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1.
Lasers Med Sci ; 38(1): 101, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-37060370

RESUMEN

To evaluate the applicability of photobiomodulation therapy (PBM-T) in the management of xerostomia and OM. Fifty-three patients with head and neck squamous cell carcinoma were randomized into two groups: Sham and PBM-T. The Sham group received artificial saliva and laser simulation, while the PBM-T group received artificial saliva and PBM-T. Xerostomia-related quality of life (QoL), the presence or absence of OM lesions, the decayed-missing-filled teeth (DMFT) index, and periodontal charts were evaluated. The results of the QoL questionnaire, DMFT index, and periodontal chart were analyzed with the Kruskal-Wallis test, followed by the Student-Newman-Keuls test, while OM findings were compared using the Mann-Whitney test. QoL scores significantly increased in the Sham group (p < 0.0001), denoting more severe xerostomia symptoms (p = 0.0074), and decreased in the PBM-T group, indicating no or very mild xerostomia. Higher grades of OM were found in the Sham group than the PBM-T group (p = 0.0001). There was no significant difference in DMFT index or periodontal charts between the groups (p > 0.05). PBM-T improved QoL in patients with head and neck cancer treated with radiotherapy, whether as radiation alone or as an adjunct to chemotherapy and surgery.


Asunto(s)
Neoplasias de Cabeza y Cuello , Terapia por Luz de Baja Intensidad , Estomatitis , Xerostomía , Humanos , Calidad de Vida , Saliva Artificial , Estomatitis/etiología , Estomatitis/radioterapia , Estomatitis/patología , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/radioterapia , Xerostomía/etiología , Xerostomía/radioterapia , Terapia por Luz de Baja Intensidad/métodos
2.
J Clin Pediatr Dent ; 47(6): 38-43, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37997233

RESUMEN

Anxiety is common in pediatric dental care, and affects the behavioral management of children. Animal-assisted therapy (AAT) has been shown to improve children's behavior. However, few studies have applied this technique in dentistry. The aim of the present study was to evaluate the applicability of dog-assisted therapy to control anxiety during pediatric dental treatment. Twenty children were selected from the Pediatric Dentistry Clinic of the Pontifical Catholic University of Campinas (PUC-Campinas), Brazil. Participants were divided into two groups: Control (n = 11; visits = 16), in which children were conditioned by methods routinely used in the clinic; and AAT (n = 9; visits = 23), in which children had contact with a dog therapist first at the reception desk and then again inside the office. The dog therapist stayed beside the dental chair with the child throughout the procedures. Corah's Dental Anxiety Scale (CS) and heart rate (HR) were used for evaluation of child anxiety. The results were tested for normality of distribution with the Shapiro-Wilk method, and subsequently analyzed in BioEstat 5.0. HR results were compared by Analysis of Variance (ANOVA) with Tukey's test, and CS scores, with the Wilcoxon test. There was a significant reduction in HR in the AAT group (p = 0.0069). In the Control group, HR did not change before, during, or after treatment (p = 0.6052). Controls showed a significant increase in anxiety measured by CS before and after treatment (p = 0.0455). In the AAT group, there was no change in CS scores before and after treatment (p = 0.3739). AAT could be an alternative to reduce anxiety during pediatric dental care.


Asunto(s)
Terapia Asistida por Animales , Odontología Pediátrica , Animales , Niño , Humanos , Perros , Ansiedad al Tratamiento Odontológico/prevención & control , Ansiedad/prevención & control , Brasil
3.
J Contemp Dent Pract ; 23(4): 388-392, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35945830

RESUMEN

AIM: To assess dentin-post bond strength and mode of failure through tensile strength testing of two endodontic post systems: CAD/CAM custom-milled fiber posts vs Splendor SAP. MATERIALS AND METHODS: Thirty extracted single-rooted mandibular premolars were sectioned 2 mm coronal to the cementoenamel junction. Root length was standardized at 15 mm, and the root canals were instrumented with #20 K-files followed by 30/0.03 and 30/0.05 ProDesign Logic rotary files, under irrigation with 2.5% NaOCl, and then submitted to final irrigation with 17% EDTA. Canals were filled with gutta-percha and AH PLUS sealer. After 24 hours, the teeth were prepared for post placement to a depth of 10 mm and randomly allocated into two experimental groups (n = 15): CAD/CAM (CC) and Splendor SAP (SS). All posts were cemented with RelyX U200 dual-cure self-adhesive resin cement. The roots were embedded in acrylic resin, and the specimens were stored for 7 days in moist heat (37°C). Tensile strength testing until failure was then performed in a universal testing machine using a crosshead speed of 0.5 mm/minute. The final failure load was tabulated for statistical analysis, and the G test was used to compare the failure modes observed under light microscopy (5× magnification). RESULTS: There was no significant difference between groups regarding tensile bond strength to root dentin (p = 0.325). Conversely, failure mode differed significantly between groups (p = 0.037). CONCLUSION: The tensile bond strength observed for the CAD/CAM and Splendor SAP post systems was similar. Adhesive failure was predominant in both groups; however, the CAD/CAM custom-milled fiber posts failed predominantly at the dentin-resin cement interface, whereas Splendor SAP posts failed mostly at the post-resin cement interface. CLINICAL SIGNIFICANCE: A strong post-dentin bond is a key to the success of dental restorations and prosthetic rehabilitation. In teeth with severe coronal decay and wide canals, both of the tested systems would be able to achieve good cervical fit.


