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1.
Int J Mol Sci ; 25(2)2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38256058

RESUMEN

Lipids are a large group of natural compounds, together with proteins and carbohydrates, and are essential for various processes in the body. After death, the organism's tissues undergo a series of reactions that generate changes in some molecules, including lipids. This means that determining the lipid change profile can be beneficial in estimating the postmortem interval (PMI). These changes can also help determine burial sites and advance the localization of graves. The aim was to explore and analyze the decomposition process of corpses, focusing on the transformation of lipids, especially triglycerides (TGs) and fatty acids (FAs), and the possible application of these compounds as markers to estimate PMI and detect burial sites. A systematic review of 24 scientific articles from the last 23 years (2000-2023) was conducted. The results show that membrane glycerophospholipids (such as phosphatidylcholine and phosphatidylglycerol, among others) are the most studied, and the most promising results are obtained, with decreasing patterns as PMI varies. Fatty acids (FAs) are also identified as potential biomarkers owing to the variations in their postmortem concentration. An increase in saturated fatty acids (SFAs), such as stearic acid and palmitic acid, and a decrease in unsaturated fatty acids (UFAs), such as oleic acid and linoleic acid, were observed. The importance of intrinsic and extrinsic factors in decomposition is also observed. Finally, as for the burial sites, the presence of fatty acids and some sterols in burial areas of animal and human remains can be verified. In conclusion, glycerophospholipids and fatty acids are good markers for estimating PMI. It has been observed that there are still no equations for estimating the PMI that can be applied to forensic practice, as intrinsic and extrinsic factors are seen to play a vital role in the decomposition process. As for determining burial sites, the importance of soil and textile samples has been demonstrated, showing a direct relationship between saturated fatty acids, hydroxy fatty acids, and some sterols with decomposing remains.


Asunto(s)
Lipidómica , Fitosteroles , Animales , Humanos , Ácidos Grasos , Cadáver , Esteroles , Glicerofosfolípidos
2.
Rev Esp Enferm Dig ; 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38501803

RESUMEN

This paper describes the clinical case of a patient diagnosed with diffuse large B-cell lymphoma with splenic involvement, focusing on the role of abdominal ultrasound (US) in this context. The patient experienced dyspepsia and progressive asthenia over several months so an abdominal US was performed. The US showed multiple heterogeneous and hypoechogenic focal splenic lesions together with a moderate left pleural effusion. Lymphoma was suspected due to these findings and the diagnosis was then confirmed with the performance of a CT scan and a biopsy that revealed the presence of a diffuse large B-cell lymphoma with metastatic disease. Chemotherapy containing rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone was administered and the patient is currently on clinical remission. This study highlights the role of abdominal ultrasound as a useful technique in the non-invasive assessment of this entity, considering an appropriate clinical context and mainly after detecting multiple hypoechogenic splenic lesions in the US.

3.
Rev Esp Enferm Dig ; 114(8): 498-499, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35255705

RESUMEN

We present the case of a 37-years old male, who consulted for an extended history of intermittent nausea and vomiting. Laboratory tests showed moderate elevated bilirubin (1.30 mg/dL) and GGT (106 U/L). An abdominal CT scan performed showed a solid 18-centimetres (cm) mass located in the right liver lobe. A biopsy of the lesion was performed, revealing metastastic cells of a well-differentiated neuroendocrine tumour (NET, G3 (Ki-67: 25%). Further study was performed with MRI, and SPECT-CT, showing a 2-cm lesion in the pancreatic tail suggestive of being the primary NET. Chromogranin A levels were high (114.100 ng/ml). In our case, despite the large size of the liver metastasis a full resection of the tumours was achieved.


