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Biomedical subjects

A Navarro

Publications and source records attributed to A Navarro.

At least 19 recordsLinked to original sources
PubMed2007

Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms.

Phenotypic variation between human populations in skin pigmentation correlates with latitude at the continental level. A large number of hypotheses involving genetic adaptation have been proposed to explain human variation in skin colour, but only limited genetic evidence for positive selection has been presented. To shed light on the evolutionary genetic history of human variation in skin colour we inspected 118 genes associated with skin pigmentation in the Perlegen dataset, studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail. We identified eight genes that are associated with the melanin pathway (SLC45A2, OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD) and presented significant differences in genetic variation between Europeans, Africans and Asians. In six of these genes we detected, by means of the EHH test, variability patterns that are compatible with the hypothesis of local positive selection in Europeans (OCA2, TYRP1 and KITLG) and in Asians (OCA2, DCT, KITLG, EGFR and DRD2), whereas signals were scarce in Africans (DCT, EGFR and DRD2). Furthermore, a statistically significant correlation between genotypic variation in four pigmentation candidate genes and phenotypic variation of skin colour in 51 worldwide human populations was revealed. Overall, our data also suggest that light skin colour is the derived state and is of independent origin in Europeans and Asians, whereas dark skin color seems of unique origin, reflecting the ancestral state in humans.

Asian People↗
PubMed2006

Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues.

MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles by repressing translation or cleaving RNA transcripts. Although the number of verified human miRNA is still expanding, only few have been functionally described. However, emerging evidences suggest the potential involvement of altered regulation of miRNA in pathogenesis of cancers and these genes are thought to function as both tumours suppressor and oncogenes. In our study, we examined by Real-Time PCR the expression of 156 mature miRNA in colorectal cancer. The analysis by several bioinformatics algorithms of colorectal tumours and adjacent non-neoplastic tissues from patients and colorectal cancer cell lines allowed identifying a group of 13 miRNA whose expression is significantly altered in this tumor. The most significantly deregulated miRNA being miR-31, miR-96, miR-133b, miR-135b, miR-145, and miR-183. In addition, the expression level of miR-31 was correlated with the stage of CRC tumor. Our results suggest that miRNA expression profile could have relevance to the biological and clinical behavior of colorectal neoplasia.

Cluster Analysis↗
PubMed2006

In vitro antibacterial activity of the peptide PsVP-10 against Streptococcus mutans and Streptococcus sobrinus with and without glycocalyx.

The antibacterial activity of the peptide PsVP-10 obtained from Pseudomonas sp. R10 against Streptococcus mutans and Streptococcus sobrinus was investigated. One hundred and twenty strains of S. mutans and 120 strains of S. sobrinus with and without glycocalyx were isolated from saliva samples in trypticase-yeast-cysteine-sucrose-bacitracin (TYCSB) agar. Bacterial identification was made by polymerase chain reaction. Glycocalyx production was observed in modified TYCSB agar and confirmed with a modified version of the microplate adherence assay. The minimum inhibitory concentration (MIC) of PsVP-10 bacteriocin was determined by means of the agar dilution method, and the time of bacterial death was calculated by means of colony-forming unit counts. The MIC of the bacteriocin PsVP-10 for both bacterial species with and without glycocalyx was < 2 mg/L and the time of bacterial death was less than 240 s for all the studied bacterial strains. Thus, bacteriocin PsVP-10 could be an interesting possibility to combat these cariogenic bacterial species.

Anti-Bacterial Agents↗
PubMed2006

Outcome and morbidity of pancreas transplantation in a single Spanish institution.