Asunto(s)
Recubrimiento Dental Adhesivo , Técnica de Perno Muñón , Diseño Asistido por Computadora , Cavidad Pulpar , Análisis del Estrés Dental , Dentina , Ensayo de Materiales , Cementos de Resina/química
4.
Lasers Med Sci ; 36(9): 1935-1940, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33786671

RESUMEN

To evaluate the use of cetrimide alone and combined with photodynamic therapy to reduce S. mutans burden in carious lesions. Sixty permanent third molars were sectioned and the coronal dentin exposed. A cariogenic challenge was performed using brain-heart infusion (BHI) medium supplemented and S. mutans ATCC 25175. Specimens were incubated in anaerobic jars at 37 °C for 15 days, with BHI renewed every 24 h. After 15 days, specimens were randomly divided into six groups (n = 10): C, control (no treatment); CHX, application of chlorhexidine 2%; CT, application of cetrimide 2%; CT+aPDT, application of cetrimide 2% followed by methylene blue dye and aPDT (antimicrobial photodynamic therapy: wavelength 660 nm, energy 4J, power 100 mW, spot size 0.0028 cm2, energy density 142 J/cm2 for 40 s); ES+aPDT, application of experimental solution (methylene blue dye with cetrimide) and aPDT; and aPDT alone. Carious tissue from each specimen was collected before and after the applications. Five decimal dilutions were performed, and the resulting solution was seeded in mitis-salivarius-bacitracin agar. Plates were incubated in anaerobic jars at 37 °C for 48 h. Analysis of variance (ANOVA) with post hoc Tukey's test was used to compare total S. mutans counts. Significant reductions in S. mutans were observed after application of CT+aPDT (0.30 (0.97), p < 0.0001) and ES+aPDT (0.52 (1.13), p < 0.0001). Cetrimide 2% with methylene blue dye, applied consecutively or as a mixture, can be used as a photosensitizing agent for aPDT to reduce S. mutans burden in dentinal caries.


Asunto(s)
Caries Dental , Fotoquimioterapia , Cetrimonio , Caries Dental/tratamiento farmacológico , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Streptococcus mutans
5.
Bioorg Med Chem Lett ; 30(19): 127454, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32736078

RESUMEN

Prostate cancer is an important cause of death in the male population and for which there is no satisfactory chemotherapy. Herein a new series of chalcone hybrids containing 2H-1,2,3-triazole core as the ring B has been synthesized and evaluated in vitro against PC-3 prostate cancer cell line. Compounds 4a, 4c and 4e significantly reduced cell viability and showed IC50 of 28.55, 15.64 and 25.56 µM, respectively. The structure-activity relationship supported by computational chemistry points that the polarity of the molecular surface area should have some relevance to the efficiency of the compounds, in particular the ratio of the partial positive charge sites and the total molecular surface area exposed to the cell environment.


Asunto(s)
Antineoplásicos/farmacología , Chalconas/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Triazoles/farmacología , Antineoplásicos/síntesis química , Chalconas/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Masculino , Estructura Molecular , Células PC-3 , Relación Estructura-Actividad Cuantitativa , Triazoles/síntesis química
6.
Pediatr Nephrol ; 35(5): 815-827, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31845056

