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1.
Revista Naval de Odontologia ; 49(1): 19-26, 2022/07/04.
Article in Portuguese, English | LILACS-Express | LILACS | ID: biblio-1379020

ABSTRACT

The objective of this study was to conduct a systematic review focused on studies that used micro-computed tomography (micro-CT) analysis to evaluate untouched canal areas after root canal preparation with continuous rotary and reciprocating kinematics. Electronic search strategies were used in LILACS, PubMed (MedLine), Science Direct, Cochrane, Scopus and Web of Science databases. An additional search for gray literature was performed on Google Scholar, OpenGrey and ProQuest. In addition, manual searches were performed on the reference list of included articles. It covered studies in English, Portuguese and Spanish, without restriction regarding the publication time. The articles selected for inclusion in this review meet all the following criteria: in vitro studies that evaluated, with the use of micro-CT, the percentage of untouched areas after root canal preparation comparing rotary and reciprocating kinematics. A total of 11 studies were selected for qualitative and quantitative analysis. One study showed that the Reciproc system has a smaller percentage of untouched channel walls in lower incisors when compared to BioRace system. Another study showed no significant differences between reciprocating systems Reciproc and WaveOne with BioRace in mesial root canals of lower molars. Similarly, they did not observe any difference between ProTaper Next and ProTaper Universal with WaveOne. A single study showed differences between XP-Endo Shaper system (rotary) compared with WaveOne Gold. The studies evaluated in the present review showed by micro-CT that none of the instrumentation systems, regardless of the kinematics used or NiTi heat treatment, was able to completely touch the root canal walls.


O objetivo deste estudo foi realizar uma revisão sistemática dos estudos que avaliaram por microtomografia computadorizada (micro - CT) as áreas não tocadas do canal radicular após o preparo com cinemática rotatória continua e reciprocante. Foram utilizadas estratégias eletrônicas de busca nas bases LILACS, PubMed (MedLine), Science Direct, Cochrane, Scopus e Web of Science. Uma busca adicional por literatura cinzenta foi realizada no Google Scholar, OpenGrey e ProQuest. A busca abrangeu estudos em inglês, português e espanhol, sem restrição em relação ao tempo de publicação. Adicionalmente, pesquisas manuais foram realizadas na lista de referências dos artigos incluídos. Os artigos selecionados foram estudos in vitro que avaliaram por micro - CT a porcentagem de áreas não tocadas após o preparo do canal radicular, comparando as cinemáticas rotatórias e reciprocante. No total 11 estudos foram selecionados para análise qualitativa e quantitativa. Um estudo mostrou que o sistema Reciproc (reciprocante) tem uma porcentagem menor de paredes não tocadas do canal em incisivos inferiores, quando comparado com o sistema BioRace (rotatório). Outro estudo não mostrou diferenças significativas entre os sistemas reciprocantes Reciproc e WaveOne e o sistema BioRace em canais radiculares mesiais de molares inferiores. Da mesma forma, não foram observadas diferenças entre ProTaper Next, ProTaper Universal (rotat órios) e WaveOne. Um único estudo apresentou diferenças entre as cinemáticas, XP - Endo Shaper (rotatório) mostrou maior porcentagem de áreas tocadas quando comparado com TRUShape e WaveOne Gold. Os estudos avaliados mostraram que nenhum dos sistemas de instrumentação, independente da cinemática, foi capaz de tocar completamente as paredes dos canais radiculares.

2.
BMC Oral Health ; 21(1): 118, 2021 03 15.
Article in English | MEDLINE | ID: mdl-33722235

ABSTRACT

BACKGROUND: The objective of this study was to measure two parameters involved in tri-dimensional implant planning: the position of the buccal and palatal bone wall and the palatal thickness. METHODS: Cone beam computed tomography (CBCT) images (Planmeca ProMax 3D) of 403 teeth (208 upper teeth and 195 lower teeth) were obtained from 49 patients referred to the Dental School of Seville from January to December 2014. The height difference between the palatal and buccal walls was measured on the most coronal point of both walls. The thickness of the palatal wall was measured 2 mm from the most coronal point of the palatal wall. RESULTS: The mean values in the maxilla were 1.7 ± 0.9 mm for central and lateral incisors, 2.2 ± 1.7 mm for canines, 1.6 ± 0.9 mm for premolars and 1.9 ± 1.5 mm for molars. In the lower jaw, the mean values were 1.3 ± 0.8 mm for incisors, 1.7 ± 1.2 mm for canines, 2.3 ± 1.3 mm for premolars, and 2.6 ± 1.7 mm for molars. In the upper jaw, more than 55% of maxillary teeth (excluding second premolars and molars) presented mean height differences greater than 1 mm. In the mandible, more than 60% of incisors showed a buccal bone thickness of 1 mm from the apical to lingual aspect. All teeth except the second premolar presented a buccal wall located more than 1 mm more apically than the lingual bone wall. CONCLUSIONS: The buccal bone wall is located more apically (greater than 1 mm) than the palatal or lingual table in most of the cases assessed. The thickness of the palatal or lingual table is also less than 2 mm in the maxilla and mandible, except in the upper canines and premolars and the lower molars.