BACKGROUND: Pancreas transplantation is nowadays the only treatment to reestablish normal blood glucose in diabetic patients. Moreover, transplantation may also prevent and possibly even revert diabetes-related complications. We present our results with the first 4 years of a pancreas transplantation program. MATERIALS AND METHODS: From February 2000 to June 2004, we performed 43 pancreas transplants in 42 recipients. In all cases the technique was enteric drainage of the exocrine secretions and systemic venous derivation to the inferior vena cava for endocrine secretions. RESULTS: A simultaneous pancreas-kidney transplant was performed in 37 (88.1%) patients, a pancreas after kidney in 4 (9.5%) patients, and a retransplant in 1 (2.4%) patient. Glycosylated hemoglobin and C peptide returned to normal values in all cases. Patient and graft survivals were 91% and 84%, respectively, after a median follow-up of 19 months. The rate of reoperations was 31% with an overall 16% graft loss. CONCLUSIONS: Our results were comparable to those of larger series.

Arteries↗
PubMed2006

Agonal period in potential non-heart-beating donors.

The shortage of donor kidneys for renal transplantation is becoming more severe as the gap between the number of patients waiting for renal transplantation and the number of cadaveric organs available continues to widen. Therefore, many centres have started using non-heart-beating (NHB) donors. There was no clear plan for maximal duration of agonal period in Maastricht category NHB donors after withdrawal of treatment in Newcastle. This withdrawal has been audited in retrospect. Our current wait time is now a maximum of 5 hours; however, previously there have been some considerably longer periods. Concern has always been expressed about poor quality with protracted periods. Nonuse in this review of 58 kidneys can be expressed against time: 0 to 2 hours 13%, 2 to 5 hours 33%, and >5 hours 45%. Therefore, though the nonuse rate was significantly different between 0 to 2 hours and >5 hours (P < .05, chi-square), there were 16 transplants performed with kidneys >2 hours and 12 transplanted >5 hours. In conclusion, although good usable kidneys can still be used with protracted withdrawal, there are considerable logistical difficulties with our 5-hour cut-off, which means that one third of potential kidneys will not be utilized.

Heart Arrest↗
PubMed2006

Diabetic donors as a source of non-heart-beating renal transplants.

Due to the organ shortage, many renal transplantation centers attempt to increase the donor pool by using non-heart-beating donors (NHBDs). These kidneys are generally regarded as "marginal" grafts. Many centers do not consider transplantation from an NHBD with a history of diabetes as it is a more suboptimal donor. We began our NHBD program in 1998 and have performed 5 renal transplants from diabetic NHBDs. Viability testing identified kidneys suitable for single or dual transplantation. Although kidneys from brain stem dead donors with diabetes have been used successfully, our data suggested that kidneys from diabetic NHBDs can also be used although we still need long-term results.

Cadaver↗
PubMed2006

Renal graft function after prolonged agonal time in non-heart-beating donors.

To deal with the increasing gap between organ demand and supply for kidney transplantation, many centers have started to use non-heart-beating (NHB) donors. When we initiated our program to utilize kidneys from such donors in 1998, we had no protocol for the maximal agonal period. This however was audited in retrospect. Our current wait time is now a maximum of 5 hours. Concern has been expressed in the past about possible deterioration in the quality of the organs with a protracted agonal time. We aimed in this study to examine the effect of prolonging agonal period on the quality of kidneys retrieved from Maastricht category III donors: A total of 40 kidneys were transplanted from 29 category III donors between 1998 and 2004. Eleven kidneys had donor agonal times of >5 hours; the remainder, agonal times <5 hours. Both groups were matched for donor and recipient factors. The mean glomerular filtration rates at 12 months for <5 hours versus >5 hours agonal time were 43.8 +/- 4.4 versus 49.8 +/- 5.8, respectively (P = .24) and at 24 months, 46.83 +/- 8.99 versus 37.67 +/- 3.85, respectively (P = .24). In conclusion, intermediate graft function is comparable to ones with shorter agonal time, although we await long-term results.

Adult↗
PubMed2006

Non-heart-beating kidney transplantation: 6-year outcomes.

