Publications by authors named "Laura Molina"

33 Publications

Compensatory hepatic adaptation accompanies permanent absence of intrahepatic biliary network due to YAP1 loss in liver progenitors.

Cell Rep 2021 Jul;36(1):109310

Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh and UPMC, Pittsburgh, PA, USA; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, PA, USA. Electronic address:

Yes-associated protein 1 (YAP1) regulates cell plasticity during liver injury, regeneration, and cancer, but its role in liver development is unknown. We detect YAP1 activity in biliary cells and in cells at the hepatobiliary bifurcation in single-cell RNA sequencing analysis of developing livers. Deletion of Yap1 in hepatoblasts does not impair Notch-driven SOX9+ ductal plate formation but does prevent the formation of the abutting second layer of SOX9+ ductal cells, blocking the formation of a patent intrahepatic biliary tree. Intriguingly, these mice survive for 8 months with severe cholestatic injury and without hepatocyte-to-biliary transdifferentiation. Ductular reaction in the perihilar region suggests extrahepatic biliary proliferation, likely seeking the missing intrahepatic biliary network. Long-term survival of these mice occurs through hepatocyte adaptation via reduced metabolic and synthetic function, including altered bile acid metabolism and transport. Overall, we show YAP1 as a key regulator of bile duct development while highlighting a profound adaptive capability of hepatocytes.
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http://dx.doi.org/10.1016/j.celrep.2021.109310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280534PMC
July 2021

Integrated genomic analysis identifies driver genes and cisplatin-resistant progenitor phenotype in pediatric liver cancer.

Cancer Discov 2021 Apr 23. Epub 2021 Apr 23.

Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris

Pediatric liver cancers (PLCs) comprise diverse diseases affecting infants, children and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of hepatoblastoma patients, all before 3 years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between 'Hepatocytic', 'Liver Progenitor' and 'Mesenchymal' molecular subgroups of hepatoblastoma. We showed that during chemotherapy, 'Liver Progenitor' cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1809DOI Listing
April 2021

Yes-Associated Protein Is Crucial for Constitutive Androstane Receptor-Driven Hepatocyte Proliferation But Not for Induction of Drug Metabolism Genes in Mice.

Hepatology 2021 May;73(5):2005-2022

Department of Pathology and Pittsburgh Liver Research Center, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Background And Aims: Constitutive androstane receptor (CAR) agonists, such as 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), are known to cause robust hepatocyte proliferation and hepatomegaly in mice along with induction of drug metabolism genes without any associated liver injury. Yes-associated protein (Yap) is a key transcription regulator that tightly controls organ size, including that of liver. Our and other previous studies suggested increased nuclear localization and activation of Yap after TCPOBOP treatment in mice and the potential role of Yap in CAR-driven proliferative response. Here, we investigated a direct role of Yap in CAR-driven hepatomegaly and hepatocyte proliferation using hepatocyte-specific Yap-knockout (KO) mice.

Approach And Results: Adeno-associated virus 8-thyroxine binding globulin promoter-Cre recombinase vector was injected to Yap-floxed mice for achieving hepatocyte-specific Yap deletion followed by TCPOBOP treatment. Yap deletion did not decrease protein expression of CAR or CAR-driven induction of drug metabolism genes (including cytochrome P450 [Cyp] 2b10, Cyp2c55, and UDP-glucuronosyltransferase 1a1 [Ugt1a1]). However, Yap deletion substantially reduced TCPOBOP-induced hepatocyte proliferation. TCPOBOP-driven cell cycle activation was disrupted in Yap-KO mice because of delayed (and decreased) induction of cyclin D1 and higher expression of p21, resulting in decreased phosphorylation of retinoblastoma protein. Furthermore, the induction of other cyclins, which are sequentially involved in progression through cell cycle (including cyclin E1, A2, and B1), and important mitotic regulators (such as Aurora B kinase and polo-like kinase 1) was remarkably reduced in Yap-KO mice. Microarray analysis revealed that 26% of TCPOBOP-responsive genes that were mainly related to proliferation, but not to drug metabolism, were altered by Yap deletion. Yap regulated these proliferation genes through alerting expression of Myc and forkhead box protein M1, two critical transcriptional regulators of CAR-mediated hepatocyte proliferation.

Conclusions: Our study revealed an important role of Yap signaling in CAR-driven hepatocyte proliferation; however, CAR-driven induction of drug metabolism genes was independent of Yap.
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http://dx.doi.org/10.1002/hep.31521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885729PMC
May 2021

Correction: mTOR inhibition affects Yap1-β-catenin-induced hepatoblastoma growth and development.

Oncotarget 2019 Sep 24;10(54):5670. Epub 2019 Sep 24.

Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

[This corrects the article DOI: 10.18632/oncotarget.26668.].
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http://dx.doi.org/10.18632/oncotarget.27218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771459PMC
September 2019

Liver Progenitors and Adult Cell Plasticity in Hepatic Injury and Repair: Knowns and Unknowns.

Annu Rev Pathol 2020 01 9;15:23-50. Epub 2019 Aug 9.

Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA; email:

The liver is a complex organ performing numerous vital physiological functions. For that reason, it possesses immense regenerative potential. The capacity for repair is largely attributable to the ability of its differentiated epithelial cells, hepatocytes and biliary epithelial cells, to proliferate after injury. However, in cases of extreme acute injury or prolonged chronic insult, the liver may fail to regenerate or do so suboptimally. This often results in life-threatening end-stage liver disease for which liver transplantation is the only effective treatment. In many forms of liver injury, bipotent liver progenitor cells are theorized to be activated as an additional tier of liver repair. However, the existence, origin, fate, activation, and contribution to regeneration of liver progenitor cells is hotly debated, especially since hepatocytes and biliary epithelial cells themselves may serve as facultative stem cells for one another during severe liver injury. Here, we discuss the evidence both supporting and refuting the existence of liver progenitor cells in a variety of experimental models. We also debate the validity of developing therapies harnessing the capabilities of these cells as potential treatments for patients with severe and chronic liver diseases.
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http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212705PMC
January 2020

Clinical aspects of visceral leishmaniasis caused by L. infantum in adults. Ten years of experience of the largest outbreak in Europe: what have we learned?

