealed specific immunoglobulin E (IgE) antibodies in the patient's serum against a 94,000 molecular-weight antigenic band. Lip open challenge was positive.

Angioedema↗
PubMed2001

Pharmacokinetics and residues of ciprofloxacin and its metabolites in broiler chickens.

The pharmacokinetic properties of ciprofloxacin and its metabolites were determined in healthy chickens after single i.v. and oral dosage of 8 mg ciprofloxacin kg(-1) bodyweight. After i.v. and oral administration, the plasma concentration-time graph was characteristic of a two-compartment open model. Mean (SD) elimination half-life and mean residence time of ciprofloxacin in plasma were 8.84 (2.13) and 8.54 (1.64) hours, respectively, after i.v. administration and 11.89 (1.95) and 13.32 (2.65) hours, respectively, after oral administration. Mean maximal plasma concentration of ciprofloxacin was 2.63 (0.20) microg ml(-1), and the interval from oral administration until maximum concentration was 0.36 (0.07) hours. The mean oral bioavailability of ciprofloxacin was found to be 69.12 (6.95) per cent. Ciprofloxacin was mainly converted to oxociprofloxacin and desethyleneciprofloxacin. Considerable kidney, liver, muscle and skin + fat tissue concentrations of ciprofloxacin and its metabolites oxociprofloxacin and desethyleneciprofloxacin were found when ciprofloxacin was administered orally (8 mg kg(-1) on 3 successive days). It was estimated that mean tissue concentrations of ciprofloxacin and its metabolites ranging between 0.011 to 0.75 microg g(-1) persisted for 5 days.

Administration, Oral↗
PubMed2001

Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients.

Molecular mechanisms of azole resistance in Candida albicans, including alterations in the target enzyme and increased efflux of drug, have been described, but the epidemiology of the resistance mechanisms has not been established. We have investigated the molecular mechanisms of resistance to azoles in C. albicans strains displaying high-level fluconazole resistance (MICs, > or =64 microg/ml) isolated from human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis. The levels of expression of genes encoding lanosterol 14alpha-demethylase (ERG11) and efflux transporters (MDR1 and CDR) implicated in azole resistance were monitored in matched sets of susceptible and resistant isolates. In addition, ERG11 genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations with a possible effect in the affinity for azoles. The analysis confirmed the multifactorial nature of azole resistance and the prevalence of these mechanisms of resistance in C. albicans clinical isolates exhibiting frank fluconazole resistance, with a predominance of overexpression of genes encoding efflux pumps, detected in 85% of all resistant isolates, being found. Alterations in the target enzyme, including functional amino acid substitutions and overexpression of the gene that encodes the enzyme, were detected in 65 and 35% of the isolates, respectively. Overall, multiple mechanisms of resistance were combined in 75% of the isolates displaying high-level fluconazole resistance. These results may help in the development of new strategies to overcome the problem of resistance as well as new treatments for this condition.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Ferrochelatase is present in Brucella abortus and is critical for its intracellular survival and virulence.

Brucella spp. are pathogenic bacteria that cause brucellosis, an animal disease which can also affect humans. Although understanding the pathogenesis is important for the health of animals and humans, little is known about virulence factors associated with it. In order for chronic disease to be established, Brucella spp. have developed the ability to survive inside phagocytes by evading cell defenses. It hides inside vacuoles, where it then replicates, indicating that it has an active metabolism. The purpose of this work was to obtain better insight into the intracellular metabolism of Brucella abortus. During a B. abortus genomic sequencing project, a clone coding a putative gene homologous to hemH was identified and sequenced. The amino acid sequence revealed high homology to members of the ferrochelatase family. A knockout mutant displayed auxotrophy for hemin, defective intracellular survival inside J774 and HeLa cells, and lack of virulence in BALB/c mice. This phenotype was overcome by complementing the mutant strain with a plasmid harboring wild-type hemH. These data demonstrate that B. abortus synthesizes its own heme and also has the ability to use an external source of heme; however, inside cells, there is not enough available heme to support its intracellular metabolism. It is concluded that ferrochelatase is essential for the multiplication and intracellular survival of B. abortus and thus for the establishment of chronic disease as well.

Animals↗
PubMed2001

The synaptic behaviour of the wild forms of Triticum turgidum and T. timopheevii.

