A novel CNN based Alzheimer's disease classification using hybrid enhanced ICA segmented gray matter of MRI.

Predicting Alzheimer's Disease (AD) from Mild Cognitive Impairment (MCI) and Cognitive Normal (CN) has become wide. Recent advancement in neuroimaging in adoption with machine learning techniques are especially useful for pattern recognition of medical imaging to assist the physician in early diagnosis of AD. It is observed that the early abnormal brain atrophy and healthy brain atrophy are same. In our endeavor, we proposed a model that differentiation MCI and CN more accurately to escalate early diagnosis of AD. In this paper, we applied both binary and multi class classification, 4463 Slide are divided in to two groups one for training and another for testing at subject level, achieves 100 % of accuracy, 100 % of sensitivity and 100 % of Specificity in the case of AD-CN. 96.2 % of accuracy, 93 % Sensitivity and 100 % Specificity in the case of AD-MCI. 98.0 % of accuracy, 96 % of sensitivity, 100 specificity in the case of CN-MCI. 86.7 % accuracy, 89.6 % of sensitivity, 86.61 % of specificity in the case of AD-MCI-CN. The model is further tested using 10 fold cross validation and obtained 98.0 % of accuracy, to differentiate CN and MCI. Our proposed framework generated results are significantly improving prediction of AD from MCI and CN than compare to the previous work flows and used to differentiate the AD at early stage.

Convolution neural network-based Alzheimer's disease classification using hybrid enhanced independent component analysis based segmented gray matter of T2 weighted magnetic resonance imaging with clinical valuation.

In recent times, accurate and early diagnosis of Alzheimer's disease (AD) plays a vital role in patient care and further treatment. Predicting AD from mild cognitive impairment (MCI) and cognitive normal (CN) has become popular. Neuroimaging and computer-aided diagnosis techniques are used for classification of AD by physicians in the early stage. Most of the previous machine learning techniques work on handpicked features. In the recent days, deep learning has been applied for many medical image applications. Existing deep learning systems work on raw magnetic resonance imaging (MRI) images and cortical surface as an input to the convolution neural network (CNN) to perform classification of AD. AD affects the brain volume and changes the gray matter texture. In our work, we used 1820 T2-weighted brain magnetic resonance volumes including 635 AD MRIs, 548 MCI MRIs, and 637 CN MRIs, sliced into 18,017 voxels. We proposed an approach to extract the gray matter from brain voxels and perform the classification using the CNN. A Gaussian filter is used to enhance the voxels, and skull stripping algorithm is used to remove the irrelevant tissues from enhanced voxels. Then, those voxels are segmented by hybrid enhanced independent component analysis. Segmented gray matter is used as an input to the CNN. We performed clinical valuation using our proposed approach and achieved 90.47% accuracy, 86.66% of recall, and 92.59% precision.

Cobalt chloride attenuates hypobaric hypoxia induced vascular leakage in rat brain: molecular mechanisms of action of cobalt chloride.

This study reports the efficacy of cobalt preconditioning in preventing hypobaric hypoxia induced vascular leakage (an indicator of cerebral edema) using male Sprague-Dawley rats as model system. Exposure of animals to hypobaric hypoxia led to a significant increase in vascular leakage, reactive oxygen species (ROS), nitric oxide (NO), and vascular endothelial growth factor (VEGF) levels. There was a marked increase in Nuclear Factor kappaB (NFkappaB) DNA binding activity and levels of pro-inflammatory cytokines such as Monocyte chemoattractant protein (MCP-1), Interferon-gamma (IFN-gamma), Interleukin-1 (IL-1), and Tumor Necrosis Factor-alpha (TNF-alpha) and cell adhesion molecules such as Vascular Cell Adhesion Molecule-1 (VCAM-1), and P-selectin. Chemical preconditioning by cobalt for 7 days (12.5 mg Co/kg b.w., oral) significantly attenuated cerebral vascular leakage and the expression of inflammatory mediators induced by hypoxia. Administration of NFkappaB inhibitor, curcumin (50 mg/kg b.w.; i.p.) appreciably inhibited hypoxia induced vascular leakage indicating the involvement of NFkappaB in causing vascular leakage. Interestingly, cobalt when administered at 12.5 mg Co/kg b.w. (i.p.), 1 h before hypoxia could not prevent the vascular leakage indicating that cobalt per se did not have an effect on NFkappaB. The lower levels of NFkappaB observed in the brains of cobalt administered animals might be due to higher levels of antioxidant and anti-inflammatory proteins (hemeoxygenase-1 and metallothionein). To conclude cobalt preconditioning inhibited hypobaric hypoxia induced cerebral vascular leakage by lowering NFkappaB DNA binding activity and its regulated pro-inflammatory mediators. This is contemplated to be mediated by cobalt induced reduction in ROS/NO and increase in HO-1 and MT.