Asunto(s)
Neoplasias Hepáticas , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Adulto , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología
4.
Liver Int ; 41(12): 2885-2891, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34392590

RESUMEN

BACKGROUND & AIMS: Patients with chronic hepatitis C and stage 3 fibrosis are thought to remain at risk of hepatocellular carcinoma after sustained virological response. We investigated this risk in a large cohort of patients with well-defined stage 3 fibrosis. METHODS: We performed a multicentre, ambispective, observational study of chronic hepatitis C patients with sustained virological response after treatment with direct-acting antivirals started between January and December 2015. Baseline stage 3 was defined in a two-step procedure: we selected patients with transient elastography values of 9.5-14.5 kPa and subsequently excluded those with nodular liver surface, splenomegaly, ascites or collaterals on imaging, thrombopenia or esophago-gastric varices. Patients were screened twice-yearly using ultrasound. RESULTS: The final sample comprised 506 patients (median age, 57.4 years; males, 59.9%; diabetes, 17.2%; overweight, 44.1%; genotype 3, 8.9%; HIV coinfection, 18.4%; altered liver values, 15.2%). Median follow-up was 33.7 (22.1-39.1) months. Five hepatocellular carcinomas and 1 cholangiocarcinoma were detected after a median of 29.4 months (95% CI: 26.8-39.3), with an incidence of 0.47/100 patients/year (95% CI: 0.17-1.01). In the multivariate analysis, only males older than 55 years had a significant higher risk (hazard ratio 7.2 [95% CI: 1.2-41.7; P = .029]) with an incidence of 1.1/100 patients/year (95% CI: 0.3-2.8). CONCLUSIONS: In a large, well-defined cohort of patients with baseline hepatitis C stage-3 fibrosis, the incidence of primary liver tumours was low after sustained virological response and far from the threshold for cost-effectiveness of screening, except in males older than 55 years.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Respuesta Virológica Sostenida
5.
Pharmacogenet Genomics ; 28(11): 245-250, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30334909

RESUMEN

OBJECTIVES: Taxanes and anthracyclines are widely used in the treatment of breast cancer, although the benefit is limited to a proportion of patients and predictive biomarkers for clinical outcome remain elusive. PATIENTS AND METHODS: We carried out a pharmacogenetic study in 181 patients with locally advanced breast cancer enrolled in a phase 2 randomized clinical trial (NCT00123929), where patients were randomly assigned to receive neoadjuvant single-agent docetaxel 100 mg/m(2) (n=84) or doxorubicin 75 mg/m(2) (n=97). We studied the association of 226 single nucleotide polymorphisms (SNPs) in 15 key drug biotransformation genes with neoadjuvant pathological tumor response residual cancer burden index to docetaxel and to doxorubicin. RESULTS: We identified a significant association for rs162561, an intronic SNP located in the cytochrome P450 family 1 subfamily B member 1 (CYP1B1) gene, with tumor response in patients treated with single-agent docetaxel (dominant model: ß=1.02, 95% confidence interval=0.49-1.55; P=1.77×10(-4)), and for rs717620, an SNP located in the promoter of the ATP-binding cassette subfamily C member 2 (ABCC2) gene, in patients treated with neoadjuvant doxorubicin (recessive model: ß=1.67; 95% confidence interval=0.26-3.11; P=0.02). CONCLUSION: We identified two polymorphisms in CYP1B1 and ABCC2 associated with tumor pathological response following docetaxel or doxorubicin neoadjuvant monotherapy, respectively. Although further validation is required, these variants could be potential predictive genetic markers for treatment outcome in breast cancer patients.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Citocromo P-450 CYP1B1/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Docetaxel/efectos adversos , Docetaxel/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Estudios de Asociación Genética , Humanos , Persona de Mediana Edad , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Polimorfismo de Nucleótido Simple/genética , Ensayos Clínicos Controlados Aleatorios como Asunto
6.
Liver Int ; 37(8): 1148-1156, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28027429