Subject(s)
Cone-Beam Computed Tomography , Maxilla , Bicuspid/diagnostic imaging , Humans , Mandible , Maxilla/diagnostic imaging , Palate/diagnostic imaging
3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-908760

ABSTRACT

The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be performed.Besides,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system disorders.Although different liquid chromatographic (LC) methods coupled with ultraviolet,fluores-cence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet required.Therefore,this review summarizes the main analytical aspects regarding the liquid chro-matographic methods developed for the analysis of perampanel,retigabine (and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage forms.Furthermore,the physicochemical and stability properties of the target compounds will also be addressed.Thus,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new (bio)analytical techniques are aimed to be imnlemented for these drugs.

4.
Comput Biol Med ; 123: 103917, 2020 08.
Article in English | MEDLINE | ID: mdl-32768052

ABSTRACT

Intestinal parasites are responsible for several diseases in human beings. In order to eliminate the error-prone visual analysis of optical microscopy slides, we have investigated automated, fast, and low-cost systems for the diagnosis of human intestinal parasites. In this work, we present a hybrid approach that combines the opinion of two decision-making systems with complementary properties: (DS1) a simpler system based on very fast handcrafted image feature extraction and support vector machine classification and (DS2) a more complex system based on a deep neural network, Vgg-16, for image feature extraction and classification. DS1 is much faster than DS2, but it is less accurate than DS2. Fortunately, the errors of DS1 are not the same of DS2. During training, we use a validation set to learn the probabilities of misclassification by DS1 on each class based on its confidence values. When DS1 quickly classifies all images from a microscopy slide, the method selects a number of images with higher chances of misclassification for characterization and reclassification by DS2. Our hybrid system can improve the overall effectiveness without compromising efficiency, being suitable for the clinical routine - a strategy that might be suitable for other real applications. As demonstrated on large datasets, the proposed system can achieve, on average, 94.9%, 87.8%, and 92.5% of Cohen's Kappa on helminth eggs, helminth larvae, and protozoa cysts, respectively.


Subject(s)
Parasites , Animals , Humans , Microscopy , Neural Networks, Computer , Support Vector Machine
5.
Med Oral Patol Oral Cir Bucal ; 24(5): e636-e642, 2019 Sep 01.
Article in English | MEDLINE | ID: mdl-31422408

ABSTRACT

BACKGROUND: Assess the reliability (by means of reproducibility and repeatability) of the PenguinRFA system, analyse the ISQ values of different implant types and correlate the ISQ with the insertion torque during the placement of the implant. MATERIAL AND METHODS: 120 rough surface implants were placed in bovine bone (type II and III). The implants were divided into groups, according to its design. Once the implants were in place, the exact insertion torque was registered. Then, primary stability was measured by means of the resonance frequency analysis with the PenguinRFA and the Osstell ISQ devices. In each implant two transducers of each device were used. Three measurements were obtained with each transducer. RESULTS: The mean ISQ (implant stability quotient) of the whole sample is 67,70 ± 5,51. The Intraclass Correlation Coefficient (ICC) is 0,933 and 0,944 for transducers 1 and 2 respectively. The reproducibility is 0,906. The mean insertion torque is 24,54 ± 8,96N. The correlation between the ISQ and the insertion torque is 0,507 p<0,000 (MultiPeg 1) and 0,468 p<0,000 (MultiPeg 2) for bone type II and 0,533 p<0,801 (MultiPeg 1) and 0,193 p<0,140 (MultiPeg 2) for bone type III. CONCLUSIONS: The results of the present trial suggest that the PenguinRFA presents excellent reproducibility and repeatability, so it could be very useful in the monitoring of the stability of implants over time. Additionally, according to the results, the correlation between the IT and the RFA is low and there are no statistically significant differences in between implant types.


