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Biomedical subjects

M Navarro

Publications and source records attributed to M Navarro.

At least 37 records · Page 2Linked to original sources

Polymorphisms in prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) and risk of colorectal cancer.

Inflammation plays a key role in the development of colorectal cancers. We have investigated the relationship between PTGS2 (COX2) polymorphisms and colorectal cancer risk in a hospital based case-control study. We recruited 292 patients with colorectal cancer and 274 controls from new patients admitted to Bellvitge Hospital, Barcelona, Spain, from 1996 to 1998. Subjects responded to a questionnaire on risk factors. Genotypes of the eight more frequent polymorphisms of PTGS2 were determined. Two polymorphisms are located in the promoter sequence, one in the untranslated region of exon 1, one in exon 3, one in intron 5, two in the untranslated region of exon 10, and one downstream of the last polyadenylation (poly-A) signal. Associations were analysed with logistic regression models assuming a dominant effect for rare variants to increase statistical power. An association was detected between colorectal cancer and a polymorphism in the untranslated region of exon 10 of PTGS2, with an odds ratio (OR) of 2.49, 95% confidence interval (CI) of 1.17-5.32, P=0.01. A nearby polymorphism downstream of the last poly-A signal also showed a nonsignificant increase in risk (OR 2.17, 95% CI 0.99-4.78, P=0.05). Analysis of haplotypes confirmed that individuals with these variants were at increased risk of colorectal cancer (OR compared to the most frequent haplotype: 2.17, 95% CI 0.97-4.84, P=0.06) Interactions between PTGS2 genotype and use of nonsteroidal anti-inflammatory drugs and risk of colorectal cancer were also explored.

Adult↗

Intrapartum fetal pulse oximetry and fetal heart rate decelerations.

OBJECTIVES: To determine the behavior of fetal oxygenation (FSpO(2)) in different patterns of fetal heart rate decelerations (FHR). METHODS: A total of 787 decelerations were studied. RESULTS: FSpO(2) decreased significantly during decelerations, especially when the alteration was prolonged. CONCLUSIONS: Modifications in FHR occur simultaneously with alterations in FSpO(2), although the latter do not persist in time. Different degrees of FSpO(2) seen prior to deceleration are an expression of fetal respiratory status.

Adolescent↗

Nicotine in alcohol deprivation increases alcohol operant self-administration during reinstatement.

Tobacco and alcohol are highly co-abused by humans. Most experimental studies have evaluated ethanol consumption in animals exposed concomitantly to nicotine. However, little is known regarding the effects of nicotine administered during periods of alcohol deprivation. In the present study, adult male Wistar rats with an extended background of operant self-administration of ethanol were alcohol-deprived and treated with nicotine (0.1, 0.2, 0.4 and 0.8 mg/kg) or saline during five consecutive days in one chamber of a place conditioning apparatus. Nicotine-induced changes in locomotion were monitored daily, whereas the expression of place conditioning was studied the day after the last nicotine injection. Forty-eight hours after testing for conditioning, the animals resumed operant self-administration of ethanol and their alcohol intake was evaluated during the next 14 days. We observed that alcohol consumption was increased in animals treated with nicotine at doses of 0.2, 0.4 and 0.8 mg/kg but not in animals treated with the dose of 0.1 mg/kg or saline. Additionally, the dose of 0.8 mg/kg of nicotine not only induced persistent changes in alcohol self-administration but also produced conditioned place aversion and depressed locomotor activity. These results indicate that nicotine administration during the ethanol deprivation period can exacerbate the maintenance of alcohol consumption.

Animals↗

Development and cell response of a new biodegradable composite scaffold for guided bone regeneration.

Composites of biodegradable polymers with different calcium phosphate ceramics and glasses, have been developed as scaffolds for applications in bone-tissue engineering. In this work, phosphate glass particles have been incorporated into the polymer, poly(95L/5DL) lactic acid (PLA) and porous structures were elaborated. Their porosity, compressive mechanical properties and biological response were evaluated. Interconnected structures with evenly distributed pores and a porosity as high as 97% were obtained. The incorporation of glass particles into the polymer showed to have a positive effect in the mechanical properties of the foams. Indeed, the compressive modulus increased from 74.5 to 120 KPa and the compressive strength from 17.5 to 20.1 KPa for the PLA and the PLA/glass foams, respectively. The biological response was evaluated by means of the MTT test, the materials resulted to be noncytotoxic.

