Laura López - Academia.edu (original) (raw)
Papers by Laura López
El zinc (Zn) es un oligoelemento esencial necesario para la actividad de más de 100 enzimas que l... more El zinc (Zn) es un oligoelemento esencial necesario para la actividad de más de 100 enzimas que lo requieren específicamente para su función catalítica. Su presencia es necesaria para múltiples actividades metabólicas y fisiológicas como el crecimiento, los mecanismos inmunes, la función reproductiva y el desarrollo neurológico (1,3).
Journal of Pediatric Gastroenterology and Nutrition, 2010
Objective: Helicobacter pylori colonizes the gastric mucosa of about half of the world's populati... more Objective: Helicobacter pylori colonizes the gastric mucosa of about half of the world's population and it has been related to extragastrointestinal diseases. The present study sought to evaluate the association between H pylori infection and iron, zinc, and copper nutritional status in symptomatic children. Patients and Methods: A cross-sectional study was carried out in 395 children (4-16 years) with upper gastrointestinal symptoms, who were tested for H pylori infection by the 13 C-urea breath test. Iron status was determined by hemoglobin, serum ferritin, and serum transferrin receptors. Copper and zinc serum concentrations were also evaluated. Epidemiological data, dietary assessment, and anthropometric indicators were analyzed as potential confounding factors. Results: Prevalence of H pylori infection was 24.3%. Anemia and iron deficiency (ID) were found in 12.0% and 14.3% of the H pylori-positive and 8.9% and 11.0% of the H pylori-negative children, respectively. There was no association between H pylori infection and anemia (odds ratio ¼ 1.54 [95% confidence interval [CI] 0.73%-3.24%]) or ID (odds ratio ¼ 1.35 [95% CI 0.67-2.70]). Crude b coefficients showed that H pylori has no significant effect on hemoglobin, serum ferritin, serum transferrin receptors, copper, and zinc concentrations. However, adjusted results suggested that H pylori-infected children had an increase of 9.74 mg/dL (95% CI 2.12-17.37 mg/dL) in copper concentrations. Conclusions: This study revealed that H pylori infection was not associated with iron deficiency, anemia, or zinc concentrations; however, a positive relation with copper status was found after adjusting for confounding factors. The contribution of H pylori infection to higher copper concentrations needs to be confirmed by additional studies.
Bone, 2003
This longitudinal study evaluated bone turnover and the interrelationship between changes in bone... more This longitudinal study evaluated bone turnover and the interrelationship between changes in bone biomarkers and habitual dietary calcium intake during pregnancy in a group of women ranging widely with regard to dietary calcium intake. Thirty-nine healthy pregnant and 30 nonpregnant women were studied. Calcium, phosphorus, 1alpha,25-dihydroxyvitamin D (1,25diHOD), bone alkaline phosphatase (bALP), carboxyterminal propeptides of type I procollagen (PICP) and carboxyterminal telopeptides of type I collagen (betaCTX and ICTP) were measured in serum and calcium, and creatinine and aminoterminal telopeptide (NTX) were determined in urine. Serum calcium and phosphorus did not change but the urinary Ca/Creat ratio and 1,25diHOD increased throughout pregnancy (P < 0.001 and P < 0.0001, respectively). Serum b-ALP and PICP increased during the last two trimesters (P < 0.0001 and P < 0.001, respectively). All studied bone resorption markers increased compared to nonpregnant values throughout pregnancy. The highest increment was observed in the third trimester. The level of significance decreased as follows: betaCTX > NTX >ICTP. Serum 1,25 diHOD versus calcium intake showed a positive and significant correlation (r = 0.51, P…
Aorn, 2011
Introduction: Mucopolysaccharidoses (MPS) are a group of systemic diseases characterised by a gen... more Introduction: Mucopolysaccharidoses (MPS) are a group of systemic diseases characterised by a genetic deficiency of lysosomal enzymes that cause the accumulation of glycosaminoglycans in different tissues. The onset of symptoms usually occurs in early childhood, causing problems of otitis media, hearing loss and airway obstruction in the ENT area. Objective: Describing the audiological findings and airway pathology found in 9 children diagnosed as having MPS. Methods: A retrospective review was performed of the clinical and audiological findings, exploratory results and therapeutic ENT procedures for 9 children diagnosed with MPS in an ENT service at a tertiary paediatric public centre in the period 2007---2010. Results: Subtypes found were 4 MPS type I, 2 moderate MPS type II, 1 severe MPS type II, 1 MPS type IV and 1 MPS type VI. All patients presented chronic middle ear effusions. A child developed mild bilateral sensorineural hearing loss; another case was diagnosed as mixed hearing loss. The remaining auditory pattern was moderate bilateral conductive hearing loss. Four patients showed secondary obstructive sleep apnoea/hypopnoea syndrome (OSAHS) due to Waldeyer ring hyperplasia; surgery could not be performed on one of them because of cervical spinal cord compression from mucopolysaccharide deposits. In 2 cases, there was OSAHS relapse. Conclusions: Children with MPS are at increased risk for developing sensorineural hearing loss.