Subject(s)
Dental Implants , Animals , Cattle , Dental Implantation, Endosseous , Dental Prosthesis Design , Dental Prosthesis Retention , Reproducibility of Results , Resonance Frequency Analysis , Torque , Vibration
6.
J Pharm Anal ; 9(3): 143-155, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31297291

ABSTRACT

The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formulation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide.

7.
Article in English | MEDLINE | ID: mdl-31182538

ABSTRACT

Ibuprofen and indomethacin are commonly used to induce ductus arteriosus closure in preterm neonates. Our group previously reported that ibuprofen decreased vancomycin clearance by 16%. In this study, we quantified the impact of indomethacin coadministration on vancomycin clearance by extending our vancomycin population pharmacokinetic model with a data set containing vancomycin concentrations measured in preterm neonates comedicated with indomethacin. The modeling data set includes concentration-time data of vancomycin administered alone or in combination with either ibuprofen or indomethacin collected in the neonatal intensive care units of UZ Leuven (Leuven, Belgium) and São Francisco Xavier Hospital (Lisbon, Portugal). The derived vancomycin pharmacokinetic model was subsequently used to propose dose adjustments that yield effective vancomycin exposure (i.e., area under the concentration-time curve from 0 to 24 h [AUC0-24] between 300 to 550 mg·h/liter, with a probability of <0.1 of subtherapeutic exposure) in preterm neonates with patent ductus arteriosus. We found that indomethacin coadministration reduced vancomycin clearance by 55%. Model simulations showed that the most recent vancomycin dosing regimen, which was based on an externally validated model, requires 20% and 60% decreases of the loading and maintenance doses of vancomycin, respectively, when aiming for optimized exposure in the neonatal population. By analyzing vancomycin data from preterm neonates comedicated with indomethacin, we found a substantial decrease in vancomycin clearance of 55% versus a previously reported 16% for ibuprofen. This decrease in clearance impacts vancomycin dosing, and we anticipate that other drugs eliminated by glomerular filtration are likely to be affected to a similar extent as vancomycin.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Ductus Arteriosus, Patent/drug therapy , Ibuprofen/therapeutic use , Indomethacin/therapeutic use , Vancomycin/pharmacokinetics , Vancomycin/therapeutic use , Adult , Female , Humans , Infant, Newborn , Male , Monte Carlo Method , Pregnancy , Young Adult
8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-753357

ABSTRACT

The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formu-lation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide.

9.
BMC Oral Health ; 18(1): 194, 2018 11 21.
Article in English | MEDLINE | ID: mdl-30463614

ABSTRACT

BACKGROUND: The objective of this paper is to anatomically describe the bone morphology in the maxillary and mandibular tooth areas, which might help in planning post-extraction implants. METHODS: CBCT images (Planmeca ProMax 3D) of 403 teeth (208 upper teeth and 195 lower teeth) were obtained from 49 patients referred to the Dental School of Seville from January to December 2014. The thickness of the facial wall was measured at the crest, point A, 4 mm below, point B, and at the apex, point C. The second parameter was the angle formed between the dental axis and the axis of the basal bone. RESULTS: A total of 403 teeth were measured. In the maxilla, 89.4% of incisors, 93.94% of canines, 78% of premolars and 70.5% of molars had a buccal bone wall thickness less than the ideal 2 mm. In the mandible, 73.5% of incisors, 49% of canines, 64% of premolars and 53% of molars had < 1 mm buccal bone thickness as measured at point B. The mean angulation in the maxilla was 11.67 ± 6.37° for incisors, 16.88 ± 7.93° for canines, 13.93 ± 8.6° for premolars, and 9.89 ± 4.8° for molars. In the mandible, the mean values were 10.63 ± 8.76° for incisors, 10.98 ± 7.36° for canines, 10.54 ± 5.82° for premolars and 16.19 ± 11.22° for molars. CONCLUSIONS: The high incidence of a buccal wall thickness of less than 2 mm in over 80% of the assessed sites indicates the need for additional regeneration procedures, and several locations may also require custom abutments to solve the angulation problems for screw-retained crowns.


