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1.
Dose Response ; 20(2): 15593258221101744, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602584

RESUMO

Lead may be passed on from a mother to their unborn fetus. If she has been exposed to lead for an extended period, the lead deposited in their bones can be stimulated to be released into the bloodstream during gestation. This study was planned to examine blood lead level at the prenatal stage and its response to markers of iron deficiency during gestation. We collected 396 samples during the second trimester of gestation from women age 19 to 45 years. Hematological markers including hemoglobin, hepcidin, total iron-binding capacity (TIBC), ferritin, and blood iron were analyzed. For the detection of blood lead, we used Atomic absorption spectroscopy. The mean blood lead level of the control group was 3.25 ± .407 µg/dL, and in the iron deficiency group, it was 7.96 ± .502 µg/dL. At the same time, the women with iron deficiency anemia showed 22.12 ± 1.02 µg/dL of mean blood lead. Pearson's approach showed a non-significant negative correlation between blood lead and hepcidin, while hemoglobin, total iron-binding capacity, ferritin, and serum iron showed a significant (.01) negative correlation with blood lead. Blood lead has no direct effect on iron deficiency markers. In contrast, iron deficiency contributes to an increase in lead accumulation during pregnancy. Iron and lead both have an impact on the heme-biosynthetic pathways. The study revealed that pre-existing iron deficiency is connected with increased lead intake and can negatively impact health in gestational females.

2.
Case Rep Hematol ; 2021: 6737829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745668

RESUMO

The distinction between classical Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) is not problematic in most instances. In rare situations, HL may present with a sinusoidal infiltrative pattern that may mimic ALCL. It is important to use a battery of immunohistochemical stains to differentiate between these two entities as therapy and clinical behavior are different. We present a case of a young woman who presents with the very unusual intrasinusoidal infiltrative pattern.

3.
Phytother Res ; 35(2): 771-789, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32945582

RESUMO

Cancer is one of the most devastating disease and leading cause of death worldwide. The conventional anticancer drugs are monotarget, toxic, expensive and suffer from drug resistance. Development of multi-targeted drugs from natural products has emerged as a new paradigm to overcome aforementioned conventionally encountered obstacles. Hispidulin (HIS), is a biologically active natural flavone with versatile biological and pharmacological activities. The anticancer, antimutagenic, antioxidative and anti-inflammatory properties of HIS have been reported. The aim of this review is to summarize the findings of several studies over the last few decades on the anticancer activity of HIS published in various databases including PubMed, Google Scholar, and Scopus. HIS has been shown to reduce the growth of cancer cells by inducing apoptosis, arresting cell cycle, inhibiting angiogenesis, invasion and metastasis via modulating multiple signaling pathways implicated in cancer initiation and progression. Multitargeted anticancer activity of HIS remains the strongest point for developing it into potential anticancer drug. We also highlighted the natural sources, anticancer mechanism, cellular targets, and chemo-sensitizing potential of HIS. This review will provide bases for design and conduct of further pre-clinical and clinical trials to develop HIS into a lead structure for future anticancer therapy.


Assuntos
Produtos Biológicos/uso terapêutico , Flavonas/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Produtos Biológicos/farmacologia , Flavonas/farmacologia , Humanos , Camundongos
4.
Comput Methods Biomech Biomed Engin ; 23(9): 524-535, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32379552

RESUMO

In the present article, we investigate the biomechanical response of a fiber reinforced solid matrix (soft tissue) saturated with an electrically conducting fluid. A constant magnetic field was exposed to the binary mixture of fluid and deformable porous solid. The governing mechanism of multiphasic deformation was based on the loading imposed at the rigid bony interface. The fluid flow through the cartilage network depends upon the rate of applied compression and strain-dependent permeability of the solid matrix. The components of the mixture were intrinsically incompressible; however, in the derivation of governing dynamics, the visco-elastic behavior of the solid and an interstitial fluid was developed. The continuum mixture theory was employed in modeling solid deformation and local fluid pressure. We incorporated strain-dependent permeability in the governing equations of binary mixture that was found in an early experimental study. The governing non-linear coupled system of partial differential equations was developed for the solid deformation and fluid pressure in the presence of Lorentz forces. In the case of strain-dependent permeability, a numerical solution is computed using the method of lines (MOL), whereas, the exact solution is provided when permeability is kept constant. Graphical results highlight the influence of various physical parameters on both solid displacement and fluid pressure.


