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1.
Med J Malaysia ; 74(5): 394-399, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31649215

RESUMEN

INTRODUCTION: Diabetic foot infection, a complication that is associated with lower-limb amputation, incurs a huge economic burden to the hospital and health care system of Malaysia. The bacteriological profile of pathogens in diabetic foot infections in Malaysia has been sparsely studied. We investigated the microbiology of diabetic foot infections in patients admitted to the district hospitals on the east coast of Malaysia. METHODS: A retrospective analysis was conducted in three district hospitals (Hospital Kuala Lipis, Hospital Bentong and Hospital Raub) in Malaysia from 1st of January 2016 to 31st December 2016. The clinical specimens were cultured using Clinical and Laboratory Standards Institute (CLSI) guidelines. Antibiotic sensitivity testing to different antibiotics was carried out using the disc diffusion method. RESULT: A total of 188 pathogens were isolated from 173 patients, with an average of 1.09 pathogens per lesion. Majority of the pathogens isolated were gram negative pathogens (73.4%). The most commonly isolated pathogens were Staphylococcus aureus (17.5%). This was followed by Klebsiella spp. (17%), Pseudomonas spp. (15.4%) and Proteus spp. (13.8%). Gram positive pathogens were sensitive to most of the antibiotics tested except penicillin and fusidic acid. Gram negative pathogens were sensitive to all antibiotics tested except ampicillin and amoxicillin/clavulanic acid. Amikacin provide coverage for all gram negative pathogens in DFI. CONCLUSION: For the management of patient with infection in diabetic foot, the choice of antibiotic therapy depends on the sensitivity of the pathogens, the severity of the infection, the patient's allergies history, toxicity and excretion of the antibiotics.


Asunto(s)
Antibacterianos/uso terapéutico , Bacterias/aislamiento & purificación , Infecciones Bacterianas/microbiología , Pie Diabético/microbiología , Hospitales de Distrito/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Asia Sudoriental/epidemiología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Pie Diabético/epidemiología , Farmacorresistencia Bacteriana , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Malasia/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
2.
Am J Hum Genet ; 105(3): 534-548, 2019 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-31422819

RESUMEN

Early-infantile encephalopathies with epilepsy are devastating conditions mandating an accurate diagnosis to guide proper management. Whole-exome sequencing was used to investigate the disease etiology in four children from independent families with intellectual disability and epilepsy, revealing bi-allelic GOT2 mutations. In-depth metabolic studies in individual 1 showed low plasma serine, hypercitrullinemia, hyperlactatemia, and hyperammonemia. The epilepsy was serine and pyridoxine responsive. Functional consequences of observed mutations were tested by measuring enzyme activity and by cell and animal models. Zebrafish and mouse models were used to validate brain developmental and functional defects and to test therapeutic strategies. GOT2 encodes the mitochondrial glutamate oxaloacetate transaminase. GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. GOT2, a member of the malate-aspartate shuttle, plays an essential role in the intracellular NAD(H) redox balance. De novo serine biosynthesis was impaired in fibroblasts with GOT2 mutations and GOT2-knockout HEK293 cells. Correcting the highly oxidized cytosolic NAD-redox state by pyruvate supplementation restored serine biosynthesis in GOT2-deficient cells. Knockdown of got2a in zebrafish resulted in a brain developmental defect associated with seizure-like electroencephalography spikes, which could be rescued by supplying pyridoxine in embryo water. Both pyridoxine and serine synergistically rescued embryonic developmental defects in zebrafish got2a morphants. The two treated individuals reacted favorably to their treatment. Our data provide a mechanistic basis for the biochemical abnormalities in GOT2 deficiency that may also hold for other MAS defects.


Asunto(s)
Alelos , Ácido Aspártico/metabolismo , Encefalopatías/genética , Proteínas de Unión a Ácidos Grasos/genética , Malatos/metabolismo , Mutación , Animales , Niño , Preescolar , Femenino , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Masculino , Ratones , Secuenciación del Exoma
3.
Biochim Biophys Acta Gen Subj ; 1863(6): 1088-1097, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30928491