Absorbable Implants↗

Tinea capitis in infants in their first year of life.

BACKGROUND: Tinea capitis is the most common type of dermatophytosis in children, but is uncommon in the first year of life. OBJECTIVES: To review clinical, mycological and epidemiological data in a series of 10 infants aged under 1 year diagnosed as having tinea capitis in three Spanish hospitals between 1998 and 2002. METHODS: A retrospective case note study. RESULTS: There were six boys and four girls with a mean of age 7 months (range 1.5-12). All the children were born in Spain, but in five cases the parents were immigrants from Africa. In these cases the isolated dermatophytes were two Trichophyton tonsurans, one T. verrucosum and two Microsporum audouinii. Four autochthonous cases were caused by M. canis and one by M. audouinii (but this one was in contact with African immigrants). In two of the five cases produced by anthropophilic dermatophytes other family members were infected by the same fungus. Most cases were treated successfully with griseofulvin. CONCLUSIONS: Although tinea capitis is rare in infants in their first year of life, the condition should be investigated if scaling and/or alopecia are present. A thorough epidemiological study of other family members is mandatory.

Antifungal Agents↗

Mutations in the shutter region of antithrombin result in formation of disulfide-linked dimers and severe venous thrombosis.

BACKGROUND: Missense mutations causing conformational alterations in serpins can be responsible for protein deficiency associated with human diseases. However, there are few data about conformational consequences of mutations affecting antithrombin, the main hemostatic serpin. OBJECTIVES: To investigate the conformational and clinical effect of mutations affecting the shutter region of antithrombin. PATIENTS AND METHODS: We identified two families with significant reduction of circulating antithrombin displaying early and severe venous thrombosis, frequently associated with pregnancy or infection. Mutations were determined by standard molecular methods. Biochemical studies were performed on plasma samples. One variant (P80S) was purified by heparin-affinity chromatography and gel filtration, and evaluated by proteomic analysis. Finally, we modelled the structure of the mutant dimer. RESULTS: We identified two missense mutations affecting the shutter region of antithrombin: P80S and G424R. Carriers of both mutations presented traces of a similar abnormal antithrombin, supporting inefficiently expressed rather than non-expressed variants. The abnormal antithrombin purified from P80S carriers is an inactive disulfide-linked dimer of mutant antithrombin whose properties are consistent with head-to-head insertion of the reactive loop. CONCLUSIONS: Our data support the conclusion that missense mutations affecting the shutter region of serpins have specific conformational effects resulting in the formation of mutant oligomers. The consequent inefficiency of secretion explains the accompanying deficiency and loss of function, but the severity of thrombosis associated with these mutations suggests that the oligomers also have new and undefined pathological properties that could be exacerbated by pregnancy or infection.

Adult↗

[Intracorneal depot steroids for the treatment of corneal rejection after keratoplasty].

PURPOSE: To introduce a new type of therapy for corneal rejection after keratoplasty with the microinjection of intrastromal depot cortisone in single or multiple doses. METHODS: Thirty-three consecutive eyes with corneal graft rejection were diagnosed and treated by one of the authors (EA) between January 1998 and November 2000. RESULTS: Of the 33 eyes, 26 were submitted to Penetrating Keratoplasty (PK), five to lamellar, and two to homoplastic keratoplasty. The most common rejection type was epithelial in 20 eyes, 11 eyes showed mixed rejection types and two eyes, endothelial. In 18 of the cases (54.54%) treatment consisted solely of intraestromal injection; in the other 15 cases some other medications were added mostly because of patient anxiety. The vast majority of the cases (81%) improved clinically within a few days after the injection. Fifty-four percent of the cases required a number of doses ranging from one to five; the rest of the cases had a greater number of sessions. Thirty-one cases have been followed up for a period longer than six months without showing increase in intraocular pressure or development of steroid lens opacities. CONCLUSION: Intrastromal depot cortisone injection is a new alternative for the treatment of corneal graft rejections after keratoplasty.

