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1.
Stem Cells ; 41(1): 26-38, 2023 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-36153788

RESUMEN

The inner ear is derived from the otic placode, one of the numerous cranial sensory placodes that emerges from the pre-placodal ectoderm (PPE) along its anterior-posterior axis. However, the molecular dynamics underlying how the PPE is regionalized are poorly resolved. We used stem cell-derived organoids to investigate the effects of Wnt signaling on early PPE differentiation and found that modulating Wnt signaling significantly increased inner ear organoid induction efficiency and reproducibility. Alongside single-cell RNA sequencing, our data reveal that the canonical Wnt signaling pathway leads to PPE regionalization and, more specifically, medium Wnt levels during the early stage induce (1) expansion of the caudal neural plate border (NPB), which serves as a precursor for the posterior PPE, and (2) a caudal microenvironment that is required for otic specification. Our data further demonstrate Wnt-mediated induction of rostral and caudal cells in organoids and more broadly suggest that Wnt signaling is critical for anterior-posterior patterning in the PPE.


Asunto(s)
Oído Interno , Vía de Señalización Wnt , Animales , Ratones , Reproducibilidad de los Resultados , Oído Interno/metabolismo , Diferenciación Celular , Ectodermo/metabolismo , Organoides , Células Madre , Regulación del Desarrollo de la Expresión Génica
2.
Environ Res ; 241: 117654, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-37980990

RESUMEN

Water is a fundamental requirement for the survival of human beings. Although water is abundantly available across the globe, access to freshwater still remains a major concern. Most of the water available is saline or brackish, which is not fit for human consumption. Desalination is the optimum solution for production of potable water from saline water. A major shortcoming of conventional desalination technologies is their dependence on fossil fuel that results in environmental degradation, global warming, etc. Therefore, sustainable desalination technology has evolved as a need of hour. Among all renewable energy resources, solar energy is abundantly available and can be potentially harvested. Therefore, solar energy can be used to drive sustainable desalination technologies. A solar still converts saline water into freshwater in a single step using solar energy. But the major drawbacks of solar still are relatively lower efficiency and lower yield. Nanofluids are widely used to overcome these limitations due to their extraordinary and unique properties. This paper critically reviews the recent research performed on the application of nanofluids in solar desalination systems. Methods of nanofluid preparation, their types and properties are also discussed in detail. Application of nanofluids in solar desalination systems is discussed with special attention on performance enhancement of solar stills. Combinations of nanofluids with various other performance enhancement techniques are also considered. The effectiveness of nanofluids in solar stills is found to be dependent majorly on the nature and concentration of the nanofluid used.


Asunto(s)
Energía Solar , Humanos , Combustibles Fósiles , Agua Dulce , Calentamiento Global , Aguas Salinas
3.
Dig Dis Sci ; 69(2): 502-509, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38135812

RESUMEN

BACKGROUND: Promoter hypermethylation of tumor suppressor genes has been demonstrated to be one of the major mechanisms of their epigenetic regulation in various reports. We have studied the promoter methylation status of PEBP1 and evaluated its correlation with gallbladder carcinogenesis. AIMS: PEBP1, an endogenous inhibitor of Raf/MEK/ERK signaling pathway, is a tumor suppressor gene. We aimed to study the expression profile of PEBP1 and understand the mechanism and significance of its deregulation in gallbladder cancer. METHODS: PEBP1 expression analysis and its promoter methylation status were investigated in 77 gallbladder carcinoma (GBC) and tissue biopsies from 28 patients of gallstone disease by RT-PCR and MS-PCR, respectively. RESULTS: Our results of the mRNA expression profiling demonstrate that PEBP1 is down-regulated in 62.3% (48/77), while 31.2% (24/77) of the gallbladder cancer biopsies show no significant change and 6.5% (5/77) show up-regulated expression compared to tissue samples of gallstone diseases. In GBC, 48.1% (N = 37) GBC biopsy samples exhibited significantly heterozygous promoter hypermethylation compared to tissue samples from gallstone diseases which show promoter hypermethylation in 3 (10.7%) samples only. In gallbladder cancer, the PEBP1 methylation is significantly associated with lymph node metastasis and shorter period of survival. CONCLUSION: PEBP1 is frequently down-regulated and hypermethylated in gallbladder cancer and its promoter hypermethylation is a frequent and early inactivating mechanism in GBC.