RESUMEN

BACKGROUND: Pyridoxal 5'-phosphate (PLP) is the active form of vitamin B6. Mammals cannot synthesize vitamin B6, so they rely on dietary uptake of the different B6 forms, and via the B6 salvage pathway they interconvert them into PLP. Humans possess three enzymes in this pathway: pyridoxal kinase, pyridox(am)ine phosphate oxidase and pyridoxal phosphatase. Besides these, a fourth enzyme has been described in plants and yeast but not in humans: pyridoxal reductase. METHODS: We analysed B6 vitamers in remnant CSF samples of PLP-treated patients and four mammalian cell lines (HepG2, Caco2, HEK293 and Neuro-2a) supplemented with PL as the sole source of vitamin B6. RESULTS: Strong accumulation of pyridoxine (PN) in CSF of PLP-treated patients was observed, suggesting the existence of a PN-forming enzyme. Our in vitro studies show that all cell lines reduce PL to PN in a time- and dose-dependent manner. We compared the amino acid sequences of known PL reductases to human sequences and found high homology for members of the voltage-gated potassium channel beta subunits and the human aldose reductases. Pharmacological inhibition and knockout of these proteins show that none of the candidates is solely responsible for PL reduction to PN. CONCLUSIONS: We show evidence for the presence of PL reductase activity in humans. Further studies are needed to identify the responsible protein. GENERAL SIGNIFICANCE: This study expands the number of enzymes with a role in B6 salvage pathway. We hypothesize a protective role of PL reductase(s) by limiting the intracellular amount of free PL and PLP.


Asunto(s)
Oxidorreductasas de Alcohol/metabolismo , Vitamina B 6 , Células CACO-2 , Células HEK293 , Células Hep G2 , Humanos , Piridoxina/metabolismo , Vitamina B 6/farmacocinética , Vitamina B 6/farmacología
4.
Inflamm Bowel Dis ; 24(4): 849-860, 2018 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-29562271

RESUMEN

Background: Vedolizumab is approved for moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). We present prospective, 1-year data of the real-world effectiveness and safety of vedolizumab in inflammatory bowel disease. Methods: Consecutive patients receiving vedolizumab for treatment of UC or CD with at least 14 weeks of follow-up, regardless of outcome, were included. Patients had clinical activity scores (Harvey-Bradshaw Index [HBI] or Simple Clinical Colitis Activity Index [SCCAI]) and inflammatory markers prospectively measured at baseline and weeks 14, 30, and 52. Clinical response was defined as a reduction ≥3 in HBI or SCCAI, clinical remission as HBI ≤4 or SCCAI ≤2, steroid-free remission as clinical remission without the need for corticosteroids, and mucosal healing (assessed at 6 months) as a Mayo endoscopic subscore of 0 or 1 or CD-SES <3. Results: A total of 132 patients were included: 61 (45%) male, 94 (71%) with CD, 42 (29%) with UC; 22% and 34% of CD and UC patients, respectively, achieved steroid-free remission by week 14. This increased to 31% in CD patients and plateaued at 35% in UC patients at 12 months. Increasing remission rates to 6 months were seen in patients with CD, but minimal improvements after 3 months of therapy occurred in those with UC. Mucosal healing was achieved in 52% of UC and 30% of CD patients. Most adverse events were minor; 74% remained on vedolizumab at 12 months. Conclusions: In this real-world study, vedolizumab demonstrated similar efficacy and safety seen in pivotal trials, with sustained clinical response in the majority of patients. Similar rates of response were seen in UC and CD patients. 10.1093/ibd/izx067_video1izx067_Video5754037470001.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Cicatrización de Heridas/efectos de los fármacos , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Terapia Biológica/efectos adversos , Biomarcadores/metabolismo , Proteína C-Reactiva/metabolismo , Chicago , Esquema de Medicación , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Inducción de Remisión
5.
J Inherit Metab Dis ; 40(6): 883-891, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28801717

RESUMEN

Pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor in numerous enzyme reactions. PLP deficiency in brain, either genetic or acquired, results in severe drug-resistant seizures that respond to vitamin B6 supplementation. The pathogenesis of vitamin B6 deficiency is largely unknown. To shed more light on the metabolic consequences of vitamin B6 deficiency in brain, we performed untargeted metabolomics in vitamin B6-deprived Neuro-2a cells. Significant alterations were observed in a range of metabolites. The most surprising observation was a decrease of serine and glycine, two amino acids that are known to be elevated in the plasma of vitamin B6 deficient patients. To investigate the cause of the low concentrations of serine and glycine, a metabolic flux analysis on serine biosynthesis was performed. The metabolic flux results showed that the de novo synthesis of serine was significantly reduced in vitamin B6-deprived cells. In addition, formation of glycine and 5-methyltetrahydrofolate was decreased. Thus, vitamin B6 is essential for serine de novo biosynthesis in neuronal cells, and serine de novo synthesis is critical to maintain intracellular serine and glycine. These findings suggest that serine and glycine concentrations in brain may be deficient in patients with vitamin B6 responsive epilepsy. The low intracellular 5-mTHF concentrations observed in vitro may explain the favourable but so far unexplained response of some patients with pyridoxine-dependent epilepsy to folinic acid supplementation.