Different wild allopolyploid species of Triticeae show extensive bivalent formation at zygotene while a considerable number of multivalents is present in cultivated polyploid wheats. To study the chromosome behaviour at early meiotic stages in wild forms of tetraploid wheats Triticum turgidum and T timopheevii (2n = 4x = 28) we have analysed the synaptic pattern in fully traced spread nuclei at mid- and late zygotene and at pachytene of wild accessions of these species. The mean number of synaptonemal complex (SC) bivalents at mid-zygotene ranged from 12.22 to 13.14 among the accessions studied indicating a strong restriction of synapsis initiation to homologous chromosomes. The mean of bivalents increased at pachytene because of the transformation of multivalents into bivalents. Ring bivalents observed at metaphase I support that SC bivalents were formed by homologous chromosomes. The average values of SC bivalents at mid-zygotene in the wild forms are much higher than the average values observed in the cultivated tetraploid wheats but similar to that of a mutant line of T turgidum with a duplication that includes Ph1, the major homoeologous pairing suppressor locus. These results suggest that the efficiency of the mechanism operating in the homologous recognition for synapsis is higher in wild wheat populations than in cultivated varieties. Apparently, a relatively detrimental modification of the pairing regulating genetic system accompanied the domestication of the wild wheat forms.

Cell Nucleus↗
PubMed2001

The effect of acenocoumarol on hemorheological parameters.

The effect of acenocoumarol on hemorheological variables was measured in 35 non-valvular chronic atrial fibrillation patients before starting oral anticoagulant therapy (basal) and one and two months after beginning treatment (INR-2,3). Fibrinogen increased significantly from the basal situation: 332+/-99 mg/dl to 386+/-96 mg/dl in the second month (p<0.05). However, this small increase in fibrinogen is not large enough to mediate other rheological changes, and whole blood filterability, blood viscosity, plasma viscosity and erythrocyte deformability and aggregability remained unchanged after treatment. These results suggest that acenocoumarol does not affect rheological parameters and can therefore be used as a "neutral drug" for rheological studies in cardiovascular patients under oral anticoagulant therapy.

Acenocoumarol↗
PubMed2001

[Use of aprotinin during pediatric heart surgery].

OBJECTIVE: To study the efficacy of high doses of aprotinin during cardiopulmonary bypass (CPBP) in pediatric patients with a tendency to intra- and postoperative bleeding: children undergoing repeated operations and those with cyanotic cardiopathy. PATIENTS AND METHODS: A simple retrospective, random sample of 71 pediatric patients with cyanogenic cardiopathy was studied. Group I (n = 36) received a test dose of 50,000 KIU in 2 min. The initial dose was 1,700,000 KIU (170 ml/m2 of body surface) i.v., at an infusion rate of 150 ml/h. CPBP circuit prime dose was 1,700,000 (170 ml/m2 of body surface), with replacement at a volume equivalent to the circuit prime. The maintenance dose was 400,000 KIU (40 ml/m2/h) i.v. Infusion was suspended 2 hours after a patient's arrival at the intensive care unit (ICU). We recorded red blood cell loss and blood product requirements in the first 24 hours in the ICU, duration of surgery, intra- and postoperative diuresis, and complications. RESULTS: Group I required 13.96 +/- 12.09 ml/kg/h of packed red cells whereas Group II required 22 +/- 16.22 ml/kg/h (p < 0.05). The volume lost was less in Group I than in Group II (0.77 +/- 0.48 ml/kg/h vs. 2.12 +/- 3.9 ml/kg/h; p < 0.05). The means for intra- and postoperative diuresis in the first 24 hours were not significantly different. CONCLUSIONS: Aprotinin significantly reduces red blood cell loss and homologous blood transfusion requirements. No complications attributable to aprotinin were observed.

Anticoagulants↗
PubMed2001

[Treatment with enoxaparin adapted to the fertility programs in women with recurrent abortion and thrombophilia].

Acquired and inherited thrombophilia are associated with recurrent pregnancy loss (RPL). Antithrombotic therapy could restore hemostatic balance and improve early placentation and gestational outcome. We evaluated the efficacy of enoxaparin adapted to the fertility program for prevention of pregnancy loss in 35 women (W) with early RPL and thrombophilia. Previous to the diagnosis of thrombophilia, they had had a total of 105 gestations of which 89 (85%) ended in early pregnancy loss. After diagnosis of thrombophilia, 35 subsequent pregnancies were treated with enoxaparin. In 5 cases assisted reproductive techniques were necessary to achieve pregnancy due to couple infertility. In 17 W who had had at least one preclinical pregnancy loss, enoxaparin (20 mg/d/s.c.) was started previous to conception and adapted to the fertility program. All the women continued with the gestational regime. Eighteen W with only clinical pregnancy loss started enoxaparin (20 mg twice per day s.c.) after biochemical pregnancy diagnosis. During gestations heparin dose was adjusted with anti Xa test, maintaining a range between 0.3 at 0.6 u/ml. With antithrombotic therapy, 30/35 (85%) of the pregnancies ended in live birth versus 16/105 (15%) of the pregnancies without treatment (p < 0.001). These results suggest that enoxaparin adapted to the fertility program can be effective in the prevention of preclinical and clinical abortion in women with thrombophilia.