Asunto(s)
Carcinoma in Situ , Colelitiasis , Neoplasias de la Vesícula Biliar , Humanos , Relevancia Clínica , Metilación de ADN , Epigénesis Genética , Neoplasias de la Vesícula Biliar/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión a Fosfatidiletanolamina
4.
Biotechnol Bioeng ; 120(1): 57-81, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36253930

RESUMEN

In the present time of speedy developments and industrialization, heavy metals are being uncovered in aquatic environment and soil via refining, electroplating, processing, mining, metallurgical activities, dyeing and other several metallic and metal based industrial and synthetic activities. Heavy metals like lead (Pb), mercury (Hg), cadmium (Cd), arsenic (As), Zinc (Zn), Cobalt (Co), Iron (Fe), and many other are considered as seriously noxious and toxic for the aquatic environment, human, and other aquatic lives and have damaging influences. Such heavy metals, which are very tough to be degraded, can be managed by reducing their potential through various processes like removal, precipitation, oxidation-reduction, bio-sorption, recovery, bioaccumulation, bio-mineralization etc. Microbes are known as talented bio-agents for the heavy metals detoxification process and fungi are one of the cherished bio-sources that show noteworthy aptitude of heavy metal sorption and metal tolerance. Thus, the main objective of the authors was to come with a comprehensive review having methodological insights on the novel and recent results in the field of mycoremediation of heavy metals. This review significantly assesses the potential talent of fungi in heavy metal detoxification and thus, in environmental restoration. Many reported works, methodologies and mechanistic sights have been evaluated to explore the fungal-assisted heavy metal remediation. Herein, a compact and effectual discussion on the recent mycoremediation studies of organic pollutants like dyes, petroleum, pesticides, insecticides, herbicides, and pharmaceutical wastes have also been presented.


Asunto(s)
Contaminantes Ambientales , Restauración y Remediación Ambiental , Metales Pesados , Contaminantes del Suelo , Humanos , Contaminantes Ambientales/toxicidad , Metales Pesados/toxicidad , Suelo , Cadmio
5.
Pediatr Dermatol ; 40(4): 669-672, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36724898

RESUMEN

We report a rare case of disseminated cysticercosis in a 7-year-old Indian girl with recent onset seizures treated with antiepileptics for 2 months. When she presented to dermatology clinic, she had multifocal subcutaneous and submucosal nodules. The subsequent diagnostic workup revealed extensive neurocysticercosis as well as orbital and myocysticercosis.


Asunto(s)
Cisticercosis , Neurocisticercosis , Femenino , Humanos , Niño , Cisticercosis/diagnóstico , Cisticercosis/tratamiento farmacológico , Neurocisticercosis/diagnóstico , Neurocisticercosis/tratamiento farmacológico , Convulsiones , Anticonvulsivantes/uso terapéutico , Tejido Subcutáneo
6.
J Allergy Clin Immunol ; 150(6): 1556-1562, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35987349

RESUMEN

BACKGROUND: Newborn screening can identify neonatal T-cell lymphopenia through detection of a low number of copies of T-cell receptor excision circles in dried blood spots collected at birth. After a positive screening result, further diagnostic testing is required to determine whether the subject has severe combined immunodeficiency or other causes of T-cell lymphopenia. Even after thorough evaluation, approximately 15% of children with a positive result of newborn screening for T-cell receptor excision circles remain genetically undiagnosed. Identifying the underlying genetic etiology is necessary to guide subsequent clinical management and family planning. OBJECTIVE: We sought to elucidate the genetic basis of patients with T-cell lymphopenia without an apparent genetic diagnosis. METHODS: We used clinical genomic testing as well as functional and immunologic assays to identify and elucidate the genetic and mechanistic basis of T-cell lymphopenia. RESULTS: We report 2 unrelated individuals with nonsevere T-cell lymphopenia and abnormal T-cell receptor excision circles who harbor heterozygous loss-of-function variants in forkhead box I3 transcription factor (FOXI3). CONCLUSION: Our findings support the notion that haploinsufficiency of FOXI3 results in T-cell lymphopenia with variable expressivity and that FOXI3 may be a key modulator of thymus development.