Parasit Vectors 2019 Jul 24;12(1):359. Epub 2019 Jul 24.

Área de Infecciosas, Servicio de Medicina Interna, Hospital Universitario de Fuenlabrada, Camino del Molino 2, 28942, Fuenlabrada, Madrid, Spain.

Background: An outbreak of leishmaniasis caused by Leishmania infantum was declared in the southwest of the Madrid region (Spain) in June 2009. This provided a unique opportunity to compare the management of visceral leishmaniasis (VL) in immunocompetent adults (IC-VL), patients with HIV (HIV-VL) and patients receiving immunosuppressants (IS-VL).

Methods: A cohort of adults with VL, all admitted to the Hospital Universitario de Fuenlabrada between June 2009 and June 2018, were monitored in this observational study, recording their personal, epidemiological, analytical, diagnostic, treatment and outcome variables.

Results: The study population was made up of 111 patients with VL (10% HIV-VL, 14% IS-VL, 76% IC-VL). Seventy-one percent of the patients were male; the mean age was 45 years (55 years for the IS-VL patients, P = 0.017). Fifty-four percent of the IC-VL patients were of sub-Saharan origin (P = 0.001). Fever was experienced by 98% of the IC-VL patients vs 73% of the LV-HIV patients (P = 0.003). Plasma ferritin was > 1000 ng/ml in 77% of the IC-VL patients vs 17% of the LV-HIV patients (P = 0.007). Forty-two percent of patients fulfilled the criteria for haemophagocytic lymphohistiocytosis. RDT (rK39-ICT) serological analysis returned sensitivity and specificity values of 45% and 99%, respectively, and ELISA/iIFAT returned 96% and 89%, respectively, with no differences in this respect between patient groups. Fourteen (13.0%) patients with VL experienced treatment failure, eight of whom were in the IC-VL group. Treatment with < 21 mg/kg (total) liposomal amphotericin B (LAB) was associated with treatment failure in the IC-VL patients [P = 0.002 (OR: 14.7; 95% CI: 2.6-83.3)].

Conclusions: IS-VL was more common than HIV-VL; the lack of experience in dealing with IS-VL is a challenge that needs to be met. The clinical features of the patients in all groups were similar, although the HIV-VL patients experienced less fever and had lower plasma ferritin concentrations. RDT (rK39-ICT) analysis returned a good specificity value but a much poorer sensitivity value than reported in other scenarios. The patients with HIV-VL, IS-VL and IC-VL returned similar serological results. Current guidelines for treatment seem appropriate, but the doses of LAB required to treat patients with HIV-VL and IS-VL are poorly defined.
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http://dx.doi.org/10.1186/s13071-019-3628-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657057PMC
July 2019

Asymptomatic immune responders to Leishmania among HIV positive patients.

PLoS Negl Trop Dis 2019 06 3;13(6):e0007461. Epub 2019 Jun 3.

WHO Collaborating Centre for Leishmaniasis, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda (Madrid), Spain.

Concomitant infection with human immunodeficiency virus (HIV) and the Leishmania parasite is a growing public health problem, the result of the former spreading to areas where the latter is endemic. Leishmania infection is usually asymptomatic in immunocompetent individuals, but the proportion of HIV+ individuals in contact with the parasite who remain asymptomatic is not known. The aim of the present work was to examine the use of cytokine release assays in the detection of asymptomatic immune responders to Leishmania among HIV+ patients with no previous leishmaniasis or current symptomatology. Eighty two HIV+ patients (all from Fuenlabrada, Madrid, Spain, where a leishmaniasis outbreak occurred in 2009) were examined for Leishmania infantum infection using molecular and humoral response-based methods. None returned a positive molecular or serological result for the parasite. Thirteen subjects showed a positive lymphoproliferative response to soluble Leishmania antigen (SLA), although the mean CD4+ T lymphocyte counts of these patients was below the normal range. Stimulation of peripheral blood mononuclear cells (PBMC) or whole blood with SLA (the lymphoproliferative assay and whole blood assay respectively), led to the production of specific cytokines and chemokines. Thus, despite being immunocompromised, HIV+ patients can maintain a Th1-type cellular response to Leishmania. In addition, cytokine release assays would appear to be useful tools for detecting these individuals via the identification of IFN-γ in the supernatants of SLA-stimulated PBMC, and of IFN-γ, MIG and IL-2 in SLA-stimulated whole blood. These biomarkers appear to be 100% reliable for detecting asymptomatic immune responders to Leishmania among HIV+ patients.
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http://dx.doi.org/10.1371/journal.pntd.0007461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6564048PMC
June 2019

Assessment of on-farm welfare for dairy cattle in southern Spain and its effects on reproductive parameters.

J Dairy Res 2019 May 30;86(2):165-170. Epub 2019 Apr 30.

Department of Animal Medicine and Surgery, Faculty of Veterinary Medicine,University of Cordoba,14014 Cordoba,Spain.

In this Research Communication we analyse the animal welfare status of dairy farms located in southern Spain and test the hypothesis that monitoring of wellbeing could increase the profitability of dairy herds by improving indices of reproduction. Twenty dairy farms were visited and a total of 1650 cows were assessed using the Welfare Quality® (WQ) protocol to determine their welfare status. These farms were selected as representatives of the main types of dairy farms found in the south of Spain. No farms attained a welfare status of 'excellent', but all obtained an adequate score for most parameters. Feeding assessment showed relatively low variability among farms, whereas housing and health assessments exhibited high variability. Significant correlations were found between a number of welfare parameter pairings: between percentage of collisions and time needed to lie down; between cleanliness of water points and cleanliness of various animal parts; between farms with access to an outdoor loafing area and an inadequate body condition score and with animal cleanliness; between the frequency of animals lying partly or completely outside of the lying area and the percentage of integument alterations and finally between the presence of respiratory problems and farm hygiene parameters. Furthermore, significant correlations between welfare parameters, reproductive indices and milk production were found. The percentage of cows exhibiting an inadequate body condition score and farms where cows took longer to lie down were correlated with the calving-first insemination interval. Animals showing a higher incidence of coughing and hampered respiration presented lower heat detection rates and milk production and finally farms with dirtier animals had lower milk production. This study is the first step towards including welfare in the recording of routine data in dairy cattle farms in southern Spain.
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http://dx.doi.org/10.1017/S0022029919000207DOI Listing
May 2019

mTOR inhibition affects Yap1-β-catenin-induced hepatoblastoma growth and development.