RESUMEN

BACKGROUND & AIMS: Chronic hepatitis C (CHC) is a major cause of cirrhosis and hepatocellular carcinoma and angiogenesis is closely related to the pathogenesis and progression of different chronic liver diseases (CLD). Thus, the intrahepatic expression of angiopoietins 1 and 2 (Ang1 and Ang2), as relevant mediators of pathological angiogenesis in several CLD, was investigated. In addition, the differential influence of structural and non-structural genomic regions of HCV on the expression of angiopoietins and the possible signalling involved were studied. METHODS: Ang1 and Ang2 expression was evaluated by western blotting and enzyme-linked immunosorbent assay (ELISA) in liver homogenates of CHC patients (n=47) and uninfected subjects (n=8). Their association with disease progression (according to METAVIR classification) was assessed by Spearman's correlation. Statistical differences among the expression of angiopoietins at different CHC stages were calculated by Mann-Whitney U-test. Finally, the in vitro expression of Angiopoietins in HCV replicons (complete or non-structural subgenomic) and the main signalling pathways involved were also examined. RESULTS: Ang2 levels were significantly higher in the liver of CHC patients compared to controls and significantly correlated with inflammation and fibrosis. Accordingly, an increased expression of Ang2 was found in all HCV replicons tested. Interestingly, the inhibition of MEK and PI3K signalling pathways exerted differential effects on Ang2 expression concerning to the genomic region of HCV. CONCLUSIONS: Hepatitis C virus induces Ang2 expression in hepatocytes through different signalling routes which may lead to the disregulation of vascular homeostasis in the liver. Thus, pharmacologic intervention on Ang2 signalling might constitute an important therapeutic tool.


Asunto(s)
Angiopoyetina 1/metabolismo , Angiopoyetina 2/metabolismo , Hepacivirus/fisiología , Hepatitis C Crónica/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Línea Celular , Progresión de la Enfermedad , Femenino , Hepatocitos/metabolismo , Humanos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Replicón , Transducción de Señal , Proteínas Virales/metabolismo
7.
Int J Cancer ; 136(10): 2427-36, 2015 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-25353672

RESUMEN

Mammographic density (MD) is an intermediate phenotype for breast cancer. Previous studies have identified genetic variants associated with MD; however, much of the genetic contribution to MD is unexplained. We conducted a two-stage genome-wide association analysis among the participants in the "Determinants of Density in Mammographies in Spain" study, together with a replication analysis in women from the Australian MD Twins and Sisters Study. Our discovery set covered a total of 3,351 Caucasian women aged 45 to 68 years, recruited from Spanish breast cancer screening centres. MD was blindly assessed by a single reader using Boyd's scale. A two-stage approach was employed, including a feature selection phase exploring 575,374 SNPs in 239 pairs of women with extreme phenotypes and a verification stage for the 183 selected SNPs in the remaining sample (2,873 women). Replication was conducted in 1,786 women aged 40 to 70 years old recruited via the Australian Twin Registry, where MD were measured using Cumulus-3.0, assessing 14 SNPs with a p value <0.10 in stage 2. Finally, two genetic variants in high linkage disequilibrium with our best hit were studied using the whole Spanish sample. Evidence of association with MD was found for variant rs11205277 (OR = 0.74; 95% CI = 0.67-0.81; p = 1.33 × 10(-10) ). In replication analysis, only a marginal association between this SNP and absolute dense area was found. There were also evidence of association between MD and SNPs in high linkage disequilibrium with rs11205277, rs11205303 in gene MTMR11 (OR = 0.73; 95% CI = 0.66-0.80; p = 2.64 × 10(-11) ) and rs67807996 in gene OTUD7B (OR = 0.72; 95% CI = 0.66-0.80; p = 2.03 × 10(-11)). Our findings provide additional evidence on common genetic variations that may contribute to MD.


