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1.
Environ Geochem Health ; 46(3): 84, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38367079

RESUMEN

Heavy metals can play an important biological role as micronutrients but also as potentially toxic elements (PTEs). Understanding the natural concentrations of PTEs-Pb and Zn included-in soils allows for the identification and monitoring of contaminated areas and their role in environmental risk assessment. In this study, we aim to determine semi-total or natural and available concentrations of Pb and Zn in topsoils (0-20 cm depth) from 337 samples under native vegetation in the State of Minas Gerais, Brazil. Additionally, we sought to interpret the spatial geochemical variability using geostatistical techniques and quality reference values for these elements in soils were established. The semi-total concentrations were determined by flame and graphite furnace atomic absorption after microwave-assisted nitric acid digestion method. The available concentrations were extracted using the Mehlich-I extractor and determined by atomic absorption spectrometer. Spatial variability was modeled using semivariance estimators: Matheron's classic, Cressie and Hawkins' robust, and Cressie median estimators, the last two being less sensitive to extreme values. This allowed the construction of digital maps through kriging of semi-total Pb and Zn contents using the median estimator, as well as other soil properties by the robust estimator. The dominance of acidic pH and low CEC values reflects highly weathered low-fertility soils. Semi-total Pb contents ranged from 2.1 to 278 mg kg-1 (median: 9.35 mg kg-1) whereas semi-total Zn contents ranged from 2.7 to 495 mg kg-1 (median: 7.7 mg kg-1). The available Pb contents ranged from 0.1 to 6.92 mg kg-1 (median: 0.54 mg kg-1) whereas available Zn contents ranged from 0.1 to 78.2 mg kg-1 (median: 0.32 mg kg-1). The highest Pb and Zn concentrations were observed near Januária, in the northern part of the territory, probably on limestone rocks from the Bambuí group. Finally, the QRVs for Pb and Zn in natural soils were lower than their background values from other Brazilian region and below the prevention values suggested by Brazilian environmental regulations.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Suelo/química , Brasil , Plomo , Contaminantes del Suelo/análisis , Monitoreo del Ambiente/métodos , Metales Pesados/análisis , Zinc
2.
J Chem Inf Model ; 63(15): 4641-4653, 2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37493573

RESUMEN

DNA-encoded libraries (DELs) are widely used in the discovery of drug candidates, and understanding their design principles is critical for accessing better libraries. Most DELs are combinatorial in nature and are synthesized by assembling sets of building blocks in specific topologies. In this study, different aspects of library topology were explored and their effect on DEL properties and chemical diversity was analyzed. We introduce a descriptor for DEL topological assignment (DELTA) and use it to examine the landscape of possible DEL topologies and their coverage in the literature. A generative topographic mapping analysis revealed that the impact of library topology on chemical space coverage is secondary to building block selection. Furthermore, it became apparent that the descriptor used to analyze chemical space dictates how structures cluster, with the effects of topology being apparent when using three-dimensional descriptors but not with common two-dimensional descriptors. This outcome points to potential challenges of attempts to predict DEL productivity based on chemical space analyses alone. While topology is rather inconsequential for defining the chemical space of encoded compounds, it greatly affects possible interactions with target proteins as illustrated in docking studies using NAD/NADP binding proteins as model receptors.


Asunto(s)
ADN , Descubrimiento de Drogas , Descubrimiento de Drogas/métodos , ADN/química , Biblioteca de Genes
3.
Molecules ; 27(2)2022 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-35056727