RESUMEN

BACKGROUND: Arterial stiffness is associated with an increased risk of cardiovascular diseases. Augmentation index (AIx@75), a measure of arterial stiffness and wave reflection, has not been evaluated in patients with primary nephrotic syndrome (PNS). We investigated whether central and peripheral vascular profiles, hemodynamic parameters, and biochemical tests are associated with AIx@75 in PNS patients. METHODS: This observational study involved 38 children and adolescents with PNS (12.14 ± 3.65 years) and 37 healthy controls (13.28 ± 2.80 years). Arterial stiffness and vascular and hemodynamic parameters were measured noninvasively using the Mobil-O-Graph® (IEM, Stolberg, Germany). In the PNS group, biochemical tests and corticosteroid dosage/treatment time were analyzed. RESULTS: Peripheral and central systolic blood pressure (SBPp, SBPc) Z-scores were significantly higher in the PNS patients. AIx@75 was significantly higher in the PNS patients (25.14 ± 9.93%) than in controls (20.84 ± 7.18%). In the control group, AIx@75 negatively correlated with weight (r = - 0.369; p = 0.025), height (r = - 0.370; p = 0.024), and systolic volume/body surface (r = - 0.448; p = 0.006). In the PNS group, a univariate linear correlation showed that AIx@75 negatively correlated with weight (r = - 0.360; p = 0.027), height (r = 0.381; p = 0.18), and systolic volume/body surface (r = - 0.447; p < 0.002) and positively with the Z-score of SBPp (r = 0.407; p = 0.011), peripheral diastolic blood pressure (DBPp, r = 0.452; p = 0.004), SBPc (r = 0.416; p = 0.009), DBPc (r = 0.407; p = 0.011), triglycerides (r = 0.525; p = 0.001), and cholesterol [total (r = 0.539; p < 0.001), LDLc (r = 0.420; p = 0.010), and non-HDLc (r = 0.511; p = 0.001)]. CONCLUSIONS: Early abnormalities of AIx@75 and vascular parameters suggest that patients with PNS, even in stable condition, present subclinical indicators for the development of cardiovascular disease.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Glucocorticoides/administración & dosificación , Síndrome Nefrótico/complicaciones , Adolescente , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Niño , Estudios Transversales , Relación Dosis-Respuesta a Droga , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/fisiopatología , Síndrome Nefrótico/orina , Análisis de la Onda del Pulso , Medición de Riesgo/métodos , Factores de Riesgo , Rigidez Vascular/fisiología
7.
Bioorg Med Chem Lett ; 29(9): 1094-1098, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30833107

RESUMEN

Human kallikreins 5 and 7 (KLK5 and KLK7) exhibit trypsin- and chymotrypsin-like activities and are involved in pathologies related to skin desquamation process. A series of new 3-acyltetramic acids were developed as a novel class of inhibitors of KLK5, KLK7 and trypsin enzymes. The nature and length of the acyl chain is crucial to the KLK5, KLK7 and trypsin inhibition activities, and the most potent compounds (but not the most selective) 2b, 2c and 2g showed low micromolar IC50 values. While very few of the compounds were selective for KLK5, the selective inhibition of trypsin against chymotrypsin was achieved. Our molecular modelling studies revealed that the double bond in 2g provided the best fit in the binding site of KLK5, while the hydrogen bonding interactions modulated the best fit of 2c in the binding site of KLK7 due to the hydrophobicity of the cavity.


Asunto(s)
Calicreínas/antagonistas & inhibidores , Pirrolidinonas/química , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Calicreínas/química , Modelos Moleculares , Simulación del Acoplamiento Molecular , Conformación Proteica , Relación Estructura-Actividad
8.
Pediatr Nephrol ; 34(2): 283-294, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30196383

RESUMEN

BACKGROUND: Posterior urethral valves (PUVs) are associated with severe consequences to the urinary tract and are a common cause of chronic kidney disease (CKD). The aim of this study was to develop clinical predictive model of CKD in a cohort of patients with PUVs. METHODS: In this retrospective cohort study, 173 patients with PUVs were systematically followed up at a single tertiary unit. The primary endpoint was CKD ≥ stage 3. Survival analyses were performed by Cox regression proportional hazard models with time-fixed and time-dependent covariables. RESULTS: Mean follow-up time was 83 months (SD, 70 months). Sixty-five children (37.6%) developed CKD stage ≥ 3. After adjustment by the time-dependent Cox model, baseline creatinine, nadir creatinine, hypertension, and proteinuria remained as predictors of the endpoint. After adjustment by time-fixed model, three variables were predictors of CKD ≥ stage 3: baseline creatinine, nadir creatinine, and proteinuria. The prognostic risk score was divided into three categories: low-risk (69 children, 39.9%), medium-risk (45, 26%), and high-risk (59, 34.1%). The probability of CKD ≥ stage 3 at 10 years age was estimated as 6%, 40%, and 70% for patients assigned to the low-risk, medium-risk, and high-risk groups, respectively (P < 0.001). The main limitation was the preclusion of some relevant variables, especially bladder dysfunction, that might contribute to a more accurate prediction of renal outcome. CONCLUSION: The model accurately predicts the risk of CKD in PUVs patients. This model could be clinically useful in applying timely intervention and in preventing the impairment of renal function.