Asunto(s)
Genómica , Receptores de Antígenos de Linfocitos T , Recién Nacido , Niño , Humanos , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T
7.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35443397

RESUMEN

Cardiovascular disease (CVD) is the supreme cause of morbidity and mortality amid patients with chronic kidney disease (CKD). In spite of alteration for known CAD risk factors, including hypertension & diabetes, mortality risk dynamically intensifying with worsening condition of CKD. CKD is non-communicable disease typically caused by diabetes and hypertension. The extremity of CKD can be proficient by a reasonable serum creatinine-based estimated eGFR, which also indicates excretory kidney function, and elevated urinary albumin measured by the urinary albumin-to-creatinine ratio (ACR), which is a best predictor of kidney damage. MATERIAL: To assess the systolic & diastolic dysfunction in patients with Chronic Kidney Disease (CKD). Fifty patients with CKD were subjected to two-dimensional and M mode echocardiography for determination of systolic and diastolic dysfunction. ECG were performed to detect MI, ischemia, LVH and other cardiovascular abnormality. All patients were evaluated clinically, biochemically and radio logically and were diagnosed as chronic kidney disease (CKD). The left ventricular ejection fraction (LVEF) and fractional shortening (FS) were taken as measures of left ventricular (LV) systolic function. Diastolic function was determined by measuring E/A ratio by spectral Doppler LV inflow velocity. Echocardiographic findings of hypertensive and normotensive patients were compared. OBSERVATION: Out of 50 patients studied, there were 35 males (70%) and 15 females (30%). Hypertension (60%) was leading cause of CKD. Echocardiography showed that left ventricular hypertrophy (LVH) was present in 74%. Systolic dysfunction as measured by reduced fractional shortening (< 25%) and decreased LVEF (< 50%) was present in 8 % and 12 % respectively. Diastolic dysfunction as denoted by E/A ratio of less than 0.75 or more than 1.8 was present in 60 % of patients. Regional wall motion abnormality (RWMA) was present in 12 %. Pericardial effusion was noted in 14 % of patients. Valvular calcification was noted in 8 % of CKD patients. Mean left ventricular internal diameter in diastole was 41 ± 6 mm. Mean Interventricular septum diameters in systole was11.9 ± 1.21 mm. Mean left atrium diameter was 29 ± 4 mm. Normotensive group was compared to hypertensive group. Statistically significant difference was noted in LVH and E/A ratio in hypertensive group as compared to normotensive group. CONCLUSION: We conclude that left ventricular diastolic dysfunction also occurs in patients who having early stage of CKD. But patients with hypertensive CKD had higher prevalence of diastolic and systolic dysfunction as compared to normotensive counterparts.


Asunto(s)
Hipertensión , Insuficiencia Renal Crónica , Disfunción Ventricular Izquierda , Albúminas , Diástole , Femenino , Humanos , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Masculino , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Función Ventricular Izquierda
8.
Future Oncol ; 17(5): 581-596, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33401962

RESUMEN

TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, can induce apoptosis in cancer cells, sparing normal cells when bound to its associated death receptors (DR4/DR5). This unique mechanism makes TRAIL a potential anticancer therapeutic agent. However, clinical trials of recombinant TRAIL protein and TRAIL receptor agonist monoclonal antibodies have shown disappointing results due to its short half-life, poor pharmacokinetics and the resistance of the cancer cells. This review summarizes TRAIL-induced apoptotic and survival pathways as well as mechanisms leading to apoptotic resistance. Recent development of methods to overcome cancer cell resistance to TRAIL-induced apoptosis, such as protein modification, combination therapy and TRAIL-based gene therapy, appear promising. We also discuss the challenges and opportunities in the development of TRAIL-based therapies for the treatment of human cancers.