Asunto(s)
Neoplasias de la Mama/genética , Cromosomas Humanos Par 1/genética , Endopeptidasas/genética , Estudio de Asociación del Genoma Completo/métodos , Glándulas Mamarias Humanas/anomalías , Proteínas/genética , Adulto , Anciano , Australia , Densidad de la Mama , Neoplasias de la Mama/etnología , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Desequilibrio de Ligamiento , Mamografía , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , España , Estudios en Gemelos como Asunto
8.
Ann Hepatol ; 14(2): 207-17, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25671830

RESUMEN

BACKGROUND: Transarterial chemoembolisation (TACE), having demonstrated survival benefits, is the treatmentof choice in intermediate-stage hepatocellular carcinoma, although there is great heterogeneity in its clinical application. MATERIAL AND METHODS: A survey was sent to the Madrid Regional hospitals to assess applicability, indications and treatment protocols. The assessment was made overall and according to the type of hospital (groups A vs. B and C). RESULTS: Seventeen out of 22 hospitals responded (8/8 group A, 9/ 14 group B-C). All do/indicate transarterial chemoembolisation, 13/17 at their own facilities. Eight of the 17 hospitals have multidisciplinary groups (5/8 A, 3/9 B-C). Nine hospitals perform > 20 procedures/year (7 group A), and 6 from group B-C request/perform < 10/year. It is performed on an "on-demand" basis in 12/17. In 5 hospitals, all the procedures use drug-eluting beads loaded with doxorubicin. The average number of procedures per patient is 2. The mean time from diagnosis of hepatocellular carcinoma to transarterial chemoembolisation is ≤ 2 months in 16 hospitals. In 11/17 hospitals, response is assessed by computed tomography. Radiological response is measured without specific criteria in 12/17 and the other five hospitals (4 group A) assessed using standardised criteria. CONCLUSION: Uniformity among the Madrid Regional hospitals was found in the indication and treatment regimen. The use of DEB-TACE has become the preferred form of TACE in clinical practice. The differentiating factors for the more specialised hospitals are a larger volume of procedures, decision-making by multidisciplinary committees and assessment of radiological response more likely to be standardised.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Quimioembolización Terapéutica/tendencias , Hospitales/tendencias , Neoplasias Hepáticas/tratamiento farmacológico , Pautas de la Práctica en Medicina/tendencias , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Adhesión a Directriz/tendencias , Encuestas de Atención de la Salud , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , España , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento
9.
Infect Dis Now ; 54(2): 104855, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38309646

RESUMEN

AIM: To assess the respective performances of a HCV screening program in a hospital setting and a HCV screening model applied concomitantly in a primary care centre. METHODS: Adult patients consecutively admitted to hospital for ambulatory surgery were screened for anti-HCV antibodies (hospital screening cohort, HPSC), as were patients receiving blood tests for medical reasons in a primary care centre (primary care screening cohort, PCSC). Serum anti-HCV and HCV RNA levels were tested by ELISA and real-time PCR, respectively. RESULTS: Seroprevalence of HCV infection was 2.2 % in the HPSC and 1.4 % in the PCSC (p = 0.044). All viraemic patients (0.2 % in HPSC and 0.1 % in PCSC) were treated with direct-acting antivirals and 85.7 % experienced a sustained virological response. CONCLUSIONS: Hospital-based HCV screening outperformed primary care-centered screening, significantly increasing HCV case findings.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Adulto , Humanos , Hepacivirus/genética , Antivirales/uso terapéutico , Estudios Seroepidemiológicos , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hospitales , Anticuerpos contra la Hepatitis C/uso terapéutico , Atención Primaria de Salud
10.
PLoS One ; 17(10): e0276136, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36240183

RESUMEN

What is the relation between seed quality and food security? Here we built a summary diagram that links the development stages of the seeds with their potential of providing grain yield. This idea was tested using cowpea as a model crop, grown in a tropical environment. Initially, seed quality attributes such as water content, dry weight, germination, vigor, and longevity were characterized during seed development. With this, we were able to elucidate at which point the late maturation phase and the acquisition of seed with superior physiological quality starts. From these data, the proposed summary diagram highlighted the seed quality as a technological basis for generating a more productive plant community. It also showed that only seeds with a high-quality profile have a better chance to establishment in an increasingly challenging agricultural environment. Overall, we bring the concept that cowpea seeds with superior quality besides being the essential input for tropical agriculture is also a strategy that can contribute food security.