Asunto(s)
Modelos Biológicos , Insuficiencia Renal Crónica/epidemiología , Uretra/anomalías , Obstrucción Uretral/complicaciones , Preescolar , Progresión de la Enfermedad , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/etiología , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Análisis de Supervivencia , Obstrucción Uretral/congénito , Obstrucción Uretral/mortalidad
9.
Pediatr Nephrol ; 34(3): 465-474, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30324507

RESUMEN

BACKGROUND: Solitary functioning kidney (SFK) is an important condition in the spectrum of congenital anomalies of the kidney and urinary tract. The aim of this study was to describe the risk factors for renal injury in a cohort of patients with congenital SFK. METHODS: In this retrospective cohort study, 162 patients with SFK were systematically followed up (median, 8.5 years). The primary endpoint was time until the occurrence of a composite event of renal injury, which includes proteinuria, hypertension, and chronic kidney disease (CKD). A predictive model was developed using Cox proportional hazards model and evaluated by c statistics. RESULTS: Among 162 children with SFK included in the analysis, 132 (81.5%) presented multicystic dysplastic kidney, 20 (12.3%) renal hypodysplasia, and 10 (6.2%) unilateral renal agenesis. Of 162 patients included in the analysis, 10 (6.2%) presented persistent proteinuria, 11 (6.8%) had hypertension, 9 (5.6%) developed CKD stage ≥ 3, and 18 (11%) developed the composite outcome. After adjustment by the Cox model, three variables remained as independent predictors of the composite event: creatinine (HR, 3.93; P < 0.001), recurrent urinary tract infection (UTI) (HR, 5.05; P = 0.002), and contralateral renal length at admission (HR, 0.974; P = 0.002). The probability of the composite event at 10 years of age was estimated as 3%, 11%, and 56% for patients assigned to the low-risk, medium-risk, and high-risk groups, respectively (P < 0.001). CONCLUSION: Our findings have shown an overall low risk of renal injury for most of infants with congenital SFK. Nevertheless, our prediction model enabled the identification of a subgroup of patients with an increased risk of renal injury over time.


Asunto(s)
Modelos Biológicos , Nomogramas , Proteinuria/diagnóstico , Insuficiencia Renal Crónica/diagnóstico , Riñón Único/complicaciones , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Humanos , Incidencia , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Proteinuria/epidemiología , Proteinuria/etiología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Riñón Único/congénito , Riñón Único/mortalidad , Riñón Único/fisiopatología
10.
Lasers Med Sci ; 34(2): 305-309, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30027423

RESUMEN

The study aims to assess the utility of dental acid etchant containing 37% phosphoric acid and methylene blue dye (DAE) as a sensitizing agent for photodynamic therapy (PDT) to reduce Streptococci mutans in dentinal caries. Forty-five permanent third molars were sectioned and the coronal dentin exposed. A cariogenic challenge was performed using brain-heart infusion (BHI) supplemented with 0.5% yeast extract, 1% glucose, 1% sucrose, and S. mutans ATCC 25175 standardized to 0.5 McFarland turbidity. Specimens were incubated in anaerobic jars at 37 °C for 15 days. During this period, BHI broth was renewed every 24 h. After 15 days, specimens were randomly divided into three groups (n = 15): DAE, application of dental acid etchant containing 37% phosphoric acid and methylene blue dye for 15 s; LLL, application of low-level laser (wavelength 660 nm, energy 4 J/cm2, power 5 W) for 15 s; and PDT, application of DAE for 15 s followed by LLL irradiation (660 nm, 4 J/cm2, 5 W). Carious tissue from each specimen was collected before and after the applications. Five decimal dilutions were performed and the resulting solution was seeded in mitis-salivarius-bacitracin agar. Plates were incubated in anaerobic jars at 37 °C for 48 h. Analysis of variance (ANOVA) with post hoc Tukey's test was used to compare total S. mutans counts. Significant reductions in S. mutans were observed after DAE application (40.70%, p < 0.0001), LLL (12.35%, p = 0.0036), and PDT (55.22%, p < 0.0001). Dental acid etchant containing 37% phosphoric acid and methylene blue dye can be used as a photosensitizing agent for PDT to reduce S. mutans burden in dentinal caries.