RESUMEN

Chagas disease (CD) can be accurately diagnosed by detecting Trypanosoma cruzi in patients' blood using polymerase chain reaction (PCR). However, parasite-derived biomarkers are of great interest for the serological diagnosis and early evaluation of chemotherapeutic efficacy when PCR may fail, owing to a blood parasite load below the method's limit of detection. Previously, we focused on the detection of specific anti-α-galactopyranosyl (α-Gal) antibodies in chronic CD (CCD) patients elicited by α-Gal glycotopes copiously expressed on insect-derived and mammal-dwelling infective parasite stages. Nevertheless, these stages also abundantly express cell surface glycosylphosphatidylinositol (GPI)-anchored glycoproteins and glycoinositolphospholipids (GIPLs) bearing nonreducing terminal ß-galactofuranosyl (ß-Galf) residues, which are equally foreign to humans and, therefore, highly immunogenic. Here we report that CCD patients' sera react specifically with synthetic ß-Galf-containing glycans. We took a reversed immunoglycomics approach that entailed: (a) Synthesis of T. cruzi GIPL-derived Galfß1,3Manpα-(CH2)3SH (glycan G29SH) and Galfß1,3Manpα1,2-[Galfß1,3]Manpα-(CH2)3SH (glycan G32SH); and (b) preparation of neoglycoproteins NGP29b and NGP32b, and their evaluation in a chemiluminescent immunoassay. Receiver-operating characteristic analysis revealed that NGP32b can distinguish CCD sera from sera of healthy individuals with 85.3% sensitivity and 100% specificity. This suggests that Galfß1,3Manpα1,2-[Galfß1,3]Manpα is an immunodominant glycotope and that NGP32b could potentially be used as a novel CCD biomarker.


Asunto(s)
Enfermedad de Chagas
4.
Molecules ; 27(17)2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-36080480

RESUMEN

Chagas disease (CD) is caused by the parasite Trypanosoma cruzi and affects 6-7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events. The development of safer, more effective therapies is hampered by the lack of biomarker(s) (BMKs) for the early assessment of therapeutic outcomes. The mammal-dwelling trypomastigote parasite stage expresses glycosylphosphatidylinositol-anchored mucins (tGPI-MUC), whose O-glycans are mostly branched with terminal, nonreducing α-galactopyranosyl (α-Gal) glycotopes. These are absent in humans, and thus highly immunogenic and inducers of specific CD anti-α-Gal antibodies. In search for α-Gal-based BMKs, here we describe the synthesis of neoglycoprotein NGP11b, comprised of a carrier protein decorated with the branched trisaccharide Galα(1,2)[Galα(1,6)]Galß. By chemiluminescent immunoassay using sera/plasma from chronic CD (CCD) patients from Venezuela and Mexico and healthy controls, NGP11b exhibited sensitivity and specificity similar to that of tGPI-MUC from genotype TcI, predominant in those countries. Preliminary evaluation of CCD patients subjected to chemotherapy showed a significant reduction in anti-α-Gal antibody reactivity to NGP11b. Our data indicated that NGP11b is a potential BMK for diagnosis and treatment assessment in CCD patients.


Asunto(s)
Enfermedad de Chagas , Trypanosoma cruzi , Biomarcadores , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/tratamiento farmacológico , Humanos , Mucinas , Trisacáridos
5.
Tech Coloproctol ; 23(2): 101-115, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30631977

RESUMEN

Pelvic floor rehabilitation is frequently recommended for defecation disorders, in both constipation and fecal incontinence. However, the lack of patient selection, together with the variety of rehabilitation methods and protocols, often jeopardize the results of this approach, causing difficulty in evaluating outcomes and addressing proper management, and above all, in obtaining scientific evidence for the efficacy of these methods for specific indications. The authors represent different gastroenterological and surgical scientific societies in Italy, and their aim was to identify the indications and agree on treatment protocols for pelvic floor rehabilitation of patients with defecation disorders. This was achieved by means of a modified Delphi method, utilizing a working team (10 members) which developed the statements and a consensus group (15 members, different from the previous ones) which voted twice also suggesting modifications of the statements.


Asunto(s)
Estreñimiento/rehabilitación , Incontinencia Fecal/rehabilitación , Gastroenterología/normas , Guías de Práctica Clínica como Asunto/normas , Sociedades Médicas/normas , Defecación , Técnica Delphi , Humanos , Italia , Diafragma Pélvico
6.
J Am Acad Dermatol ; 78(6): 1068-1076, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29307643

