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R Pardo

Publications and source records attributed to R Pardo.

At least 19 recordsLinked to original sources

Association study of polymorphisms in LRP1, tau and 5-HTT genes and Alzheimer's disease in a sample of Colombian patients.

Analysis of genetic susceptibility factors for Alzheimer's disease (AD) in populations with different genetic and environmental background may be useful to understand AD etiology. There are few genetic association studies of AD in Latin America. In the present work, we analyzed polymorphisms in 3 candidate genes; the LDL receptor related protein-1, the microtubule-associated protein Tau and the serotonin transporter genes in a sample of 106 Colombian AD patients and 97 control subjects. We did not find a significant allelic or genotypic association with any of the three polymorphisms analyzed using different statistical analysis, including a neural network model or different sample stratifications. To date, APOE polymorphisms are the only genetic risk factors identified for AD in the Colombian population. It may be factible that future combination of high-throughput genotyping platforms and multivariate analysis models may lead to the identification of other genetic susceptibility factors for AD in the Colombian population.

Aged↗

Natural radiation doses to the population in a granitic region in Spain.

The global average effective dose from natural radiation sources is estimated to be 2.4 mSv y(-1). Nevertheless, local variations in the radiation exposure may differ by orders of magnitude. In this paper, we study a rural area in western Salamanca (Spain) where doses are potentially well above the stated average value. Its geology consists mostly of granite and schist, presenting various uranium mineralisations, some of which were exploited in former years. Water samples, both surface and groundwater, were collected in selected villages and measured by liquid-scintillation spectrometry. 222Rn in dwellings was determined in dwellings by means of short-term measurements, using Picorad vials and long-term measurements with CR-39 detectors. The committed effective doses to the inhabitants due to indoor 222Rn and 222Rn and 226Ra in drinking water were assessed using the dose conversion factors proposed in the UNSCEAR 2000 report.

Air Pollutants, Radioactive↗

[Prognostic significance and clinic utility of serum and immunohistochemical cathepsin B levels in colorectal cancer].

BACKGROUND: Aproximately one third of node-negative colorectal cancer recur suggesting the presence of micrometastasis not detected by conventional histopathologic methods. We think that the role of enzymes like Cathepsin B play in the process of invasion and metastasis in colorectal cancer might identify at earlier stages patients with high risk of shorter survival and who need more aggressive treatment. Our porpuse is to evaluate the prognostic significance of preoperative serum and inmunohistochemical levels of cathepsin B to identify colorectal carcinomas with worse prognostic. METHODS: Fifty five patients undergoing surgical treatment for colorectal cancer from 1998 to 2000. As a control group sera from 23 patients with acute appendicitis. Serum levels of cathepsin B were obtained preoperatively (KRKA, Novo Slovenia;ng/ml); cathepsin B inmunoreactivity was determinated after surgical treatment, (C-19, Santa Cruz Biotechnology). Serum levels of CEA (Inmulit 2000 CEA), and CA 19,9 (Inmulite Gi-Ma, Diagnostic Products Corporation, Los Angeles, CA), and p53 expression (Dako) were determinated in patients with colorectal cancer. Survival analysis was realized using Cox and Kaplan-Meier methods (SPSS 10.0 for Windows). RESULTS: The mean age of patients with colorectal cancer was 68 years (range 39-87 years). 29 males and 26 females. Tumor size was 4.6 cms., range 1-12. Rectal localization, 32.2%. Moderately differentiated, 49.1%. The median serum and inmunohistochemical levels of cathepsin B were 5.74 ng/ml and 29.56% in patients with acute appendicitis respectively. Preoperative serum levels in patients with colorectal cancer were: CEA, 46.04 ng/ml (range 0.21-7.32 ); CA 19,9, 110.52 UI/ml, (range 2.5-1920); and Cathepsin B, 6.94 ng/ml, range 3.57-11.6). Inmunohistochemical results were: p53, 44.36%, (range 0-95); Cathepsin B, 66.9% (range 10-90). Serum and inmunhistochemical values were significantly increased in patients with colorectal cancer when compared with control group, p=0,011 and p=0,000. High serum levels of cathepsib B were significantly associated wiyh shorter survival of patients with colorectal cancer in univariate and multivariate methods, p=0.041;HR 1.281 95%CI (1.043-1.716) and p= 0.022; HR 1.338.955 CI (1.043-1.716). CONCLUSIONS: Cathepsin B can be used like an independent prognostic tumoral marker in colorectal cancer. Preoperative serum levels over 6.94 ng/ml, are associated with worse prognostic and shorter survival.

Adult↗

Apolipoprotein E genotyping in a sample of Colombian patients with Alzheimer's disease.