Asunto(s)
Grabado Ácido Dental , Caries Dental/tratamiento farmacológico , Caries Dental/microbiología , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Streptococcus mutans/efectos de los fármacos , Recuento de Colonia Microbiana , Humanos , Luz , Streptococcus mutans/crecimiento & desarrollo , Streptococcus mutans/efectos de la radiación
11.
Drug Dev Ind Pharm ; 44(9): 1498-1505, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29683352

RESUMEN

Losartan (Los), a non-peptidic orally active agent, reduces arterial pressure through specific and selective blockade of angiotensin II receptor AT1. However, this widely used AT1 antagonist presents low bioavailability and needs once or twice a day dosage. In order to improve its bioavailability, we used the host: guest strategy based on ß-cyclodextrin (ßCD). The results suggest that Los included in ßCD showed a typical pulsatile release pattern after oral administration to rats, with increasing the levels of plasma of Los. In addition, the inclusion compound presented oral efficacy for 72 h, in contrast to Los alone, which shows antagonist effect for only 6 h. In transgenic (mREN2)L27 rats, the Los/ßCD complex reduced blood pressure for about 6 d, whereas Los alone reduced blood pressure for only 2 d. More importantly, using this host: guest strategy, sustained release of Los for over a week via the oral route can be achieved without the need for encapsulation in a polymeric carrier. The proposed preformulation increased the efficacy reducing the dose or spacing between each dose intake.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/química , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Receptor de Angiotensina Tipo 1/metabolismo , Administración Oral , Animales , Antihipertensivos/química , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Química Farmacéutica/métodos , Portadores de Fármacos/química , Losartán , Masculino , Polímeros/química , Ratas , Ratas Transgénicas , Ratas Wistar , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacología
12.
Bioorg Med Chem Lett ; 27(2): 314-318, 2017 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-27914800

RESUMEN

Human kallikrein 1 (KLK1) is the most extensively studied member of this family and plays a major role in inflammation processes. From Ugi multicomponent reactions, isomannide-based peptidomimetic 10 and 13 where synthesized and showed low micromolar values of IC50 for KLK1 The most active compound (10) presented competitive mechanism, with three structural modifications important to interact with active site residues which corroborates its KLK1 inhibition. Finally, the most active compound also showed good ADMET profile, which indicates compound 10 as a potential hit in the search for new KLK1 inhibitors with low side effects.


Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Descubrimiento de Drogas , Inhibidores Enzimáticos/farmacología , Calicreínas/antagonistas & inhibidores , Peptidomiméticos/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Calicreínas/metabolismo , Modelos Moleculares , Estructura Molecular , Peptidomiméticos/síntesis química , Peptidomiméticos/química , Relación Estructura-Actividad
13.
Bioorg Med Chem Lett ; 27(16): 3661-3665, 2017 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-28729054

RESUMEN

Hepatitis C infection is a cause of chronic liver diseases such as cirrhosis and carcinoma. The current therapy for hepatitis C has limited efficacy and low tolerance. The HCV encodes a serine protease which is critical for viral replication, and few protease inhibitors are currently on the market. In this paper, we describe the synthesis and screening of novel isosorbide-based peptidomimetic inhibitors, in which the compounds 1d, 1e, and 1i showed significant inhibition of the protease activity in vitro at 100µM. The compound 1e also showed dose-response (IC50=36±3µM) and inhibited the protease mutants D168A and V170A at 100µM, indicating it as a promising inhibitor of the HCV NS3/4A protease. Our molecular modeling studies suggest that the activity of 1e is associated with a change in the interactions of S2 and S4 subsites, since that the increased flexibility favors a decrease in activity against D168A, whereas the appearance of a hydrophobic cavity in the S4 subsite increase the inhibition against V170A strain.