RESUMEN

BACKGROUND: Cutaneous lymphoma diagnosed after anti-tumor necrosis factor-α therapy (anti-TNF-α) has been reported in the literature, yet a clear link between both events remains elusive. OBJECTIVE: To review our experience with cutaneous lymphoma diagnosed during or after the use of anti-TNF-α therapies. METHODS: This is a multicenter retrospective study and a literature review. RESULTS: A total of 22 cases, including 20 cutaneous T-cell lymphomas (CTCLs) and 2 cutaneous B-cell lymphomas, were identified. In the CTCL group, 75% of the patients received an anti-TNF-α agent for a presumed inflammatory skin condition. Mycosis fungoides and Sézary syndrome were the most common subtypes of CTCL diagnosed. Advanced disease (stage IIB to IVA) was commonly seen at time of diagnosis and required aggressive therapy, including stem cell transplant in 3 patients; 2 patients in whom cutaneous B-cell lymphomas was diagnosed had an indolent course. A total of 31 cases were gathered from a literature search. LIMITATIONS: This is a retrospective study. CONCLUSIONS: Our findings suggest that the disease of most of the identified patients was misdiagnosed as psoriasis or eczema; therefore, a comprehensive morphologic and molecular review of skin biopsy specimens and peripheral blood samples should be considered before initiation of anti-TNF-α therapy in patients with poorly defined dermatitis or atypical presentations of psoriasis.


Asunto(s)
Progresión de la Enfermedad , Inmunoterapia/métodos , Linfoma Cutáneo de Células T/tratamiento farmacológico , Linfoma Cutáneo de Células T/patología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anciano , Estudios de Cohortes , Bases de Datos Factuales , Diagnóstico Tardío , Femenino , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Masculino , Persona de Mediana Edad , Micosis Fungoide/diagnóstico , Micosis Fungoide/tratamiento farmacológico , Micosis Fungoide/patología , Pronóstico , Estudios Retrospectivos , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/tratamiento farmacológico , Síndrome de Sézary/patología , Resultado del Tratamiento , Adulto Joven
7.
Parasitology ; 145(13): 1758-1764, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29898796

RESUMEN

Outbreaks of Old World cutaneous leishmaniasis (CL) have significantly increased due to the conflicts in the Middle East, with most of the cases occurring in resource-limited areas such as refugee settlements. The standard methods of diagnosis include microscopy and parasite culture, which have several limitations. To address the growing need for a CL diagnostic that can be field applicable, we have identified five candidate neoglycoproteins (NGPs): Galα (NGP3B), Galα(1,3)Galα (NGP17B), Galα(1,3)Galß (NGP9B), Galα(1,6)[Galα(1,2)]Galß (NGP11B), and Galα(1,3)Galß(1,4)Glcß (NGP1B) that are differentially recognized in sera from individuals with Leishmania major infection as compared with sera from heterologous controls. These candidates contain terminal, non-reducing α-galactopyranosyl (α-Gal) residues, which are known potent immunogens to humans. Logistic regression models found that NGP3B retained the best diagnostic potential (area under the curve from receiver-operating characteristic curve = 0.8). Our data add to the growing body of work demonstrating the exploitability of the human anti-α-Gal response in CL diagnosis.


Asunto(s)
Anticuerpos Antihelmínticos/aislamiento & purificación , Antígenos Helmínticos/aislamiento & purificación , Glicoproteínas/química , Leishmaniasis Cutánea/diagnóstico , Adolescente , Adulto , Animales , Área Bajo la Curva , Bancos de Muestras Biológicas , Epítopos/inmunología , Femenino , Humanos , Leishmania major , Masculino , Persona de Mediana Edad , Medio Oriente , Análisis de Regresión , Adulto Joven
8.
Phytother Res ; 31(6): 906-914, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28425219

RESUMEN

The multidrug resistance (MDR) phenotype is considered as a major cause of the failure in cancer chemotherapy. The acquisition of MDR is usually mediated by the overexpression of drug efflux pumps of a P-glycoprotein. The development of compounds that mitigate the MDR phenotype by modulating the activity of these transport proteins is an important yet elusive target. Here, we screened the saponification and enzymatic degradation products from Salvia hispanica seed's mucilage to discover modulating compounds of the acquired resistance to chemotherapeutic in breast cancer cells. Preparative-scale recycling HPLC was used to purify the hydrolysis degradation products. All compounds were tested in eight different cancer cell lines and Vero cells. All compounds were noncytotoxic at the concentration tested against the drug-sensitive and multidrug-resistant cells (IC50  > 29.2 µM). For the all products, a moderate vinblastine-enhancing activity from 4.55-fold to 6.82-fold was observed. That could be significant from a therapeutic perspective. Copyright © 2017 John Wiley & Sons, Ltd.