Oncotarget 2019 Feb 19;10(15):1475-1490. Epub 2019 Feb 19.

Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Hepatoblastoma (HB) is the most common pediatric liver malignancy. Around 80% of HB demonstrate simultaneous activation of β-catenin and Yes-associated protein 1 (Yap1). The mechanism by which these signaling pathways contribute to HB pathogenesis remain obscure. Recently, mTORC1 activation was reported in human HB cells and in a murine HB model driven by β-catenin and Yap1. Here, we directly investigate the therapeutic impact of mTOR inhibition following HB development in the Yap1-β-catenin model. HB were established by hydrodynamic tail vein injection of Sleeping Beauty transposase and plasmids coding for ΔN90-β-catenin and S127A-Yap1. Five weeks after injection, when HB were evident, mice were randomized into Rapamycin diet-fed or basal-diet-fed groups for 5-weeks. Tumor growth was monitored via ultrasound imaging and mice in both groups were euthanized after 5-weeks for molecular analysis. Transcriptomic analysis showed a strong correlation in gene expression between HB in the Yap1-β-catenin model and HB patient cohorts. Rapamycin treatment decreased HB burden, almost normalizing liver weight to body weight ratio. Ultrasound imaging showed reduction in tumor growth over the duration of Rapamycin treatment as compared to controls. Majority of HB in the controls exhibited crowded fetal or embryonal histology, while remnant tumors in the experimental group showed well-differentiated fetal morphology. Immunohistochemistry confirmed inhibition of mTORC1 in the Rapamycin group. Thus, Rapamycin reduces HB in a clinically relevant model driven by β-catenin and Yap1, supporting use of mTORC1 inhibitors in their therapy. We also show the utility of standard and 3D ultrasound imaging for monitoring liver tumors in mice.
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http://dx.doi.org/10.18632/oncotarget.26668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407673PMC
February 2019

β-Catenin and Yes-Associated Protein 1 Cooperate in Hepatoblastoma Pathogenesis.

Am J Pathol 2019 05 19;189(5):1091-1104. Epub 2019 Feb 19.

Department of Gynecology, Shiyan Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan, China; Pittsburgh Liver Research Center, Pittsburgh, Pennsylvania. Electronic address:

Hepatoblastoma (HB), the most common pediatric primary liver neoplasm, shows nuclear localization of β-catenin and yes-associated protein 1 (YAP1) in almost 80% of the cases. Co-expression of constitutively active S127A-YAP1 and ΔN90 deletion-mutant β-catenin (YAP1-ΔN90-β-catenin) causes HB in mice. Because heterogeneity in downstream signaling is being identified owing to mutational differences even in the β-catenin gene alone, we investigated if co-expression of point mutants of β-catenin (S33Y or S45Y) with S127A-YAP1 led to similar tumors as YAP1-ΔN90-β-catenin. Co-expression of S33Y/S45Y-β-catenin and S127A-YAP1 led to activation of Yap and Wnt signaling and development of HB, with 100% mortality by 13 to 14 weeks. Co-expression with YAP1-S45Y/S33Y-β-catenin of the dominant-negative T-cell factor 4 or dominant-negative transcriptional enhanced associate domain 2, the respective surrogate transcription factors, prevented HB development. Although histologically similar, HB in YAP1-S45Y/S33Y-β-catenin, unlike YAP1-ΔN90-β-catenin HB, was glutamine synthetase (GS) positive. However, both ΔN90-β-catenin and point-mutant β-catenin comparably induced GS-luciferase reporter in vitro. Finally, using a previously reported 16-gene signature, it was shown that YAP1-ΔN90-β-catenin HB tumors exhibited genetic similarities with more proliferative, less differentiated, GS-negative HB patient tumors, whereas YAP1-S33Y/S45Y-β-catenin HB exhibited heterogeneity and clustered with both well-differentiated GS-positive and proliferative GS-negative patient tumors. Thus, we demonstrate that β-catenin point mutants can also collaborate with YAP1 in HB development, albeit with a distinct molecular profile from the deletion mutant, which may have implications in both biology and therapy.
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http://dx.doi.org/10.1016/j.ajpath.2019.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521893PMC
May 2019

Evaluation of a pattern of culture for detecting Streptococcus agalactiae carriage using GBS modified medium.

Enferm Infecc Microbiol Clin (Engl Ed) 2019 Dec 2;37(10):682. Epub 2019 Jan 2.

Laboratorio Clínico, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España.

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http://dx.doi.org/10.1016/j.eimc.2018.12.005DOI Listing
December 2019

Cellular Markers of Active Disease and Cure in Different Forms of -Induced Disease.

Front Cell Infect Microbiol 2018 13;8:381. Epub 2018 Nov 13.

WHO Collaborating Centre for Leishmaniasis, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.