Asunto(s)
Antivirales/química , Hepacivirus/enzimología , Isosorbida/química , Serina Proteasas/química , Inhibidores de Serina Proteinasa/química , Antivirales/síntesis química , Antivirales/farmacología , Sitios de Unión , Dominio Catalítico , Hepacivirus/efectos de los fármacos , Isosorbida/síntesis química , Isosorbida/farmacología , Simulación del Acoplamiento Molecular , Mutación , Peptidomiméticos , Serina Proteasas/genética , Serina Proteasas/metabolismo , Inhibidores de Serina Proteinasa/síntesis química , Inhibidores de Serina Proteinasa/farmacología , Termodinámica , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo
14.
Pediatr Nephrol ; 32(11): 2165-2169, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28799058

RESUMEN

BACKGROUND: The search for risk factors for chronic kidney disease in children with focal segmental glomerulosclerosis (FSGS) is important in defining prognosis and individualized treatment. This study preliminarily investigated whether CD44 immunostaining in glomerular parietal epithelial cells (PECs) is a prognostic marker in pediatric FSGS. METHODS: In this retrospective study, 26 patients with FSGS, biopsied from 1985 to 2010, were evaluated. Immunohistochemistry for CD44 was performed in all cases. For analysis purposes, patients were grouped according to whether or not they were positive for CD44 in PECs. The primary outcome was a decline in baseline estimated glomerular filtration rate (eGFR) of 50% or more. RESULTS: Median follow-up was 6.9 years. Median renal survival was 14.5 years and probability of a 50% decline of eGRF was 30% in 10 years. Nine children exhibited the primary outcome and 7 developed end-stage renal disease (ESRD). In comparison with PEC CD44-negative patients (n = 18), PEC CD44-positive patients (n = 8) presented lower baseline eGFR (99 ± 41 versus 141 ± 44 ml/min/1.73 m2, p = 0.035) and a significant decline in eGFR (-38.6 ± 39.5 versus -5.6 ± 25.3 ml/min/1.73 m2/year, p = 0.018). No difference was observed in FSGS subtypes or other glomerular features. Presence of CD44 staining in PECs was significantly associated with the decline in baseline eGFR of 50% or more. Renal survival was significantly reduced in PEC CD44-positive patients (3.8 vs 14.6 years in C4d-negative, p < 0.05). CONCLUSION: Our preliminary findings indicate, for the first time, that positivity for CD44 in PECs seems to be a pathological marker of renal function deterioration in pediatric patients with FSGS.


Asunto(s)
Biomarcadores/metabolismo , Glomeruloesclerosis Focal y Segmentaria/patología , Receptores de Hialuranos/metabolismo , Glomérulos Renales/patología , Adolescente , Niño , Preescolar , Progresión de la Enfermedad , Células Epiteliales/metabolismo , Femenino , Tasa de Filtración Glomerular , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Humanos , Inmunohistoquímica , Fallo Renal Crónico/etiología , Glomérulos Renales/metabolismo , Masculino , Estudios Retrospectivos , Análisis de Supervivencia
15.
Pediatr Nephrol ; 32(7): 1211-1220, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28233100

RESUMEN

BACKGROUND: Data on the risk factors for chronic kidney disease in children with immunoglobulin A nephropathy (IgAN) are scarce. This study was aimed at investigating whether glomerular C4d immunostaining is a prognostic marker in pediatric IgAN. METHODS: In this retrospective cohort study, 47 patients with IgAN biopsied from 1982 to 2010 were evaluated. Immunohistochemistry for C4d was performed in all cases. For analysis, patients were grouped according to positivity or not for C4d in the mesangial area. Primary outcome was a decline in baseline estimated glomerular filtration rate (eGFR) by 50% or more. RESULTS: Median follow-up was 8.3 years. Median renal survival was 13.7 years and the probability of a 50% decline in eGFR was 13% over 10 years. Nine children exhibited the primary outcome and 4 developed end-stage renal disease (ESRD). Compared with C4d-negative patients (n = 37), C4d-positive patients (n = 10) presented higher baseline proteinuria (1.66 ± 0.68 vs 0.47 ± 0.19 g/day/1.73 m2, p < 0.001), a progressive decline in eGFR (−10.04 ± 19.38 vs 1.70 ± 18.51 ml/min/1.73 m2/year; p = 0.045), and more frequently achieved the primary outcome (50.0 vs 10.8%, p = 0.013), and ESRD (30.0 vs 2.7%, p = 0.026). No difference was observed in Oxford classification variables. Baseline proteinuria, endocapillary hypercellularity and mesangial C4d deposition were associated with primary outcome in univariate analysis. Proteinuria and mesangial C4d deposition at baseline independently predicted the decline in eGFR. Renal survival was significantly reduced in C4d-positive patients (8.6 vs 15.1 years in C4d-negative patients, p < 0.001). CONCLUSIONS: In this exclusively pediatric cohort, positivity for C4d in the mesangial area was an independent predictor of renal function deterioration in IgAN.