Asunto(s)
Neoplasias de la Mama/patología , Resistencia a Antineoplásicos , Oligosacáridos/farmacología , Mucílago de Planta/química , Salvia/química , Vinblastina/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Chlorocebus aethiops , Humanos , Semillas/química , Células Vero
9.
Anticancer Drugs ; 27(6): 508-18, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26918391

RESUMEN

N-ω-chloroacetyl-L-ornithine (NCAO) is an ornithine decarboxylase (ODC) inhibitor that is known to exert cytotoxic and antiproliferative effects on three neoplastic human cancer cell lines (HeLa, MCF-7, and HepG2). Here, we show that NCAO has antiproliferative activity in 13 cancer cell lines, of diverse tissue origin from human and mice, and in a mouse cancer model in vivo. All cell lines were sensitive to NCAO after 72 h of treatment (the EC50 ranged from 1 to 50.6 µmol/l). The Ca Ski cell line was the most sensitive (EC50=1.18±0.07 µmol/l) and MDA-MB-231 was the least sensitive (EC50=50.6±0.3 µmol/l). This ODC inhibitor showed selectivity for cancer cells, exerting almost no cytotoxic effect on the normal Vero cell line (EC50>1000 µmol/l). NCAO induced apoptosis and inhibited tumor cell migration in vitro. Furthermore, in vivo, this compound (at 50 and 100 mg/kg, daily intraperitoneal injection for 7 days) exerted potent antitumor activity against both solid and ascitic tumors in a mouse model using the myeloma (Ag8) cell line. At these same two doses, the toxicological evaluation showed that NCAO has no obvious systemic toxicity. The current results suggest that the antitumor activity is exerted by apoptosis related not only to a local but also a systemic cytotoxic effect exerted by NCAO on tumor cells. The applications for NCAO as an antitumor agent may be extensive; however, further studies are needed to ascertain the antitumor activity on other types of tumor in vivo and to determine the precise molecular mechanism of its activity.


Asunto(s)
Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales/métodos , Neoplasias/tratamiento farmacológico , Ornitina/análogos & derivados , Animales , Apoptosis/efectos de los fármacos , Ascitis/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Neoplasias/patología , Ornitina/farmacología , Pruebas de Toxicidad Subcrónica , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
10.
Breast Cancer Res Treat ; 154(3): 441-53, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26564481

RESUMEN

Hereditary cancer predisposition gene testing allows the identification of individuals at high risk of cancer that may benefit from increased surveillance, chemoprevention, and prophylactic surgery. In order to implement clinical genetic strategies adapted to each population's needs and intrinsic genetic characteristic, this review aims to present the current status of knowledge about the spectrum of BRCA pathogenic variants in Latin American populations. We have conducted a comprehensive review of 33 studies published between 1994 and 2015 reporting the prevalence and/or spectrum of BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) variants. The combined sample size for these studies consisted of 4835 individuals from 13 countries in Latin America and the Caribbean, as well as in Hispanics in the United States. A total of 167 unique pathogenic variants have been reported in the existing literature. In unselected breast cancer cases, the prevalence ranged from 1.2 to 27.1%. Some countries presented a few recurrent pathogenic variants, while others were characterized by diverse, non-recurrent variants. The proportion of BRCA pathogenic variants shared between Hispanics in the United States and Latin American populations was estimated at 10.4%. Within Latin America and the Caribbean, 8.2% of the BRCA variants reported were present in more than one country. Countries with high prevalence of BRCA pathogenic variants may benefit from more aggressive testing strategies, while testing of recurrent variant panels might present a cost-effective solution for improving genetic testing in some, but not all, countries.


Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Pruebas Genéticas , Neoplasias de la Mama/genética , Región del Caribe , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genética de Población , Hispánicos o Latinos , Humanos , América Latina , Mutación , Neoplasias Ováricas/genética , Estados Unidos
11.
Crit Care Med ; 42(4): 771-80, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24365860

RESUMEN

OBJECTIVES: To perform a complete immunological characterization of compensatory anti-inflammatory response syndrome in patients with sepsis and to explore the relationship between these changes and clinical outcomes of 28-day mortality and secondary infections. DESIGN: Prospective single-center study conducted between April 2011 and December 2012. SETTING: ICUs from Hospital Universitario San Vicente Fundación at Medellin, Colombia. PATIENTS: One hundred forty-eight patients with severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At days 0, 1, 3, 5, 10, and 28, we determined the expression of HLA-DR in monocytes and the apoptosis and the proliferation index in T lymphocytes, as well as the levels of tumor necrosis factor-α, interleukin-6, interleukin-1ß, interleukin-10, and transforming growth factor-ß in both plasma and cell culture supernatants of peripheral blood mononuclear cells. The mean percentage of HLA-DR was 60.7 at enrollment and increased by 0.9% (95% CI, 0.7-1.2%) per day. The mean percentage of CD4 T cells and CD8 T cells AV+/7-AAD- at enrollment was 37.2% and 20.4%, respectively, but it diminished at a rate of -0.5% (95% CI, -0.7% to -0.3%) and -0.3% (95% CI, -0.4% to -0.2%) per day, respectively. Plasma levels of interleukin-6 and interleukin-10 were 290 and 166 pg/mL and decreased at a rate of -7.8 pg/mL (95% CI, -9.5 to -6.1 pg/mL) and -4 pg/mL (95% CI, -5.1 to -2.8 pg/mL) per day, respectively. After controlling for confounders, only sustained plasma levels of interleukin-6 increase the risk of death (hazard ratio 1.003; 95% CI, 1.001-1.006). CONCLUSIONS: We found no evidence to support a two-phase model of sepsis pathophysiology. However, immunological variables did behave in a mixed and time-dependent manner. Further studies should evaluate changes over time of interleukin-6 plasma levels as a prognostic biomarker for critically ill patients.


Asunto(s)
Antígenos HLA-DR/biosíntesis , Mediadores de Inflamación/inmunología , Leucocitos Mononucleares/inmunología , Sepsis/inmunología , APACHE , Anciano , Apoptosis , Proliferación Celular , Comorbilidad , Femenino , Humanos , Mediadores de Inflamación/sangre , Unidades de Cuidados Intensivos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Estudios Prospectivos , Grupos Raciales , Sepsis/sangre
12.
J Infect Dis ; 207(1): 152-63, 2013 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-23100559

RESUMEN

Retinochoroiditis manifests in patients infected with Toxoplasma gondii. Here, we assessed 30 sibships and 89 parent/case trios of presumed ocular toxoplasmosis (POT) to evaluate associations with polymorphisms in the NOD2 gene. Three haplotype-tagging single-nucleotide polymorphisms (tag-SNPs) within the NOD2 gene were genotyped. The family-based association test showed that the tag-SNP rs3135499 is associated with retinochoroiditis (P = .039). We then characterized the cellular immune response of 59 cases of POT and 4 cases of active ocular toxoplasmosis (AOT). We found no differences in levels of interferon γ (IFN-γ) and interleukin 2 produced by T-helper 1 cells when comparing patients with AOT or POT to asymptomatic individuals. Unexpectedly, we found an increased interleukin 17A (IL-17A) production in patients with POT or OAT. In patients with POT or AOT, the main cellular source of IL-17A was CD4(+)CD45RO(+)T-bet(-)IFN-γ(-) T-helper 17 cells. Altogether, our results suggest that NOD2 influences the production of IL-17A by CD4(+) T lymphocytes and might contribute to the development of ocular toxoplasmosis.