Increased numbers of peripheral blood mononucleocytes (PBMC) and increased IFN-γ secretion following challenge of blood samples with soluble antigen (SLA), have been proposed as biomarkers of specific cell-mediated immunity, indicating that treatment of visceral leishmaniasis (VL) has been successful. However, infection may manifest as cutaneous leishmaniasis (CL), and less commonly as localized leishmanial lymphadenopathy (LLL) or mucosal leishmaniasis (ML). The present work examines the value of these biomarkers as indicators of cured leishmaniasis presenting in these different forms. Blood samples were collected before and after treatment from patients living in Fuenlabrada (Madrid, Spain), an endemic area recently the center of a leishmaniasis outbreak. All samples were subjected to -specific PCR, serological tests (IFAT and rK39-ICT), and the SLA-cell proliferation assay (SLA-CPA), recording PBMC proliferation and the associated changes in IFN-γ production. Differences in the results recorded for the active and cured conditions were only significant for VL. PCR returned positive results in 67% of patients with active VL and in 3% of those with cured leishmaniasis. Similarly, rK39-ICT returned a positive result in 77% of active VL samples . 52% in cured VL samples, and IFAT in 90% . 56%; in the SLA-CPA, PBMC proliferation was seen in 16% . 90%, and an associated increase in IFN-γ production of 14 and 84%, respectively. The present findings reinforce the idea that PBMC proliferation and increased IFN-γ production in SLA-stimulated PBMC provide biomarkers of clinical cure in VL. Other tests are urgently needed to distinguish between the cured and active forms of the other types of clinical leishmaniasis caused by .
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http://dx.doi.org/10.3389/fcimb.2018.00381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243388PMC
September 2019

Dysregulated Bile Transporters and Impaired Tight Junctions During Chronic Liver Injury in Mice.

Gastroenterology 2018 10 30;155(4):1218-1232.e24. Epub 2018 Jun 30.

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address:

Background & Aims: Liver fibrosis, hepatocellular necrosis, inflammation, and proliferation of liver progenitor cells are features of chronic liver injury. Mouse models have been used to study the end-stage pathophysiology of chronic liver injury. However, little is known about differences in the mechanisms of liver injury among different mouse models because of our inability to visualize the progression of liver injury in vivo in mice. We developed a method to visualize bile transport and blood-bile barrier (BBlB) integrity in live mice.

Methods: C57BL/6 mice were fed a choline-deficient, ethionine-supplemented (CDE) diet or a diet containing 0.1% 3,5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) for up to 4 weeks to induce chronic liver injury. We used quantitative liver intravital microscopy (qLIM) for real-time assessment of bile transport and BBlB integrity in the intact livers of the live mice fed the CDE, DDC, or chow (control) diets. Liver tissues were collected from mice and analyzed by histology, immunohistochemistry, real-time polymerase chain reaction, and immunoblots.

Results: Mice with liver injury induced by a CDE or a DDC diet had breaches in the BBlB and impaired bile secretion, observed by qLIM compared with control mice. Impaired bile secretion was associated with reduced expression of several tight-junction proteins (claudins 3, 5, and 7) and bile transporters (NTCP, OATP1, BSEP, ABCG5, and ABCG8). A prolonged (2-week) CDE, but not DDC, diet led to re-expression of tight junction proteins and bile transporters, concomitant with the reestablishment of BBlB integrity and bile secretion.

Conclusions: We used qLIM to study chronic liver injury, induced by a choline-deficient or DDC diet, in mice. Progression of chronic liver injury was accompanied by loss of bile transporters and tight junction proteins.
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http://dx.doi.org/10.1053/j.gastro.2018.06.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174089PMC
October 2018

Negative Anion Gap in a Teenager with Epilepsy.

Clin Chem 2018 07;64(7):1127-1128

Department of Laboratory Medicine, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain;

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http://dx.doi.org/10.1373/clinchem.2017.282376DOI Listing
July 2018

Hepatocyte-Derived Lipocalin 2 Is a Potential Serum Biomarker Reflecting Tumor Burden in Hepatoblastoma.

Am J Pathol 2018 08 18;188(8):1895-1909. Epub 2018 Jun 18.

Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address:

Hepatoblastoma (HB) is the most common pediatric liver malignant tumor. Previously, we reported co-activation of β-catenin and Yes-associated protein-1 (YAP1) in 80% of HB. Hepatic co-expression of active β-catenin and YAP1 via sleeping beauty transposon/transposase and hydrodynamic tail vein injection led to HB development in mice. Here, we identify lipocalin 2 (Lcn2) as a target of β-catenin and YAP1 in HB and show that serum Lcn2 values positively correlated with tumor burden. Lcn2 was strongly expressed in HB tumor cells in our mouse model. A tissue array of 62 HB cases showed highest LCN2 expression in embryonal and lowest in fetal, blastemal, and small cell undifferentiated forms of HB. Knockdown of LCN2 in HB cells had no effect on cell proliferation but reduced NF-κB reporter activity. Next, liver-specific Lcn2 knockout (KO) mice were generated. No difference in tumor burden was observed between Lcn2 KO mice and wild-type littermate controls after sleeping beauty transposon/transposase and hydrodynamic tail vein injection delivery of active YAP1 and β-catenin, although Lcn2 KO mice with HB lacked any serum Lcn2 elevation, demonstrating that transformed hepatocytes are the source of serum Lcn2. More blastemal areas and inflammation were observed within HB in Lcn2 KO compared with wild-type tumors. In conclusion, Lcn2 expressed in hepatocytes appears to be dispensable for the pathogenesis of HB. However, transformed hepatocytes secrete serum Lcn2, making Lcn2 a valuable biomarker for HB.
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http://dx.doi.org/10.1016/j.ajpath.2018.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099390PMC
August 2018

Dual catenin loss in murine liver causes tight junctional deregulation and progressive intrahepatic cholestasis.

Hepatology 2018 06 19;67(6):2320-2337. Epub 2018 Apr 19.

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.