Asunto(s)
Serina/metabolismo , Vitamina B 6/metabolismo , Encéfalo/metabolismo , Células Cultivadas , Glicina/sangre , Glicina/metabolismo , Humanos , Fosfato de Piridoxal/sangre , Fosfato de Piridoxal/metabolismo , Piridoxina/sangre , Serina/sangre , Vitamina B 6/sangre , Deficiencia de Vitamina B 6/sangre , Deficiencia de Vitamina B 6/metabolismo
6.
Neurosci Lett ; 638: 12-20, 2017 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-27919712

RESUMEN

A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-ß (Aß) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities. In the present report, we investigated whether extracts derived from two ubiquitous Mediterranean plants namely, the prickly pear Opuntia ficus-indica (EOFI) and the brown alga Padina pavonica (EPP) alleviate neurodegenerative phenotypes in yeast (Saccharomyces cerevisiae) and fly (Drosophila melanogaster) models of AD and PD. Pre-treatment with EPP or EOFI in the culture medium significantly improved the viability of yeast expressing the Arctic Aß42 (E22G) mutant. Supplementing food with EOFI or EPP dramatically ameliorated lifespan and behavioural signs of flies with brain-specific expression of wild-type Aß42 (model of late-onset AD) or the Arctic Aß42 variant (model of early-onset AD). Additionally, we show that either extract prolonged the survival of a PD fly model based on transgenic expression of the human α-syn A53T mutant. Taken together, our findings suggest that the plant-derived extracts interfere with shared mechanisms of neurodegeneration in AD and PD. This notion is strengthened by evidence demonstrating that EOFI and to a greater extent EPP, while strongly inhibiting the fibrillogenesis of both Aß42 and α-syn, accumulate remodelled oligomeric aggregates that are less effective at disrupting lipid membrane integrity. Our work therefore opens new avenues for developing therapeutic applications of these natural plant extracts in the treatment of amyloidogenic neurodegenerative disorders.


Asunto(s)
Enfermedades Neurodegenerativas/metabolismo , Fármacos Neuroprotectores/farmacología , Opuntia/química , Phaeophyceae/química , Extractos Vegetales/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Animales , Drosophila melanogaster , Humanos , Mutación , Enfermedades Neurodegenerativas/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Extractos Vegetales/uso terapéutico , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/fisiología , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
7.
Atherosclerosis ; 240(2): 415-23, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25897793

RESUMEN

OBJECTIVE: To verify the safety and effectiveness of traditional Chinese red yeast rice-extract (RYR) for reduction of LDL cholesterol. METHODS: Systematic literature review and meta-analysis. Medline and EMBASE were searched until November 2014. We selected randomized studies in which RYR with a known content of the active substance monacolin K was tested against placebo or an active control group. Outcome measures were the effect of RYR on LDL cholesterol and incidence of adverse reactions with emphasis on liver and kidney injury and muscle symptoms. RESULTS: Twenty studies were analyzed. Quality of safety assessment was low in the majority of studies. RYR lowered LDL cholesterol with 1.02 mmol/L [-1.20; -0.83] compared to placebo. Effect of RYR on LDL was not different from statin therapy (0.03 mmol/L [-0.36; 0.41]). The incidence of liver and kidney injury was 0-5% and the risk was not different between treatment and control groups (risk difference -0.01 [-0.01; 0.0] and 0.0 [-0.01; 0.02]). CONCLUSIONS: RYR exerts a clinically and statistically significant reduction of 1.02 mmol/L LDL cholesterol. Only when the mild profile of adverse reactions can be affirmed in studies with adequate methodology for safety assessment, RYR might be a safe and effective treatment option for dyslipidemia and cardiovascular risk reduction in statin intolerant patients.


Asunto(s)
Anticolesterolemiantes/uso terapéutico , Productos Biológicos/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Medicina Tradicional China , Anticolesterolemiantes/efectos adversos , Productos Biológicos/efectos adversos , Biomarcadores/sangre , Distribución de Chi-Cuadrado , LDL-Colesterol/sangre , Suplementos Dietéticos/efectos adversos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/sangre , Hipercolesterolemia/diagnóstico , Lovastatina/uso terapéutico , Oportunidad Relativa , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento
8.
Environ Monit Assess ; 186(5): 3139-48, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24415133

RESUMEN

The seasonal variability of inorganic and organic nutrients and stable isotopes and their relations with plankton and environmental conditions were monitored in Lake Chasicó. Principal component analysis evidenced the strong influence of the river runoff on several biogeochemical variables. Silicate concentrations were controlled by diatom biomass and river discharge. Higher values of nitrate and soluble reactive phosphorus (SRP) indicated agricultural uses in the river basin. Elevated pH values (∼ 9) inhibiting nitrification in the lake explained partially the dominance of ammonium: ∼ 83 % of dissolved inorganic nitrogen (DIN). The low DIN/SRP ratio inferred nitrogen limitation, although the hypotheses of iron and CO2 limitation are relevant in alkaline lakes. Particulate organic matter (POM) and dissolved organic matter (DOM) were mainly of autochthonous origin. The main allochthonous input was imported by the river as POM owning to the arid conditions. Dissolved organic carbon was likely top-down regulated by the bacterioplankton grazer Brachionus plicatilis. The δ(13)C signature was a good indicator of primary production and its values were influenced probably by CO2 limitation. The δ(15)N did not evidence nitrogen fixation and suggested the effects of anthropogenic activities. The preservation of a good water quality in the lake is crucial for resource management.