Asunto(s)
Vigna , Agricultura , Seguridad Alimentaria , Germinación , Semillas , Agua
11.
Plants (Basel) ; 11(10)2022 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-35631735

RESUMEN

The rapid and uniform establishment of crop plants in the field underpins food security through uniform mechanical crop harvesting. In order to achieve this, seeds with greater vigor should be used. Vigor is a component of physiological quality related to seed resilience. Despite this importance, there is little knowledge of the association between events at the molecular level and seed vigor. In this study, we investigated the relationship between gene expression during germination and seed vigor in soybean. The expression level of twenty genes related to growth at the beginning of the germination process was correlated with vigor. In this paper, vigor was evaluated by different tests. Then we reported the identification of the genes Expansin-like A1, Xyloglucan endotransglucosylase/hydrolase 22, 65-kDa microtubule-associated protein, Xyloglucan endotransglucosylase/hydrolase 2, N-glycosylase/DNA lyase OGG1 and Cellulose synthase A catalytic subunit 2, which are expressed during germination, that correlated with several vigor tests commonly used in routine analysis of soybean seed quality. The identification of these transcripts provides tools to study vigor in soybean seeds at the molecular level.

12.
Future Microbiol ; 17: 1363-1379, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36169348

RESUMEN

Aims: This study aimed to evaluate the antibacterial effect of two new cationic surfactants based on phenylalanine-arginine (LPAM) and tryptophan-arginine (LTAM). Materials & methods: Antibacterial activity, mechanism of action and interactions with Staphylococcus aureus enzymes were measured through microbiological, flow cytometry and molecular docking assays, respectively. Results & conclusion: These compounds showed antibacterial activity in the range of 4.06-16.24 µg/ml against planktonic cells and no activity against mature biofilms, since they caused a loss of membrane integrity and increased DNA damage, as revealed by flow cytometry analysis. In silico assays revealed the existence of molecular bonds such as hydrogen bonds, mainly with DNA. Therefore, these compounds have promising pharmacological activity against MRSA strains.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus , Triptófano/farmacología , Pruebas de Sensibilidad Microbiana , Arginina/farmacología , Arginina/química , Tensoactivos/farmacología , Simulación del Acoplamiento Molecular , Infecciones Estafilocócicas/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas , Fenilalanina/farmacología
14.
Colloids Surf B Biointerfaces ; 207: 112017, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34391169

RESUMEN

In the past two decades, the increase in microbial resistance to conventional antimicrobials has spurred scientists around the world to search tirelessly for new treatments. Synthetic amino acid-based surfactants constitute a promising alternative to conventional antimicrobial compounds. In this work, two new cationic amino acid-based surfactants were synthesized and their physicochemical, antifungal and antibiofilm properties evaluated. The surfactants were based on phenylalanine-arginine (LPAM) and tryptophan-arginine (LTAM) and prepared from renewable raw materials using a simple chemical procedure. The critical micelle concentrations of the new surfactants were determined by conductivity and fluorescence. Micellization of LPAM and LTAM took place at 1.05 and 0.54 mM, respectively. Both exhibited good antifungal activity against fluconazole-resistant Candida spp. strains, with a low minimum inhibitory concentration (8.2 µg/mL). Their mechanism of action involves alterations in cell membrane permeability and mitochondrial damage, leading to death by apoptosis. Furthermore, when LPAM and LTAM were applied with Amphotericin B, a significant synergistic effect was observed against all the studied Candida strains. These new cationic surfactants are also able to disperse biofilms of Candida spp. at low concentrations. The results indicate that LPAM and LTAM have potential application to combat the advance of fungal resistance as well as microbial biofilms.