Subject(s)
Cone-Beam Computed Tomography , Mandible/anatomy & histology , Maxilla/anatomy & histology , Tooth Root/anatomy & histology , Adult , Bone Remodeling , Dental Implants , Female , Humans , Male , Mandible/diagnostic imaging , Maxilla/diagnostic imaging , Tooth/anatomy & histology , Tooth/diagnostic imaging
10.
Transplant Proc ; 50(5): 1424-1427, 2018 06.
Article in English | MEDLINE | ID: mdl-29880365

ABSTRACT

BACKGROUND: The goal of this study was to evaluate the predictive factors of mortality in patients after liver transplantation in an intensive care unit from the University Hospital. METHODS: This observational study was conducted by using a database analysis of University Hospital. The sample consisted of patients after liver transplantation registered in the database. The study variables of Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Disease Classification II (APACHE II), Model for End-Stage Liver Disease, and Child-Pugh scores, and the days of hospitalization in intensive care unit, mechanical ventilation time, and reintubation rate, were correlated. Statistical analysis was performed by using the χ2 test or Fisher exact test, the Mann-Whitney test, and logistic regression analysis. RESULTS: Fifty-eight individuals were analyzed. In the death group, the days of hospitalization in the intensive care unit were within 12 ± 14 days, the time of mechanical ventilation was 180 ± 148 hours, the APACHE II value was 17.6 ± 7.3, the Sequential Organ Failure Assessment score was 8.2 ± 2.7, and reintubation was 40%. In the multivariate regression, the predictive indexes of mortality were the mortality given by APACHE II (odds ratio, 1.1; CI, 1.03-1.17; P = .004), mechanical ventilation time (odds ratio, 1.02; CI, 1.01-1.04; P = .001), and reintubation (odds ratio, 9.06; CI, 1.83-44.9; P = .007). An increase of 1 unit in APACHE II mortality increases the risk of death by 10.2%, and each hour of mechanical ventilation increases the risk of death by 2.6%. CONCLUSIONS: The time of mechanical ventilation, orotracheal reintubation, and the mortality given by APACHE II were the variables that best predicted death in this study.


Subject(s)
Intensive Care Units/statistics & numerical data , Liver Transplantation/mortality , APACHE , Adult , Aged , Cohort Studies , Female , Hospital Mortality , Hospitals, University , Humans , Male , Middle Aged , Organ Dysfunction Scores , Prognosis , Respiration, Artificial , Retrospective Studies
11.
Acta Neurol Scand ; 138(3): 203-211, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29732549

ABSTRACT

OBJECTIVES: Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) for focal-onset seizures (FOS). Pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to assess dose selection, identify significant AED drug interactions, and quantitate relationships between exposure and safety and efficacy outcomes from Phase 3 trials of adjunctive ESL. METHODS: Eslicarbazepine (the primary active metabolite of ESL) population PK was evaluated using data from 1351 subjects enrolled in 14 studies (11 Phase 1 and three Phase 3 studies) after multiple oral doses ranging from 400 to 1200 mg. Population PK and PD models related individual eslicarbazepine exposures to safety outcomes and efficacy responses. RESULTS: Eslicarbazepine PK was described by a one-compartment model with linear absorption and elimination. The probability of a treatment-emergent adverse event (TEAE; dizziness, headache, or somnolence) was higher with an initial dose of ESL 800 mg than with an initial dose of ESL 400 mg QD. Body weight, sex, region, and baseline use of carbamazepine (CBZ) or lamotrigine were also found to influence the probability of TEAEs. Eslicarbazepine exposure influenced serum sodium concentration, standardized seizure frequency, and probability of response; better efficacy outcomes were predicted in patients not from Western Europe (WE; vs WE patients) and those not taking CBZ (vs taking CBZ) at baseline. CONCLUSIONS: Pharmacokinetic and PK/PD modeling were implemented during the development of ESL for adjunctive treatment of FOS in adults. This quantitative approach supported decision-making during the development of ESL, and contributed to dosing recommendations and labeling information related to drug interactions.


Subject(s)
Anticonvulsants/pharmacokinetics , Dibenzazepines/pharmacokinetics , Adult , Aged , Anticonvulsants/adverse effects , Dibenzazepines/adverse effects , Dose-Response Relationship, Drug , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Female , Humans , Male , Middle Aged , Seizures/drug therapy
12.
Acta Anaesthesiol Scand ; 62(4): 464-473, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29159892