Asunto(s)
Antineoplásicos/farmacología , Terapia Genética/métodos , Neoplasias/terapia , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Ensayos Clínicos como Asunto , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Humanos , Neoplasias/genética , Neoplasias/patología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/agonistas , Proteínas Recombinantes/uso terapéutico , Transducción de Señal/efectos de los fármacos , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/uso terapéutico , Resultado del Tratamiento
9.
Nutr J ; 20(1): 51, 2021 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-34092255

RESUMEN

BACKGROUND: Children with severe acute malnutrition (SAM) have inadequate levels of fatty acids (FAs) and limited capacity for enteral nutritional rehabilitation. We hypothesized that topical high-linoleate sunflower seed oil (SSO) would be effective adjunctive treatment for children with SAM. METHODS: This study tested a prespecified secondary endpoint of a randomized, controlled, unblinded clinical trial with 212 children with SAM aged 2 to 24 months in two strata (2 to < 6 months, 6 to 24 months in a 1:2 ratio) at Dhaka Hospital of icddr,b, Bangladesh between January 2016 and December 2017. All children received standard-of-care management of SAM. Children randomized to the emollient group also received whole-body applications of 3 g/kg SSO three times daily for 10 days. We applied difference-in-difference analysis and unsupervised clustering analysis using t-distributed stochastic neighbor embedding (t-SNE) to visualize changes in FA levels in blood from day 0 to day 10 of children with SAM treated with emollient compared to no-emollient. RESULTS: Emollient therapy led to systematically higher increases in 26 of 29 FAs over time compared to the control. These effects were driven primarily by changes in younger subjects (27 of 29 FAs). Several FAs, especially those most abundant in SSO showed high-magnitude but non-significant incremental increases from day 0 to day 10 in the emollient group vs. the no-emollient group; for linoleic acid, a 237 µg/mL increase was attributable to enteral feeding and an incremental 98 µg/mL increase (41%) was due to emollient therapy. Behenic acid (22:0), gamma-linolenic acid (18:3n6), and eicosapentaenoic acid (20:5n3) were significantly increased in the younger age stratum; minimal changes were seen in the older children. CONCLUSIONS: SSO therapy for SAM augmented the impact of enteral feeding in increasing levels of several FAs in young children. Further research is warranted into optimizing this novel approach for nutritional rehabilitation of children with SAM, especially those < 6 months. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02616289 .


Asunto(s)
Desnutrición Aguda Severa , Adolescente , Bangladesh , Niño , Preescolar , Emolientes , Ácidos Grasos , Humanos , Lactante , Aceite de Girasol
10.
J Contemp Dent Pract ; 22(2): 172-178, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34257178