Non-heart-beating donor kidneys (NHBD) are being used to increase the donor pool due to the scarcity of cadaveric heart beating donors (HBD). We evaluated the long-term outcomes of renal transplantation using NHBD kidneys, comparing the first 100 NHBD kidneys transplanted at our facility to the next consecutive cadaveric HBD kidneys for graft survival, recipient survival, and quality of graft function. Recipient survival (P = .22) and graft survival (P = .19) at 6 years did not differ between recipients of NHBD (83%, 80%) and HBD (89%, 87%) kidneys. Quality of graft function using the mean glomular filtration rates were significantly lower in the NHBD group up to 3 months following discharge (41 +/- 2 vs 47 +/- 2, P = .007) but were then comparable up to 6 years following transplantation (43 +/- 5 vs 46 +/- 4, P = .55).

Adolescent↗
PubMed2006

Lercanidipine is an effective and well tolerated antihypertensive drug regardless the cardiovascular risk profile: The LAURA study.

To determine whether the antihypertensive effectiveness of lercanidipine was independent of the different cardiovascular risk levels. Patients with treated or untreated mild-to-moderate essential hypertension were included in a multicentre, prospective, non-comparative, open-label study. Patients received lercanidipine (10 mg/day, uptitrated to 20 mg/day) during 6 months. A total of 3175 patients, age 63 +/- 10 years, 51% women, were included. The cardiovascular risk was low in 237 patients, medium in 1396, high in 722, and very high in 820. At baseline, blood pressure (BP) was 159.5 +/- 11.7/95.2 +/- 7.4 mmHg. BP was progressively higher according to increase in cardiovascular risk. After 6 months of treatment, BP was 136.0 +/- 9.7/79.7 +/- 6.8 mmHg. The decrease in systolic BP and diastolic BP at each follow-up visit compared with baseline was statistically significant both in the intergroup and intragroup comparisons (p < 0.001). Mean decreases of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were -18.5/-13.8 mmHg in the low risk group, -23/-15.2 mmHg in the medium risk group, -24.4/-16.1 mmHg in the high risk group, and -27.4/-17.4 mmHg in the very high risk group. Most frequent side effects were oedema (5.1%), headache (3.3%), flushes (2.5%), and asthenia (1%). Only 1.7% of patients discontinued antihypertensive medication because of adverse events. Tolerability of lercanidipine was independent of the cardiovascular risk group. Lercanidipine was effective and well-tolerated in patients with mild-to-moderate hypertension in the daily practice. The effectiveness and safety of the drug were independent of the degree of cardiovascular risk.

Aged↗
PubMed2006

Apolipoprotein D expression in substantia nigra of Parkinson disease.

Apolipoprotein D (apo D), a lipocalin transporter of small hydrophobic molecules could play an important role in several neurodegenerative diseases. However, its role in those diseases remains unclear. Increments of apo D have been reported in relation with injury and degeneration in the nervous system. Recently increases of apo D level have been reported in schizophrenia, a neuropathologic disease where the oxidative stress and lipid abnormalities may be involved. Apo D could act as a sequestering molecule binding excess of arachidonic acid in cells. In order to determine the relationship between apo D expression and other neurodegenerative pathologies related to oxidative damage, we studied the presence of apo D in the substantia nigra of control and Parkinson disease (PD) subjects. We found dopaminergic neurons were not immunoreactive for apo D, control or PD subjects. However, surrounding glial cells showed immunostaining for apo D and signal increases in PD cases. These findings support the role of apolipoprotein D in neuroprotection and the importance of glia in the amount of this protein in the central nervous system.

Aged↗
PubMed2006

[Experience with intranasal zolmitriptan in cluster headache].