Assuntos
Cartilagem Articular/fisiologia , Elasticidade , Campos Magnéticos , Estresse Mecânico , Humanos , Modelos Biológicos , Permeabilidade , Porosidade , Pressão , Viscosidade
5.
J Family Med Prim Care ; 8(10): 3367-3371, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31742170

RESUMO

BACKGROUND: To compare the efficacy and safety of intravenous levetiracetam and phenytoin in status epilepticus. METHODOLOGY: A prospective, randomized controlled, nonblinded study was conducted in children 1 month to 12 years of age with active seizure and with status epilepticus. A total of 104 children were randomly allocated to either group 1 (levetiracetam) or group 2 (phenytoin) on the basis of computer-generated random number table. Children already on antiepileptic drugs, very sick children with shock, impending respiratory failure, or head injury, and children hypersensitive to phenytoin or levetiracetam were excluded. Data analysis was done by IBM SPSS statistics. RESULTS: The mean age was 4.09 years with a male preponderance with the most common type of seizure being generalized type (74%). The seizures were controlled in all 104 patients initially within 40 min. Seizure control for 24 h was significantly better in group 1 (96%) when compared with group 2 (59.6%) (P = 0.0001). Minibolus of drug was given in 28.8% in group 1 and 46.2% in group 2 (P = 0.068). The seizure recurrence in groups 1 and 2 in the first hour was 1.9% and 5.8%, respectively (P = 0.61), whereas the recurrence between 1 and 24 h was significantly more in group 1 (34.6%) when compared with group 2 (3.8%) (P = 0.0001). The mean time to control seizure was comparable between both the groups (P = 0.71). There was no significant adverse effect in both the groups. CONCLUSION: Levetiracetam is more effective than phenytoin for seizure control for 24 h in children with status epilepticus, and it is safe and effective as a second-line therapy.

6.
Ultrastruct Pathol ; 43(4-5): 162-169, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31631752

RESUMO

Ingestion of a toxic dose of the analgesic drug, acetaminophen (also called paracetamol or APAP), is among the most common causes of acute liver injury in humans. We tested the hypothesis that the combined polyphenolic compounds, resveratrol (RES) and quercetin (QUR), can substantially protect against hepatocyte ultrastructural damage induced by a toxic dose of APAP in a rat model of APAP-induced acute liver injury. The model group of rats received a single dose of APAP (2 g/kg), whereas the protective group of rats was pretreated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP. All rats were then sacrificed 24 hours post APAP ingestion. Harvested liver tissues were prepared for transmission electron microscopy (TEM) staining, and liver homogenates were assayed for biomarkers of inflammation, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and oxidative stress, such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx). In addition, blood samples were assayed for the liver injury enzyme alanine aminotransferase (ALT) as an indicator of liver damage. TEM images showed that APAP overdose induced acute liver injury as demonstrated by profound hepatocyte ultrastructural alterations, which were substantially protected by RES+QUR. In addition, APAP significantly (p < 0.05) modulated TNF-α, IL-6, MDA, SOD, GPx, and ALT biomarkers, which were completely protected by RES+QUR. Thus, RES+QUR effectively protects against APAP-induced acute liver injury in rats, possibly via the inhibition of inflammation and oxidative stress.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/ultraestrutura , Animais , Hepatócitos/patologia , Microscopia Eletrônica de Transmissão , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley , Resveratrol/farmacologia
7.
Math Biosci Eng ; 16(2): 603-618, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30861658

RESUMO

In order to understand the interaction between magnetic field and biological tissues in a physiological system, we present a mathematical model of flow-induced deformation in absorbing porous tissues in the presence of a uniform magnetic field. The tissue is modeled as a deformable porous material in which high cavity pressure drives fluid through the tissue where it is absorbed by capillaries and lymphatics. A biphasic mixture theory is used to develop the model under the assumptions of small solid deformation and strain-dependent linear permeability. A spherical cavity formed during injection of fluid in the tissue is used to find fluid pressure and solid displacement as a function of radial distance and time. The governing nonlinear PDE for fluid pressure is solved numerically using method of lines whereas tissue solid displacement is computed by employing trapezoidal rule. The effect of magnetic parameter on fluid pressure, solid displacement and tissue permeability is illustrated graphically.