β-Catenin, the downstream effector of the Wnt signaling, plays important roles in hepatic development, regeneration, and tumorigenesis. However, its role at hepatocyte adherens junctions (AJ) is relatively poorly understood, chiefly due to spontaneous compensation by γ-catenin. We simultaneously ablated β- and γ-catenin expression in mouse liver by interbreeding β-catenin-γ-catenin double-floxed mice and Alb-Cre transgenic mice. Double knockout mice show failure to thrive, impaired hepatocyte differentiation, cholemia, ductular reaction, progressive cholestasis, inflammation, fibrosis, and tumorigenesis, which was associated with deregulation of tight junctions (TJ) and bile acid transporters, leading to early morbidity and mortality, a phenotype reminiscent of progressive familial intrahepatic cholestasis (PFIC). To address the mechanism, we specifically and temporally eliminated both catenins from hepatocytes using adeno-associated virus 8 carrying Cre-recombinase under the thyroid-binding globulin promoter (AAV8-TBG-Cre). This led to a time-dependent breach of the blood-biliary barrier associated with sequential disruption of AJ and TJ verified by ultrastructural imaging and intravital microscopy, which revealed unique paracellular leaks around individual hepatocytes, allowing mixing of blood and bile and leakage of blood from one sinusoid to another. Molecular analysis identified sequential losses of E-cadherin, occludin, claudin-3, and claudin-5 due to enhanced proteasomal degradation, and of claudin-2, a β-catenin transcriptional target, which was also validated in vitro.

Conclusion: We report partially redundant function of catenins at AJ in regulating TJ and contributing to the blood-biliary barrier. Furthermore, concomitant hepatic loss of β- and γ-catenin disrupts structural and functional integrity of AJ and TJ via transcriptional and posttranslational mechanisms. Mice with dual catenin loss develop progressive intrahepatic cholestasis, providing a unique model to study diseases such as PFIC. (Hepatology 2018;67:2320-2337).
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http://dx.doi.org/10.1002/hep.29585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893443PMC
June 2018

Lymphoproliferative response after stimulation with soluble leishmania antigen (SLA) as a predictor of visceral leishmaniasis (VL) relapse in HIV+ patients.

Acta Trop 2016 Dec 28;164:345-351. Epub 2016 Sep 28.

WHO Collaborating Centre for Leishmaniasis, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.

The introduction of HAART resulted in the decrease of Leishmania/HIV co-infection cases; nevertheless, the number of relapses remains high and secondary prophylaxis is recommended. However, secondary prophylaxis is not necessary in all patients, and presents a high risk of toxicity and an elevated cost. Our aim was to study whether specific cellular response to Leishmania infantum (measured by cell proliferation response after stimulation with soluble Leishmania antigen (SLA)), could be a useful tool to attempt a secondary prophylaxis withdrawal. In June 2009 an outbreak of leishmaniasis by Leishmania infantum was declared in the southeast of Madrid, and since January 2013, we recruited 10 HIV+ patients that had been treated for visceral leishmaniasis. 6 patients had positive SLA-cell proliferation test. The mean CD4 cell counts of those patients with positive SLA were 140 cel/mm3 and 40 cel/mm3 in those with negative SLA test. 3 patients with positive SLA-cell proliferation test (CD4 count: 336, 307, 625) were not on prophylaxis, and the other 3 patients (CD4 count: 152, 189, 359) were on secondary prophylaxis that was withdrawn after the positive SLA-cell proliferation test with no posterior relapses (mean follow up 60 weeks). From the 4 patients, which had negative SLA-cell proliferation test and continued on prophylaxis, 3 had positive PCR for Leishmania at the end of the follow-up and 2 presented clinical relapses. The performance of SLA-cell proliferation test can be a useful tool that can permit us to try withdrawal of the prophylaxis in Leishmania/HIV co-infected patients with low CD4 counts under clinical supervision, diminishing risk of toxicity and cost.
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http://dx.doi.org/10.1016/j.actatropica.2016.09.026DOI Listing
December 2016

Immobilization of oxalate decarboxylase on a Zn-IMAC resin.

Biochem Biophys Rep 2015 Dec 28;4:98-103. Epub 2015 Aug 28.

Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.

Oxalate decarboxylase, a bicupin enzyme coordinating two essential manganese ions per subunit, catalyzes the decomposition of oxalate into carbon dioxide and formate in the presence of oxygen. Current efforts to elucidate its catalytic mechanism are focused on EPR studies of the Mn. We report on a new immobilization strategy linking the enzyme's N-terminal His-tag to a Zn-loaded immobilized metal affinity resin. Activity is lowered somewhat due to the expected crowding effect. High-field EPR spectra of free and immobilized enzyme show that the resin affects the coordination environment of the active site Mn ions only minimally. The immobilized preparation was used to study the effect of varying pH on the same sample. Repeated freeze-thaw cycles lead to break down of the resin beads and some enzyme loss from the sample. However, the EPR signal increases due to higher packing efficiency on the sample column.
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http://dx.doi.org/10.1016/j.bbrep.2015.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668902PMC
December 2015

Oestrus synchronisation in postpartum dairy cows using repetitive prostaglandin doses: Comparison between D-cloprostenol and dinoprost.

Acta Vet Hung 2015 Mar;63(1):79-88

University of Córdoba, Campus de Rabanales Department of Animal Medicine and Surgery Ctra Madrid-Cádiz km 396 14071 Córdoba Spain.

This trial evaluated the reproductive performance in an early routine oestrus induction programme using two different PGF2α preparations in dairy cattle. D-cloprostenol sodium (n = 192; Group A) or dinoprost (n = 187; Group B) was administered between days 35 and 42 post partum. Also, a group of non-treated cows (n = 135; Group C) was included as control. Pedometers were used to detect oestrus, and also secondary oestrous signs and vaginal mucus quality were assessed prior to artificial insemination (AI). When oestrus was not detected for 14 days after PGF2α administration, the treatment was repeated, up to a maximum of three times. There were no differences between the study groups in oestrus detection (A = 73.48%, B = 73.01%, C = 79.26%; P = 0.428), good mucus quality (A = 96.45%, B = 91.30%, C = 93.45%; P = 0.203) and the presence of mounting lesions (A = 98.58, B = 94.93%, C = 98.13; P = 0.414). First-service pregnancy rates were 19.78%, 15.64% and 32.03% in Groups A, B and C, respectively (P = 0.003). There were no inter-group differences for the interval from parturition to first AI. However, a significantly shorter interval from parturition to conception (92.17 days, 99.45 days, 118.93 days; P = 0.002) and significantly less services per conception (2.12, 2.18, 2.66; P = 0.003) were observed in Groups A and B in comparison with Group C. The use of PGF2α resulted in better fertility in a repetitive, routine postpartum programme, although no differences between Dcloprostenol and dinoprost were detected.
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http://dx.doi.org/10.1556/AVet.2014.028DOI Listing
March 2015

An S-locus independent pollen factor confers self-compatibility in 'Katy' apricot.