The SELL project described here is the design and development of a tool for assisting the learnin... more The SELL project described here is the design and development of a tool for assisting the learning of Logic in the context of a wholly online CS degree using a web-based learning environment. This tool should provide guidance, interactive feedback, and continuous assessment for Logic course students, covering major topics in an introductory course (natural deduction, resolution and semantics in propositional and predicate logic). The process of the design, implementation, use and development of the resulting tool, coined Logic E-learning Assistant, is presented.
Revista Española de Cardiología, 2008
Rev Esp Cardiol. 2008;61(2):201-5 201
Geoscience and Remote Sensing IEEE International Symposium, 2010
... Jamal Chioua for his personal communication of invaluable field data and suggestions. REFEREN... more ... Jamal Chioua for his personal communication of invaluable field data and suggestions. REFERENCES ... [2] O. Álvarez, A. Izquierdo, B. Tejedor, et al., The influence of sediment load on tidal dynamics, a case study: Cádiz Bay, Estuarine, Coastal and Shelf Science 48, pp. ...
![Research paper thumbnail of [Effectiveness of population-based interventions on the prevention of overweight in children and adolescents]](https://attachments.academia-assets.com/46751214/thumbnails/1.jpg)
](Medicina clínica, Jan 2, 2010
Journal of medicinal chemistry, Jan 26, 2012
Alzheimer&amp... more Alzheimer's disease, characterized by deposits of amyloid β-peptide (Aβ), is the most common neurodegenerative disease, but it still lacks a specific treatment. We have discovered five chemically unrelated inhibitors of the in vitro aggregation of the Aβ17-40 peptide by screening two commercial chemical libraries. Four of them (1-4) exhibit relatively low MCCs toward HeLa cells (17-184 μM). The usefulness of compounds 1-4 to inhibit the in vivo aggregation of Aβ1-42 has been demonstrated using two fungi models, Saccharomyces cerevisiae and Podospora anserina, previously transformed to express Aβ1-42. Estimated IC(50)s are around 1-2 μM. Interestingly, addition of any of the four compounds to sonicated preformed P. anserina aggregates completely inhibited the appearance of SDS-resistant oligomers. This combination of HTP in vitro screening with validation in fungi models provides an efficient way to identify novel inhibitory compounds of Aβ1-42 aggregation for subsequent testing in animal models.
Materials science & engineering. C, Materials for biological applications, 2013
Biocompatible and biodegradable poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(HB-co-HHx)] subs... more Biocompatible and biodegradable poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(HB-co-HHx)] substrates were modified to improve the attachment of porcine urothelial cell culture. The pristine copolymer exhibits excellent mechanical properties to replace the bladder tissue, but its surface lacks chemical functionalities to interact with cells. Thus, wet chemical treatments based on NaOH and ethylenediamine in aqueous [ED(aq)] and isopropanol [ED(isoOH)] media to functionalize the P(HB-co-HHx) films surfaces were compared. Among these treatments, short ED(aq) treatment was able to decrease the hydrophobicity, rendering a surface with amino groups and without a significant alteration of the mechanical properties. Furthermore, to enhance the interaction with urothelial cells, laminin derived YIGSR sequence was covalently bound to these amino functionalized substrates. The focal attachment was clearly improved with this last treatment, comparing with those results found with the unmodified and first-step functionalized P(HB-co-HHx).
