Stroke is the leading cause of disability in adults world-wide. Well-recognized environmental risk factors for stroke include hypertension, smoking, diabetes mellitus, atrial fibrillation and atherosclerosis. Ischemic stroke, which accounts for ~85% of all stroke, is mainly caused by either intracranial thrombosis or extracranial embolism; hemorrhagic stroke can be classified as either intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH). Metalloproteins and metals play key roles in epigenetic events in living organisms, including hypertension, the most important modifiable risk factor for stroke. For example, Zinc (Zn) is located in the catalytic site of angiotensin-converting enzyme (ACE), a component of the renin-angiotensin system which is important for blood pressure regulation., Cadmium, lead, selenium, calcium, magnesium, sodium, potassium and other metals are well recognized to be associated with stroke risk and prognosis. Concentrations of metalloproteins in the blood plasma are important factors in a number of diseases including iron overload (hemochromatosis) and copper overload (Wilson’s disease). Exposure to toxic metals and pollutants in the air, water or food can lead to altered metabolism, which may alter levels of metalloproteins in plasma. Metalloproteins may be important for disease diagnosis. Thus, this study sought to develop a method of detecting metals and metalloproteins levels for distinguishing stroke types. In search of these, different analytical techniques such as affinity chromatography, size exclusion chromatography (SEC), inductively coupled plasma mass spectrometry (ICPMS) and electrospray mass spectrometry (ESIMS) were used.
Insulin glargine is a long-acting analogue of human insulin that has been used to manage hyperglycemia in patients with diabetes mellitus (DM) for nearly 20 years. Insulin glargine has a relatively constant concentration-time profile that mimics basal levels of insulin and allows for once-daily administration. MYL-1501D is a biosimilar insulin glargine designed to offer greater access of insulin glargine to patients, with comparable efficacy and safety to the marketed reference product. We conducted a comprehensive panel of studies based on a formal analysis of critical quality attributes to characterize the structural and functional properties of MYL-1501D and reference insulin glargine products available in the United States and European Union. MYL-1501D was comprehensively shown to have high similarity to the reference products in terms of protein structure, metabolic activity (both in vitro cell-based assays and in vivo rabbit bioassays), and in vitro cell-based assays for mitogenic activity. The structural analyses demonstrated that the primary protein sequence was identical, and secondary and tertiary structures are similar between the proposed biosimilar and the reference products. Insulin receptor binding affinity and phosphorylation studies also established analytical similarity. MYL-1501D demonstrated high similarity in different metabolic assays of glucose uptake, adipogenesis activity, and inhibition of stimulated lipolysis. Rabbit bioassay studies showed MYL-1501D and EU-approved insulin glargine are highly similar to US-licensed insulin glargine. These product quality studies show high similarity between MYL-1501D and licensed or approved insulin glargine products and suggest the potential of MYL-1501D as an alternative cost-effective treatment option for patients and clinicians.
& In the last three decades, chiral high-performance liquid chromatography (HPLC) has proven to be one of the best methods for the direct separation and analysis of enantiomers because it can separate a wide variety of nonvolatile compounds. A mixture of chiral 2-(1H-imidazol-1-yl) cyclohexanol stereoisomers were prepared in-house and chirally resolved using R-(-)-mandelic acid. Chiral resolution of the selector was confirmed using circular dichroism spectropolarimetry and chiral capillary electrophoresis. A new chiral imidazolium-based surface-confined ionic liquid stationary phase was synthesized using this chiral selector and investigated for the separation of phenanthro[3,4-c] phenanthrene (hexahelicene), an atropisomeric polyaromatic hydrocarbon (PAH). Hexahelicene enantiomers were successfully separated under normal phase conditions using hexane=dichloromethane mobile phases.
Stroke is the most common cause of morbidity and death in the Western world, following ischemic heart disease and cancer. Stroke can be of two types, ischemic or hemorrhagic, with ischemic stroke accounting for approximately 85% of the total number of strokes. Well-recognized environmental risk factors for stroke include hypertension, smoking, diabetes mellitus, atrial fibrillation, and atherosclerosis. Computed tomography (CT) scanning is used to diagnose hemorrhagic stroke but is relatively ineffective and may remain normal in patients with mild ischemic strokes. Magnetic Resonance Imaging (MRI) is more sensitive in detecting ischemia than CT, especially in the diagnosis of mild stroke but it is still not 100% sensitive or precise. A simple and low-cost, rapid blood test to confirm a clinical and imaging diagnosis of ischemic stroke would be extremely useful. Based on this, the central idea of this paper is to develop a method that would be applicable to a statistically viable sample set to provide candidate biomarkers for distinguishing stroke types. In search of these candidate biomarkers, different analytical separation techniques have been used to screen for major differences in the proteomes of patients plasma samples with proteomics for identification.
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