Asunto(s)
Monitoreo del Ambiente , Lagos/química , Nitrógeno/análisis , Fósforo/análisis , Argentina , Ambiente , Nitrógeno/normas , Isótopos de Nitrógeno/análisis , Isótopos de Nitrógeno/normas , Material Particulado/análisis , Material Particulado/normas , Fósforo/normas , Plancton , Ríos/química , Estaciones del Año
9.
J Dent ; 40(12): 1103-8, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23000470

RESUMEN

OBJECTIVES: Evaluate erosive potential of beverages, using exposure times from 3 to 30 min, and to analyse the relationship between erosion and several drink parameters. METHODS: pH, calcium, phosphate and fluoride concentration, saturation, titratable-acidity to pH 5.5 and the viscosity of sixteen beverages were measured or calculated. Enamel samples (N = 90) were serially exposed to 1 ml of the beverages for 3, 6, 9, 15 and 30 min and erosion was measured as the loss of calcium to the beverage. Rate of erosion per min was calculated by linear curve fitting using all exposure times. Linear regression analysis was performed to determine the correlation between erosion and the drink parameters. A limited multivariate analysis was performed for the outcome parameter with the highest univariate correlations (erosion per minute) and 4 drink variables. RESULTS: A negative relationship was observed only for pH for all exposure times. Only for erosion per min a significant relationship with pH and saturation was found. In a model for erosion per min using only saturation, fluoride concentration, titratable acidity and viscosity, both saturation and viscosity were shown to have a significant effect (p = 0.01 and p = 0.05, respectively). CONCLUSION: Exposure times between 3 and 30 min result in very different estimates of erosive potential. There is no sound theoretical ground for preferring one or other exposure time/outcome as being more clinically relevant. CLINICAL RELEVANCE: This study shows that effect of the choice of study methodology on the measurement of erosive potential of beverages is large.


Asunto(s)
Bebidas/efectos adversos , Erosión de los Dientes/inducido químicamente , Bebidas Alcohólicas/efectos adversos , Bebidas Alcohólicas/análisis , Animales , Bebidas/análisis , Calcio/análisis , Bebidas Gaseosas/efectos adversos , Bebidas Gaseosas/análisis , Bovinos , Citrus paradisi , Citrus sinensis , Esmalte Dental/química , Bebidas Energéticas/efectos adversos , Bebidas Energéticas/análisis , Fluoruros/análisis , Frutas , Concentración de Iones de Hidrógeno , Electrodos de Iones Selectos , Malus , Fosfatos/análisis , Espectrofotometría Atómica , , Factores de Tiempo , Viscosidad
10.
Am J Obstet Gynecol ; 202(5): 455.e1-9, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20452487

RESUMEN

OBJECTIVE: The purpose of this study was to evaluate cervical changes and delivery at term during pregnancy in rats after various progestin treatments. STUDY DESIGN: Pregnant rats were treated by various routes and vehicles with progesterone, 17-alpha-hydroxyprogesterone caproate (17P), R5020, and RU-486. Delivery time was determined and cervical ripening was assessed in vivo by collagen light-induced fluorescence. RESULTS: The cervix is rigid in the progesterone injection, 17P, and vaginal R5020 groups vs controls. Vaginal progesterone had no effect. RU-486 treatment softened the cervix during preterm delivery. Only subcutaneous injected progesterone, R5020 (subcutaneous and vaginal), and topical progesterone in sesame and fish oil inhibits delivery. Delivery is not changed by subcutaneous injection of 17P, vaginal progesterone, oral progesterone, and topical progesterone in Replens (Crinone; Columbia Labs, Livingston, NJ). CONCLUSION: Inhibition of cervical ripening and delivery by progestins depends on many factors that include their properties, the route of administration, and the vehicle. This study suggests reasons that the present treatments for preterm labor are not efficacious.