Abortion, Habitual↗
PubMed2001

Preoperative evaluation of sentinel lymph node status in melanoma by means of (99m)Tc-MIBI and lymphoscintigraphy: a case report.

Previous reports have shown that (99m)Tc-sestamibi (MIBI) could detect clinically occult metastatic melanoma lesions. This article reports on a patient with invasive melanoma of the right heel in whom the sentinel node status was preoperatively evaluated with this tracer. Although regional lymph nodes were clinically negative, (99m)Tc-MIBI scintigraphy showed focal increased tracer uptake in the right groin that corresponded to the location of 2 sentinel nodes visualized by lymphoscintigraphy with (99m)Tc-colloidal rhenium sulfide performed the same day. A gamma-probe was used intraoperatively to guide the excision of the sentinel nodes that were further classified as metastatic by histopathology. This double-technique approach is technically feasible and has the potential of selecting a group of patients who might benefit from a selective complete lymphadenectomy.

Humans↗
PubMed2000

Electronic transport through ballistic chaotic cavities: reflection symmetry, direct processes, and symmetry breaking.

We extend previous studies on transport through ballistic chaotic cavities with spatial left-right (LR) reflection symmetry to include the presence of direct processes. We first analyze fully LR-symmetric systems in the presence of direct processes and compare the distribution w(T) of the transmission coefficient T with that for an asymmetric cavity with the same "optical" S matrix. We then study the problem of "external mixing" of the symmetry caused by an asymmetric coupling of the cavity to the outside. We first consider the case where symmetry breaking arises because two symmetrically positioned waveguides are coupled to the cavity by means of asymmetric tunnel barriers. Although this system is asymmetric with respect to the LR operation, there is an effect of the symmetry of the cavity it was constructed from. Second, we break LR symmetry in the absence of direct processes by asymmetrically positioning the two waveguides and compare the results with those for the completely asymmetric case.

Journal Article↗
PubMed2000

Participation of tyrosine phosphorylation in cytoskeletal reorganization, alpha(IIb)beta(3) integrin receptor activation, and aspirin-insensitive mechanisms of thrombin-stimulated human platelets.

BACKGROUND: Fibrinogen binding to the active conformation of the alpha(IIb)beta(3) integrin receptor (glycoprotein IIb/IIIa) and cytoskeletal reorganization are important events in platelet function. Tyrosine phosphorylation of platelet proteins plays an essential role in platelet signal transduction pathways. We studied the participation of tyrosine kinases on these aspects of platelet reactivity and their importance in cyclooxygenase (COX)-1-independent mechanisms in thrombin-stimulated human platelets. METHODS AND RESULTS: Using washed platelets from normal donors and tyrphostin-A47 and aspirin as tyrosine kinase and COX-1 inhibitors, respectively, we found that tyrphostin-A47 downregulated (1) the thrombin-activated conformational change of alpha(IIb)beta(3), (2) actin polymerization and cytoskeletal reorganization, and (3) the quantity of tyrosine-phospho-rylated proteins associated with the reorganized cytoskeleton. The latter are important components of multimolecular signaling complexes. Concomitantly, platelet aggregation and secretion were significantly reduced. Aspirin did not affect receptor activation or tyrosine phosphorylation but did decrease the initial (30-second) burst of actin polymerization. Importantly, aspirin significantly amplified the inhibitory effect of tyrphostin-A47 on all aspects of platelet reactivity that we evaluated. CONCLUSIONS: Tyrosine protein phosphorylation is a regulatory control system of the inside-out mechanism of alpha(IIb)beta(3) activation and cytoskeletal assembly in thrombin-stimulated human platelets. Inhibition of these aspects of platelet function with tyrphostin-A47 is amplified when platelets are treated with aspirin. Therefore, tyrosine phosphorylation is a major component of early signaling events and of COX-1-independent mechanisms of thrombin-induced platelet reactivity. The study results may indicate a novel target for therapeutic intervention.

Aspirin↗