RESUMEN

AIM: To compare the dimensional accuracy of polyether, polyvinyl siloxane, and polyether polyvinyl siloxane hybrid impression materials using closed tray, open tray splinted, and open tray nonsplinted coping impression techniques and to find out the best suitable impression material and technique combination for implant impressions. MATERIALS AND METHODS: The sample size of the study was 45. The combinations of materials and techniques were divided into nine groups, namely polyvinyl siloxane with closed tray, polyvinyl siloxane with open tray nonsplinted copings, polyvinyl siloxane with open tray splinted copings, polyether with closed tray, polyether with open tray nonsplinted copings, polyether with open tray splinted copings, polyvinyl siloxane-polyether hybrid with closed tray, polyvinyl siloxane-polyether hybrid with open tray nonsplinted copings, and polyvinyl siloxanepolyether hybrid with open tray splinted copings. Five samples of each group were evaluated. A total of 45 impressions were taken. A stainless steel master metal framework with three internal hex implants was fabricated and used to generate the samples. A common condensation silicone putty spacer was applied over the impression copings attached to the implants, which was then duplicated. All trays were fabricated on this duplicated silicone die using light cure acrylic resin. Trays to be used for open tray techniques had their top removed for gaining access to screws of the impression copings. Splinting of coping for OS group was done using pattern resin. Impressions were poured, and master cast was generated. Interimplant distance was measured using stereomicroscope and an image analyzing software. RESULTS: Open nonsplinted technique resulted in significantly better replication of implant positions compared to open splinted and closed techniques. Hybrid impression material depicted significantly better dimensional accuracy than polyether and polyvinyl siloxane. Hybrid open nonsplinted depicted least mean difference in interimplant distance, followed by hybrid open splinted and polyether open splinted groups. Polyvinyl siloxane closed tray showed maximum difference in interimplant distance in comparison with other groups. CONCLUSION: Polyvinyl siloxane-polyether hybrid impression material and open nonsplinted technique gave best replication of implant positions on the master cast. CLINICAL SIGNIFICANCE: Accuracy of impressions and casts is of great importance for the fabrication and long-term clinical success of precisely fitting implant-retained prostheses.


Asunto(s)
Implantes Dentales , Técnica de Impresión Dental , Resinas Acrílicas , Materiales de Impresión Dental , Modelos Dentales
11.
Kidney Int ; 98(6): 1578-1588, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32619496

RESUMEN

When multiple living donor candidates come forward to donate a kidney to the same recipient, some living donor programs evaluate one candidate at a time to avoid unnecessary evaluations. Evaluating multiple candidates concurrently rather than sequentially may be cost-effective from a societal perspective if it reduces the time recipients spend on dialysis. We used a simple decision tree to estimate the cost-effectiveness of evaluating two to four candidates simultaneously rather than sequentially as potential kidney donors for the same intended recipient. Evaluating two donor candidates simultaneously cost $1,266 (CAD) more than if they were evaluated sequentially, but living donation occurred one month earlier. This translated into $6,931 in averted dialysis costs and a total cost-savings of $5,665 per intended recipient. Simultaneous evaluations also resulted in one percent more living donor transplants and overall gains in quality-of-life as recipients spent less time on dialysis. If recipients were free from dialysis at the start of donor candidate evaluations, simultaneous evaluations also reduced the rate of dialysis initiation by two percent. Benefits were also observed in the three- and four-candidate scenarios. Thus, living donor programs should consider evaluating up to four living donor candidates simultaneously when they come forward for the same recipient as health care system costs incurred are more than offset by avoided dialysis costs.


Asunto(s)
Trasplante de Riñón , Donadores Vivos , Análisis Costo-Beneficio , Humanos , Riñón , Trasplante de Riñón/economía , Diálisis Renal
12.
Invest New Drugs ; 38(4): 934-945, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-31432292

RESUMEN

In our previous study, we screened the anti-cancer properties of 10 benzothiazole derivatives in cervical cancer cell lines. In the present study, we aimed to delineate the mechanism of the apoptotic pathway (whether intrinsic or extrinsic) following the treatment of N-(4-(benzo[d]thiazol-2-yl)phenyl)-5-chloro-2-methoxybenzamide (named as A-07) on cervical cancer cell lines. Cellular stress by reactive oxygen species was measured using DCFDA dye by flowcytometry. Protein expression and localization was checked by immunofluorescence for γH2A.X, TP53, and CASP-3. Expression profiles of BAX and BCL-2 was done by semi-quantitative RT-PCR and PARP-1 (Poly(ADP-ribose) polymerase-1) by Western blot analysis. Bioinformatic studies were done using PDB websites, metaPocket 2.0 server, YASARA software and Discovery Studio 3.5 Visualizer. We demonstrate that the compound A-07 leads to ROS generation and double strand breaks in SiHa and C-33A cells. The induction of apoptosis in SiHa cells is associated with increased nuclear expression of the tumor suppressor protein, TP53. The shift in BAX/BCL-2 ratio, increased expression of Caspase-3 and cleaved Poly(ADP-ribose) polymerase-1 favour apoptotic signal in SiHa. In silico studies revealed that A-07 has inhibiting capabilities to the E6/E6AP/P53 complex. Our data suggest that treatment of A-07 causes p53 and caspase dependent apoptosis in HPV 16 infected SiHa cells.