Asunto(s)
Maduración Cervical/efectos de los fármacos , Progestinas/farmacología , 17-alfa-Hidroxiprogesterona/farmacología , Animales , Femenino , Aceites de Pescado , Lípidos , Embarazo , Nacimiento Prematuro/prevención & control , Progesterona/administración & dosificación , Progesterona/farmacología , Promegestona/farmacología , Ratas , Ratas Sprague-Dawley , Aceite de Sésamo , Cremas, Espumas y Geles Vaginales
11.
Bioconjug Chem ; 19(3): 731-9, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18278853

RESUMEN

The genetic engineering, expression, and validation of a fusion protein of avidin (AV) and a chimeric monoclonal antibody (mAb) to the human insulin receptor (HIR) is described. The 15 kDa avidin monomer was fused to the carboxyl terminus of the heavy chain of the HIRMAb. The fusion protein heavy chain reacted with antibodies specific for human IgG and avidin, and had the same affinity for binding to the HIR extracellular domain as the original chimeric HIRMAb. The fusion protein qualitatively bound biotinylated ligands, but was secreted fully saturated with biotin by COS cells, owing to the high level of biotin in tissue culture medium. Chinese hamster ovary (CHO) cells were permanently transfected with a tandem vector expressing the fusion protein genes, and high expressing cell lines were isolated by methotrexate amplification and dilutional cloning. The product expressed by CHO cells had high binding to the HIR, and migrated as a homogeneous species in size exclusion HPLC and native polyacrylamide gel electrophoresis. The CHO cells were adapted to a 4 week culture in biotin depleted medium, and the HIRMAb-AV fusion protein expressed under these conditions had 1 unoccupied biotin binding site per molecule, based on a [3H]-biotin ultrafiltration assay. The HIRMAb-AV increased biotin uptake by human cells >15-fold, and mediated the endocytosis of fluorescein-biotin, as demonstrated by confocal microscopy. In summary, the HIRMAb-AV fusion protein is a new drug targeting system for humans that can be adapted to monobiotinylated drugs or nucleic acids.


Asunto(s)
Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/farmacología , Biotina/química , Proteínas Mutantes Quiméricas/genética , Proteínas Mutantes Quiméricas/farmacología , Receptores de Droga/efectos de los fármacos , Animales , Anticuerpos Monoclonales/biosíntesis , Avidina/química , Biotina/farmacocinética , Western Blotting , Células CHO , Células COS , Línea Celular Tumoral , Chlorocebus aethiops , Cromatografía Líquida de Alta Presión , Cricetinae , Cricetulus , ADN Complementario/biosíntesis , ADN Complementario/genética , Diálisis , Sistemas de Liberación de Medicamentos , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Ingeniería Genética , Humanos , Microscopía Confocal , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacología , Albúmina Sérica Bovina/química , Ultrafiltración
12.
Caries Res ; 42(2): 98-104, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18277070

RESUMEN

The influence of beverage composition on the measurement of erosive potential is unclear. The aim of this study was to evaluate whether beverage composition influences the measurement of erosive potential and to evaluate the influence of exposure in small and large volumes. Eleven beverages were included: water (control), 3 alcopops, 2 beers and 5 soft drinks. For each beverage 15 bovine enamel samples were used: 5 for chemical and 10 for profilometric analysis. After exposure to the beverages (63 min) the resulting solutions were analyzed for Ca and inorganic phosphorus (P(i)) content. The samples for optical profilometry were submersed sequentially in 500 ml or in 1 ml of the drinks for 3, 6, 9, 15 and 30 min (total 63 min). For some of the beverages high baseline concentrations of Ca (energy drink) or P(i) (cola drink, cola lemon drink, beer, beer lemon) were found. Some of the beverages showed a good correlation between the chemical methods. Profilometry (both for 1 and 500 ml) showed generally lower enamel losses than the chemical methods. Lower enamel losses were found for the profilometry 1 ml compared to the profilometry 500 ml only for the cola drinks. It can be concluded that the composition of the beverages had a significant effect on the determination of the erosive potential with chemical analyses. Drink composition also influenced the effect of small versus large exposure volumes, indicating the need for standardization of exposure parameters.


Asunto(s)
Bebidas/análisis , Esmalte Dental/efectos de los fármacos , Desmineralización Dental/diagnóstico , Erosión de los Dientes/inducido químicamente , Animales , Bebidas/efectos adversos , Calcio/análisis , Bovinos , Solubilidad del Esmalte Dental , Concentración de Iones de Hidrógeno , Análisis de los Mínimos Cuadrados , Fósforo/análisis , Erosión de los Dientes/diagnóstico
13.
J Gene Med ; 9(7): 605-12, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17471587