PLoS One 2013 14;8(1):e53947. Epub 2013 Jan 14.

Fruit Tree Breeding Department, Instituto Valenciano de Investigaciones Agrarias, Moncada, Valencia, Spain.

Loss of pollen-S function in Prunus self-compatible cultivars has been mostly associated with deletions or insertions in the S-haplotype-specific F-box (SFB) genes. However, self-compatible pollen-part mutants defective for non-S-locus factors have also been found, for instance, in the apricot (Prunus armeniaca) cv. 'Canino'. In the present study, we report the genetic and molecular analysis of another self-compatible apricot cv. termed 'Katy'. S-genotype of 'Katy' was determined as S(1)S(2) and S-RNase PCR-typing of selfing and outcrossing populations from 'Katy' showed that pollen gametes bearing either the S(1)- or the S(2)-haplotype were able to overcome self-incompatibility (SI) barriers. Sequence analyses showed no SNP or indel affecting the SFB(1) and SFB(2) alleles from 'Katy' and, moreover, no evidence of pollen-S duplication was found. As a whole, the obtained results are compatible with the hypothesis that the loss-of-function of a S-locus unlinked factor gametophytically expressed in pollen (M'-locus) leads to SI breakdown in 'Katy'. A mapping strategy based on segregation distortion loci mapped the M'-locus within an interval of 9.4 cM at the distal end of chr.3 corresponding to ∼1.29 Mb in the peach (Prunus persica) genome. Interestingly, pollen-part mutations (PPMs) causing self-compatibility (SC) in the apricot cvs. 'Canino' and 'Katy' are located within an overlapping region of ∼273 Kb in chr.3. No evidence is yet available to discern if they affect the same gene or not, but molecular markers seem to indicate that both cultivars are genetically unrelated suggesting that every PPM may have arisen independently. Further research will be necessary to reveal the precise nature of 'Katy' PPM, but fine-mapping already enables SC marker-assisted selection and paves the way for future positional cloning of the underlying gene.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053947PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544744PMC
July 2013

Imported malaria in pregnancy in Madrid.

Malar J 2012 Apr 11;11:112. Epub 2012 Apr 11.

Internal Medicine Department, University Hospital Fuenlabrada, Madrid, Spain.

Background: Malaria in pregnancy is associated with maternal and foetal morbidity and mortality in endemic areas, but information on imported cases to non-endemic areas is scarce.The aim of this study was to describe the clinical and epidemiological characteristics of malaria in pregnancy in two general hospitals in Madrid, Spain.

Methods: Retrospective descriptive study of laboratory-confirmed malaria in pregnant women at the Fuenlabrada University Hospital and the Príncipe de Asturias University Hospital, in Madrid, over a six- and 11-year period, respectively. Relevant epidemiological, clinical and laboratory data was obtained from medical records.

Results: There were 19 pregnant women among 346 malaria cases (5.4%). The average age was 27 years. The gestational age (trimester) was: 53% 3rd, 31% 1st, 16% 2nd. All but one were multigravidae. Three were HIV positive. All were sub-Saharan immigrants: two were recently arrived immigrants and seventeen (89%) had visited friends and relatives. None had taken prophylaxis nor seeked pre-travel advice.

Presentation: 16 symptomatic patients (fever in fourteen, asthenia in two), three asymptomatic. Median delay in diagnosis: 7.5 days. Laboratory tests: anaemia (cut off Hb level 11 g/dl) 78.9% (mild 31.6%, moderate 31.6%, severe 15.8%) thrombocytopaenia 73.7%, hypoglycaemia 10.5%. All cases were due to Plasmodium falciparum, one case of hyperparasitaemia. Quinine + clindamycin prescribed in 84%.

Outcomes: no severe maternal complications or deaths, two abortions, fifteen term pregnancies, no low-birth-weight newborns, two patients were lost to follow-up.

Conclusions: Though cases of malaria in pregnancy are uncommon, a most at risk group is clearly defined: young sub-Saharan mothers visiting friends and relatives without pre-travel counselling and recently-arrived immigrants. The most common adverse maternal and foetal effects were anaemia and stillbirth. Given that presentation can be asymptomatic, malaria should always be considered in patients with unexplained anaemia arriving from endemic areas. These findings could help Maternal Health programme planners and implementers to target preventive interventions in the immigrant population and should create awareness among clinicians.
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http://dx.doi.org/10.1186/1475-2875-11-112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350381PMC
April 2012

Physical mapping of a pollen modifier locus controlling self-incompatibility in apricot and synteny analysis within the Rosaceae.

Plant Mol Biol 2012 Jun 6;79(3):229-42. Epub 2012 Apr 6.

Instituto Valenciano de Investigaciones Agrarias-IVIA, Apartado Oficial, 46113 Moncada, Valencia, Spain.