Administration, Topical↗

[The Connecticut Chemosensorial Clinical Research Center olfaction test: values in healthy volunteers].

OBJECTIVE: To know the values of the olfactory test (CCCRC) performed in healthy people. To analyse how the age and sex affect the test. MATERIAL AND METHODS: Descriptive study in 100 volunteers with no olfactory disorders. We used CCCRC olfactory test, which it has an odor threshold component, an odor identification component and a composite score. We analysed how age and sex variables affect olfactory test data, listing a t-Student test. The size sample is calculated to 0.05 alfa error. RESULTS: Threshold test data mean was 5.8. Identification test data mean was 7.5. Composite score mean was 6.7. CONCLUSION: Age is a significant factor in our study but not sex. Sample size is sufficient to analyze normal values. Our results are similar to other authors.

Adolescent↗

Neuroanatomical relationship between type 1 cannabinoid receptors and dopaminergic systems in the rat basal ganglia.

Dopamine and endocannabinoids are neurotransmitters known to play a role in the activity of the basal ganglia motor circuit. While a number of studies have demonstrated functional interactions between type 1 cannabinoid (CB1) receptors and dopaminergic systems, we still lack detailed neuroanatomical evidence to explain their relationship. Single- and double-labeling methods (in situ hybridization and immunohistochemistry) were employed to determine both the expression and localization of CB1 receptors and tyrosine hydroxylase (TH) in the basal ganglia. In the striatum, we found an intense signal for CB1 receptor transcripts but low signal for CB1 receptor protein, whereas in the globus pallidus and substantia nigra we found the opposite; no hybridization signal but intense immunoreactivity. Consequently, CB1 receptors are synthesized in the striatum and mostly transported to its target areas. No co-expression or co-localization of CB1 receptors and TH was found. In the caudate-putamen, globus pallidus and substantia nigra, TH-immunoreactive fibers were interwoven with the CB1 receptor-immunoreactive neuropil and fibers. Our data suggest that the majority of the striatal CB1 receptors are located presynaptically on inhibitory GABAergic terminals, in a position to modulate neurotransmitter release and influence the activity of substantia nigra dopaminergic neurons. In turn, afferent dopaminergic fibers from the substantia nigra innervate CB1 receptor-expressing striatal neurons that are known to also express dopamine receptors. In conclusion, these data provide a neuroanatomical basis to explain functional interactions between endocannabinoid and dopaminergic systems in the basal ganglia.

Animals↗

Albendazole sulphoxide enantiomers in pregnant rats' embryo concentrations and developmental toxicity.

Three single oral doses (8.5, 10, and 14 mg/kg) of a racemic formulation of albendazole sulphoxide (ABZSO) were administered to pregnant rats on day 10 of gestation. Mother plasma and embryo concentrations of ABZSO enantiomers and albendazole sulphone (ABZSO(2)) were determined 9 h after administration. The (-)-ABZSO enantiomer showed higher peak concentrations in both maternal plasma and embryo than the (+) enantiomer. An increase in embryo concentrations of ABZSO enantiomers and ABZSO(2) was only observed when dose rose to 14 mg/kg. There was an increase in resorption when the dose increased, but significant differences were only found in the higher dose group when compared with the other groups. The incidence of external and skeletal malformations (mostly of the tail, vertebrae and ribs) rose significantly in the 10 mg/kg group, producing almost 20% and 90% of malformed fetuses, respectively, and gross external and skeletal abnormalities in the thoracic region and limbs were also found.

Abnormalities, Multiple↗

The identification of circular extrachromosomal DNA in the nuclear genome of Trypanosoma brucei.