Clinical journal of the American Society of Nephrology : CJASN, Jan 5, 2014
Background and objectives Atypical hemolytic uremic syndrome is characterized by vascular endothe... more Background and objectives Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused by complement dysregulation. Consistently, complement inhibition therapies are highly effective in most patients with atypical hemolytic uremic syndrome. Recently, it was shown that a significant percentage of patients with early-onset atypical hemolytic uremic syndrome carry mutations in diacylglycerol kinase-«, an intracellular protein with no obvious role in complement. These data support an alternative, complement-independent mechanism leading to thrombotic microangiopathy that has implications for treatment of early-onset atypical hemolytic uremic syndrome. To get additional insights into this new form of atypical hemolytic uremic syndrome, the diacylglycerol kinase-« gene in a cohort with atypical hemolytic uremic syndrome was analyzed.
Nature chemical biology, 2014
SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor... more SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor (D2R), but it contains structural features associated with orthosteric D2R antagonists. Using a functional complementation system to control the identity of individual protomers within a dimeric D2R complex, we converted the pharmacology of the interaction between SB269652 and dopamine from allosteric to competitive by impairing ligand binding to one of the protomers, indicating that the allostery requires D2R dimers. Additional experiments identified a 'bitopic' pose for SB269652 extending from the orthosteric site into a secondary pocket at the extracellular end of the transmembrane (TM) domain, involving TM2 and TM7. Engagement of this secondary pocket was a requirement for the allosteric pharmacology of SB269652. This suggests a new mechanism whereby a bitopic ligand binds in an extended pose on one G protein-coupled receptor protomer to allosterically modulate the binding of a ligand to the orthosteric site of a second protomer.
The Journal of biological chemistry, Jan 28, 2014
Background: Selective and potent positive allosteric modulators (PAMs) of the M 1 mAChR have been... more Background: Selective and potent positive allosteric modulators (PAMs) of the M 1 mAChR have been recently described. Results: Use of structural analogues and mutagenic mapping identified the mechanistic basis for increased PAM activity. Conclusion: Combined analytical, structure-function, and modeling approaches uncover allosteric mechanisms at the M 1 mAChR. Significance: New chemical space can be explored in the development of tailored M 1 mAChR PAMs.
El zinc (Zn) es un oligoelemento esencial necesario para la actividad de más de 100 enzimas que l... more El zinc (Zn) es un oligoelemento esencial necesario para la actividad de más de 100 enzimas que lo requieren específicamente para su función catalítica. Su presencia es necesaria para múltiples actividades metabólicas y fisiológicas como el crecimiento, los mecanismos inmunes, la función reproductiva y el desarrollo neurológico (1,3).
Journal of Pediatric Gastroenterology and Nutrition, 2010
Objective: Helicobacter pylori colonizes the gastric mucosa of about half of the world's populati... more Objective: Helicobacter pylori colonizes the gastric mucosa of about half of the world's population and it has been related to extragastrointestinal diseases. The present study sought to evaluate the association between H pylori infection and iron, zinc, and copper nutritional status in symptomatic children. Patients and Methods: A cross-sectional study was carried out in 395 children (4-16 years) with upper gastrointestinal symptoms, who were tested for H pylori infection by the 13 C-urea breath test. Iron status was determined by hemoglobin, serum ferritin, and serum transferrin receptors. Copper and zinc serum concentrations were also evaluated. Epidemiological data, dietary assessment, and anthropometric indicators were analyzed as potential confounding factors. Results: Prevalence of H pylori infection was 24.3%. Anemia and iron deficiency (ID) were found in 12.0% and 14.3% of the H pylori-positive and 8.9% and 11.0% of the H pylori-negative children, respectively. There was no association between H pylori infection and anemia (odds ratio ¼ 1.54 [95% confidence interval [CI] 0.73%-3.24%]) or ID (odds ratio ¼ 1.35 [95% CI 0.67-2.70]). Crude b coefficients showed that H pylori has no significant effect on hemoglobin, serum ferritin, serum transferrin receptors, copper, and zinc concentrations. However, adjusted results suggested that H pylori-infected children had an increase of 9.74 mg/dL (95% CI 2.12-17.37 mg/dL) in copper concentrations. Conclusions: This study revealed that H pylori infection was not associated with iron deficiency, anemia, or zinc concentrations; however, a positive relation with copper status was found after adjusting for confounding factors. The contribution of H pylori infection to higher copper concentrations needs to be confirmed by additional studies.