RESUMEN

BACKGROUND: The present study examines whether chromosomal derived forms of therapeutic genes can be delivered to brain following intravenous administration. The brain expression of a rat tyrosine hydroxylase (TH) cDNA is compared to the brain expression of a plasmid DNA encoding the 18 kb rat TH gene. METHODS: TH gene expression is measured in cell culture and in vivo in brain in experimental Parkinson's disease (PD). A total of four eukaryotic expression plasmids encoding rat TH were engineered wherein the size of the TH expression cassette ranged from 1.5 kb, in the case of the cDNA form of the gene, to 17.5 kb, in the case of the largest size genomic construct. The TH expression plasmids were delivered to either cultured cells or to rat brain in vivo with Trojan horse liposomes (THLs), which target the non-viral plasmid DNA to cells via cell membrane receptors. RESULTS: The pattern of TH gene expression in cell culture and in vivo was similar: the cDNA form of the TH gene was fast-acting with short duration of action, and the genomic form of the TH gene was slow-acting with longer duration of action. The most sustained replacement of striatal TH enzyme activity in experimental PD was produced by combination gene therapy where both the cDNA and the genomic forms of the TH gene were administered simultaneously. CONCLUSIONS: Eukaryotic expression plasmids encoding genomic forms of therapeutic genes, as large as 18 kb, can be successfully incorporated in THLs and delivered to brain following intravenous administration.


Asunto(s)
Encéfalo/enzimología , ADN Complementario/genética , Terapia Genética/métodos , Genoma/genética , Enfermedad de Parkinson/terapia , Tirosina 3-Monooxigenasa/genética , Animales , Encéfalo/metabolismo , Células Cultivadas , Cuerpo Estriado/enzimología , Humanos , Liposomas , Neuroglía/enzimología , Plásmidos/metabolismo , Ratas , Mapeo Restrictivo , Tirosina 3-Monooxigenasa/metabolismo
14.
Caries Res ; 39(5): 371-9, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16110208

RESUMEN

This study aimed at evaluating the effect of 1 and 4% titanium tetrafluoride (TiF4) gels, amine fluoride (AmF) 1 and 0.25% and a fluoride varnish (FP) on the prevention of dental erosion. Two experimental groups served as controls, one with no pretreatment and another one pretreated with a fluoride-free varnish (FP-blanco). Dental erosion was modelled using bovine enamel samples submitted to alternate cycles of acid exposure in citric acid and remineralization in artificial saliva. Calcium loss of all samples involved in the study was quantified by atomic absorption spectroscopy and erosion depths were estimated. Two samples of each experimental group were also analyzed by white light confocal microscopy. The cumulative erosion depth (in mum) after 72 min was: TiF4 gel 1% 8.29 +/- 0.39; TiF4 gel 4% 8.27 +/- 0.55; AmF 1% 8.69 +/- 0.66; AmF 0.25% 8.86 +/- 0.33; FP 3.43 +/- 1.07; FP-blanco 14.86 +/- 1.59 and control 9.77 +/- 0.49. A statistically significant protective effect (p < or = 0.001) was found only for the group pretreated with the fluoride varnish. Within the limitations of an in vitro study it may be concluded that topical applications of the fluoride varnish tested have a protective effect on the prevention of dental erosion.


Asunto(s)
Aminas/uso terapéutico , Cariostáticos/uso terapéutico , Fluoruros Tópicos/uso terapéutico , Fluoruros/uso terapéutico , Fluoruros de Estaño/uso terapéutico , Titanio/uso terapéutico , Erosión de los Dientes/prevención & control , Animales , Bovinos , Esmalte Dental/efectos de los fármacos , Evaluación Preclínica de Medicamentos
15.
Am J Hematol ; 70(4): 306-12, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12210812

RESUMEN

Sickle cell anemia (SCA) results in chronic volume overload of the heart due to hemodilution. Previous echocardiographic studies of cardiac function in children with SCA have not accounted for these abnormal loading conditions. The objectives of this study were to (1) determine how the degree of anemia and transfusion status relate to cardiac findings and (2) evaluate cardiac function using load-independent parameters of function. We evaluated 77 patients with SCA, ages 2 to 22 years (mean +/- SD = 11.7 +/- 4.7), using physical examination, electrocardiography, and echocardiography. We compared two groups of patients. Group 1 consisted of 57 non-transfused patients, and Group 2 consisted of 20 patients on a chronic transfusion protocol. Group 1 patients exhibited a significantly lower hemoglobin, higher cardiac output, and larger left ventricular (LV) end-diastolic dimension and LV mass than groups 2 (P < 0.05). However, the velocity of circumferential fiber shortening-wall stress index (a load-independent measure of systolic function) was normal and not statistically different between the two groups. Conversely, the LV myocardial performance index (a measure of combined systolic and diastolic function) was significantly higher in Group 2 (P < 0.001), possibly indicating impaired myocardial diastolic function. SCA in children results in a volume-overloaded heart with a significant increase in LV dimensions and mass, both proportional to the degree of anemia. Despite these abnormal loading conditions, systolic function is preserved. Patients on a chronic transfusion protocol may develop diastolic dysfunction despite iron chelation therapy.