Asunto(s)
Antifúngicos , Fluconazol , Anfotericina B/farmacología , Antifúngicos/farmacología , Arginina , Biopelículas , Candida , Farmacorresistencia Fúngica , Fluconazol/farmacología , Pruebas de Sensibilidad Microbiana , Fenilalanina , Tensoactivos/farmacología , Triptófano
15.
Future Microbiol ; 16: 375-387, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33870731

RESUMEN

Aim: To evaluate the activity of diclofenac sodium and synergism with oxacillin against clinical strains of SARM in plactonic cells, antibiofilm and biofilm. Materials & methods: Synergism activity was assessed using the fractional inhibitory concentration index and its possible mechanism of action by flow cytometry. Results: The synergistic activity of diclofenac sodium with oxacillin was observed against plactonic cells, antibiofilm and in biofilm formed from clinical methicillin-resistant Staphylococcus aureus strains. Conclusion: This combination caused damage to the integrity of the membrane and ruptures in the DNA of the cells, leading to apoptosis.


Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Diclofenaco/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Oxacilina/farmacología , Biopelículas/crecimiento & desarrollo , Membrana Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Sinergismo Farmacológico , Pruebas de Sensibilidad Microbiana
16.
Clin Pharmacol Ther ; 109(2): 462-470, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32757270

RESUMEN

Capecitabine-induced hand-foot syndrome (CiHFS) is a common dermatological adverse reaction affecting around 30% of patients with capecitabine-treated cancer, and the main cause of dose reductions and chemotherapy delays. To identify novel genetic factors associated with CiHFS in patients with cancer, we carried out an extreme-phenotype genomewide association study in 166 patients with breast and colorectal capecitabine-treated cancer with replication in a second cohort of 85 patients. We discovered and replicated a cluster of four highly correlated single-nucleotide polymorphisms associated with susceptibility to CiHFS at 20q13.33 locus (top hit = rs6129058, hazard ratio = 2.40, 95% confidence interval = 1.78-3.20; P = 1.2 × 10-8 ). Using circular chromosome conformation capture sequencing, we identified a chromatin contact between the locus containing the risk alleles and the promoter of CDH4, located 90 kilobases away. The risk haplotype was associated with decreased levels of CDH4 mRNA and the protein it encodes, R-cadherin (RCAD), which mainly localizes in the granular layer of the epidermis. In human keratinocytes, CDH4 downregulation resulted in reduced expression of involucrin, a protein of the cornified envelope, an essential structure for skin barrier function. Immunohistochemical analyses revealed that skin from patients with severe CiHFS exhibited low levels of RCAD and involucrin before capecitabine treatment. Our results uncover a novel mechanism underlying individual genetic susceptibility to CiHFS with implications for clinically relevant risk prediction.


Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Cadherinas/genética , Capecitabina/efectos adversos , Síndrome Mano-Pie/etiología , Síndrome Mano-Pie/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Capecitabina/uso terapéutico , Línea Celular , Femenino , Predisposición Genética a la Enfermedad/genética , Haplotipos/genética , Humanos , Queratinocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Regiones Promotoras Genéticas/genética , Riesgo
17.
Neural Regen Res ; 15(6): 988-995, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31823868