Assuntos
Injeções , Campos Magnéticos , Solo , Algoritmos , Fenômenos Biomecânicos , Encéfalo/fisiologia , Simulação por Computador , Humanos , Hidrodinâmica , Modelos Lineares , Modelos Biológicos , Dinâmica não Linear , Porosidade , Pressão , Estresse Mecânico
8.
J Biol Regul Homeost Agents ; 32(3): 607-611, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29921388

RESUMO

Tuberculosis (TB) is one of the major public health problem among contagious diseases in Pakistan. TB diagnosis mainly depends on sputum smear microscopy. The main objective of this study was to evaluate the effects of household bleach on sputum smear microscopy to concentrate acid fast bacilli for the diagnosis of pulmonary tuberculosis. Sputum specimens of 200 suspected TB patients were collected for the study. Smears were prepared from the purulent part of sputum sample before and after bleach treatment, heat fixed and stained with the ZN technique. The obtained data were analyzed by chi-squared test using SPSS software. Out of 200 isolates, 22 (11%) patients had positive smears for acid fast bacilli (AFB) by direct ZN staining. After treatment with household bleach (NaOCL) and centrifugation, the number of AFB positive patients were increased from 22 (11%) to 37 (18.5%). The bleach-concentration method for sputum samples significantly increased the TB detection rate as compared to direct sputum smear microscopy. Thus, a shift from direct sputum microscopy to bleach-concentration technique should be considered a better method for detection of AFB in sputum through smear microscopy.


Assuntos
Clareadores/química , Mycobacterium tuberculosis , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Feminino , Humanos , Masculino , Microscopia/métodos
9.
Math Med Biol ; 35(2): 145-180, 2018 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28339681

RESUMO

We report the results of some recent experiments to visualize tear film dynamics. We then study a mathematical model for tear film thinning and tear film breakup (TBU), a term from the ocular surface literature. The thinning is driven by an imposed tear film thinning rate which is input from in vivo measurements. Solutes representing osmolarity and fluorescein are included in the model. Osmolarity causes osmosis from the model ocular surface, and the fluorescein is used to compute the intensity corresponding closely to in vivo observations. The imposed thinning can be either one-dimensional or axisymmetric, leading to streaks or spots of TBU, respectively. For a spatially-uniform (flat) film, osmosis would cease thinning and balance mass lost due to evaporation; for these space-dependent evaporation profiles TBU does occur because osmolarity diffuses out of the TBU into the surrounding tear film, in agreement with previous results. The intensity pattern predicted based on the fluorescein concentration is compared with the computed thickness profiles; this comparison is important for interpreting in vivo observations. The non-dimensionalization introduced leads to insight about the relative importance of the competing processes; it leads to a classification of large vs small TBU regions in which different physical effects are dominant. Many regions of TBU may be considered small, revealing that the flow inside the film has an appreciable influence on fluorescence imaging of the tear film.


Assuntos
Modelos Biológicos , Lágrimas/fisiologia , Simulação por Computador , Olho/anatomia & histologia , Olho/diagnóstico por imagem , Fluoresceína , Fluorescência , Humanos , Hidrodinâmica , Conceitos Matemáticos , Concentração Osmolar , Reologia
10.
Nanoscale ; 9(40): 15434-15440, 2017 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-28976512

RESUMO

Thermoresponsive targeting is used to deliver therapeutic agents at hyperthermic conditions (39-45 °C). However, available thermoresponsive drug delivery systems (TDDS), including liposomes, have a complex method of preparation involving toxic solvents and reagents. The objective of this in vitro study was to prepare and characterize thermoresponsive lipid nanoparticles (TLN) for treating glioblastoma, the most aggressive brain tumor whose treatment is limited by a low blood brain barrier (BBB) permeability of drugs. Thermoresponsive lipids were prepared by mixing liquid and solid fatty acids (0.1 : 1 to 2 : 1 ratio) and lipid mixtures exhibiting a solid-liquid phase transition at 39 °C were identified by plotting melting point against liquid contents. TLN were prepared by a hot melt encapsulation method using mono- or double-surfactant systems. TLN showed desirable size (<270 nm), zeta potential (-35 to -50 mV), spherical morphology and stability by FTIR studies. In the drug release studies, paclitaxel release was slow at 37 °C, however, it was released abruptly at 39 °C due to the faster diffusion rate from liquid state nanoparticles. During cytotoxicity studies, the unloaded TLN were non-toxic whereas paclitaxel loaded TLN showed higher cytotoxicity to glioblastoma cells at 39 °C (69% cell viability after one hour) compared to 37 °C (82% cell viability). The TLN showed higher permeability across an in vitro model of BBB at 39 °C due to a deformable liquid state which can squeeze through the tight junctions of the BBB. In conclusion, this study demonstrated that the TLN can be used as a safe and effective alternative to traditional TDDS with higher potential to target glioblastoma cells across the BBB.


