Evaluation of Sertraline as an antioxidant, anti-inflammatory and anticataract

Sertraline can also protect against environmental causes of free radicals such as smoking. Cigarette tar is a source of free radicals which has been found to damage erythrocyte membranes. It was also found that Sertraline and its conjugate metabolites could protect erythrocytes from the membranous damage that is caused by smoking. The ability of Sertraline is claimed to exert many beneficial effects on health, including protection against various diseases such as osteoporosis, lung cancer, and cardiovascular disease. The studies showed that there has been a reduction in the risk of cardiovascular disease in subjects, who had a high intake of flavonoids. Progressive disorder of the lung parenchyma and airways or also known as chronic obstructive pulmonary disease (COPD) which happens to be the third-leading cause of death in the USA. Therapies thus far for COPD, unfortunately, is said to be partially effective with possibilities of side effects.

Ocular Vascular Changes: Choroidal Thickness as an Early Biomarker for Alzheimer’s Disease?

Alzheimer’s disease (AD) is an age-related neurodegenerative and progressive disorder representing the most common form of dementia among the elderly [...]

Quantifying Remission Probability in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a chronic progressive disorder and is associated with significant morbidity and mortality. The concept of T2DM remission and the reversal of diabetic parameters to normal levels has been gaining momentum over the past years. T2DM remission is increasingly being recognized by various global guidelines. Multiple models have been developed and validated for quantifying the extent of remission achieved. Based on favorable clinical evidence, T2DM remission can be considered as the therapeutic goal in diabetes management and, in select cases, as an alternative to expensive treatment options, which can be burdensome as T2DM progresses. This narrative review discusses the available strategies, such as lifestyle interventions, physical activity, bariatric surgery, medical nutrition therapy, and non-insulin glucose-lowering medications, for achieving T2DM remission. Although the concept of T2DM remission has emerged as a real-world option, effective implementation in routine clinical practice may not be feasible until long-term studies prove the efficacy of different approaches in this regard.

Potential Therapeutic Effects of Ursodeoxycholic Acid in Comparison to Ramipril in a Rat model of Diabetic Nephropathy

Background & Aim Diabetic nephrectomy (DN) is a chronic progressive disorder that complicates long standing diabetes. Albuminuria is a prominent clinical feature of DN. Ursodeoxycholic acid (UDCA) is a physiologic hydrodrophillic bile acid that is therapeutically used in the treatment of primary biliary cirrhosis. It is known to alleviate endoplasmic reticulum (ER) stress in podocytes. In comparison to Ramipril as a standard ACEI therapy of DN, the present study was designed to investigate the effect of UDCA treatment on DN in association with renal biomarkers changes. Method Four groups of male Wister rats (6 per group) were designed; Normal control group, DN untreated group (High fat diet + STZ injection of 45 mg/kg + uninephrectomy), DN/Ramipril group; (1 mg/kg/d orally for 12 weeks) and DN/UDCA group (40 mg/kg/d orally for 12 weeks). Results DN rats treated with UDCA for 12 weeks exhibited significant decrease in ER stress marker, ATF6 with mean percentage value of 73.8% and improvement of podocyte structural deformities that is accompanied by a significant reduction in albuminuria by mean percentage value of 43.8% comparatively to Ramipril that caused reduction in ATF6 level with mean percentage value of 65.5% and reduction in albuminuria by mean percentage value of 50.2%. The remarkable improvement in metabolic profile and the neutral effect on blood pressure in UDCA treated group could explain the renoprotection at histopathological basis rather than the proved hemodynamic effect of ramipril. Conclusion Participation of ER stressmediated apoptosis in the pathophysiology of diabetic nephropathy make the UDCA a potential therapeutic option or add-on therapy due to its anti-apoptotic property apart from classic metabolic and hemodynamic aspects.

LXR agonist Prevents Peripheral Neuropathy and modifies PNS immune cells in Aged Mice

Peripheral neuropathy is a common and progressive disorder in the elderly that interferes with daily activities and increases the risk of injury. It is of importance to find efficient treatments to treat or delay this age-related neurodegeneration. We previously demonstrated that activation of the cholesterol sensor Liver X receptor (LXR) with the potent agonist GW3965, alleviates pain in a diet-induced obesity model. Because cholesterol had also been linked to neuropathy during aging, we sought to test whether LXR activation may improve neuropathy and pain in aged mice by treating 21-month-old mice for 3 months with GW3965. Treatment resulted in a significant increase in nerve fibers of the sub-basal plexus, accompanied by a change in polarization, metabolism, and cholesterol content of macrophages in the sciatic nerve. These results suggest that activation of the LXR may block the progression of neuropathy associated with aging by modifying nerve-immune cell cholesterol, thereby providing new pathways to target in efforts to delay neuropathy during aging.

The Beneficial Role of Natural Endocrine Disruptors: Phytoestrogens in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia with a growing incidence rate primarily among the elderly. It is a neurodegenerative, progressive disorder leading to significant cognitive loss. Despite numerous pieces of research, no cure for halting the disease has been discovered yet. Phytoestrogens are nonestradiol compounds classified as one of the endocrine-disrupting chemicals (EDCs), meaning that they can potentially disrupt hormonal balance and result in developmental and reproductive abnormalities. Importantly, phytoestrogens are structurally, chemically, and functionally akin to estrogens, which undoubtedly has the potential to be detrimental to the organism. What is intriguing, although classified as EDCs, phytoestrogens seem to have a beneficial influence on Alzheimer’s disease symptoms and neuropathologies. They have been observed to act as antioxidants, improve visual-spatial memory, lower amyloid-beta production, and increase the growth, survival, and plasticity of brain cells. This review article is aimed at contributing to the collective understanding of the role of phytoestrogens in the prevention and treatment of Alzheimer’s disease. Importantly, it underlines the fact that despite being EDCs, phytoestrogens and their use can be beneficial in the prevention of Alzheimer’s disease.