Mechanism of tert-butylhydroperoxide induced cytotoxicity in U-937 macrophages by alteration of mitochondrial function and generation of ROS.

tert-Butylhydroperoxide has been reported to inhibit growth and induce apoptosis in number of cell types, but little is known about the molecular mechanism mediating these effects. In the present study, we determined the molecular pathways that lead to apoptosis after treatment of cells with t-BOOH. The cells were exposed to different concentrations of t-BOOH (100-750 microM) for 1-4 h and various parameters such as cytotoxicity, ROS (reactive oxygen species) generation, MMP (mitochondrial membrane potential), intracellular Ca++ levels and expression of various proteins involved in apoptosis were determined. Exposure of U-937 cells to t-BOOH induced cytotoxicity in a time dependent manner with about 50% toxicity at 400 microM t-BOOH in 4h. t-BOOH treatment resulted in a time dependent increase in reactive oxygen species levels, Ca++ influx and annexin V positive cells. There was a significant fall in MMP following exposure to t-BOOH with time. t-BOOH treatment of U-937 cells leads to apoptosis, which is accompanied by activation of caspase-3. The caspase-3 inhibitor (Ac-DEVD-CHO) inhibits the cytotoxicity induced by t-BOOH, indicating a direct link between caspase-3 activation and cell death. This activation of apoptosis is accompanied by release of cytochrome c, down regulation of anti-apoptotic protein Bcl-2 levels with concurrent increase in pro-apoptotic proteins Bax and Bad levels. These observations indicate that t-BOOH induces cell death in U-937 macrophages by apoptosis, which is mediated through mitochondrial pathway.

Quercetin protects C6 glial cells from oxidative stress induced by tertiary-butylhydroperoxide.

The anti-oxidant and cyto-protective activity of quercetin against tertiary-butylhydroperoxide (t-BOOH) induced oxidative stress on C6 glial cells is reported. Exposure of the cells to t-BOOH resulted in a significant increase in cytotoxicity, reactive oxygen species (ROS) generation and lipid peroxidation. There was a significant increase in DNA strand breaks and fall in reduced GSH levels in cells exposed to t-BOOH. A significant increase in calcium ion influx was noticed in cells exposed to t-BOOH. Pre-treatment of cells with quercetin, vitamin C (vit C), Trolox, and deferoxamine (DFO) significantly inhibited t-BOOH induced cytotoxicity and ROS generation. Pretreatment of cells with quercetin, Trolox and DFO inhibited the DNA damage, maintained higher GSH levels and prevented calcium influx significantly. Although vit C protected the cells from cytotoxicity induced by t-BOOH, the intracellular Ca(2+) levels were significantly higher than the control cells. However, anti-oxidants like butylated hydroxy toluene (BHT), vitamin E (vit E), N-acetyl cysteine (NAC) did not have significant cytoprotection against t-BOOH induced oxidative injury in C6 glial cells.

Cytoprotective and antioxidant activity of Rhodiola imbricata against tert-butyl hydroperoxide induced oxidative injury in U-937 human macrophages.

The present study reports cytoprotective and antioxidant activity of aqueous and alcoholic extracts of Rhodiola imbricata rhizome on tert-butyl hydroperoxide (tert-BHP) induced cytotoxicity in U-937 human macrophages. There was an increase in cytotoxicity and apoptosis significantly in the presence of tert-BHP over control cells. The tert-BHP induced cytotoxicity can be attributed to enhanced reactive oxygen species (ROS) production which in turn is responsible for fall in reduced glutathione (GSH) levels; further there was a significant decrease in mitochondrial potential and increase in apoptosis and DNA fragmentation. Both aqueous and alcoholic extracts of Rhodiola rhizome at a concentration of 250 microg/ml were found to inhibit tert-BHP induced free radical production, apoptosis and to restore the anti-oxidant levels to that of the control cells. The alcoholic extract of Rhodiola showed higher cytoprotective activities than aqueous extract. These observations suggest that the alcoholic and aqueous extracts of Rhodiola have marked cytoprotective and antioxidant activities.