Assuntos
Barreira Hematoencefálica , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Lipídeos/química , Nanopartículas , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Humanos , Paclitaxel/administração & dosagem , Tamanho da Partícula , Permeabilidade , Temperatura
11.
Public Health Action ; 7(2): 168-174, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28695092

RESUMO

Setting: Although neonatal mortality is gradually decreasing worldwide, 98% of neonatal deaths occur in low- and middle-income countries, where hospital care for sick and premature neonates is often unavailable. Médecins Sans Frontières Operational Centre Brussels (MSF-OCB) managed eight specialised neonatal care units (SNCUs) at district level in low-resource and conflict-affected settings in seven countries. Objective: To assess the performance of the MSF SNCU model across different settings in Africa and Southern Asia, and to describe the set-up of eight SNCUs, neonate characteristics and clinical outcomes among neonates from 2012 to 2015. Design: Multicentric descriptive study. Results: The MSF SNCU model was characterised by an absence of high-tech equipment and an emphasis on dedicated nursing and medical care. Focus was on the management of hypothermia, hypoglycaemia, feeding support and early identification/treatment of infection. Overall, 11 970 neonates were admitted, 41% of whom had low birthweight (<2500 g). The main diagnoses were low birthweight, asphyxia and neonatal infections. Overall mortality was 17%, with consistency across the sites. Chances of survival increased with higher birthweight. Conclusion: The standardised SNCU model was implemented across different contexts and showed in-patient outcomes within acceptable limits. Low-tech medical care for sick and premature neonates can and should be implemented at district hospital level in low-resource settings.


Contexte: La mortalité néonatale diminue progressivement dans le monde, mais 98% des décès néonataux surviennent encore dans les pays à revenu faible et moyen, où les soins hospitaliers pour les nouveaux-nés malades et prématurés sont souvent indisponibles. Médecins Sans Frontières Centre d'Opérations Bruxelles (MSF-OCB) a géré huit unités spécialisées de soins néonataux (SNCU) au niveau du district dans des contextes de faibles ressources et affectés par des conflits dans sept pays.Objectif: Evaluer la performance du modèle de MSF-SNCU dans différents contextes en Afrique et en Asie du Sud Est. Les objectifs ont été de décrire la mise en place des huit SNCU, les caractéristiques des nouveau-nés et les résultats cliniques de 2012 à 2015.Schema: Etude descriptive multicentrique.Résultats: Le modèle de MSF-SNCU a été caractérisé par l'absence de machines de haute technologie et l'accent mis sur des soins infirmiers dévoués et des soins médicaux. La prise en charge s'est concentrée sur la gestion de l'hypothermie, de l'hypoglycémie, du soutien à l'alimentation et de l'identification/du traitement précoces d'une infection. Dans l'ensemble, 11 970 nouveau-nés ont été admis, dont 41% ont eu un faible poids de naissance (<2500 g). Les principaux diagnostics ont été un faible poids de naissance, une hypoxie et des infections néonatales. La mortalité d'ensemble a été de 17%, similaire dans les différents sites. Les chances de survie ont augmenté parallèlement au poids de naissance.Conclusion: Le modèle standardisé de SNCU a été mis en œuvre dans différents contextes et les résultats pour les nouveau-nés hospitalisés se sont avérés être dans des limites acceptables. Des soins médicaux de basse technologie pour les nouveau-nés malades et prématurés peuvent et doivent être mis en œuvre au niveau des hôpitaux de district dans les contextes de faibles ressources.