Asunto(s)
Complemento C4b/análisis , Mesangio Glomerular/patología , Glomerulonefritis por IGA/patología , Fallo Renal Crónico/patología , Fragmentos de Péptidos/análisis , Biomarcadores/análisis , Biomarcadores/metabolismo , Biopsia , Niño , Complemento C4b/metabolismo , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Mesangio Glomerular/metabolismo , Glomerulonefritis por IGA/orina , Humanos , Inmunohistoquímica , Fallo Renal Crónico/orina , Masculino , Fragmentos de Péptidos/metabolismo , Pronóstico , Proteinuria/orina , Estudios Retrospectivos , Factores de Riesgo
16.
Regul Toxicol Pharmacol ; 86: 193-198, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28284712

RESUMEN

This study examined in rats the subchronic toxicity and anti- HSV-1activity after oral administration of dolabelladienetriol (D1), a diterpene isolated from the seaweed Dictyota pfaffii. In subchronic toxicity (SCT) tests, female rats received D1 by gavage 15 mg/kg/day (n = 5) for 50 days, and general behavior, death, hematological, biochemical and histological changes in the liver, kidney, stomach, and duodenum were determined. For the anti-HSV-1 activity, female mice were infected and treated orally with a dose of 20 mg/kg (n = 5) twice a day with D1 and any lesions in the skin were then recorded for 18 days. Dolabelladienetriol in SCT did not significantly change behavior, body weight, hematological or biochemical profiles. The liver and kidneys, however, showed some alterations in rats treated with D1, similar to those in rats treated with ACV, while the other tissues had no significant changes. The anti-HSV-1 activity of D1 had a similar efficacy to the ACV drug control in mice. Our results showed that D1 has potential commercial development as a new HSV-1drug.


Asunto(s)
Antivirales/toxicidad , Herpesvirus Humano 1/efectos de los fármacos , Algas Marinas/química , Animales , Animales de Laboratorio , Femenino , Ratones , Ratas , Ratas Wistar , Pruebas de Toxicidad Subcrónica
17.
Gen Dent ; 65(2): 47-50, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28253182

RESUMEN

This study compared the capacity of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) to that of a combination of lysozyme, lactoferrin, and lactoperoxidase (LLL) in root canal disinfectant for reducing the Streptococcus mutans counts from dentinal caries. Forty human permanent third molars were selected, and flat dentin surfaces were created. Carious lesions were induced using a microbiological model. The specimens were randomly divided into 2 groups (n = 20) according to the type of agent used: group 1, CPP-ACP; group 2, LLL. The S mutans counts were performed before application and after the first, second, and third applications of the agents. The duration of each application was 3 minutes. Carious dentin specimens were homogenized, diluted, and seeded onto mitis salivarius-bacitracin plates for viable counts of S mutans. Results showed that there was no significant reduction in the number of S mutans in group 1 after the applications of CPP-ACP (P > 0.05). In group 2, a significant reduction of S mutans was observed after the third application of LLL (P < 0.01). These results indicate that 3 applications of LLL enzymes can be used to reduce the number of S mutans in dentinal caries lesions.


Asunto(s)
Caseínas/uso terapéutico , Caries Dental/microbiología , Lactoferrina/uso terapéutico , Lactoperoxidasa/uso terapéutico , Muramidasa/uso terapéutico , Streptococcus mutans/efectos de los fármacos , Carga Bacteriana/efectos de los fármacos , Caseínas/farmacología , Caries Dental/tratamiento farmacológico , Quimioterapia Combinada , Humanos , Lactoferrina/administración & dosificación , Lactoferrina/farmacología , Lactoperoxidasa/administración & dosificación , Lactoperoxidasa/farmacología , Muramidasa/administración & dosificación , Muramidasa/farmacología
18.
Inflamm Res ; 65(10): 757-70, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27351940

RESUMEN

BACKGROUND AND AIM: IgA nephropathy is one of the leading causes of primary glomerulonephritis worldwide and an important etiology of renal disease in young adults. IgA nephropathy is considered an immune complex-mediated disease. METHODS: This review article summarizes recent evidence on the pathophysiology of IgA nephropathy. RESULTS: Current studies indicate an ordered sequence of multi-hits as fundamental to disease occurrence. Altered glycan structures in the hinge region of the heavy chains of IgA1 molecules act as auto-antigens, potentially triggering the production of glycan-specific autoantibodies. Recognition of novel epitopes by IgA and IgG antibodies leads to the formation of immune complexes galactose deficient-IgA1/anti-glycan IgG or IgA. Immune complexes of IgA combined with FcαRI/CD89 have also been implicated in disease exacerbation. These nephritogenic immune complexes are formed in the circulation and deposited in renal mesangium. Deposited immune complexes ultimately induce glomerular injury, through the release of pro-inflammatory cytokines, secretion of chemokines and the resultant migration of macrophages into the kidney. The TfR1/CD71 receptor has a pivotal role in mesangial cells. New signaling intracellular mechanisms have also been described. CONCLUSION: The knowledge of the whole pathophysiology of this disease could provide the rational bases for developing novel approaches for diagnosis, for monitoring disease activity, and for disease-specific treatment.