Bone, 2003
This longitudinal study evaluated bone turnover and the interrelationship between changes in bone... more This longitudinal study evaluated bone turnover and the interrelationship between changes in bone biomarkers and habitual dietary calcium intake during pregnancy in a group of women ranging widely with regard to dietary calcium intake. Thirty-nine healthy pregnant and 30 nonpregnant women were studied. Calcium, phosphorus, 1alpha,25-dihydroxyvitamin D (1,25diHOD), bone alkaline phosphatase (bALP), carboxyterminal propeptides of type I procollagen (PICP) and carboxyterminal telopeptides of type I collagen (betaCTX and ICTP) were measured in serum and calcium, and creatinine and aminoterminal telopeptide (NTX) were determined in urine. Serum calcium and phosphorus did not change but the urinary Ca/Creat ratio and 1,25diHOD increased throughout pregnancy (P < 0.001 and P < 0.0001, respectively). Serum b-ALP and PICP increased during the last two trimesters (P < 0.0001 and P < 0.001, respectively). All studied bone resorption markers increased compared to nonpregnant values throughout pregnancy. The highest increment was observed in the third trimester. The level of significance decreased as follows: betaCTX > NTX >ICTP. Serum 1,25 diHOD versus calcium intake showed a positive and significant correlation (r = 0.51, P…
Aorn, 2011
Introduction: Mucopolysaccharidoses (MPS) are a group of systemic diseases characterised by a gen... more Introduction: Mucopolysaccharidoses (MPS) are a group of systemic diseases characterised by a genetic deficiency of lysosomal enzymes that cause the accumulation of glycosaminoglycans in different tissues. The onset of symptoms usually occurs in early childhood, causing problems of otitis media, hearing loss and airway obstruction in the ENT area. Objective: Describing the audiological findings and airway pathology found in 9 children diagnosed as having MPS. Methods: A retrospective review was performed of the clinical and audiological findings, exploratory results and therapeutic ENT procedures for 9 children diagnosed with MPS in an ENT service at a tertiary paediatric public centre in the period 2007---2010. Results: Subtypes found were 4 MPS type I, 2 moderate MPS type II, 1 severe MPS type II, 1 MPS type IV and 1 MPS type VI. All patients presented chronic middle ear effusions. A child developed mild bilateral sensorineural hearing loss; another case was diagnosed as mixed hearing loss. The remaining auditory pattern was moderate bilateral conductive hearing loss. Four patients showed secondary obstructive sleep apnoea/hypopnoea syndrome (OSAHS) due to Waldeyer ring hyperplasia; surgery could not be performed on one of them because of cervical spinal cord compression from mucopolysaccharide deposits. In 2 cases, there was OSAHS relapse. Conclusions: Children with MPS are at increased risk for developing sensorineural hearing loss.
The SELL project described here is the design and development of a tool for assisting the learnin... more The SELL project described here is the design and development of a tool for assisting the learning of Logic in the context of a wholly online CS degree using a web-based learning environment. This tool should provide guidance, interactive feedback, and continuous assessment for Logic course students, covering major topics in an introductory course (natural deduction, resolution and semantics in propositional and predicate logic). The process of the design, implementation, use and development of the resulting tool, coined Logic E-learning Assistant, is presented.
Revista Española de Cardiología, 2008
Rev Esp Cardiol. 2008;61(2):201-5 201
Geoscience and Remote Sensing IEEE International Symposium, 2010
... Jamal Chioua for his personal communication of invaluable field data and suggestions. REFEREN... more ... Jamal Chioua for his personal communication of invaluable field data and suggestions. REFERENCES ... [2] O. Álvarez, A. Izquierdo, B. Tejedor, et al., The influence of sediment load on tidal dynamics, a case study: Cádiz Bay, Estuarine, Coastal and Shelf Science 48, pp. ...