Marco de referencia: La mortalidad neonatal ha disminuido de manera gradual en todo el mundo, pero el 98% de las muertes neonatales ocurre en los países de bajos y medianos ingresos, que no suelen contar con una atención hospitalaria de los neonatos prematuros. El centro operativo de Bruselas de Médecins Sans Frontières (MSF-OCB) administra ocho unidades de atención neonatal especializada (SNCU) en entornos de bajos recursos y afectados por conflictos, a nivel distrital en siete países.Objetivo: Evaluar el desempeño del modelo SNCU de MSF en diferentes entornos en África y el sureste asiático. Se describe la puesta en marcha de ocho unidades, las características de los neonatos y los desenlaces clínicos del 2012 al 2015.Método: Fue este un estudio descriptivo multicéntrico.Resultados: El modelo SNCU de MSF se caracterizó por la falta de dispositivos de alta tecnología y una prioridad atribuida a la prestación de atención médica y de enfermería por parte de profesionales dedicados. Se concedió un interés especial al manejo de la hipotermia, la hipoglucemia, el apoyo alimentario y la detección precoz y el tratamiento de las infecciones. Se ingresaron 11 970 neonatos, de los cuales el 41% consistió en lactantes con bajo peso al nacer (<2500 g). Los principales diagnósticos fueron bajo peso al nacer, asfixia perinatal e infecciones neonatales. En general, la mortalidad fue 17%, en proporción uniforme en todos los centros. Las probabilidades de supervivencia aumentaban con un mayor peso al nacer.Conclusión: El modelo normalizado SNCU se introdujo en diferentes contextos y ofreció a los pacientes ingresados desenlaces dentro de límites aceptables. La atención médica de los neonatos prematuros y enfermos en plataformas de baja tecnología es viable y se debería introducir en los hospitales de nivel distrital de los entornos con bajos recursos.

12.
Front Genet ; 7: 159, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27683585

RESUMO

Potato virus Y has emerged as a threatening problem in all potato growing areas around the globe. PVY reduces the yield and quality of potato cultivars. During the last 30 years, significant genetic changes in PVY strains have been observed with an increased incidence associated with crop damage. In the current study, computational approaches were applied to predict Potato derived miRNA targets in the PVY genome. The PVY genome is approximately 9 thousand nucleotides, which transcribes the following 6 genes:CI, NIa, NIb-Pro, HC-Pro, CP, and VPg. A total of 343 mature miRNAs were retrieved from the miRBase database and were examined for their target sequences in PVY genes using the minimum free energy (mfe), minimum folding energy, sequence complementarity and mRNA-miRNA hybridization approaches. The identified potato miRNAs against viral mRNA targets have antiviral activities, leading to translational inhibition by mRNA cleavage and/or mRNA blockage. We found 86 miRNAs targeting the PVY genome at 151 different sites. Moreover, only 36 miRNAs potentially targeted the PVY genome at 101 loci. The CI gene of the PVY genome was targeted by 32 miRNAs followed by the complementarity of 26, 19, 18, 16, and 13 miRNAs. Most importantly, we found 5 miRNAs (miR160a-5p, miR7997b, miR166c-3p, miR399h, and miR5303d) that could target the CI, NIa, NIb-Pro, HC-Pro, CP, and VPg genes of PVY. The predicted miRNAs can be used for the development of PVY-resistant potato crops in the future.

13.
J Clin Diagn Res ; 10(12): BC01-BC06, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28208841

RESUMO

INTRODUCTION: Cystic Fibrosis (CF) is an autosomal recessive disorder and the incidence of this disease is undermined in Northern India. The distinguishable salty character of the sweat belonging to individuals suffering from CF makes sweat chloride estimation essential for diagnosis of CF disease. AIM: The aim of this prospective study was to elucidate the relationship of sweat chloride levels with clinical features and pattern of CF. MATERIALS AND METHODS: A total of 182 patients, with clinical features of CF were included in this study for quantitative measurement of sweat chloride. Sweat stimulation and collection involved pilocarpine iontophoresis based on the Gibson and Cooks methodology. The quantitative estimation of chloride was done by Schales and Schales method with some modifications. Cystic Fibrosis Trans Membrane Conductance Regulator (CFTR) mutation status was recorded in case of patients with borderline sweat chloride levels to correlate the results and for follow-up. RESULTS: Out of 182 patients having clinical features consistent with CF, borderline and elevated sweat chloride levels were present in 9 (5%) and 41 (22.5%) subjects respectively. Elevated sweat chloride levels were significantly associated with wheeze, Failure To Thrive (FTT), history of CF in Siblings, product of Consanguineous Marriage (CM), digital clubbing and steatorrhoea on univariate analysis. On multivariate analysis only wheeze, FTT and steatorrhoea were found to be significantly associated with elevated sweat chloride levels (p<0.05). Among the nine borderline cases six cases were positive for at least two CFTR mutations and rest of the three cases were not having any mutation in CFTR gene. CONCLUSION: The diagnosis is often delayed and the disease is advanced in most patients at the time of diagnosis. Sweat testing is a gold standard for diagnosis of CF patients as genetic mutation profile being heterozygous and unlikely to become diagnostic test.