Asunto(s)
Glomerulonefritis por IGA , Animales , Glomerulonefritis por IGA/genética , Glomerulonefritis por IGA/inmunología , Humanos
19.
Nephrology (Carlton) ; 21(12): 995-1002, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27414046

RESUMEN

IgA nephropathy (IgAN) is one of the leading causes of glomerulonephritis characterized by the findings of IgA and IgG immune deposits in the mesangium of kidney biopsies from patients with persistent microscopic haematuria. IgAN is frequently detected among adolescents and young adults. IgAN presents a highly variable course that includes a spectrum from a very mild disease to end-stage renal disease (ESRD). There are several clinical and histological factors that strongly determined the final outcome of patients with IgAN. Pathological variables associated with unfavorable outcomes are mesangial hypercellularity, segmental glomerulosclerosis, endocapillary hypercellularity and interstitial fibrosis/tubular atrophy, according to the Oxford classification. Moreover, some studies also suggest a role for complement activation in the pathogenesis of IgAN. In this regard, staining for C4d may be an independent risk factor for the development of ESRD in IgAN. Despite the growing number of studies assessing IgAN risk factors, this kind of investigation in paediatric patients is still very limited. The aim of this article is to revise pathological markers related to deterioration of renal function in paediatric patients with IgAN, particularly those that can independently affect renal survival.


Asunto(s)
Glomerulonefritis por IGA/patología , Glomeruloesclerosis Focal y Segmentaria/patología , Fallo Renal Crónico/patología , Glomérulos Renales/patología , Adolescente , Factores de Edad , Atrofia , Biomarcadores/análisis , Biopsia , Niño , Activación de Complemento , Complemento C4b/análisis , Progresión de la Enfermedad , Femenino , Fibrosis , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/fisiopatología , Glomeruloesclerosis Focal y Segmentaria/inmunología , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/fisiopatología , Pruebas de Función Renal , Glomérulos Renales/inmunología , Glomérulos Renales/fisiopatología , Masculino , Fragmentos de Péptidos/análisis , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo
20.
J Contemp Dent Pract ; 17(1): 42-8, 2016 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27084862

RESUMEN

AIM: The aim of this study is to evaluate the impact of endodontic retreatment on push-out bond strength and dentin interface of two resin cements used for fiber postcementation during endodontic retreatment. MATERIALS AND METHODS: The root canals of 40 extracted human canines were prepared, obturated and divided into four groups (n = 10). Gutta-percha was partially removed and fiber posts were immediately cemented in groups 1 and 2 using Panavia F with ED Primer and RelyX™ U200, respectively. In groups 3 and 4, the root canal access was sealed with temporary restorative cement, specimens were stored for 30 days, endodontically retreated, and fiber posts were cemented using the resin cements applied to groups 1 and 2, respectively. Push-out tests and scanning electron microscopy analyses of different areas were performed. Data from push-out bond strengths were analyzed by one-way analysis of variance and Tukey's tests. RESULTS: Higher bond strength values were detected in the apical third for group 1 than group 3 (p < 0.05). No differences were observed in other comparisons between the same third of different groups (p > 0.05). Comparisons between different thirds in the same group revealed a higher bond strength in the apical third for group 1. Scanning electron microscopy showed formation of hybrid layer and extensive resin tags in group 1. No hybrid layer was observed in groups 2 and 4. CONCLUSION: Endodontic retreatment had adverse effects on the push-out bond strength and dentinal interface of Panavia F with ED Primer when used for fiber postcementation specifically in the apical third, but not on RelyX™ U200. CLINICAL SIGNIFICANCE: A significant interaction was detected between endodontic retreatment and resin cement, which indicated that endodontic retreatment might adversely affect the push-out bond strength and dentinal interface of Panavia F with ED Primer when used for fiber postcementation specifically in the apical third.


Asunto(s)
Recubrimiento Dental Adhesivo , Técnica de Perno Muñón , Cementos de Resina , Diente Canino , Dentina , Gutapercha , Humanos , Ensayo de Materiales , Retratamiento
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