RESUMEN

Among collagen members in the collagen superfamily, type XIX collagen has raised increasing interest in relation to its structural and biological roles. Type XIX collagen is a Fibril-Associated Collagen with Interrupted Triple helices member, one main subclass of collagens in this superfamily. This collagen contains a triple helix composed of three polypeptide segments aligned in parallel and it is associated with the basement membrane zone in different tissues. The molecular structure of type XIX collagen consists of five collagenous domains, COL1 to COL5, interrupted by six non-collagenous domains, NC1 to NC6. The most relevant domain by which this collagen exerts its biological roles is NC1 domain that can be cleavage enzymatically to release matricryptins, exerting anti-tumor and anti-angiogenic effect in murine and human models of cancer. Under physiological conditions, type XIX collagen expression decreases after birth in different tissues although it is necessary to keep its basal levels, mainly in skeletal muscle and hippocampal and telencephalic interneurons in brain. Notwithstanding, in amyotrophic lateral sclerosis, altered transcript expression levels show a novel biological effect of this collagen beyond its structural role in basement membranes and its anti-tumor and anti-angiogenic properties. Type XIX collagen can exert a compensatory effect to ameliorate the disease progression under neurodegenerative conditions specific to amyotrophic lateral sclerosis in transgenic SOD1G93A mice and amyotrophic lateral sclerosis patients. This novel biological role highlights its nature as prognostic biomarker of disease progression in and as promising therapeutic target, paving the way to a more precise prognosis of amyotrophic lateral sclerosis.

18.
Med Clin (Barc) ; 131(2): 73-7, 2008 Jun 14.
Artículo en Español | MEDLINE | ID: mdl-18588833

RESUMEN

Ultrasonography is the first choice for screening patients with suspected liver lesions. However, due to lack of contrast agents, ultrasonography is less sensitive and specific compared with computed tomography and magnetic resonance imaging. The advent of microbubble contrast agents increases both sensitivity and specificity dramatically. Real-time evaluation of the vascular phase can currently be achieved by combining new microbubble specific methods with second-generation contrast agents. The enhancement pattern in the vascular phase, combined with the behavior in the liver-specific late phase, allows the characterization of the most frequent focal liver lesions, with an accuracy similar to those of dynamic computed tomography and magnetic resonance imaging.


Asunto(s)
Medios de Contraste , Neoplasias Hepáticas/diagnóstico por imagen , Humanos , Ultrasonografía/métodos
19.
Biomedica ; 37(4): 571-576, 2017 Dec 01.
Artículo en Español | MEDLINE | ID: mdl-29373776

RESUMEN

Introducción. El caseinato de sodio, una sal de la caseína utilizada como agente proinflamatorio en ratones, es capaz de inducir granulopoyesis en vivo e incrementar la producción de citocinas esenciales en dicho evento.Objetivo. Evaluar si el caseinato de sodio es capaz de inducir un efecto biológico en células de origen linfoide y la producción de citocinas involucradas con este linaje.Materiales y métodos: Se utilizaron ratones hembra BALB/c de 8 a 12 semanas de edad. Los animales se inyectaron cuatro veces, con intervalos de 48 horas, por vía intraperitoneal con 1 ml de caseinato de sodio (10 % de SFB p/v). La población de linfocitos B y la incorporación de bromodesoxiuridina (BrdU) se analizaron mediante citometría de flujo. La detección de la interleucina 7 se evaluó mediante la técnica de ELISA.Resultados. Tras la inyección por vía intraperitoneal, el número de linfocitos B 220+ provenientes del bazo de ratones tratados con caseinato de sodio aumentó comparados con los que solo recibieron el vehículo como tratamiento (89,01±1,03 Vs. 75,66±2,08), así como la incorporación de BrdU en células B220+ (38,59±4,48 Vs. 11,82±1,04). Se evidenció, asimismo, el incremento en la concentración de la interleucina 7 (IL-7) en el suero de los ratones tratados con caseinato de sodio, comparados con los que solo recibieron el vehículo (62,1±17,5 Vs. 26,9±4,4 pg/ml).Conclusión. El caseinato de sodio fue capaz de aumentar el número de linfocitos B en bazo de ratones, así como inducir la producción de IL-7, citocina clave para la linfopoyesis B.