ABSTRACT

BACKGROUND: Obese patients require specific perioperative care when compared with non-obese patients. The present study aimed to analyse the ability of size descriptors to estimate propofol induction dose in class II and III obese patients. METHODS: A cross-sectional study on adult patients with body mass index (BMI) equal to or greater than 35 kg/m2 and on adult patients with BMI lower than 35 kg/m2 was carried out. General anaesthesia was induced with remifentanil, propofol and rocuronium. Propofol infusion was started at 2000 mg/h until loss of consciousness. Bioelectrical impedance analysis and Brice modified interview was completed during pre- and post-operative evaluation, respectively. Measurements of propofol plasma concentration were performed using gas chromatography/ion trap-mass spectrometry. RESULTS: Forty patients were enrolled in the study. The median values of fat free mass (FFM) in BMI < 35 kg/m2 and BMI ≥ 35 kg/m2 groups were 70% and 55% of total body weight, respectively. Our results did not demonstrate a strong correlation level between the studied size descriptors and propofol induction dose in both groups. Nevertheless, when propofol doses were normalized by FFM, an apparent convergence of the empirical cumulative distribution functions was observed. CONCLUSION: None of the size descriptors was seen to be an effective predictor of the propofol induction dose in class II and III obese patients when a fixed infusion rate was used. Due to the observed variability between patients, guiding propofol induction dose against a clinical endpoint of unconsciousness appears more appropriate in order to avoid side effects related both with under or overdosing of propofol.


Subject(s)
Anesthetics, Intravenous/administration & dosage , Body Weight , Obesity/metabolism , Propofol/administration & dosage , Adolescent , Adult , Aged , Arterial Pressure , Body Composition , Body Mass Index , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Reproducibility of Results , Young Adult
13.
Genet Mol Res ; 14(4): 14956-66, 2015 Nov 24.
Article in English | MEDLINE | ID: mdl-26634457

ABSTRACT

We evaluated the genetic association of growth traits [weight adjusted to 205 days of age (W205), 365 days of age (W365), and 550 days of age (W550); weight gain between 205 days of age and 365 days of age (WG1) and between 365 days of age and 550 days of age (WG2)] and reproductive traits [age at first calving (AFC); first calving interval (FCI)] with stayability in the herd (STAY), using Bayesian inference in linear and threshold models. We defined STAY as the probability of a cow calving three or more times before the age of 76 months, given that she had calved at least once. We assigned binary codes (0, failure; 1, success) to each female. We used a sire model for analysis and formed different contemporary groups for the investigated traits. We analyzed the results by applying a two-trait sire model that included STAY (threshold trait) and linear traits (W205, W365, W550, WG1, WG2, AFC, and FCI). We used Gibbs sampling to estimate variance components and heritabilities. In all the analyses, we found that the mean heritability estimates for STAY were of moderate magnitude (0.20-0.25). The mean heritabilities for W205, W365, W550, WG1, WG2, AFC, and FCI were 0.20, 0.23, 0.39, 0.08, 0.14, 0.12, and 0.11, respectively. We observed wide variation in the posterior distributions of genetic correlations; however, with the exception of those obtained for the reproductive traits, the mean estimates were of low magnitude. Selection for WG2 can results in favorable correlated response in STAY.


Subject(s)
Cattle/genetics , Quantitative Trait, Heritable , Reproduction/genetics , Animals , Bayes Theorem , Body Weight/genetics , Brazil , Breeding , Cattle/growth & development , Cattle/physiology , Female , Genetic Association Studies , Linear Models , Longevity/genetics , Models, Genetic , Phenotype , Weight Gain/genetics
14.
Eur J Neurol ; 22(5): 815-25, e56, 2015 May.
Article in English | MEDLINE | ID: mdl-25649051

ABSTRACT

BACKGROUND AND PURPOSE: Opicapone (OPC) is a novel third generation catechol-O-methyltransferase (COMT) inhibitor that enhances levodopa availability. This study investigated the effects of OPC in comparison with placebo on levodopa pharmacokinetics, tolerability and safety, COMT activity and motor response to levodopa in Parkinson's disease (PD) patients with motor fluctuations. METHODS: This was a randomized, multicentre, double-blind and placebo-controlled study in four parallel groups of PD patients treated with standard-release 100/25 mg levodopa/carbidopa or levodopa/benserazide and with motor fluctuations (wearing-OFF phenomenon). Subjects were sequentially assigned to be administered, once-daily, up to 28 days (maintenance phase), placebo (n = 10) or 5 (n = 10), 15 (n = 10) and 30 mg (n = 10) OPC. Two levodopa tests were performed, one at baseline and another following the maintenance phase. Subjects kept a diary to record motor fluctuations (ON/OFF periods) throughout the study. RESULTS: In relation to placebo, levodopa exposure (AUC0-6) increased 24.7%, 53.9% and 65.6% following 5, 15 and 30 mg OPC, respectively. Maximum COMT inhibition (Emax) ranged from 52% (5 mg OPC) to 80% (30 mg OPC). The study was not designed to detect any significant differences in motor performance, but the exploratory analysis performed shows improvement in various motor outcomes, including a dose-dependent change in absolute OFF time corresponding to a percentage decrease of 4.16% (P > 0.05), 29.55% (P > 0.05) and 32.71% (P < 0.05) with 5, 15 and 30 mg OPC, respectively. Treatments were generally well tolerated and safe. CONCLUSIONS: OPC is a promising new COMT inhibitor that significantly decreased COMT activity, increased systemic exposure to levodopa and improved motor response.