Asunto(s)
Amidas/farmacología , Antineoplásicos/farmacología , Benzotiazoles/farmacología , Papillomavirus Humano 16 , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular Tumoral , Daño del ADN , Femenino , Humanos , Proteínas Oncogénicas Virales/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Especies Reactivas de Oxígeno/metabolismo , Proteínas Represoras/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virología
13.
Emerg Infect Dis ; 25(10): 1962-1964, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31538924

RESUMEN

We describe a case of hantavirus pulmonary syndrome in a patient exposed to Sin Nombre virus in a coastal county in California, USA, that had no previous record of human cases. Environmental evaluation coupled with genotypic analysis of virus isolates from the case-patient and locally trapped rodents identified the likely exposure location.


Asunto(s)
Síndrome Pulmonar por Hantavirus/epidemiología , Virus Sin Nombre , Adulto , Animales , California/epidemiología , Vectores de Enfermedades , Humanos , Peromyscus/virología , Filogenia , Roedores/virología , Virus Sin Nombre/genética
14.
World J Urol ; 37(9): 1965-1972, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30523400

RESUMEN

PURPOSE: The effect of living donor kidney allograft size on recipient outcomes is not well understood. In this study, we sought to investigate the relationship between preoperatively measured donor kidney volume and recipient estimated glomerular filtration rate (eGFR) in living donor kidney transplantation (LDKT). METHODS: We studied computed tomography (CT) donor kidney volumes and recipient outcomes for 438 LDKTs at the Toronto General Hospital between 2007 and 2016. Estimated glomerular filtration rate (eGFR) was calculated at 1, 3, and 6 months and a multivariable linear regression model was fitted to study the effect of donor kidney volume on recipient eGFR. RESULTS: The mean volume and weight of the donated kidneys were 157.3 (± 32.3) cc and 186.7 (± 48.7) g, respectively. Kidney volume was significantly associated with eGFR on multivariable analysis (P < 0.001). Specifically, for every 10 cc increase in kidney volume, there was a 1.68 mL/min, 1.25 mL/min and 0.97 mL/min rise in recipient eGFR at 1, 3, and 6 months, respectively. CONCLUSIONS: Donor kidney volume is a strong independent predictor of recipient eGFR in LDKT, and therefore, may be a valuable addition to predictive models of eGFR after transplant. Further research may determine if the inclusion of donor kidney volume in matching algorithms can improve recipient outcomes.


Asunto(s)
Tasa de Filtración Glomerular , Trasplante de Riñón , Riñón/anatomía & histología , Riñón/diagnóstico por imagen , Nefrectomía , Tomografía Computarizada por Rayos X , Adulto , Femenino , Humanos , Riñón/fisiología , Donadores Vivos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Recolección de Tejidos y Órganos
15.
Diabetes Obes Metab ; 21(6): 1388-1398, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30761725