INTRODUCTION: The objective is to analyse our experience with the new intranasal formulation of zolmitriptan 5 mg in the symptomatic treatment of cluster headache in daily clinical practice. PATIENTS AND METHODS: We collected a total of 18 patients with cluster headache and experience with intranasal zolmitriptan; 17 had used subcutaneous sumatriptan and 8 oral triptans. The main reasons for trying intranasal zolmitriptan were: poor tolerability in 12 patients and insufficient efficacy in 6. RESULTS: Among the 17 patients experienced in subcutaneous sumatriptan, 12 (71 %) preferred nasal zolmitriptan, 2 (18 %) subcutaneous sumatriptan and 2 (12 %) did not express any preference. The reasons for preferring intranasal zolmitriptan were: higher convenience (n = 6), better tolerability (n = 5), lower price (n = 2) and higher efficacy (n = 1). Seven out of the 8 patients who had taken oral triptans preferred nasal zolmitriptan, in all cases due to higher subjective efficacy. A total of 11 patients showed efficacy within 30 minutes. Only 3 patients referred to adverse events, always mild. CONCLUSIONS: The 5 mg nasal formulation of zolmitriptan is a potential new option for the symptomatic treatment of cluster headache. This formulation should be considered in patients with poor tolerability to subcutaneous sumatriptan and in those attacks where quick access to inhaled oxygen is not possible. These results suggest that a controlled trial with nasal zolmitriptan in this indication would be worthwhile.

Administration, Intranasal↗
PubMed2006

[Symptomatic treatment of migraine with zolmitriptan: experience with 82 patients].

OBJECTIVES: To analyze our experience with the new, 5 mg intranasal formulation of zolmitriptan in the symptomatic treatment of migraine attacks. PATIENTS AND METHODS: This series includes 82 patients who had treated an average of 7 migraine attacks. Eighty patients had taken oral triptans and 20 subcutaneous sumatriptan. The main reasons for using nasal zolmitriptan were: poor efficacy of oral triptans (41.5 % of the patients), use of subcutaneous sumatriptan (24.4%) or medical criteria (34.5%). RESULTS: Among the 80 patients who had been treated with oral triptans, 50 (62.5 %) preferred nasal zolmitriptan, 14 (17.5 %) oral triptans and the remaining 16 (20 %) did not express any preference. The main reasons for this preference were shorter speed of action and better efficacy. Within those 20 patients who were using subcutaneous sumatriptan, 8 (40 %) preferred subcutaneous sumatriptan, 5 (25%) nasal zolmitriptan and 7 (35%) did not express any preference. The reasons for preference of intranasal zolmitriptan over subcutaneous sumatriptan were greater convenience, better tolerability and lower price. A total of 55 patients noticed efficacy within 60 min. Half experienced at least one adverse event, always mild. The most frequent were local: bad taste (n=23) or nasal irritation/itching (n=8). CONCLUSIONS: The new intranasal formulation of 5 mg zolmitriptan is a good option for the symptomatic treatment of migraine, which could be considered as an intermediate between oral triptans and the subcutaneous formulation of sumatriptan.

Administration, Intranasal↗
PubMed2005

Theoretical structure and vibrational analysis of ethyl methanesulfonate, CH3SO2OCH2CH3.

Ethyl methanesulfonate, CH3SO2OCH2CH3, is well-known as an alkylating agent in mutagenic and carcinogenic processes. Its electronic structure and that of the methanesulfonate anion (CH3SO3-) were determined using optimization methods based on density functional theory and Moller-Plesset second-order perturbation theory. For CH3SO2OCH2CH3, two conformations with symmetries C(s) and C1 are obtained, the former being more stable than the latter. Natural bond orbital (NBO) calculations show the C(s) conformation provides a more favorable geometry of the lone pairs of the oxygen atom linking the ethyl group. The NBO technique also reveals the characteristics of the methanesulfonate anion as a leaving group due to the rearrangement of the excess electronic charge after alkylation. Furthermore, the infrared spectra of CH3SO2OCH2CH3 are reported for the liquid and solid states as well as the Raman spectrum of the liquid. Comparison to experiment of the conformationally averaged IR spectrum of C(s) and C1 provides evidence of the predicted conformations in the solid IR spectrum. These experimental data along with the calculated theoretical force constants are used to define a scaled quantum mechanical force field for the target molecule, which allowed the measured frequencies to be reproduced with a final root-mean-square deviation of 9 cm(-1) and, thus, a reliable assignment of the vibrational spectrum.

Journal Article↗
PubMed2005

Infrared and Raman spectra and quantum chemistry calculations for 2,2,2-trifluoroethyl trichloromethanesulfonate, CCl3SO2OCH2CF3.