Immunomodulatory effects of Premna tomentosa extract against Cr (VI) induced toxicity in splenic lymphocytes--an in vitro study.

Premna tomentosa (L. Verbanacae) is a widely used medicinal plant. Our earlier studies show that the extract of P. tomentosa leaves prevents acetaminophen-induced hepatotoxicity owing to its antioxidant property. In the present study, we have investigated the immunomodulatory effects of P. tomentosa extract against Chromium (VI) induced immunosuppression in splenic lymphocytes. Chromium (Cr) addition at a concentration of 5 microg showed an increase in cytotoxicity, apoptosis and reactive oxygen species (ROS) and a decrease in lymphocyte proliferation and antioxidant levels, whereas pre-treatment of the cells with P. tomentosa extract (at 500 microg concentration) resulted in decreased cytotoxicity and ROS levels. Further, the drug treatment also maintained antioxidant levels and restored lymphocyte proliferation similar to that of control cells. The results indicated that the leaf extract of P. tomentosa has cytoprotective and immunomodulatory activities.

Evaluation of antioxidant activity of leaf extract of Seabuckthorn (Hippophae rhamnoides L.) on chromium(VI) induced oxidative stress in albino rats.

The present study reports the antioxidant activity of Seabuckthorn (Hippophae rhamnoides), family Elaegnaceae, on chromium induced oxidative stress in male albino rats. Oxidative stress was induced in the rats by force-feeding of potassium dichromate equivalent to a dose of 30mg/kg body weight (BW) of chromium(VI) for 30 days. Administration of chromium decreased the body weight and increased organ to body weight ratio significantly. Chromium treatment significantly decreased reduced glutathione (GSH), and increased malondialdehyde (MDA) and creatine phosphokinase (CPK) levels; further it also enhanced glutamate oxaloacetate transferase (GOT) and glutamate pyruvate transferase (GPT) levels in the serum. Different doses of the alcoholic leaf extract of Seabuckthorn were evaluated for the protection against the chromium induced oxidative stress. The results show that the leaf extract at a concentration of 100 and 250mg/kg BW protected the animals from the chromium induced oxidative injury significantly.

Cytoprotective activity of Amla (Emblica officinalis) against chromium (VI) induced oxidative injury in murine macrophages.

The cytoprotective and immunomodulating properties of Emblica officinalis (Amla) against chromium (VI) induced oxidative damage are reported. Chromium (VI) at 1 micro g/mL concentration was highly cytotoxic. It enhanced free radical production and decreased reduced glutathione (GSH) levels and glutathione peroxidase (GPx) activity in macrophages. The presence of Amla resulted in an enhanced cell survival, decreased free radical production and higher antioxidant levels similar to that of control cells. Further, chromium (VI) treatment resulted in decreased phagocytosis and gamma-interferon (gamma-IFN) production while Amla inhibited chromium induced immunosuppression and restored both phagocytosis and gamma-IFN production by macrophages significantly.

Cyto-protective and immunomodulating properties of Amla (Emblica officinalis) on lymphocytes: an in-vitro study.

The fruits extracts of Emblica officinalis (Amla) has been reported to have strong anti-oxidant properties. There is a paucity of studies on the immunomodulatory properties of fruit extracts of Amla in immuno-compromised states, with the emphasis on lymphocytes. Therefore, the aim of the study was to determine the anti-oxidant and immunomodulatory properties of Amla using chromium (VI) as an immunosuppressive agent. Chromium (Cr) treatment results in enhanced cytotoxicity, free radical production, lipid peroxidation and decreased glutathione peroxidase (GPx) activity and diminished glutathione (GSH) levels. There was a significant inhibition of both lipopolysaccharide and concanavalin-A-stimulated lymphocyte proliferation. Chromium also inhibited Con A stimulated interleukin-2 and gamma-interferon production significantly. Further, there was enhanced apoptosis and DNA fragmentation in the presence of Cr. Amla significantly inhibited Cr-induced free radical production and restored the anti-oxidant status back to control level. Amla also inhibited apoptosis and DNA fragmentation induced by Cr. Interestingly, Amla relieved the immunosuppressive effects of Cr on lymphocyte proliferation and even restored the IL-2 and gamma-IFN production considerably.