14.
Saudi J Kidney Dis Transpl ; 25(3): 544-51, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24821150

RESUMO

Acute kidney injury (AKI) in the intensive care unit (ICU) is commonly caused by severe sepsis and septic shock. There is limited data regarding the incidence and outcomes of patients developing AKI treated with early goal-directed therapy (EGDT). Our aim was to observe the incidence and outcomes of patients with AKI in severe sepsis and septic shock, treated with EGDT as compared with historic controls. Study subjects included all adults admitted to the ICU with a diagnosis of severe sepsis and septic shock prior to (historic controls) and after introduction of EGDT (intervention group). Two groups were compared for incidence of AKI, length of ICU and hospital stay, incidence and requirement for renal replacement therapy, serum creatinine at discharge, maximum RIFLE (Risk, injury, failure, loss, end stage) in each group and 28-day mortality. Two groups were well matched for age, sex, (April 16, 2014) and acute physiological and chronic health evaluation (APACHE) II scores. We found no significant difference in the incidence of AKI (51% vs. 46%). There was no statistical difference in any of the above outcomes, including 28-day mortality in historic controls versus patients treated with EGDT. Septic AKI is a complex syndrome. The incidence and outcomes have not improved despite advances in sepsis management and EGDT. Very early detection of septic AKI and targeted therapies may improve outcomes.


Assuntos
Injúria Renal Aguda/terapia , Antibacterianos/uso terapêutico , Hidratação , Unidades de Terapia Intensiva , Sepse/terapia , Choque Séptico/terapia , APACHE , Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Pressão Arterial , Biomarcadores/sangue , Gasometria , Estudos de Casos e Controles , Pressão Venosa Central , Terapia Combinada , Creatinina/sangue , Feminino , Hidratação/efeitos adversos , Hidratação/mortalidade , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Terapia de Substituição Renal , Arábia Saudita/epidemiologia , Sepse/sangue , Sepse/diagnóstico , Sepse/mortalidade , Sepse/fisiopatologia , Choque Séptico/sangue , Choque Séptico/diagnóstico , Choque Séptico/mortalidade , Choque Séptico/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
15.
Crit Care Res Pract ; 2014: 410430, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24818017

RESUMO

Background. The objective of this study is to evaluate the impact of an ED sepsis protocol on the time to antibiotics for emergency department (ED) patients with severe sepsis. Methods. Quasiexperimental prospective study was conducted at the emergency department. Consecutive patients with severe sepsis were included before and after the implementation of a sepsis protocol. The outcome measures were time from recognition of severe sepsis/septic shock to first antibiotic dose delivery and the appropriateness of initial choice of antibiotics based on the presumed source of infection. Results. There were 47 patients in preintervention group and 112 patients in postintervention group. Before implementation, mean time from severe sepsis recognition to delivery of antibiotics was 140 ± 97 minutes. During the intervention period, the mean time was 68 ± 67 minutes, with an overall reduction of 72 minutes. The protocol resulted in an overall improvement of 37% in the compliance, as 62% received appropriate initial antibiotics for the presumed source of infection as compared to 25% before the start of protocol. Conclusion. Implementation of ED sepsis protocol improved the time from recognition of severe sepsis/septic shock to first antibiotic dose delivery as well as the appropriateness of initial antibiotic therapy.

16.
Blood ; 123(19): 2988-96, 2014 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-24682267

RESUMO

In this study, we define the genetic landscape of mantle cell lymphoma (MCL) through exome sequencing of 56 cases of MCL. We identified recurrent mutations in ATM, CCND1, MLL2, and TP53. We further identified a number of novel genes recurrently mutated in patients with MCL including RB1, WHSC1, POT1, and SMARCA4. We noted that MCLs have a distinct mutational profile compared with lymphomas from other B-cell stages. The ENCODE project has defined the chromatin structure of many cell types. However, a similar characterization of primary human mature B cells has been lacking. We defined, for the first time, the chromatin structure of primary human naïve, germinal center, and memory B cells through chromatin immunoprecipitation and sequencing for H3K4me1, H3K4me3, H3Ac, H3K36me3, H3K27me3, and PolII. We found that somatic mutations that occur more frequently in either MCLs or Burkitt lymphomas were associated with open chromatin in their respective B cells of origin, naïve B cells, and germinal center B cells. Our work thus elucidates the landscape of gene-coding mutations in MCL and the critical interplay between epigenetic alterations associated with B-cell differentiation and the acquisition of somatic mutations in cancer.