S-locus products (S-RNase and F-box proteins) are essential for the gametophytic self-incompatibility (GSI) specific recognition in Prunus. However, accumulated genetic evidence suggests that other S-locus unlinked factors are also required for GSI. For instance, GSI breakdown was associated with a pollen-part mutation unlinked to the S-locus in the apricot (Prunus armeniaca L.) cv. 'Canino'. Fine-mapping of this mutated modifier gene (M-locus) and the synteny analysis of the M-locus within the Rosaceae are here reported. A segregation distortion loci mapping strategy, based on a selectively genotyped population, was used to map the M-locus. In addition, a bacterial artificial chromosome (BAC) contig was constructed for this region using overlapping oligonucleotides probes, and BAC-end sequences (BES) were blasted against Rosaceae genomes to perform micro-synteny analysis. The M-locus was mapped to the distal part of chr.3 flanked by two SSR markers within an interval of 1.8 cM corresponding to ~364 Kb in the peach (Prunus persica L. Batsch) genome. In the integrated genetic-physical map of this region, BES were mapped against the peach scaffold_3 and BACs were anchored to the apricot map. Micro-syntenic blocks were detected in apple (Malus × domestica Borkh.) LG17/9 and strawberry (Fragaria vesca L.) FG6 chromosomes. The M-locus fine-scale mapping provides a solid basis for self-compatibility marker-assisted selection and for positional cloning of the underlying gene, a necessary goal to elucidate the pollen rejection mechanism in Prunus. In a wider context, the syntenic regions identified in peach, apple and strawberry might be useful to interpret GSI evolution in Rosaceae.
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http://dx.doi.org/10.1007/s11103-012-9908-zDOI Listing
June 2012

The economic and nutrition transition in Equatorial Guinea coincided with a double burden of over- and under nutrition.

Econ Hum Biol 2010 Mar 31;8(1):80-7. Epub 2009 Oct 31.

Centro Nacional de Medicina Tropical, Instituto de Salud Carlos III, Sinesio Delgado 6, Pabellón 13, Madrid 28029, Spain.

We assess trends in children's nutritional status in Equatorial Guinea, a country in socioeconomic transition. Nationally representative samples were conducted in 1997, at the start of the economic take off, and again in 2004. Children aged 0-60 months were included in the surveys (N=436, 552). Both surveys included a sociodemographic, dietary and health questionnaire, and anthropometric measurements from which height-for-age (HAZ); weight-for-age (WAZ) and weight-for-height (WHZ) Z-scores were calculated. Between 1997 and 2004, the prevalence of child overweight for all children increased from 21.8% to 31.7%, especially in urban areas (from 18.2% to 29.4%, p=0.01). Stunting prevalence among children >or=2 years old decreased (from 57.9% to 45.3%, p<0.02), but for all age groups remained very high (34.7% overall, 46.5% rural and 28.5% urban in 2004). The economic take off in Equatorial Guinea appeared to coincide with substantial increases in the prevalence of child overweight whereas the prevalence of stunting decreased even if it remained high. The results suggest that the country is undergoing a nutrition transition and acquiring the concomitant double burden of under and over nutrition.
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http://dx.doi.org/10.1016/j.ehb.2009.10.001DOI Listing
March 2010

Nutritional and socio-economic factors associated with Plasmodium falciparum infection in children from Equatorial Guinea: results from a nationally representative survey.

Malar J 2009 Oct 8;8:225. Epub 2009 Oct 8.

Centro Nacional de Medicina Tropical, Instituto de Salud Carlos III, Sinesio Delgado 6, Pab 13, Madrid 28029, Spain.

Background: Malaria has traditionally been a major endemic disease in Equatorial Guinea. Although parasitaemia prevalence on the insular region has been substantially reduced by vector control in the past few years, the prevalence in the mainland remains over 50% in children younger than five years. The aim of this study is to investigate the risk factors for parasitaemia and treatment seeking behaviour for febrile illness at country level, in order to provide evidence that will reinforce the EG National Malaria Control Programme.

Methods: The study was a cross-sectional survey of children 0 to 5 years old, using a multistaged, stratified, cluster-selected sample at the national level. It included a socio-demographic, health and dietary questionnaires, anthropometric measurements, and thick and thin blood smears to determine the Plasmodium infection. A multivariate logistic regression model was used to determine risk factors for parasitaemia, taking into account the cluster design.

Results: The overall prevalence of parasitemia was 50.9%; it was higher in rural (58.8%) compared to urban areas (44.0%, p = 0.06). Age was positively associated with parasitemia (p < 0.0001). In rural areas, risk factors included longer distance to health facilities (p = 0.01) and a low proportion of households with access to protected water in the community (p = 0.02). Having had an episode of cough in the 15 days prior to the survey was inversely related to parasitemia (p = 0.04). In urban areas, the risk factors were stunting (p = 0.005), not having taken colostrum (p = 0.01), and that someone in the household slept under a bed net (p = 0.002); maternal antimalarial medication intake during pregnancy (p = 0.003) and the household socio-economic status (p = 0.0002) were negatively associated with parasitemia. Only 55% of children with fever were taken outside their homes for care, and treatment seeking behaviour differed substantially between rural and urban populations.

Conclusion: Results suggest that a national programme to fight malaria in Equatorial Guinea should take into account the differences between rural and urban communities in relation to risk factors for parasitaemia and treatment seeking behaviour, integrate nutrition programmes, incorporate campaigns on the importance of early treatment, and target appropriately for bed nets to reach the under-fives.
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http://dx.doi.org/10.1186/1475-2875-8-225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766384PMC
October 2009

Nutritional status and its correlates in Equatorial Guinean preschool children: results from a nationally representative survey.

Food Nutr Bull 2008 Mar;29(1):49-58

National Centre of Tropical Medicine, Instituto de Salud Carlos III, Madrid, Spain. [corrected]

Background: In Equatorial Guinea, as a result of the recent growth of the oil industry, there is an opportunity to address important public health problems through public and private initiatives. To propose effective nutrition and public health strategies, it is important first to have reliable information on the nutritional status of the population and the underlying factors affecting it.

Objective: To assess the nutritional status and the prevalence of anemia among Equatoguinean children in a nationally representative sample and to identify the risk factors associated with the nutritional problems detected.

Methods: The study was a cross-sectional survey using a multistaged, stratified, cluster-selected sample. The survey included a sociodemographic, health, and dietary questionnaire and measurement of hematocrit and anthropometric features, from which nutritional indicators based on the National Center for Health Statistics (NCHS) reference and the World Health Organization (WHO) standards were calculated. Logistic regression models were used for the multivariate analysis. A total of 552 children aged 0 to 60 months were surveyed.