Asunto(s)
Anemia de Células Falciformes/complicaciones , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/etiología , Adolescente , Adulto , Anemia de Células Falciformes/patología , Niño , Preescolar , Femenino , Ferritinas/sangre , Pruebas de Función Cardíaca , Humanos , Sobrecarga de Hierro , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad
16.
Adv Dent Res ; 11(4): 448-52, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9470503

RESUMEN

The aim of the present study was to investigate the cariostatic effect of titanium tetrafluoride (TiF4) on in situ-induced lesions on human root surfaces. Analysis of the samples was carried out by quantitative microradiography (TMR) and confocal laser scanning microscopy (CLSM). Pre-molar roots, sectioned into four pieces, were used for sample preparation. Before they were mounted into the recesses prepared in the acrylic intra-oral appliances, two root pieces from each tooth were treated with 4% TiF4 for 1 min, while the remaining two pieces served as controls. The appliances were worn by 12 volunteers for 4 wks. After 4 wks with no fluoride supplementation, the root pieces were removed and analyzed by TMR and CLSM. The TMR results showed that the TiF4 treatment reduced lesion depth and total mineral loss by 56% and 62%, respectively. CLSM images agreed well with the TMR measurements. A dense light-reflecting surface layer with almost intact subsurface structures was evident in the TiF4-treated samples.


Asunto(s)
Cariostáticos/uso terapéutico , Caries Dental/prevención & control , Fluoruros/uso terapéutico , Microrradiografía , Microscopía Confocal , Titanio/uso terapéutico , Raíz del Diente/efectos de los fármacos , Diente Premolar , Caries Dental/diagnóstico por imagen , Caries Dental/patología , Evaluación Preclínica de Medicamentos , Humanos , Técnicas In Vitro , Microrradiografía/métodos , Microscopía Confocal/métodos , Propiedades de Superficie , Raíz del Diente/diagnóstico por imagen , Raíz del Diente/ultraestructura
17.
Caries Res ; 29(5): 337-42, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-8521433

RESUMEN

The aim was to study the effect of two different water rinsing procedures after toothbrushing with an NaF-containing dentifrice on the degree of de- or remineralization of enamel and dentine at approximal and buccal sites. Seven adults, wearing complete dentures, participated in two experimental periods (A and B) in a randomised order. During period A, they brushed with the dentifrice for 2 min, followed by 1-min active mouthrinse with the toothpaste-foam combined with 10 ml of water. No more water was used after the slurry had been spat out. During period B, the brushing was followed by 3 thorough rinsings of approximately 15 ml water each. These two procedures were carried out twice daily, i.e. in the morning (after breakfast) and in the evening (just before bedtime), during 3 months. Demineralized enamel and dentine samples were mounted at two locations--approximally and buccally--in the first molar region of the upper prostheses. Quantitative microradiography (TMR) was used to assess the lesion depth (ld) and the mineral loss (delta Z). The results showed that the approximally located samples continued to lose mineral during both periods A and B. However, the ld and delta Z values for enamel (p < 0.01) and dentine (p < 0.05) increased less during A than B. The buccally located enamel and dentine samples remineralized during the experiment, but no statistically significant differences were found for the ld and delta Z values of either enamel or dentine between periods A and B.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Cariostáticos/uso terapéutico , Dentífricos , Antisépticos Bucales , Fluoruro de Sodio/uso terapéutico , Desmineralización Dental/etiología , Cepillado Dental , Agua , Anciano , Cariostáticos/administración & dosificación , Cariostáticos/análisis , Esmalte Dental/efectos de los fármacos , Esmalte Dental/patología , Dentina/efectos de los fármacos , Dentina/patología , Dentadura Completa , Femenino , Humanos , Masculino , Microrradiografía , Persona de Mediana Edad , Minerales/análisis , Saliva/química , Fluoruro de Sodio/administración & dosificación , Fluoruro de Sodio/análisis , Desmineralización Dental/patología , Remineralización Dental
18.
Am J Orthod Dentofacial Orthop ; 105(3): 293-6, 1994 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8135216

RESUMEN

In the present in vivo study, the cariostatic potential of a titanium tetrafluoride (TiF4) solution applied topically around orthodontic brackets was investigated with quantitative microradiography. Also characteristics of the TiF4-treated enamel surface were examined with scanning electron microscopy (SEM). Ten pairs of premolars to be extracted for orthodontic treatment were used in the first part of this study. Brackets were bonded on all teeth with an orthodontic adhesive, and 10 randomly selected premolars served as controls, whereas a similar number were treated with 1% TiF4 around brackets for 60 seconds. After 4 weeks with no topical fluoride supplementation, all teeth were extracted and stored for analysis. Results indicated the 1% TIF4 solution reduced lesion depths and total mineral loss, at the bracket periphery, significantly during the 4-week period. The presence of a surface coating was demonstrated by SEM micrographs. It was concluded that TiF4 may provide a high level performance as a prophylactic agent for orthodontic purposes.