Subject(s)
Antiparkinson Agents/pharmacokinetics , Catechol O-Methyltransferase Inhibitors/pharmacology , Catechol O-Methyltransferase/drug effects , Levodopa/pharmacokinetics , Oxadiazoles/pharmacology , Parkinson Disease/drug therapy , Aged , Aged, 80 and over , Antiparkinson Agents/administration & dosage , Antiparkinson Agents/adverse effects , Benserazide/administration & dosage , Carbidopa/administration & dosage , Catechol O-Methyltransferase Inhibitors/administration & dosage , Double-Blind Method , Drug Combinations , Female , Humans , Levodopa/administration & dosage , Levodopa/adverse effects , Male , Middle Aged , Oxadiazoles/administration & dosage , Treatment Outcome
15.
Cell Death Differ ; 21(10): 1588-99, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24853299

ABSTRACT

The production, accumulation and aggregation of amyloid beta (Aß) peptides in Alzheimer's disease (AD) are influenced by different modulators. Among these are iron and iron-related proteins, given their ability to modulate the expression of the amyloid precursor protein and to drive Aß aggregation. Herein, we describe that lipocalin 2 (LCN2), a mammalian acute-phase protein involved in iron homeostasis, is highly produced in response to Aß1-42 by choroid plexus epithelial cells and astrocytes, but not by microglia or neurons. Although Aß1-42 stimulation decreases the dehydrogenase activity and survival of wild-type astrocytes, astrocytes lacking the expression of Lcn2 are not affected. This protection results from a lower expression of the proapoptotic gene Bim and a decreased inflammatory response. Altogether, these findings show that Aß toxicity to astrocytes requires LCN2, which represents a novel mechanism to target when addressing AD.


Subject(s)
Acute-Phase Proteins/genetics , Amyloid beta-Peptides/pharmacology , Apoptosis Regulatory Proteins/biosynthesis , Astrocytes/metabolism , Lipocalins/biosynthesis , Lipocalins/genetics , Membrane Proteins/biosynthesis , Oncogene Proteins/genetics , Proto-Oncogene Proteins/biosynthesis , Alzheimer Disease , Amyloid beta-Protein Precursor/metabolism , Animals , Astrocytes/cytology , Bcl-2-Like Protein 11 , Cells, Cultured , Epithelial Cells/metabolism , Heme Oxygenase (Decyclizing)/biosynthesis , Inflammation/immunology , Iron/metabolism , Lipocalin-2 , Mice , Mice, Inbred C57BL , Microglia/metabolism , Neurons/metabolism , Rats
16.
Caries Res ; 48(3): 228-36, 2014.
Article in English | MEDLINE | ID: mdl-24481085

ABSTRACT

UNLABELLED: Sound evidence on the effectiveness of fluoride varnishes (FV) to reduce caries incidence in preschool children is lacking. OBJECTIVE: To assess whether the application of FV in preschool children at 6-month intervals decreases the incidence of caries and produces any adverse effects. METHODS: A randomized, examiner- and patient-blind, placebo-controlled, parallel-group design, clinical trial, comprising 1- to 4-year-old children, 100 in each group (FV or placebo varnish, PV), was conducted in Rio de Janeiro, Brazil. Two trained pediatric dentists performed the clinical examinations (kappa = 0.85). Dental caries was recorded at the d2 (cavitated enamel) and d3 (dentine) levels using the International Caries Diagnosis and Assessment System. RESULTS: At baseline, the mean age of the participants was 2.4 years (SD 0.9) and the mean d3mfs was 0.8 (SD 1.9). Most of the children brushed their teeth with fluoride toothpaste and consumed fluoridated tap water. After 24 months, 89 and 92 children of the test and the control groups were analyzed, respectively. A total of 32 (35.9%) children in the FV group and 43 (46.7%) in the PV group presented new dentine caries lesions (χ(2) test; p = 0.14), showing relative and absolute risk reductions of 23% (95% CI: -9.5 to 45.9) and 11% (95% CI: -3.5 to 25.0). The mean caries increment differences between the test and control groups were -0.8 (95% CI: -2.0 to 0.4) at the d2 level and -0.7 (95% CI: -1.9 to 0.4) at the d3 level. Only 2 minor complaints regarding the intervention were reported. CONCLUSION: Although safe and well accepted, twice-yearly professional FV application, during 2 years, did not result in a significant decrease in caries incidence.