Nuclear extrachromosomal DNA elements have been identified in several kinetoplastids such as Leishmania and Trypanosoma cruzi, but never in Trypanosoma brucei. They can occur naturally or arise spontaneously as the result of sublethal drug exposure of parasites. In most cases, they are represented as circular elements and are mitotically unstable. In this study we describe the presence of circular DNA in the nucleus of Trypanosoma brucei. This novel type of DNA was termed NR-element (NlaIII repeat element). In contrast to drug-induced episomes in other kinetoplastids, the T. brucei extrachromosomal NR-element is not generated by drug selection. Furthermore, the element is stable during mitosis over many generations. Restriction analysis of tagged NR-element DNA, unusual migration patterns during pulsed field gel electrophoresis (PFGE) and CsCl/ethidium bromide equilibrium centrifugation demonstrates that the NR-element represents circular DNA. Whereas it has been found in all field isolates of the parasites we analysed, it is not detectable in some laboratory strains notably the genome reference strain 927. The DNA sequence of this element is related to a 29 bp repeat present in the subtelomeric region of VSG-bearing chromosomes of T. brucei. It has been suggested that this subtelomeric region is part of a transition zone on chromosomes separating the relatively stable telomeric repeats from the recombinationaly active region downstream of VSG genes. Therefore, we discuss a functional connection between the occurrence of this circular DNA and subtelomeric recombination events in T. brucei.

Animals↗

Posterior urethral valves: prognostic factors.

OBJECTIVE: To determine which variables besides bladder dysfunction can help to predict the outcome of renal function in boys with posterior urethral valves (PUV). PATIENTS AND METHODS: All 40 patients with PUV in this retrospective study were diagnosed and began treatment in our hospital within the first 3 months of life, and have had >or= 5 years of follow-up. At the time of diagnosis, 33 were in renal insufficiency (RI) and seven had normal renal function (RF). At the time of the study 16 were in chronic renal failure (CRF) and 24 had normal RF. We compared their RF (initial and during follow-up), vesico-ureteric reflux (VUR), urinary tract infection (UTI), proteinuria, hypertension, renal echogenicity, final patient age and initial management. RESULTS: The mean serum creatinine values before and after initial treatment were worse in boys who developed CRF than in those who did not (P = 0.08); the mean glomerular filtrate rate (GFR) at 1 year old was 52 mL/min/1.73 m2 in the former and 102 in the latter (P < 0.001). Proteinuria was present during the follow-up in 79% of patients in CRF and in only 17% of those with normal RF. All patients who developed CRF had echogenic renal changes while only 53% of the others had (P < 0.01). Other variables showed no statistically significant differences (VUR, UTI, hypertension and final patient age). Of 33 patients in RI at diagnosis, nine were treated by valve ablation and 24 by temporary pyelo-ureterostomy. The initial mean serum creatinine value was worse in the latter than in the former (20.8 vs 13.0 mg/L). However, at 1 year old the mean GFR was better in the latter than in the former (P < 0.05). These GFR differences persisted during the first years of life but had disappeared by the fifth. CONCLUSIONS: The most significant prognostic factor for the future development of CRF is the GFR at 1 year old. The onset of proteinuria during the follow-up is associated with a worse prognosis. Echogenic renal changes may help to identify those dysplastic kidneys that will develop RI. Neonatal boys in RI who underwent pyelo-ureterostomy had better RF during the first years of life than those who underwent valve ablation.

Adolescent↗

Determination of total arsenic levels by hydride generation atomic absorption spectrometry in foods from south-east Spain: estimation of daily dietary intake.

The total concentration of arsenic in different foods from south-east Spain was determined by hydride generation atomic absorption spectrometry. Mineralization was carried out with an HNO(3)-HClO(4) mixture in a thermostated sand bath. Arsenic determination was performed by the standard addition method. Analyses of NIST and CBR-CEC reference materials demonstrated the reliability and accuracy of the technique. The highest arsenic levels were found in seafood, cereals, meat and meat by-products. In meat and meat by-products, the total arsenic measured in meat was significantly higher than that in sausages (p<0.05). In cereals, arsenic concentrations in corn and white rice samples were significantly higher (p<0.01) than those measured in wheat by-products. Mean arsenic concentrations in cheese were statistically lower than those in other dairy products (p<0.01). New data have been provided on the total arsenic content of a variety of foods in Spain, which is important for making exposure estimates. The estimated daily intake of total arsenic in the Spanish diet was 221 microg As day(-1).