Apolipoprotein E e4 (APOEe4) allele has been associated with an increased risk for Alzheimer's disease (AD) in diverse populations. Few studies have been carried out in Hispano-Americans and results are inconclusive due to ethnic diversity. This study determined the frequency of APOE alleles in a group of 61 Caucasian-Mestizos patients with probable AD, and 61 age- and sex-matched controls. APOEe4 frequency was 36.8% for patients, and 8.2% for controls (P < 0.0001; OR 7.6). Genotype frequencies differ between the two groups (P < 0.0001). Genotype 3/3 was the most common. Frequency of genotypes 3/4, 4/4 and 2/4 were higher in patients than in the controls. Our results show a highly significant association of APOEe4 with AD, and implies the importance of APOEe4 as a risk factor in this population.

Aged↗

Characterization of the metabotropic glutamate receptors mediating phospholipase C activation and calcium release in cerebellar granule cells: calcium-dependence of the phospholipase C response.

In this study we have determined the metabotropic glutamate receptors (mGluRs) involved in the glutamate activation of phospholipase C (PLC) and Ca(2+) mobilization in cerebellar granule cells at 9 days in vitro; and studied the Ca(2+) modulation of the PLC response. Both PLC activation and Ca(2+) signalling were found to be mediated exclusively by the mGluR1 subtype, although both group I mGluRs, mGluR1 alpha and mGluR5, could be detected in cell extracts. Exposure of cells to medium devoid of Ca(2+) for various times before agonist stimulation reduced the PLC response, which was quickly recovered following the re-exposure of cells to Ca(2+)-containing medium. The extent of the glutamate response correlated well with changes in the cytosolic Ca(2+) concentration. On the other hand, loading of the intracellular Ca(2+) stores by a transient depolarization followed by washing in nondepolarizing buffer, allowed glutamate to release stored Ca(2+) in the majority of cells and enhanced glutamate activation of PLC. Under such conditions, the absence of extracellular Ca(2+) during stimulation and the chelation of cytosolic Ca(2+) with BAPTA/AM inhibited both glutamate-elicited Ca(2+) response and PLC activation. Overall, these results indicate that the mGluR-mediated activation of PLC depends on the presence of extracellular Ca(2+) and can be modulated by moderate changes of cytosolic Ca(2+). Furthermore, ryanodine reduced PLC stimulation by glutamate in predepolarized cells but not in control cells, suggesting that ryanodine receptors could play a role in the potentiation of the mGluR-mediated activation of PLC by Ca(2+) release in predepolarized cells.

Animals↗

Effects of oxidative stress on phospholipid signaling in rat cultured astrocytes and brain slices.

Although reactive oxygen species (ROS) are conventionally viewed as toxic by-products of cellular metabolism, a growing body of evidence suggests that they may act as signaling molecules. We have studied the effects of hydrogen peroxide (H(2)O(2))-induced oxidative stress on phospholipid signaling in cultured rat cortical astrocytes. H(2)O(2) stimulated the formation of phosphatidic acid and the accumulation of phosphatidylbutanol, a product of the phospholipase D (PLD)-catalyzed transphosphatidylation reaction. The effect of exogenous H(2)O(2) on the PLD response was mimicked by menadione-induced production of endogenous H(2)O(2). Oxidative stress also elicited inositol phosphate accumulation resulting from phosphoinositide phospholipase C (PLC) activation. The PLD response to H(2)O(2) was totally suppressed by chelation of both extracellular and cytosolic Ca(2+) with EGTA and BAPTA/AM, respectively. Furthermore, H(2)O(2)-induced PLD stimulation was completely abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide and chelerythrine and by PKC down-regulation. Activation of PLD by H(2)O(2) was also inhibited by the protein-tyrosine kinase inhibitor genistein. Finally, H(2)O(2) also stimulated both PLC and PLD in rat brain cortical slices. These results show for the first time that oxidative stress elicits phospholipid breakdown by both PLC and PLD in rat cultured astrocytes and brain slices.

Animals↗

Clinical utility of reflex studies in assessing cervical radiculopathy.

We prospectively studied the diagnostic utility of upper limb segmental reflexes in patients with suspected cervical radiculopathy (CR). Fifty-three patients (29 men and 24 women), referred for electrodiagnostic testing, were positive for at least one of four clinical criteria for CR: abnormal (1) history, (2) motor (myotomal) examination, (3) sensory (dermatomal) examination, and (4) changes in deep tendon reflexes (DTR). All underwent electrodiagnostic assessment, needle electrode examination (NEE), specialized segmental reflexes (heteronymous and Hoffman's reflexes [H reflexes]), and neuroimaging. The clinical diagnosis was supported in all 32 patients who entered the study with two or more clinical signs for CR. Abnormal NEE was found in 90% of subjects with three clinical signs, 59% with two signs, and only 10% of those with one sign. H reflexes demonstrated a sensitivity of 72% and specificity of 85% for detection of CR and were particularly helpful when forming conclusions in the 21 subjects with only one clinical sign for CR. Specialized segmental H-reflex studies of the upper limb were as sensitive and specific as neuroimaging (magnetic resonance imaging).

Adult↗