Asunto(s)
Interleucina-17/metabolismo , Proteína Adaptadora de Señalización NOD2/genética , Polimorfismo de Nucleótido Simple/genética , Toxoplasmosis Ocular/genética , Adulto , Alelos , Brasil , Linfocitos T CD4-Positivos/inmunología , Proliferación Celular , Estudios de Cohortes , Citocinas/análisis , Haplotipos , Humanos , Inmunofenotipificación , Interleucina-17/inmunología , Proteína Adaptadora de Señalización NOD2/inmunología , Fenotipo , Polimorfismo de Nucleótido Simple/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Células TH1/inmunología , Células Th17/inmunología , Toxoplasmosis Ocular/inmunología
13.
ChemMedChem ; : e202400273, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940296

RESUMEN

Sirtuin 6 (Sirt6), an NAD+-dependent deacylase, has emerged as a promising target for aging-related diseases and cancer. Advancing the medicinal chemistry of Sirt6 modulators is crucial for the development of chemical probes aimed at unraveling the intricate biological functions of Sirt6 and unlocking its therapeutic potential. A proprietary DNA-encoded library yielded Sirt6 inhibitor 2-Pr, displaying remarkable inhibitory activity and isoform-selectivity, and featuring a chemical structure distinct from reported Sirt6 modulators. In this study, we explore the inhibitory mechanism of 2-Pr, evaluating the impact of chemical modifications and presenting a crystal structure of the Sirt6/ADP-ribose/2-Pr complex. Notably, co-crystal structure analysis reveals an unexpected and unprecedented binding mode of Sirt6, with 2-Pr spanning the acyl channel of the enzyme, extending into the acetyl-lysine binding pocket, and reaching toward the C-site. This unique binding mode guides potential avenues for developing potent and selective Sirt6 inhibitors.

14.
Dig Liver Dis ; 56(5): 770-777, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38461046

RESUMEN

The practice of recto-colonic water irrigation to treat constipation has been used since ancient times with different, uncontrolled, and variably performing methods which have been considered interchangeably all alike. The use of better-performing devices with a standardized methodology is relatively recent, and the term Trans Anal Irrigation (TAI) defines a methodology performed with devices able to control the timing, volume, and pressure of the water introduced into the rectum and colon utilizing a catheter or a cone through the anus. Such practice has been implemented with favorable responses in patients with refractory chronic constipation secondary to neurological diseases. However, since the role of Trans Anal Irrigation as a therapeutic aid in chronic functional constipation and functional evacuation disorders is not yet fully clarified and standardized, a group of clinical investigators with recognized expertise in these clinical conditions intends to clarify the elements that characterize a TAI procedure that can benefit patients with functional constipation and functional defecation disorders defined according to the lastly updated Rome Diagnostic Criteria. Finally, the paper deals with adherence and practical implementation of TAI.


Asunto(s)
Canal Anal , Estreñimiento , Irrigación Terapéutica , Estreñimiento/terapia , Humanos , Irrigación Terapéutica/métodos , Enfermedad Crónica , Canal Anal/fisiopatología
15.
Carbohydr Res ; 536: 109015, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38198982

RESUMEN

The protozoan parasite Leishmania (Viannia) braziliensis is among Latin America's most widespread Leishmania species and is responsible for tegumentary leishmaniasis (TL). This disease has multiple clinical presentations, with cutaneous leishmaniasis (CL) being the most frequent. It manifests as one or a few localized skin ulcers, which can spread to other body areas. Hence, early diagnosis and treatment, typically with pentavalent antimonials, is critical. Traditional diagnostic methods, like parasite culture, microscopy, or the polymerase chain reaction (PCR) for detection of the parasite DNA, have limitations due to the uneven distribution of parasites in biopsy samples. Nonetheless, studies have revealed high levels of parasite-specific anti-α-Gal antibodies in L. (V.) braziliensis-infected patients. Previously, we demonstrated that the neoglycoprotein NGP28b, consisting of the L. (Leishmania) major type-2 glycoinositolphospholipid (GIPL)-3-derived trisaccharide Galpα1,6Galpα1,3Galfß conjugated to bovine serum albumin (BSA) via a linker, acts as a reliable serological biomarker (BMK) for L. (V.) braziliensis infection in Brazil. This indicates the presence of GIPL-3 or a similar structure in this parasite, and its terminal trisaccharide either functions as or is part of an immunodominant glycotope. Here, we explored whether extending the trisaccharide with a mannose unit would enhance its efficacy as a biomarker for the serological detection of L. (V.) braziliensis. We synthesized the tetrasaccharide Galpα1,6Galpα1,3Galfß1,3Manpα(CH2)3SH (G31SH) and conjugated it to maleimide-functionalized BSA to afford NGP31b. When we assessed the efficacy of NGP28b and NGP31b by chemiluminescent enzyme-linked immunosorbent assay on a cohort of CL patients with L. (V.) braziliensis infection from Bolivia and Argentina against a healthy control group, both NGPs exhibited similar or identical sensitivity, specificity, and accuracy. This finding implies that the mannose moiety at the reducing end is not part of the glycotope recognized by the parasite-specific anti-α-Gal antibodies in patients' sera, nor does it exert a relevant influence on the terminal trisaccharide's conformation. Moreover, the mannose does not seem to inhibit glycan-antibody interactions. Therefore, NGP31b is a viable and dependable BMK for the serodiagnosis of CL caused by L. (V.) braziliensis.