Arsenic↗

Application of matrix solid-phase dispersion to the determination of a new generation of fungicides in fruits and vegetables.

A method based on matrix solid-phase dispersion (MSPD) and gas chromatography to determine eight fungicides in fruits and vegetables is described. Fungicide residues were identified and quantified using nitrogen-phosphorus detection and electron-capture detection connected in parallel and confirmed by mass spectrometric detection. The method required 0.5 g of sample, C18 bonded silica as dispersant sorbent, silica as clean-up sorbent and ethyl acetate as eluting solvent. Recoveries from spiked orange, apple, tomato, artichoke, carrot and courgette samples ranged from 62 to 102% and relative standard deviations were less than 15% in the concentration range 0.05-10 mg kg(-1). Detection and quantitation limits ranged 3-30 microg kg(-1) and 10-100 microg kg(-1), respectively, with linear calibration curves up to 10 mg kg(-1). The analytical characteristics of MSPD compared very favourably with the results of a classical multiresidue method, which uses ethyl acetate and anhydrous sodium sulphate for the extraction.

Chromatography, Gas↗

The value of fat-suppressed T2 or STIR sequences in distinguishing lipoma from well-differentiated liposarcoma.

The objective of this study was to evaluate the diagnostic value of fat-suppressed T2-weighted (FS-T2) images or short tau inversion recovery (STIR) imaging in distinguishing lipoma from lipoma-like subtype of well-differentiated liposarcoma. Spin-echo T1-weighted and STIR or fat-suppression T2-weighted sequences were performed in 60 lipomas and 32 lipoma-like well-differentiated liposarcomas, histologically proven, looking for thick septa or nodules in T1-weighted images and linear, nodular, or amorphous hyperintensities on FS-T2/STIR sequences. Fourteen lipomas (23.3%) showed thick septa and/or nodules on T1, whereas on FS-T2 or STIR sequences only seven (11.7%) displayed hyperintense nodules and/or septa. All well-differentiated liposarcomas contained these signs on FS-T2 or STIR sequences. The presence of hyperintense septa or nodules in a predominantly lipomatous tumor on FS-T2/STIR sequences helps to differentiate malignant tumors from lipomas. Employing the presence of hyperintense nodules and/or septa as criteria of malignancy specificity was 76.6% and sensitivity 100%. Overdiagnoses of well-differentiated liposarcoma can occur due to the presence of non-lipomatous areas within lipomas.

Adipose Tissue↗

Vasculogenesis and angiogenesis in the subcardinal venous plexus of quail mesonephros: spatial and temporal morphological analysis.

Vasculogenesis and angiogenesis are involved in a coordinated program for the development of the mesonephric subcardinal venous plexus of quail embryo. Vasculogenesis occurs between days 3 and 4 of incubation, while angiogenesis takes place from day 5 to day 7. Examination of vascular corrosion casts and whole mounts, and tissue sections labelled with specific markers to hemangioblast lineage (QH1, LEP100 and AcPase activity), allowed us to distinguish six phases in the formation of subcardinal plexus. (1) Appearance of isolated angioblast-like cells where the subcardinal plexus will form. (2) Alignment of angioblast-like cells into cellular strands. (3) Formation of compact vascular cords by association of angioblast-like strands. (4) Polygonal interconnection of vascular cords to constitute the primary subcardinal plexus. In this stage, isolated angioblast-like cells were present inside inter-vascular spaces. (5) The splitting of primary inter-vascular spaces by angiogenic sprouts to form secondary subcardinal plexus (outward angiogenesis). Isolated angioblast-like cells were not present in this stage. (6) Expansion of the secondary subcardinal plexus by insertion of slender transcapillary tissue pillars (inward angiogenesis) and angiogenic sprouts. We also describe three morphogenetic gradients during the development of the subcardinal plexus: ventral-to-dorsal, cranial-to-caudal and lateral-to-medial.

Animals↗