Objectives: (1) To assess the risk of Obstructive Sleep Apnea (OSA) using a pre-designed questionnaire; (2) To assess the periodontal parameters like pocket probing depth (PPD) and clinical attachment loss (CAL) in the study subjects and (3) To determine the association between the shared risk factors of OSA and periodontitis.
Background Of The Study: Periodontitis is a microbially associated, host-mediated inflammatory disease that results in the loss of periodontal attachment. It has multifactorial etiology and has been linked to an array of systemic diseases.
Alpha-1 acid glycoprotein (AGP) is a significant drug binding acute phase protein that is present in rats. AGP levels are known to increase during tissue injury, cancer and infection. Accordingly, when determining effective drug ranges and toxicity limits, consideration of drug binding to AGP is essential.
View Article and Find Full Text PDFSafety margin, a key aspect of any non-clinical toxicity studies, is calculated by dividing the systemic exposure (AUC) at NOAEL (No Adverse Effect Level) in toxicity studies by the clinical exposure. The validity of using total plasma concentration (C) to calculate AUC is often discussed, as it is the unbound plasma concentration (C) that elicits the pharmacological and toxicological effects. Data regarding plasma protein binding across species was collected for 114 MSD small molecule compounds which had been discontinued from development either due to non-clinical toxicity or due to clinical Adverse Effects.
View Article and Find Full Text PDFThe purpose of this research was to assess variability in pharmacokinetic profiles (PK variability) in preclinical species and identify the risk factors associated with the properties of a drug molecule that contribute to the variability. Exposure data in mouse, rat, dog, and monkey for a total of 16,592 research compounds studied between 1999 and 2013 were included in the analysis. Both in vivo study parameters and in silico/experimental physicochemical properties of the molecules were analyzed.
View Article and Find Full Text PDFSuvorexant (Belsomra) is a dual orexin receptor antagonist approved for the treatment of insomnia. Because of its pharmacology within the central nervous system, intended therapeutic indication, and first-in-class status, an assessment of suvorexant abuse liability potential was required prior to marketing approval. The nonclinical abuse liability potential studies for suvorexant included: 1) rat drug-dependence model to assess physical dependence following abrupt cessation; 2) rat drug-discrimination model to examine the potential similarity of the interoceptive or subjective effects of suvorexant to those elicited by zolpidem and morphine; 3) self-administration model to assess the relative reinforcing efficacy of suvorexant in rhesus monkeys conditioned to self-administer methohexital.
View Article and Find Full Text PDFCombating Type-2 diabetes mellitus is a pivotal challenge in front of the present world. Several lines of therapy are in practice for resisting this deadly disease which often culminates with cardiovascular complexities, neuropathy and retinopathy. Among various therapies, administration of alpha glucosidase inhibitors is common and widely practiced.
View Article and Find Full Text PDFPurpose: The purpose of the study was to differentiate ischemic central retinal vein occlusion (CRVO) from nonischemic CRVO during the early acute phase using plasma homocysteine as a biochemical marker.
Methods: Fasting plasma homocysteine, serum vitamin B12, and folate levels were measured in 108 consecutive unilateral elderly adult (age >50 years) ischemic CRVO patients in the absence of local and systemic disease and compared with a total of 144 age and sex matched nonischemic CRVO patients and 120 age and sex matched healthy control subjects.
Results: Homocysteine level was significantly increased in the patients with ischemic CRVO in comparison with nonischemic CRVO patients (p = 0.
Locoweed plants in the southwestern United States often harbour a slow-growing endophytic fungus, Undifilum oxytropis (Phylum: Ascomycota; Order: Pleosporales), which produces a toxic alkaloid, swainsonine. Consumption of U. oxytropis by grazing animals induces a neurological disorder called locoism for which the toxic alkaloid swainsonine has been reported to be the causal agent.
View Article and Find Full Text PDFUndifilum oxytropis (Phylum: Ascomycota; Family: Pleosporaceae) is a slow growing endophytic fungus that produces a toxic alkaloid, swainsonine. This endophyte resides in locoweeds, which are perennial flowering legumes. Consumption of this fungus by grazing animals induces a neurological disorder called locoism.
View Article and Find Full Text PDFThe application of terahertz time-domain spectroscopy (THz-TDS) and imaging to differentiate flat and curved surfaces in reflection via the THz Gouy phase shift is demonstrated. For a THz-TDS system that is aligned for reflection from a flat surface, the presence of a curved surface displaces the image focal plane from the detector plane, resulting in a Gouy phase shift. The potential of utilizing this configuration for estimating the number and size of curved objects is discussed with particular emphasis on agriculture crop yield estimates.
View Article and Find Full Text PDFIn previous studies, the free radical generating toxin tertiary butylhydroperoxide (t-BuOOH) was found to induce significant cell death in human cortical neuronal cells (HCN2 cells). Pretreatment with the poly (ADP-ribose) polymerase (PARP) inhibitor nicotinamide was able to prevent HCN2 cell death. In this study it is observed that apoptosis is induced following the addition of t-BuOOH at 6 h as indicated by TUNEL-positive cells.
View Article and Find Full Text PDFGenistein, a soy isoflavone, has been shown to mimic the pharmacological actions of the endogenous steroid estrogen with which it has structural similarities. There is now evidence that the genistein can prevent disorders-like heart diseases, cancer and diabetes as well. However, very few studies have looked at the effect of genistein on the central nervous system.
View Article and Find Full Text PDFEnvironmental homogeneity is being continuously disturbed and affected by artificially introduced loads of chemical toxicants that also include heavy metals. The Tiljala wetlands of the eastern fringe of Calcutta, West Bengal (India) are a virtual sink for the deposition of urban and industrial wastes that get admixed with the aquatic environment. We have selected Lemna minor (duckweed), as a representative of the biota surviving therein for the present study.
View Article and Find Full Text PDFCytoskeleton disruption is a process by which oxidative stress disrupts cellular function. This study compares and contrasts the effect of oxidative stress on the three major cytoskeleton filaments, microfilaments (MFs), microtubule (MT), and vimentin in human cortical neuronal cell line (HCN2). HCN2 cells were treated with 100 microM tertiary butylhydroperoxide (t-BuOOH), a free radical generating neurotoxin for 1, 3, or 6 h.
View Article and Find Full Text PDFIt is well known that the generation of oxygen radicals can cause neuronal death by both apoptosis and necrosis, which may lead to the onset of neurodegenerative diseases. In previous in vivo studies, nicotinamide was found to prevent both DNA fragmentation and apoptosis that were induced by free radical generating toxins like tertiary butylhydroperoxide (t-BuOOH). Nicotinamide is a precursor for NAD and is an inhibitor of the enzyme poly(ADP-ribose) polymerase (PARP).
View Article and Find Full Text PDFIn previous studies with mice the oxygen radical generating neurotoxin tertiary butylhydroperoxide (t-BuOOH) was used to mimic the oxidative injury that has been implicated in neurodegenerative diseases. In addition, previous studies have shown that the poly (ADP-ribose) polymerase (PARP) inhibitor nicotinamide is able to prevent DNA fragmentation and apoptosis that is induced by t-BuOOH in mouse brain. However, the molecular mechanism(s) by which nicotinamide is able to protect human brain cells at the cellular level is not clear.
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