Medicina clínica, Jan 2, 2010
Journal of medicinal chemistry, Jan 26, 2012
Alzheimer&amp... more Alzheimer's disease, characterized by deposits of amyloid β-peptide (Aβ), is the most common neurodegenerative disease, but it still lacks a specific treatment. We have discovered five chemically unrelated inhibitors of the in vitro aggregation of the Aβ17-40 peptide by screening two commercial chemical libraries. Four of them (1-4) exhibit relatively low MCCs toward HeLa cells (17-184 μM). The usefulness of compounds 1-4 to inhibit the in vivo aggregation of Aβ1-42 has been demonstrated using two fungi models, Saccharomyces cerevisiae and Podospora anserina, previously transformed to express Aβ1-42. Estimated IC(50)s are around 1-2 μM. Interestingly, addition of any of the four compounds to sonicated preformed P. anserina aggregates completely inhibited the appearance of SDS-resistant oligomers. This combination of HTP in vitro screening with validation in fungi models provides an efficient way to identify novel inhibitory compounds of Aβ1-42 aggregation for subsequent testing in animal models.
Materials science & engineering. C, Materials for biological applications, 2013
Biocompatible and biodegradable poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(HB-co-HHx)] subs... more Biocompatible and biodegradable poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(HB-co-HHx)] substrates were modified to improve the attachment of porcine urothelial cell culture. The pristine copolymer exhibits excellent mechanical properties to replace the bladder tissue, but its surface lacks chemical functionalities to interact with cells. Thus, wet chemical treatments based on NaOH and ethylenediamine in aqueous [ED(aq)] and isopropanol [ED(isoOH)] media to functionalize the P(HB-co-HHx) films surfaces were compared. Among these treatments, short ED(aq) treatment was able to decrease the hydrophobicity, rendering a surface with amino groups and without a significant alteration of the mechanical properties. Furthermore, to enhance the interaction with urothelial cells, laminin derived YIGSR sequence was covalently bound to these amino functionalized substrates. The focal attachment was clearly improved with this last treatment, comparing with those results found with the unmodified and first-step functionalized P(HB-co-HHx).
Clinical journal of the American Society of Nephrology : CJASN, Jan 5, 2014
Background and objectives Atypical hemolytic uremic syndrome is characterized by vascular endothe... more Background and objectives Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused by complement dysregulation. Consistently, complement inhibition therapies are highly effective in most patients with atypical hemolytic uremic syndrome. Recently, it was shown that a significant percentage of patients with early-onset atypical hemolytic uremic syndrome carry mutations in diacylglycerol kinase-«, an intracellular protein with no obvious role in complement. These data support an alternative, complement-independent mechanism leading to thrombotic microangiopathy that has implications for treatment of early-onset atypical hemolytic uremic syndrome. To get additional insights into this new form of atypical hemolytic uremic syndrome, the diacylglycerol kinase-« gene in a cohort with atypical hemolytic uremic syndrome was analyzed.
Nature chemical biology, 2014
SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor... more SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor (D2R), but it contains structural features associated with orthosteric D2R antagonists. Using a functional complementation system to control the identity of individual protomers within a dimeric D2R complex, we converted the pharmacology of the interaction between SB269652 and dopamine from allosteric to competitive by impairing ligand binding to one of the protomers, indicating that the allostery requires D2R dimers. Additional experiments identified a 'bitopic' pose for SB269652 extending from the orthosteric site into a secondary pocket at the extracellular end of the transmembrane (TM) domain, involving TM2 and TM7. Engagement of this secondary pocket was a requirement for the allosteric pharmacology of SB269652. This suggests a new mechanism whereby a bitopic ligand binds in an extended pose on one G protein-coupled receptor protomer to allosterically modulate the binding of a ligand to the orthosteric site of a second protomer.
The Journal of biological chemistry, Jan 28, 2014
Background: Selective and potent positive allosteric modulators (PAMs) of the M 1 mAChR have been... more Background: Selective and potent positive allosteric modulators (PAMs) of the M 1 mAChR have been recently described. Results: Use of structural analogues and mutagenic mapping identified the mechanistic basis for increased PAM activity. Conclusion: Combined analytical, structure-function, and modeling approaches uncover allosteric mechanisms at the M 1 mAChR. Significance: New chemical space can be explored in the development of tailored M 1 mAChR PAMs.