Chronic and progressive deficits after a single closed head injury in mice

Background: Acute injury following brain trauma may evolve into a chronic and progressive disorder. Assessment of chronic consequences of TBI must distinguish between effects of age and injury. Methods: C57BL/6 mice receive single closed head injury (CHI) and are analyzed at 14DPI or 180DPI for cortical atrophy and 7DPI or 180DPI for behavioral outcomes. Results: CHI induces ipsilesional atrophy at 14DPI that increases 180 DPI due to an effect of age. On open field, injured mice develop a turn bias at 180DPI not present at 7DPI. On rotarod, injured mice have shorter latencies at 7DPI, but not at 180DPI due to worsening performance of aging uninjured mice. On beam walk, both groups at 180DPI more slowly traverse a 2cm and 1cm beam than at 7DPI. Foot-faults show no significant effects of age or injury. Limb position was assessed using DeeplabcutTM markerless tracking followed by computation of absition (integral of limb displacement over time) using custom Python scripts. On the 2cm beam, age increased absition in all limbs of uninjured mice and both forelimbs of injured mice. Injury increased left hindlimb absition at 7DPI. On the 1cm beam both forelimbs and the left hindlimb of injured mice at 180DPI have larger absition than uninjured mice at 180DPI or injured mice at 7DPI. These data suggest chronic and progressive motor deficits of injured mice at 180DPI. Conclusions: A single impact produces ipsilesional cortical atrophy and chronic and progressive motor deficits. Quantitative behavioral analysis reveals deficits not seen using standard outcomes.

Gaucher disease: achievements and prospects

Gaucher disease (GD) is the most common lysosomal storage disorder, resulting from a deficiency in the activity of a lysosomal enzyme glucocerebrosidase, which is involved in the catabolism of sphingolipids. The phenomenal progress in understanding the pathogenesis and development of specific therapy of this disease over the past 60 years dramatically changed the clinical phenotype of GD, turning a severe progressive disorder into an asymptomatic metabolic defect. The evolution of the understanding of GD associated with fundamental discoveries in the field of cell biology, biochemistry and genetics may be of interest to a wide audience as a model of the effective work of the scientific community in the treatment of rare metabolic pathology.

GWAS Hits for Bilateral Convergent Strabismus with Exophthalmos in Holstein Cattle Using Imputed Sequence Level Genotypes

Bilateral convergent strabismus with exophthalmos (BCSE) is a malformation of the eyes and is recognized as a mild but progressive disorder that affects cattle in the first two years of life. This most likely inherited disorder is rarely described in cattle resembling autosomal dominantly inherited forms of human progressive external ophthalmoplegia (PEO). In German Braunvieh cattle, two linked genome regions were found that could be responsible for the development and/or progression of BCSE. The goal of this study was to phenotypically characterize BCSE in Holstein cattle from Germany and Switzerland as well as to identify associated genome regions by GWAS. The clinicopathological phenotype of 52 BCSE-affected Holstein cattle was in accordance with the phenotype described in German Braunvieh cattle, but in addition, signs of degeneration and cellular infiltration in the eye muscles were found. By using imputed sequence level genotype data, three genome-wide significant GWAS hits were revealed on different chromosomes that were not detected by initial GWAS based on high density SNP array data highlighting the usefulness of this approach for mapping studies. The associated genome regions include the ABCC4 gene as well as markers adjacent to the NCOR2 and DNAJC3 genes all illustrating possible functional candidate genes. Our results challenge a monogenic mode of inheritance and indicate a more complex inheritance of BCSE in Holstein cattle. Furthermore, in comparison to previous results from German Braunvieh cattle, it illustrates an obvious genetic heterogeneity causing BSCE in cattle. Subsequent whole genome sequencing (WGS)-based analyses might elucidate pathogenic variants in the future.

Con-Ker: A Convolutional Neural Network Based Approach for Keratoconus Detection and Classification

The paper is on the detection of keratoconus a corneal progressive disorder leading to the thinning and also protrusion of the cornea associated with symptoms like astigmatism, increased sensitivity to bright light, glare, clouded vision, eye irritation, and others, In recent times there has been increasing in a number of keratoconus cases. Keratoconus is normally described as a non-inflammatory pathology. The main contribution of the paper is to facilitate detection and also classification of the keratoconus based on the progression using Convolution neural networks. The paper is about the implementation of different CNN algorithms which will classify the disorder based on the progression into 4 different classes. The CNN algorithms analyze the corneal topography of the eye and classify based on the severity of the disorder. We introduce an effective CNN model called CON-KER for the detection and classification of the disorder. Further CNN algorithms like Alexnet and Vgg 19 were implemented for the same. The results show that the CON-KER model has yielded an accuracy of 96.26% compared to other algorithms like vgg19 which yielded 94.76% and AlexNet with 86% accuracy. This work can help by assisting the ophthalmologist in reducing diagnostic errors and also help in the rapid screening of the patients.