Anti-oxidant and immunomodulatory properties of seabuckthorn (Hippophae rhamnoides)--an in vitro study.

This study was designed to determine the anti-oxidant and immunomodulatory properties of seabuckthorn (Hippophae rhamnoides) using lymphocytes as a model system. Chromium(VI) as potassium dichromate was used to induce oxidative damage. The production of free radicals by chromium and the ability of alcoholic leaf and fruit extracts of seabuckthorn to inhibit the oxidative damage induced by chromium was investigated. Addition of chromium (10 microg/ml) to the cells resulted in enhanced cytotoxicity, apoptosis, free radical production and decreased glutathione (reduced) levels. Chromium also caused a significant inhibition of lymphocyte proliferation induced by both lipopolysaccharide and concanavalin A. Alcoholic extracts of leaves and fruits of seabuckthorn at a concentration of 500 microg/ml were found to inhibit chromium-induced free radical production, apoptosis, DNA fragmentation and restored the anti-oxidant status to that of control cells. In addition, these extracts also were able to arrest the chromium-induced inhibition of lymphocyte proliferation. These observations suggest that the alcoholic extracts of leaves and fruits of seabuckthorn have marked cytoprotective properties, which could be attributed to the anti-oxidant activity.

Effect of Kombucha tea on chromate(VI)-induced oxidative stress in albino rats.

The effect of Kombucha tea (KT) on oxidative stress induced changes in rats subjected to chromate treatment are reported. KT feeding alone did not show any significant change in malondialdehyde (MDA) and reduced glutathione (GSH) levels, but did enhance humoral response and delayed type of hypersensitivity (DTH) response appreciably over control animals. Chromate treatment significantly enhanced plasma and tissue MDA levels, decreased DTH response considerably, enhanced glutathione peroxidase and catalase activities; however, no change in GSH, superoxide dismutase and antibody titres was noticed. KT feeding completely reversed the chromate-induced changes. These results show that Kombucha tea has potent anti-oxidant and immunopotentiating activities.

Characteristics of Clostridium thermocellum strain SS8: A broad saccharolytic thermophile.

Clostridium thermocellum SS8 produced both carboxymethylcellulase (CMCase) and Avicelase when grown on cellulose. CMCase activity was unaffected by Ca(2+), Mg(2+), dithionate or dithiothreitol (DTT). Avicelase activity increased 2-fold with 5 mM DTT and 10 mM Ca(2+). Cellulase and amylase were produced when a celluloseadapted culture was grown on starch. The mould grew best on sucrose and was inhibited by NaCl above 10 g/l.

Production of ethanol from straw and bamboo pulp by primary isolates of Clostridium thermocellum.

Clostridium thermocellum strains SS8 and GS1 grew poorly on crude blopolymers but termented them easily after alkall treatment. With 1% alkall-extracted rice straw (AERS) and dellgnified bamboo pulp (DBP), the ethanol-to-substrate (E/S) ratios were almost the same as those obtained when using fillter paper. Increasing the substrate concentrations decreased the percentage substrate degraded and the E/S ratio and concomitantly increased the amount of reducing sugars accumulated. A maximum amount of 8.6 g ethanol/l was produced by strain SS8 out of 37.5 g DBP degraded. Strain GS1 accumulated reducing sugars at substrate concentrations >50 g/l, thereby accounting for about 70% of AERS degraded. This strain produced cellulase on both cellulose and cellobiose. Both the strains grew in the presence of 1.5% (v/v) ethanol. Strain SS8 fermented starch, but the ethanol yield was low compared to that from cellulose. About 75% of starch degraded accumulated as reducing sugars at a substrate concentration of 40 g/l. The Inhibitory effects of ethanol (2 to 4%) were less drastic when growing cultures were challenged than when they were formed in situ. The effect of ethanol depended upon the phase of the culture.