Assuntos
Linfócitos B/metabolismo , Cromatina/genética , Genômica , Linfoma de Célula do Manto/genética , Mutação , Proteínas Mutadas de Ataxia Telangiectasia/genética , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Cromatina/metabolismo , Ciclina D1/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Epigênese Genética , Exoma/genética , Redes Reguladoras de Genes , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Histona-Lisina N-Metiltransferase/genética , Histonas/genética , Histonas/metabolismo , Humanos , Linfoma de Célula do Manto/patologia , Metilação , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Proteína do Retinoblastoma/genética , Análise de Sequência de DNA , Complexo Shelterina , Proteínas de Ligação a Telômeros/genética , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética
17.
Invest Ophthalmol Vis Sci ; 55(2): 1133-42, 2014 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-24458153

RESUMO

PURPOSE: We developed a mathematical model predicting dynamic changes in fluorescent intensity during tear film thinning in either dilute or quenching regimes and we model concomitant changes in tear film osmolarity. METHODS: We solved a mathematical model for the thickness, osmolarity, fluorescein concentration, and fluorescent intensity as a function of time, assuming a flat and spatially uniform tear film. RESULTS: The tear film thins to a steady-state value that depends on the relative importance of the rates of evaporation and osmotic supply, and the resulting increase of osmolarity and fluorescein concentrations are calculated. Depending on the initial thickness, the rate of osmotic supply and the tear film thinning rate, the osmolarity increase may be modest or it may increase by as much as a factor of eight or more from isosmotic levels. Regarding fluorescent intensity, the quenching regime occurs for initial concentrations at or above the critical fluorescein concentration where efficiency dominates, while lower concentrations show little change in fluorescence with tear film thinning. CONCLUSIONS: Our model underscores the importance of using fluorescein concentrations at or near the critical concentration clinically so that quenching reflects tear film thinning and breakup. In addition, the model predicts that, depending on tear film and osmotic factors, the osmolarity within the corneal compartment of the tear film may increase markedly during tear film thinning, well above levels that cause marked discomfort.


Assuntos
Fluoresceína/metabolismo , Corantes Fluorescentes/metabolismo , Modelos Teóricos , Lágrimas/metabolismo , Piscadela/fisiologia , Fluorofotometria , Humanos , Concentração Osmolar , Lágrimas/química , Volatilização
18.
J Anim Physiol Anim Nutr (Berl) ; 98(4): 620-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23782414

RESUMO

This study was planned to investigate the comparative effect of vitamins C (L-ascorbic acid), E (DL-α-tocopherol acetate), probiotics, lower than normal protein level (14%) and combination of these treatments on immune response of male broiler breeders after zinc-induced moulting. One hundred and eighty birds at the age of 65 weeks were induced to moult by mixing zinc oxide (ZnO) in feed at the rate 3000 IU/kg of feed. Upon completion of moulting, birds were divided into six groups (five replicates per group) in a completely randomized design and were fed vitamin C (500 IU/kg), vitamin E (100 IU/kg), lower protein level, probiotics (50 mg/l), and a combination of these components, while one group was kept as control. After completion of moulting phase (5 weeks), the treatment effects were tested as in vitro macrophages engulfment percentage, nitric oxide (NO) production, serum antibody titres against Newcastle disease (ND) and infectious bronchitis (IB). The results showed that in vitro macrophage engulfment percentage in unopsonized conditions was significantly higher in vitamin E-supplemented group. In addition, in opsonized condition, the macrophage engulfment percentage was significantly higher in both vitamin E- and C-supplemented groups. The NO (opsonized and unopsonized) production and antibody titre against ND and IB were significantly higher in vitamin E-supplemented group. It was concluded that vitamin E is a better option for enhanced immune response in broiler breeders after zinc-induced moulting.