Asunto(s)
Leishmania braziliensis , Leishmaniasis Cutánea , Humanos , Leishmania braziliensis/genética , Manosa , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/tratamiento farmacológico , Glicoproteínas , Trisacáridos
16.
Front Oncol ; 14: 1338250, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38634046

RESUMEN

Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. Results: No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Conclusion: Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.

17.
Mol Carcinog ; 52 Suppl 1: E127-38, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23776089

RESUMEN

Studies have shown that DNA repair capacity (DRC) is significantly decreased in breast cancer patients, but the molecular causes of inter-individual variation in DRC are unknown. We hypothesized that genetic variation in the nucleotide excision repair pathway genes can modulate DRC and breast cancer risk in Puerto Rican women. A total of 228 breast cancer cases and 418 controls were recruited throughout Puerto Rico. For all study participants, eight single nucleotide polymorphisms (SNPs) in the genes XPC, XPD, and RAD23B were genotyped using a TaqMan PCR, and the DRC levels of UV induced-DNA damage was measured in peripheral lymphocytes using a host cell reactivation assay. After adjustment for confounders, RAD23B rs1805329 (Ala249Val) was found to be significantly associated with breast cancer risk under all models tested (P < 0.001). There was also a significant association between breast cancer risk and RAD23B rs10739234 (intronic) under the recessive model (P = 0.003, OR: 2.72, 95% CI: 1.40-5.30). In cases, there was a statistically significant difference in mean DRC per genotype for RAD23B rs1805329 (P < 0.001) and XPC rs2607775 (P = 0.002). When we modeled the combined effect of multiple SNPs that each independently affected DRC on cancer risk, we observed incremental augmentations in risk with increasing number of risk genotypes at those loci (P overall model <0.001). The increase in adverse genotypes was also correlated with a progressive decrease in DRC values. Our data indicate an additive effect of the NER SNPs on DRC and breast cancer risk in Puerto Rican women.


Asunto(s)
Neoplasias de la Mama/etiología , Enzimas Reparadoras del ADN/genética , Reparación del ADN/genética , Proteínas de Unión al ADN/genética , Polimorfismo de Nucleótido Simple/genética , Proteína de la Xerodermia Pigmentosa del Grupo D/genética , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Pronóstico , Puerto Rico , Factores de Riesgo
18.
J Dairy Sci ; 96(5): 3238-46, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23497991

RESUMEN

The effect of sampling time on milk fatty acid (FA) composition after separately adding 3 plant oils to an oil-free control diet (67% cereal-soybean-based concentrate and 33% alfalfa hay) was studied in 12 Malagueña goats. Individual animals were randomly allocated to 1 of the 4 treatments: control, 48 g/d of added high oleic (OSO) or regular (RSO) sunflower oil, or linseed oil (LO). Individual milk samples were taken at 0 (covariate), 1, 12, 24, 72, 120, 192, 312, and 504 h after the beginning of the experiment. Milk FA contents (g/100g of total FA methyl esters) were analyzed in a completely randomized design with repeated measures using PROC MIXED of SAS (SAS Institute Inc., Cary, NC). Comparing results of 15 chosen FA (for example, medium-chain saturated FA trans-11 C18:1, cis-9,trans-11 C18:2, trans-10 C18:1, and C18:3n-3) indicated that throughout the duration of the experiment, feeding the control diet had little influence on the concentrations of most FA in milk. Most changes in milk FA composition due to oil supplementation had occurred within 192 h since the beginning of the experiment. However, the concentrations of 2 FA (trans-10 C18:1 in RSO and C18:3n-3 in LO treatments) continued to change until 504 h. By comparing FA values in milk fat from oil treatments with those of the control at the same sampling times, typical value differences for the 3 supplementary oils found at 504 h (21 d) were also observed at 312 h from the beginning of the experiment (13 d) and even earlier in some FA, such as medium-chain saturated FA at 120 h in RSO and LO and at 72 h in OSO, cis-9,trans-11 C18:2 and trans-10 C18:1 at 24h in RSO, trans-11 C18:1 at 12h in RSO and LO, and C18:3n-3 at 1h in LO. In the conditions assayed in these experiments, reliable results of milk FA changes were obtained at sampling times shorter than 21 d. Monitoring early changes in milk FA after the addition of plant oils to diets could help in the study of rumen and mammary metabolism of dietary FA.