RESUMEN

AIMS: To examine the relationship between normal plasma uric acid (PUA) levels, renal haemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of type 1 diabetes (T1D) durations in adolescents, young adults and older adults. MATERIALS AND METHODS: PUA, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), and plasma renin and aldosterone were measured during a euglycaemic clamp in people with T1D: 27 adolescents (mean ± SD age 16.8 ± 1.9 years), 52 young adults (mean ± SD age 25.6 ± 5.5 years) and 66 older adults (mean ± SD age 65.7 ± 7.5 years). RESULTS: PUA was highest in patients with the longest T1D duration: 197 ± 44 µmol/L in adolescents versus 264 ± 82 µmol/L in older adults (P < 0.001). Higher PUA correlated with lower GFR only in older adults, even after correcting for age, glycated haemoglobin and sex (ß = -2.12 ± 0.56; P = 0.0003), but not in adolescents or young adults. Higher PUA correlated with lower carotid AIx (ß = -1.90, P = 0.02) in adolescents. In contrast, PUA correlated with higher cfPWV (P = 0.02) and higher plasma renin (P = 0.01) in older adults with T1D. CONCLUSIONS: The relationship between higher PUA with lower GFR, increased arterial stiffness and renin angiotensin aldosterone system (RAAS) activation was observed only in older adults with longstanding T1D. T1D duration may modify the association between PUA, renal haemodynamic function and RAAS activation, leading to renal vasoconstriction and ischaemia. Further work must determine whether pharmacological PUA-lowering prevents or reverses injurious haemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes.


Asunto(s)
Diabetes Mellitus Tipo 1 , Riñón , Ácido Úrico/sangre , Rigidez Vascular/fisiología , Adolescente , Adulto , Factores de Edad , Anciano , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Tasa de Filtración Glomerular/fisiología , Hemodinámica/fisiología , Humanos , Riñón/irrigación sanguínea , Riñón/fisiología , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Estudios Retrospectivos , Adulto Joven
16.
Diabetes Obes Metab ; 21(3): 575-583, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30311395

RESUMEN

OBJECTIVE: Our aim was to define the relationships between plasma biomarkers of kidney injury and intrarenal haemodynamic function (glomerular filtration rate [GFR], effective renal plasma flow [ERPF], renal vascular resistance [RVR]) in adults with type 1 diabetes (T1D). METHODS: The study sample comprised patients with longstanding T1D (duration ≥50 years), among whom 44 were diabetic kidney disease (DKD) resistors (eGFR >60 mL/min/1.73 m2 and <30 mg/d urine albumin excretion) and 22 had DKD, in addition to 73 control participants. GFRINULIN and ERPFPAH were measured, RVR was calculated, and afferent (RA )/efferent (RE ) areteriolar resistances were derived from Gomez equations. Plasma neutrophil gelatinase-associated lipocalin (NGAL), ß2 microglobulin (B2M), osteopontin (OPN) and uromodulin (UMOD) were measured using immunoassay kits from Meso Scale Discovery. RESULTS: Plasma NGAL, B2M and OPN were higher and UMOD was lower in DKD patients vs DKD resistors and non-diabetic controls. In participants with T1D, plasma NGAL inversely correlated with GFR (r = -0.33; P = 0.006) and ERPF (r = -0.34; P = 0.006), and correlated positively with RA (r = 0.26; P = 0.03) and RVR (r = 0.31; P = 0.01). In participants without T1D, NGAL and B2M inversely correlated with GFR (NGAL r = -0.18; P = 0.13 and B2M r = -0.49; P < 0.0001) and with ERPF (NGAL r = -0.19; P = 0.1 and B2M r = -0.42; P = 0.0003), and correlated positively with RA (NGAL r = 0.19; P = 0.10 and B2M r = 0.3; P = 0.01) and with RVR (NGAL r = 0.20; P = 0.09 and B2M r = 0.34; P = 0.003). Differences were significant after adjusting for age, sex, HbA1c, SBP and LDL. There were statistical interactions between T1D status, B2M and intrarenal haemodynamic function (P < 0.05). CONCLUSIONS: Elevated NGAL relates to intrarenal haemodynamic dysfunction in T1D, whereas elevated NGAL and B2M relate to intrarenal haemodynamic dysfunction in adults without T1D. These data may define a diabetes-specific interplay between tubular injury and intrarenal haemodynamic dysfunction.