Assuntos
Ácido Ascórbico/farmacologia , Galinhas/imunologia , Proteínas Alimentares/administração & dosagem , Muda , Probióticos , alfa-Tocoferol/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Ácido Ascórbico/administração & dosagem , Células Cultivadas , Dieta/veterinária , Macrófagos Peritoneais , Masculino , Óxido Nítrico/metabolismo , Vitaminas , alfa-Tocoferol/administração & dosagem
19.
Transpl Infect Dis ; 15(5): E196-200, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24093964

RESUMO

Pituitary aspergillosis is a very rare disease, documented in only 12 cases. Although seen in both immunocompetent and immunocompromised patients, serious invasive sequelae, such as meningoencephalitis and death, have been noted in immunocompromised patients. Immunocompromised patients are susceptible and require complex multidisciplinary care to contain the spread of infection and maximize outcomes. This is the first case report, to our knowledge, of pituitary aspergillosis in the setting of an organ transplant. A 68-year-old woman presented with cephalgia, left temporal hemianopsia, and ptosis. Non-contrast magnetic resonance imaging of the head revealed a sellar mass, which was believed to be a benign pituitary adenoma. She underwent trans-sphenoidal resection, and subsequent histopathologic examination showed aspergillosis. She was subsequently started on voriconazole. On postoperative day 3, she developed a left anterior cerebral artery ischemic stroke, likely from Aspergillus angioinvasion and occlusion. Her mental status declined further and she died when care was withdrawn.


Assuntos
Antifúngicos/administração & dosagem , Aspergilose/diagnóstico , Infarto da Artéria Cerebral Anterior/complicações , Transplante de Rim/efeitos adversos , Doenças da Hipófise/diagnóstico , Voriconazol/administração & dosagem , Idoso , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Aspergilose/cirurgia , Aspergillus/efeitos dos fármacos , Aspergillus/isolamento & purificação , Evolução Fatal , Feminino , Humanos , Hifas , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Infarto da Artéria Cerebral Anterior/diagnóstico , Infarto da Artéria Cerebral Anterior/microbiologia , Doenças da Hipófise/complicações , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/cirurgia , Hipófise/microbiologia , Esporos Fúngicos
20.
Br Poult Sci ; 54(4): 471-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23829581

RESUMO

1. L-carnitine is a quaternary ammonium compound biologically synthesised from the amino acids methionine and lysine while vitamin E (α-tocopherol) is an important antioxidant. The objective of the present study was to evaluate the ameliorative effects of L-carnitine and vitamin E upon haematological and serum biochemical parameters in ochratoxin A intoxicated birds. 2. Day-old White Leghorn cockerels were acclimatised for 2 d, divided in 12 groups with 20 birds in each group. From d 3 of age, they were given different combinations of ochratoxin A (1.0 and 2.0 mg/kg), L-carnitine (1 g/kg) and vitamin E (200 mg/kg) in feed. Haematological (erythrocyte count, leucocyte count, haemoglobin concentration and haematocrit percentage) and serum biochemical parameters (serum urea, creatinine, albumin, total proteins and alanine aminotransferase) were evaluated. 3. Results confirmed that L-carnitine and vitamin E given alone or combined with 1.0 mg/kg ochratoxin A ameliorated toxin induced alterations in haematological and serum biochemical parameters. This amelioration, however, did not occur when ochratoxin of 2.0 mg/kg was given. 4. L-carnitine and vitamin E in combination have the ability to ameliorate ochratoxin altered haematological and serum biochemical parameters. However, the optimum ratio of L-carnitine + vitamin E, to be used to assure such mitigation of ochratoxin A altered changes in haematological and serum biochemical parameters in cockerels, has yet to be determined. The combination used in this study was indeed sufficient to ameliorate the alterations induced by ochratoxin A up to 1.0 mg/kg feed.


Assuntos
Antioxidantes/farmacologia , Carnitina/farmacologia , Galinhas/fisiologia , Ocratoxinas/toxicidade , alfa-Tocoferol/farmacologia , Ração Animal/análise , Animais , Antioxidantes/administração & dosagem , Análise Química do Sangue/veterinária , Carnitina/administração & dosagem , Dieta/veterinária , Testes Hematológicos/veterinária , Masculino , Ocratoxinas/administração & dosagem , alfa-Tocoferol/administração & dosagem
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