Results: The overall prevalence of stunting (< -2 height-for-age z-scores [HAZ]) was 29.7% based on the NCHS reference and 35.2% based on WHO standards; the risk factors associated with stunting were age (p < .0001), low socioeconomic status (p = .01), and fishing by a member of the household (p = .003) The prevalence of mild anemia (hemoglobin < 110 g/L) was 69.3%, and that of moderate or severe anemia (hemoglobin < 80 g/L) was 8.3%. The only significant risk factor associated with moderate to severe anemia was low household socioeducational level (p = .01).

Conclusions: Stunting and anemia are public health problems in Equatorial Guinea. Integrated strategies, including fighting poverty and improving maternal education, should be undertaken.
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http://dx.doi.org/10.1177/156482650802900106DOI Listing
March 2008

Early manganese-toxicity response in Vigna unguiculata L.--a proteomic and transcriptomic study.

Proteomics 2008 Jan;8(1):149-59

Institute for Plant Nutrition, Faculty of Natural Sciences, Leibniz University Hannover, Herrenhaeuser Strasse 2, Hannover, Germany.

The apoplast is known to play a predominant role in the expression of manganese (Mn) toxicity in cowpea (Vigna unguiculata L.) leaves. To unravel early Mn-toxicity responses after 1-3 days Mn treatment also in the leaf symplast, we studied the symplastic reactions induced by Mn in two cultivars differing in Mn tolerance on a total cellular level. Comparative proteome analyses of plants exposed to low or high Mn allowed to identify proteins specifically affected by Mn, particularly in the Mn-sensitive cowpea cultivar. These proteins are involved in CO(2) fixation, stabilization of the Mn cluster of the photosystem II, pathogenesis-response reactions and protein degradation. Chloroplastic proteins important for CO(2) fixation and photosynthesis were of lower abundance upon Mn stress suggesting scavenging of metabolic energy for a specific stress response. Transcriptome analyses supported these findings, but additionally revealed an upregulation of genes involved in signal transduction only in the Mn-sensitive cultivar. In conclusion, a coordinated interplay of apoplastic and symplastic reactions seems to be important during the Mn-stress response in cowpea.
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http://dx.doi.org/10.1002/pmic.200700478DOI Listing
January 2008

Impact of different strategies to control Plasmodium infection and anaemia on the island of Bioko (Equatorial Guinea).

Malar J 2006 Feb 6;5:10. Epub 2006 Feb 6.

Centro Nacional de Medicina Tropical, Instituto de Salud Carlos III, c/Sinesio Delgado, 6, PO Box 28029, Madrid, Spain.

Background: On the island of Bioko (Equatorial Guinea), insecticide-treated nets (ITNs) have been the main tool used to control malaria over the last 13 years. In 2004, started an indoor residual spraying (IRS) campaign to control malaria. The purpose of this study is to asses the impact of the two control strategies on the island of Bioko (Equatorial Guinea), with regards to Plasmodium infection and anaemia in the children under five years of age.

Methods: Two transversal studies, the first one prior to the start of the IRS campaign and the second one year later. Sampling was carried out by stratified clusters. Malaria infection was measured by means of thick and thin film, and the packed cell volume (PCV) percentage. Data related to ITN use and information regarding IRS were collected. The Pearson's chi-square and logistic regression statistical tests were used to calculate odds ratios (OR).

Results: In the first survey, 168 children were sampled and 433 children in the second one. The prevalence of infection was 40% in 2004, and significantly lower at 21.7% in 2005. PCV was 41% and 39%, respectively. 58% of the children surveyed in 2004 and 44.3% in 2005 had slept under an ITN. 78% of the dwellings studied in 2005 had been sprayed. In the 2005 survey, sleeping without a mosquito net meant a risk of infection 3 times greater than sleeping protected with a net hanged correctly and with no holes (p < 0.05).

Conclusion: IRS and ITNs have proven to be effective control strategies on the island of Bioko. The choice of one or other strategy is, above all, a question of operational feasibility and availability of local resources.
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http://dx.doi.org/10.1186/1475-2875-5-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1403786PMC
February 2006

[Evaluation of the Robobact system for processing stool cultures: another step towards automation in the microbiology laboratory].

Enferm Infecc Microbiol Clin 2005 Feb;23(2):58-61

Laboratorio de Microbiología, C.E.P Carabanchel Area 11, Aguacate 13, 28044 Madrid, Spain.

Objective: The objective of this study was to evaluate the Robobact system (DIESSE Diagnostica Senese S.p.A., Italy) for processing stool specimens and to compare it with conventional methodology.

Method: A total of 240 stool specimens from outpatients in Madrid (Spain) were studied. The samples were processed simultaneously with both the Robobact system and a conventional method.

Results: Overall, 13 isolates of Campylobacter spp., 12 of Salmonella spp., 4 of Yersinia enterocolitica and 1 of Shigella spp. were obtained. The Robobact method failed to identify 1 of the 13 Campylobacter spp. isolates and 2 of the 12 Salmonella spp. isolates. The single Shigella spp. isolate was detected only by the Robobact system. All the Robobact results were available at 24 hours.

Conclusions: Robobact is a fast, useful tool for microbiological processing of stool specimens.
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http://dx.doi.org/10.1157/13071606DOI Listing
February 2005

[Successful treatment with voriconazol of a Pseudallescheria boydii fungus ball in a HIV positive patient and previous tuberculosis].

Rev Iberoam Micol 2003 Jun;20(2):64-7

Servicio de Microbiología, Hospital Universitario 12 de Octubre, Madrid, Spain.

We herein describe a patient with a Pseudallescheria boydii fungus ball in a tuberculous lung cavity, which was successfully treated four years earlier. The patient was HIV positive classified as C3 with a previous history of i.v. heroin abuse. The clinical presumptive diagnosis was radiologically established combined with histological examination. Culture of tissue confirmed and proved the fungal etiology. In vitro MIC values for voriconazole (0.5 mg/ml) guided antifungal prophylactic treatment before surgical eradication of the fungus ball since the patient was immunosuppressed. We discuss the clinical spectrum of P. boydii infections and currently medical approach.
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June 2003
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