Subject(s)
Cariostatic Agents/therapeutic use , Dental Caries/prevention & control , Fluorides, Topical/therapeutic use , Cariostatic Agents/administration & dosage , Child, Preschool , DMF Index , Dental Enamel/pathology , Dentin/pathology , Female , Fluorides, Topical/administration & dosage , Follow-Up Studies , Humans , Infant , Intention to Treat Analysis , Male , Oral Hygiene/education , Placebos , Prospective Studies , Risk Assessment , Risk Reduction Behavior , Single-Blind Method , Social Class , Tooth, Deciduous/pathology , Toothbrushing/methods , Toothpastes/therapeutic use , Treatment Outcome
17.
Transplant Proc ; 45(3): 1126-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23622643

ABSTRACT

INTRODUCTION: Neurological postsurgical complications are a significant cause of morbidity and mortality occur in transplant recipients impacting their survival. METHODS: We analyzed the medical records of 269 patients who underwent transplantation between 2000 and 2011, after application of the exclusion criteria Neurological complications were examined according to the period in which they appeared: immediate (1-30 day) early (31-180 days), and late (after 180 days). The survival analysis was based on the first complication. RESULTS: The majority of transplant recipients were males (73.2%) and white (97.1%) with an overall median age of 49 (range, 18-73) years. Regarding the etiology for transplantation, the most common causes were hepatitis C virus (56.5%) and alcohol (33.1%). Complications, appearing in 29.4% (immediate), 31.5% (early), and 39.1% (late) cases, were encephalopathy, confusion, tremors, headache, and stroke. Patients who had the first complication between 1 and 6 months showed greater mortality than those who had one after 6 months. CONCLUSIONS: Neurological complications led to longer hospital stays with greater early morbidity and mortality. Knowledge of these complications appears to be extremely important for the multidisciplinary transplantation team to decrease its prevalence as well as to diagnose and treat early.


Subject(s)
Liver Transplantation , Nervous System Diseases/etiology , Survival , Adolescent , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
18.
Caries Res ; 47(3): 226-33, 2013.
Article in English | MEDLINE | ID: mdl-23295625

ABSTRACT

Depending on toothpaste formulation, part of the fluoride is insoluble and would not be totally absorbable in the gastrointestinal tract, thus changing dental fluorosis risk estimation. This hypothesis was tested with formulations with either all fluoride in a soluble form (NaF/SiO2-based toothpaste, 1,100 µg F/g as labeled, 1,129.7 ± 49.4 µg F/g soluble fluoride as analyzed) or with around 20% of insoluble fluoride (Na2FPO3/CaCO3-based toothpaste, 1,450 µg F/g as labeled, 1,122.4 ± 76.4 µg F/g soluble fluoride as analyzed). Toothpastes were evaluated either fresh or after accelerated aging, which increased insoluble fluoride to 40% in the Na2FPO3/CaCO3-based toothpaste. In a blind, crossover clinical trial conducted in five legs, 20 adult volunteers ingested 49.5 µg of total fluoride/kg body weight from each formulation or purified water (control). Whole saliva and urine were collected as bioavailability indicators, and pharmacokinetics parameters calculated showed significantly (p < 0.05) lower fluoride bioavailability for Na2FPO3/CaCO3 toothpaste, which was reduced further after aging. A significant correlation between the amount of soluble fluoride ingested, but not total fluoride, and fluoride bioavailability was found (r = 0.57, p < 0.0001). The findings suggest that the estimated fluorosis risk as a result of ingestion of Na2FPO3/CaCO3-based toothpastes should be calculated based on the toothpaste's soluble rather than total fluoride concentration.