Asunto(s)
Fluoruros Tópicos/uso terapéutico , Fluoruros/uso terapéutico , Soportes Ortodóncicos , Titanio/uso terapéutico , Desmineralización Dental/prevención & control , Niño , Esmalte Dental/efectos de los fármacos , Esmalte Dental/ultraestructura , Fluoruros/farmacología , Fluoruros Tópicos/farmacología , Humanos , Microrradiografía , Microscopía Electrónica de Rastreo , Soportes Ortodóncicos/efectos adversos , Titanio/farmacología , Desmineralización Dental/etiología
19.
Am J Orthod Dentofacial Orthop ; 101(4): 303-7, 1992 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-1532684

RESUMEN

This study was designed to investigate the cariostatic potential in vivo of a visible light-curing adhesive for the bonding of orthodontic brackets. The fluoride release of the adhesive in water and saliva was also measured. Ten orthodontic patients with premolars to be extracted participated. One bracket with Heliosit-Orthodontic (no fluoride) was positioned on the buccal surface of one premolar (control), and another bracket with Orthodontic cement VP 862 (containing fluoride) was positioned on the experimental contralateral premolar. The adhesives were cured with a Heliolux II lamp, and the teeth were extracted after 4 weeks. The patients used a fluoride toothpaste during the experiment. The mineral content of the enamel adjacent to the brackets was determined by quantitative microradiography. The fluoride release from disk-shaped plates of the fluoride adhesive was measured in water for a 6-month period and in human saliva for 24 hours. The fluoride adhesive reduced lesion depths by about 48% than the nonfluoride adhesive (P less than 0.05, t test). The largest release of fluoride from the plates in water was observable within the first week. However, a significant amount of fluoride was still released after 6 months. The fluoride release in saliva was significantly lower in human saliva at pH 7 than in water (P less than 0.01, t test). When salivary pH was lowered to 4, to mimic a cariogenic challenge, the amount of fluoride released increased up to the value measured in water. It was concluded that the regular use of fluoride toothpastes is insufficient to inhibit lesion development around orthodontic brackets.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Recubrimiento Dental Adhesivo , Caries Dental/prevención & control , Cementos Dentales/química , Cementos Dentales/uso terapéutico , Fluoruros Tópicos/administración & dosificación , Fluoruros Tópicos/uso terapéutico , Fluoruros , Soportes Ortodóncicos , Uretano/uso terapéutico , Adhesivos/química , Bisfenol A Glicidil Metacrilato , Preparaciones de Acción Retardada , Caries Dental/etiología , Fluoruros Tópicos/análisis , Fluoruros Tópicos/química , Humanos , Concentración de Iones de Hidrógeno , Metacrilatos , Microrradiografía , Soportes Ortodóncicos/efectos adversos , Ácidos Polimetacrílicos/química , Poliuretanos , Saliva/química , Uretano/química , Agua
20.
Scand J Dent Res ; 99(5): 372-7, 1991 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1754838

RESUMEN

Shark enamel consists of nearly pure fluorapatite and has been shown to demineralize in an in situ caries model. The present study was conducted to investigate whether additional fluoride supplementation in the form of mouthrinsing would inhibit lesion development in shark enamel. The study slabs of shark enamel were mounted in dental appliances. Six individuals wore the appliances while rinsing daily with a neutral 0.2% NaF solution for 4 wk. The specimens were analyzed by means of quantitative microradiography, and the data compared with a previous study using untreated shark enamel and the same participants. It was found that fluoride rinsing did not measurably inhibit enamel demineralization in 4 wk. Scanning electron microradiographs showed that calcium fluoride-like material was not formed on shark enamel after neutral fluoride treatment, supporting a previous study. The present study indicates, therefore, that formation of a calcium fluoride-like material on the enamel surface may be essential for the cariostatic effect of topical agents.


Asunto(s)
Fluoruro de Calcio/química , Caries Dental/prevención & control , Esmalte Dental/ultraestructura , Tiburones , Fluoruro de Sodio/uso terapéutico , Desmineralización Dental/prevención & control , Adolescente , Animales , Carbonatos/análisis , Niño , Esmalte Dental/química , Modelos Animales de Enfermedad , Humanos , Microrradiografía , Microscopía Electrónica de Rastreo , Antisépticos Bucales , Fluoruro de Sodio/administración & dosificación
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