Asunto(s)
Alimentación Animal , Ácidos Grasos/análisis , Aceite de Linaza/farmacología , Leche/química , Ácidos Oléicos/farmacología , Aceites de Plantas/farmacología , Animales , Dieta/veterinaria , Suplementos Dietéticos , Femenino , Cabras/metabolismo , Cabras/fisiología , Aceite de Girasol , Factores de Tiempo
19.
J Dairy Sci ; 96(12): 7532-7, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24119803

RESUMEN

A crossover experiment was designed to compare the effects of 2 ways of feeding linseed oil on milk fat fatty acid (FA) composition. Ten lactating goats, trained to keep competent their inborn reticular groove reflex, received a daily dose of linseed oil (38 g/d) either with their solid (concentrate) feed (CON) or emulsified in skim milk and bottle-fed (BOT). Two groups of 5 goats received alternative and successively each of the treatments in two 15-d periods. α-Linolenic acid in milk fat rose up to 13.7% in the BOT versus 1.34% in the CON treatment. The n-6 to n-3 FA ratio was significantly reduced in goats receiving bottle-fed linseed oil (1.49 vs. 0.49). Contents of rumen biohydrogenation intermediates of dietary unsaturated FA were high in milk fat of goats under the CON treatment but low in those in the BOT treatment. These results point to a clear rumen bypass of the bottle-fed linseed oil. This strategy allows obtaining milk fat naturally very rich in n-3 FA and very low in trans FA. Translating this approach into practical farm conditions could enable farmers to produce milk enriched in specific FA.


Asunto(s)
Ácidos Grasos Omega-3/análisis , Cabras , Aceite de Linaza/farmacología , Leche/química , Reticulum/fisiología , Animales , Estudios Cruzados , Grasas Insaturadas en la Dieta/metabolismo , Ácidos Grasos/análisis , Femenino , Aceite de Linaza/administración & dosificación , Reflejo , Ácidos Grasos trans/farmacología , Ácido alfa-Linolénico/análisis
20.
J Clin Nurs ; 22(23-24): 3522-31, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23786630

RESUMEN

AIMS AND OBJECTIVES: To identify studies on cardiovascular changes resulting from sexual activity, as well as the occurrence of sexual dysfunction after acute myocardial infarction. BACKGROUND: Many patients with acute myocardial infarction experience sexual dysfunction, mainly due to fear of dying and/or of having another heart attack. DESIGN: The research was an integrative literature review. METHODS: Searched databases included Lilacs, Medline and PubMed, and the following were inclusion criteria: national and international articles published from 2000-2011, written in Portuguese, Spanish or English. RESULTS: The results indicate that many patients with coronary heart disease experience sexual dysfunction whether from fear of experiencing another acute myocardial infarction or due to the side effects of medication. Studies show there are few cardiovascular changes during sexual activity. CONCLUSIONS: Because sexual dysfunction negatively affects the lives of people, providing guidance to individuals with cardiovascular disease, especially after an acute myocardial infarction, may be a crucial factor in determining quality of life and should be incorporated into clinical practice. RELEVANCE TO CLINICAL PRACTICE: Despite the subject's importance, there are few studies on nursing guidance concerning sexual activity; moreover, addressing sexuality with patients is still a challenge for nurses.


Asunto(s)
Infarto del Miocardio/fisiopatología , Disfunciones Sexuales Fisiológicas , Humanos
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