Asunto(s)
Biomarcadores/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Nefropatías Diabéticas/diagnóstico , Hemodinámica/fisiología , Riñón/irrigación sanguínea , Riñón/fisiopatología , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Canadá , Estudios de Casos y Controles , Estudios Transversales , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/fisiopatología , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Lipocalina 2/análisis , Lipocalina 2/sangre , Longevidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Flujo Sanguíneo Regional/fisiología , Resistencia Vascular/fisiología , Microglobulina beta-2/análisis , Microglobulina beta-2/sangre
17.
Transpl Int ; 32(10): 1030-1043, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31250484

RESUMEN

Patients from ethnocultural minorities have reduced access to live donor kidney transplant (LDKT). To explore early pretransplant ethnocultural disparities in LDKT readiness, and the impact of the interactions with the transplant program, we assessed if patients had a potential live donor (LD) identified at first pretransplant assessment, and if patients with no LD initially received LDKT subsequently. Single-center, retrospective cohort of adults referred for kidney transplant (KT) assessment. Multivariable logistic regression assessed the association between ethnicity and having a potential LD. Cox proportional hazard analysis assessed the association between no potential LD initially and subsequent LDKT. Of 1617 participants, 66% of Caucasians indicated having a potential LD, compared with 55% of South Asians, 44% of African Canadians, and 41% of East Asians (P < 0.001). In multivariable logistic regression analysis, the odds of having a potential LD identified was significantly lower for African, East and South Asian Canadians. No potential LD at initial KT assessment was associated with lower likelihood of LDKT subsequently (hazard ratio [HR], 0.14; [0.10-0.19]). Compared to Caucasians, African, East and South Asian and African Canadians are less likely to have a potential LD identified at first KT assessment, which predicts a lower likelihood of subsequent LDKT.


Asunto(s)
Trasplante de Riñón/estadística & datos numéricos , Donadores Vivos/estadística & datos numéricos , Grupos Raciales/estadística & datos numéricos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
18.
Healthc Manage Forum ; 32(4): 202-207, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31091997

RESUMEN

The Living Kidney Donation Program at the Toronto General Hospital, University Health Network sought to develop a comprehensive, secure, accurate, and up-to-date information system for the purposes of quality improvement, research, and performance evaluation. The Comprehensive Living Kidney Donor Database (CLiKeD) houses comprehensive demographic, medical, psychosocial, and evaluation data on living kidney donor candidates abstracted from multiple health information sources. Data are routinely audited to ensure high data quality. Over 3,500 living kidney donor candidates are currently included in CLiKeD. The development of this data system will allow for regular performance assessments of the program, implementation of quality improvement initiatives, and the completion of high-impact, clinically relevant research. In addition, the conception and development of CLiKeD has been instrumental in improving documentation of personal health information at the point of care.


Asunto(s)
Bases de Datos Factuales , Almacenamiento y Recuperación de la Información/normas , Trasplante de Riñón , Donadores Vivos , Exactitud de los Datos , Humanos , Mejoramiento de la Calidad
19.
J Exp Ther Oncol ; 12(4): 307-315, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30476387

RESUMEN

OBJECTIVE: Although mucoepidermoid carcinoma is the most common primary malignancy of the salivary glands, the sclerosing morphologic variant of this tumor is extremely rare and only 26 cases have been reported till date in the english literature. This report describes a case involving a 35-year-old female with an intermediate-grade sclerosing mucoepidermoid carcinoma of parotid gland and we review the litreture. Immunohitochemical markers, Her-2/neu and MIB-1 evaluated to help predict the clinical outcome and to determine whether an association exists between the histologic grade and immunohistochemical findings. A PAS stain revealed cytic spaces filled with basophilic material. We found MIB-1 labeling indices of >50% and strong positivity for Her-2/neu suggesting poor prognosis. Our case did not show any correlation between MIB-1 index and tumor grade as shown in other case reports. This unusual but distinctive variant of mucoepidermoid carcinoma can be difficult to recognize and is frequently misdiagnosed as a benign lesion.


Asunto(s)
Carcinoma Mucoepidermoide , Adulto , Productos Biológicos , Femenino , Humanos , Antígeno Ki-67 , Glándula Parótida , Neoplasias de las Glándulas Salivales , Coloración y Etiquetado
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