Subject(s)
Intestinal Absorption , Sodium Fluoride/metabolism , Toothpastes/chemistry , Adolescent , Adult , Analysis of Variance , Biological Availability , Calcium Carbonate/metabolism , Cross-Over Studies , Female , Fluorides/metabolism , Fluorides/urine , Fluorosis, Dental/etiology , Humans , Linear Models , Male , Phosphates/metabolism , Saliva/chemistry , Silicates/metabolism , Single-Blind Method , Sodium Fluoride/adverse effects , Solubility , Statistics, Nonparametric , Toothpastes/adverse effects , Young Adult
19.
Nutr Hosp ; 27(6): 1999-2005, 2012.
Article in English | MEDLINE | ID: mdl-23588451

ABSTRACT

INTRODUCTION: Since the excess of body fat is associated with higher morbid-mortality rates (mainly in adults), precise, reliable, cost-effective, and broadly applicable methods are necessary for its assessment in population-based studies and in clinical practice. OBJECTIVE: To evaluate the correlation between body fat estimated either by bioelectrical impedance or by the sum of skinfold thicknesses and anthropometric indicators of fat distribution. METHODS: A cross-sectional study was conducted enrolled 348 undergraduate students (median 21 years), from the Federal University of Pernambuco, Northeast Brazil. RESULTS: 262 of the subjects were women. Mean body fat assessed by bioelectrical impedance was 22.3 ± 6.2% in women and 15.2 ± 4.2% in men. Body fat obtained by the sum of skinfold thicknesses was similar to that assessed by bioelectrical impedance only in men. A strong correlation was observed between body fat assessed by bioelectrical impedance and that assessed by the sum of the skinfold thicknesses, waist circumference and waist-to-height ratio. Regarding the conicity index, there was a moderate correlation for men and a weak correlation for women. CONCLUSIONS: The sum of skinfold thicknesses surrogate of body fat percentage and can be used to assess body fat when BIA is not available in the field. Additional information about central fat distribution can be supply by measuring the waist circumference or waist-to-height ratio.


Subject(s)
Anthropometry , Body Fat Distribution , Electric Impedance , Body Mass Index , Cross-Sectional Studies , Data Collection , Female , Humans , Male , Skinfold Thickness , Socioeconomic Factors , Young Adult
20.
Epilepsy Res ; 96(1-2): 132-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21680153

ABSTRACT

OBJECTIVE: To evaluate the pharmacokinetics of eslicarbazepine acetate (ESL) at steady-state in adults with partial-onset seizures who have taken ESL for at least 1 year with one or two concomitant antiepileptic drugs (AEDs). METHODS: Blood samples for the pharmacokinetic assessment were taken at pre-dose, and 1, 2, 3, 4, 6, 8, 12 and 24h post-dose at steady-state in 51 patients stabilised on chronic (beyond 1 year) treatment with ESL 400mg (n=7), 800mg (n=26) or 1200mg (n=18) once-daily. Most patients (n=29, 56.9%) were receiving 2 concomitant AEDs, and most frequent co-medications were carbamazepine (n=34, 66.7%) and valproic acid (n=19, 37.3%). Plasma concentrations of ESL and its metabolites eslicarbazepine, R-licarbazepine and oxcarbazepine (OXC) were determined by a validated chiral method using liquid chromatography coupled to mass spectrometry. RESULTS: Similarly to earlier findings in healthy subjects, plasma ESL concentrations were consistently below the lower limit of quantification (50ng/mL). The major compound in plasma was the active metabolite eslicarbazepine, which reached maximum concentrations (C(max)) 2h post-dose; thereafter, its plasma concentrations declined with a mean apparent half-life of 13, 14, and 20h in patients receiving ESL doses of 400, 800, and 1200mg once daily, respectively. Eslicarbazepine C(max) were 9.7, 15.5 and 23.0µg/mL, and areas under the plasma concentration-time curve over the dosing interval (AUC(0-24)) were 132.5, 205.4 and 336.1µgh/mL in patients receiving ESL doses of 400, 800 and 1200mg once-daily, respectively. Eslicarbazepine main pharmacokinetic parameters (C(max) and AUC(0-24)) were dose-proportional. R-licarbazepine and OXC were minor metabolites. CONCLUSIONS: Following once-daily oral administration of ESL 400mg, 800mg and 1200mg to epilepsy patients treated concomitantly with one or two other AEDs, ESL was rapidly converted to eslicarbazepine, which was the primary active compound found in plasma. Systemic exposure to eslicarbazepine was dose-proportional.


Subject(s)
Anticonvulsants/blood , Anticonvulsants/therapeutic use , Dibenzazepines/blood , Dibenzazepines/therapeutic use , Seizures/blood , Seizures/drug therapy , Adult , Anticonvulsants/chemistry , Carbamazepine/analogs & derivatives , Carbamazepine/blood , Carbamazepine/therapeutic use , Dibenzazepines/chemistry , Dose-Response Relationship, Drug , Female , Humans , International Cooperation , Male , Middle Aged , Oxcarbazepine , Tandem Mass Spectrometry , Time Factors , Young Adult
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