The infrared spectra of CCl3SO2OCH2CF3 were obtained in the gaseous, liquid and solid states and complemented with the Raman spectrum of the liquid. Quantum chemistry calculations using the density functional theory (DFT) were used to predict the most stable geometry and conformation of the studied molecule. The harmonic vibrational frequencies and force field were also calculated. Comparison with related molecules and with the predicted frequencies was used as the basis for the assignment of the observed spectral features. Subsequently, a scaling of the original force field by means of a least square procedure was made in order to reproduce as well as possible the experimental frequencies, leading to a final root mean square deviation of 10.6 cm(-1).

Alkanesulfonates↗
PubMed2005

Pancreas islet transplantation in patients with type 1 diabetes mellitus after kidney transplantation.

Diabetic patients with end-stage renal disease have a high mortality rate. A combined kidney-pancreas transplant is associated with greater life expectancy. Pancreas islet transplantation is an alternative involving a lower degree of morbidity. We present two patients, of 41 and 37 years of age, with a long history of diabetes mellitus (C-peptide negative), both with a previous kidney transplant, who had been treated with 22 and 28 U of insulin/d, respectively. Both patients had frequent episodes of unawareness hypoglycemia. Pancreatic islets were infused to a total of 7809 and 19,180 IE/kg, respectively. Basal posttransplant C peptide levels were 2.9 and 1.3 ng/mL. After the implant, one patient required occasional doses of insulin, and the other patient more than 50% reduced dose. After the first implant neither patient had any episodes of unawareness hypoglycemia. HbA1c at 4 months were 6.2% and 6.9%. There were no transplant-related complications.

Adult↗
PubMed2005

Does donor cardiopulmonary resuscitation time affect outcome in uncontrolled non-heart-beating donor renal transplants?

Uncontrolled non-heart-beating donors offer the opportunity to significantly expand the potential pool of kidney donors but are associated with a variable duration of cardiopulmonary resuscitation (CPR), where cardiac output is only 30% to 40% of normal. We were concerned that prolonged CPR would adversely affect the function of transplanted kidneys. In our series of 46 uncontrolled donors the mean duration of CPR was 60 minutes, which also represents a realistic cutoff point for CPR duration. Taking a cutoff point of 60 minutes, we found no differences in kidney discard rates following viability assessment, primary nonfunction rate, or duration of delayed graft function. We therefore conclude that if formal viability assessment is performed, kidneys may be retrieved from uncontrolled non-heart-beating donors irrespective of duration of CPR.

Cardiac Output↗
PubMed2005

Internal assessment of a novel islet isolation facility in Spain.

UNLABELLED: Islet transplantation is a promising therapy in the treatment of diabetes mellitus. Herein we present the result from the first series of islet isolations carried out in our new islet isolation facility. The aims of study were to analyze the influence of various donor characteristics on the success of islet isolation and compare these outcomes with other European and American groups. Data from 22 completed islet isolation were used to compare donor and isolation variables among successful (>300,000 IEQs) versus unsuccessful isolations. The successful isolation rate from our laboratory was 31.8%. We did not see any significant differences between successful and unsuccessful groups according to donor characteristics, although age was close to significance (38.57 +/- 10.29 versus 48.33 +/- 12.39; P = .08). Donor age (1.12 [1.23; 0.99]) and body mass index (0.065 [1.32; 3.08]) were associated with isolation success in a logistic regression model. We did not find differences among intraprocedure variables with the exception of IEQ prepurification (409,073 +/- 115,041 versus 263,776 +/- 128,988; P < .05). IEQpre and IEQpost were positively correlated (P < .05). In comparison with other groups, we observed differences in some cases related to islet yield prepurification (P < .05) but not postpurification. Purity from our islet preparations was the highest from all considered groups (P < .05). Recovery was similar in all groups. CONCLUSIONS: In our experience, donor characteristics have no influence on the success rate. The digestion step is a critical factor for success. Our results with respect to IE yield were close to that of experienced groups.

Adult↗