Asunto(s)
Linfocitos B/efectos de los fármacos , Caseínas/farmacología , Linfopoyesis/efectos de los fármacos , Animales , Médula Ósea/efectos de los fármacos , Caseínas/administración & dosificación , Caseínas/toxicidad , División Celular , Femenino , Inyecciones Intraperitoneales , Interleucina-7/biosíntesis , Interleucina-7/sangre , Interleucina-7/genética , Recuento de Linfocitos , Linfocinas/biosíntesis , Linfocinas/genética , Ratones , Ratones Endogámicos BALB C , Bazo/citología , Bazo/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos
20.
Rev. peru. med. exp. salud publica ; 39(2): 170-177, abr.-jun. 2022. tab, graf
Artículo en Español | LILACS | ID: biblio-1395056

RESUMEN

RESUMEN Objetivos: Conocer la diversidad genética de Aedes aegypti en el corredor vial transfronterizo Central-Alto Paraná de Paraguay, con registros de casos de dengue. Materiales y métodos: Se seleccionaron veinte hembras adultas de la eclosión de huevos de Ae. aegypti procedentes de casas geolocalizadas en los departamentos de Alto Paraná, Caaguazú, Cordillera y Central, entre el 2018 y 2019. Se extrajo ADN del tejido de las hembras para amplificación aleatoria de sus patrones polimórficos mediante amplificación aleatoria del ADN polimórfico por PCR (RAPD-PCR), usando cebadores H3 y B03 a fin de conocer parámetros genéticos de diversidad poblacional. Las relaciones entre las poblaciones de mosquitos según la localidad fueron visualizadas mediante análisis no apareado de la media aritmética. Las áreas idóneas de distribución geográfica real y potencial de estas poblaciones de Ae. aegypti fueron analizadas mediante DIVA-GIS 7.3.0 y MAXENT. Resultados: Se identificaron 40 loci mediante perfiles RAPD-PCR, con diferenciación génica moderada (Gst = 0,12). El corredor transfronterizo presentó condiciones bioclimáticas para la presencia de poblaciones variantes de Ae. aegypti, siendo determinantes en la distribución la precipitación del trimestre más cálido y la temperatura media del trimestre más seco. Conclusiones: Se evidencia que existe diversidad genética moderada en las poblaciones de Ae. aegypti procedentes de zonas con registros de casos de dengue ubicadas en el corredor vial transfronterizo que une los departamentos Central y Alto Paraná de Paraguay. El estudio de variabilidad genética de Ae. aegypti es de gran utilidad para la vigilancia entomoepidemiológica y evaluación de posibles eventos de resistencia al control químico.


ABSTRACT Objective: To determine the genetic diversity of Aedes aegypti in the Central-Alto Paraná cross-border road corridor of Paraguay, an area that has reports of dengue cases. Materials and methods: Twenty adult females were selected from hatching Ae. aegypti eggs from households geolocated in the departments of Alto Paraná, Caaguazú, Cordillera and Central, between 2018 and 2019. DNA was extracted from the tissue of females for amplifying their polymorphic patterns by random amplification of polymorphic DNA by PCR (RAPD-PCR), using primers H3 and B03 in order to identify genetic parameters of population diversity. The relationships between mosquito populations according to locality were observed by unpaired arithmetic mean analysis. We used DIVA-GIS 7.3.0 and MAXENT to analyze the suitable areas of actual and potential geographic distribution of these Ae. aegypti populations. Results: Forty loci were identified by RAPD-PCR profiling, with moderate gene differentiation (Gst = 0.12). The cross-border corridor presented bioclimatic conditions for the presence of variant populations of Ae. aegypti, with precipitation in the warmest quarter and mean temperature in the driest quarter being determinant in the distribution. Conclusions: There is evidence of moderate genetic diversity in Ae. aegypti populations from areas that have reported dengue cases in the cross-border road corridor linking the Central and Alto Paraná departments of Paraguay. The study of genetic variability of Ae. aegypti is very useful for entomo-epidemiological surveillance and evaluation of possible resistance to chemical control.


Asunto(s)
Polimorfismo Genético , Aedes , Mosquitos Vectores , Variación Genética , Técnica del ADN Polimorfo Amplificado Aleatorio , Control de Vectores de las Enfermedades , Enfermedades Transmitidas por Vectores
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