Introduction: Pharmacokinetic/pharmacodynamic modelling has emerged as a valuable technique for understanding drug exposure and response relationships in drug development. Pharmacokinetic data are often obtained by taking multiple blood samples, which may disturb physiological parameters and complicate study designs. Wearable automatic blood sampling systems can improve this limitation by collecting dried blood samples at programmable time points without disrupting cardiovascular parameters.
View Article and Find Full Text PDFConducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the years to improve both the data quality and the well being of our animal subjects. Of particular interest for us has been the use of telemetry-based data acquisition for conducting studies on cardiovascular (CV) function.
View Article and Find Full Text PDFIntroduction: A safety pharmacology study detects and evaluates potential side effects of a new drug on physiological function at therapeutic levels and above and, in most cases, prior to the initiation of clinical trials. The aim of this study was to investigate the effects of environmental and biological factors on resting heart rate (HR), a representative cardiac parameter in cardiovascular safety pharmacology.
Methods: Over twenty years, 143 dogs (Beagles, Labradors and mongrels) received implanted telemetry transmitters to measure aortic pressure (AP), left ventricular pressure (LVP), Electrocardiogram (ECG) and body temperature.
In this study, we propose a 3D non-linear finite element (FE) unit-cell model to investigate the post-yield behavior of mineralized collagen fibril arrays (FAY). We then compare the predictions of the model with recent micro-tensile and micropillar compression tests in both axial and transverse directions. The unit cell consists of mineralized collagen fibrils (MCFs) embedded in an extrafibrillar matrix (EFM), and the FE mesh is equipped with cohesive interactions and a custom plasticity model.
View Article and Find Full Text PDFDifficult airway and intubation can have dangerous sequela for patients if not managed promptly. This issue is even more challenging among obstetric patients. Several studies have aimed to determine whether the test to predict a difficult airway or difficult intubation, is higher in accuracy.
View Article and Find Full Text PDFIn this study, 3D finite element analyses (FEA) are conducted to quantify the orthotropic elastic properties and investigate the load transfer mechanism of bone at the sub-lamellar level. Three finite element (FE) unit cells with periodic boundary conditions are presented to model a two-scale microstructure of bone including a mineralized collagen fibril (MCF), the extrafibrillar matrix (EFM) and the resulting fibril array (FAY) under arbitrary loading. The axial and transverse elastic properties of the FAY computed by FEA are calibrated with unique experimental results on ovine micro-samples showing a coherent fibril orientation.
View Article and Find Full Text PDFPantothenate Kinase-associated Neurodegeneration (PKAN) is an autosomal recessive disorder that is caused by variation in pantothenate kinase-2 gene () gene on chromosome 20. The common presentation of this disease includes progressive dystonia, Parkinsonism, retinopathy, cognitive impairment, and spasticity. The typical magnetic resonance imaging finding is sign in globus pallidus and not pathogenic and not found in all patients.
View Article and Find Full Text PDFDyskinesia refers to any involuntary movement, such as chorea, dystonia, ballism that affect any part of the body. Levodopa-induced dyskinesia is a neurological disorder that afflicts many patients with Parkinson disease usually 5 years after the onset of levodopa therapy and can cause severe disability. The pathophysiology of this dyskinesia is complex and not fully understood.
View Article and Find Full Text PDFPantothenate Kinase-Associated Neurodegeneration (PKAN) is an autosomal recessive disorder characterized by a mutation in the 2 gene. The clinical presentation may range from only speech disorder to severe generalized dystonia, spasticity, Visual loss, dysphagia and dementia. The hallmark of this disease is eyes of the tiger sign in the medial aspect of bilateral globus pallidus on T2-weighted MRI that is a hyperintense lesion surrounded by hypointensity.
View Article and Find Full Text PDFPantothenate kinase-associated neurodegeneration (PKAN) is the most common form of neurodegeneration with brain iron accumulation, it is an autosomal recessive disease due to mutation in PANK 2 on chromosome 20, which causes the accumulation of iron in basal ganglia and production of free radicals that cause degeneration of the cells. Deferiprone is an iron chelator that was used in treatment of thalassemia patients, it can cross the blood-brain barrier and reverse the iron deposition in the brain. Five patients with genetically confirmed PKAN received 15 mg/kg deferiprone twice daily.
View Article and Find Full Text PDFCaspian J Intern Med
January 2017
Background: Stiff person syndrome (SPS) is a rare neurological disease resulting in stiffness and spasm of muscles. It initially affects the axial muscles and then spread to limb muscles. Emotional stress exacerbated the symptoms and signs of the disease.
View Article and Find Full Text PDFObjective: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. Metformin is a biguanide commonly used to improve PCOS symptoms. Effect of metformin on the levels of serum homocysteine (Hcy) in PCOS women is unclear.
View Article and Find Full Text PDFIntroduction: Children are more risk-prone group of the population and low birth weight (LBW) is the leadingcause of newborns' mortality and morbidity. LBW is defined as child's birth weight lower than 2500 g. Many maternal and fetal factors are determined as risk factors of LBW.
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