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1.
Parkinsonism Relat Disord ; 105: 24-31, 2022 12.
Article in English | MEDLINE | ID: mdl-36332289

ABSTRACT

Parkinson's disease is a nervous system abnormality marked by decreased dopamine levels in the brain. Parkinson's disease inhibits one's ability to move. Speech difficulty, changes in movement and handwriting, and other symptoms are common with Parkinson's disease. A collection of hand drawings is employed to predict Parkinson's disease. There are 102 spiral images in the hand drawing dataset. Due to the minimal size of the dataset, augmentation is utilized to increase it. After that, the augmented images are utilized to train several machine learning and deep learning models, as well as pre-trained networks like RESNET50, VGG16, AlexNet, and VGG19. The performance metrics of hybrid models of deep learning with machine learning and hybrid models of deep learning (for feature extraction) with deep learning (for classification) are then compared. It was observed that the hybrid model of RESNET-50 and SVM performed well with better performance measures compared to other Machine Learning, Deep Learning and Hybrid Models with an accuracy score of 98.45%, sensitivity score of 0.99 and specificity score of 0.98.


Subject(s)
Parkinson Disease , Humans , Parkinson Disease/diagnosis , Machine Learning , Brain
2.
Stud Health Technol Inform ; 294: 194-198, 2022 May 25.
Article in English | MEDLINE | ID: mdl-35612055

ABSTRACT

A need to enhance healthcare sector amidst pandemic arises. Many technological developments in Artificial Intelligence (AI) are being constantly leveraged in different fields of healthcare. One such advancement, Federated Learning(FL) has acquired recognition primarily due to its decentralized, collaborative nature of building AI models. The most significant feature in FL is that, raw data remain with the data sources throughout the training process and thus preventing its exposure. Hence, FL is more suitable and inevitable in healthcare domain as it deals with private sensitive data which needs to be protected. However, privacy threats still exist in FL, necessitating a requirement for further improvement in privacy protection This paper discusses about the concepts and applications of FL in healthcare and presents a novel approach for enhancing privacy preservation in Federated Learning.


Subject(s)
Artificial Intelligence , Privacy , Delivery of Health Care , Health Facilities , Learning
3.
Stud Health Technol Inform ; 294: 277-278, 2022 May 25.
Article in English | MEDLINE | ID: mdl-35612074

ABSTRACT

The tremendous shift in technology has led to many unconnected things getting interconnected via IoT. IoT is one of the major modes of collecting data from various networked resources and other connected devices. The broad range of IoT, with its huge heterogeneity in handling data, addresses many challenges in the realm of healthcare. Blockchain technology has elevated the use of distributed storage in a positive way. The recent emergence of this technology has paved way for potentially enormous utilization in various fields. Blockchain technology in the fields of IT, finance, industries, government, healthcare, media, and law enforcement has altered the service quality levels to an ethical ideal. Blockchain, in conjunction with IoT, facilitates decentralized collection and storage of data. Integrating blockchain with IoT has emerged as a cutting-edge tool for the decentralized sharing of medical records, monitoring of patients, ensuring the privacy of patient records, predicting the quantum of insurance, and managing supply chains.


Subject(s)
Biomedical Technology , Blockchain , Internet of Things , Humans , Privacy
4.
SN Comput Sci ; 2(3): 136, 2021.
Article in English | MEDLINE | ID: mdl-33728414

ABSTRACT

In response to the coronavirus (COVID-19) pandemic, Government and public health authorities around the world are developing contact tracing apps as a way to trace and slow the unfold of the virus. There is major divergence among nations, however, between a "privacy-first" approach that protects citizens' information at the price of very restricted access for public health authorities and a "data-first" approach that stores massive amounts of knowledge that, whereas of immeasurable price to epidemiologists. Contact tracing apps work by gathering information from people who have tested positive for the virus and so locating and notifying individuals with whom those people are in shut contact, oftentimes by use of GPS, Bluetooth, or wireless technology. All of the user's information is employed and picked up, the study found that users' information would be created anonymous, encrypted, secured, and can be transmitted on-line and stored solely in an aggregated format. Contact tracing apps use either a centralized or a decentralized approach to work the user's information. Apps that use a centralized approach have high privacy risks. In this paper, the researcher's contributions related to the security and privacy of Contact tracing apps have been discussed and, later research gaps have been identified with proposed solutions.

5.
Carbohydr Polym ; 225: 115240, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31521287

ABSTRACT

Pectin was extracted from the waste custard apple peel using ultrasound technique and optimized the extraction process by RSM. The various significant process parameters such as liquid-solid ratio, ultra-sonication time, temperature and pH of solution were studied in the range of 10-25 mL g-1, 10-30 min, 50-80 °C, and 1-3, respectively. The maximum yield of pectin (8.93%) was attained at the optimum condition of 23.52 mL g-1 of liquid-solid ratio, 18.04  min of ultra-sonication time, 63.22 °C of temperature and 2.3 pH of solution. The extracted and commercially available fresh pectin (for comparison purposes) were characterized by various analytical techniques namely, FTIR, DSC, XRD, SEM, and NMR to evaluate their functional groups, thermal properties, crystallinities, morphological and structural characteristics, respectively. The extracted pectin was a toxic free compound as determined by its anti nutritional property study and about 20 mg/mL of antioxidant presented in it.

6.
J Fluoresc ; 26(5): 1541-8, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27380200

ABSTRACT

Here we have demonstrated a novel single step technique of synthesis of highly fluorescent carbon nanoparticles (CNPs) from broth constituent and in vivo bioimaging of Caenorhabditis elegans (C. elegans) with the synthesized CNPs has been presented. The synthesized CNPs has been characterized by the UV-visible (UV-Vis) absorption spectroscopy, transmission electron microscopy (TEM) and Raman studies. The sp (2) cluster size of the synthesized samples has been determined from the measured Raman spectra by fitting it with the theoretical skew Lorentzian (Breit-Wigner- Fano (BWF)) line shape. The synthesised materials are showing excitation wavelength dependent tunable photoluminescence (PL) emission characteristics with a high quantum yield (QY) of 3 % at a very low concentration of CNPs. A remarkable increase in the intensity of PL emission from 16 % to 39 % in C. elegans has also been observed when the feeding concentration of CNPs to C. elegans is increased from 0.025 % to 0.1 % (w/v). The non-toxicity and water solubility of the synthesized material makes it ideal candidate for bioimaging.


Subject(s)
Caenorhabditis elegans/metabolism , Carbon/chemistry , Fluorescent Dyes/chemistry , Molecular Imaging/methods , Nanoparticles/chemistry , Animals , Caenorhabditis elegans/chemistry , Microscopy, Electron, Transmission
7.
Ecotoxicol Environ Saf ; 121: 253-7, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25838071

ABSTRACT

Lipid from microalgae is one of the putative oil resources to facilitate the biodiesel production during this era of energy dissipation and environmental pollution. In this study, the key parameters such as biomass productivity, lipid productivity and lipid content were evaluated at the early stationary phase of Chlamydomonas reinhardtii, CC1010 cultivated in nutrient starved (nitrogen, phosphorous), glucose (0.05%, 0.1%, 0.15% and 0.2%) and vitamin B12 supplementation (0.001%, 0.002% and 0.003%) in Tris-Acetate-Phosphate (TAP) medium. The lipid content in nitrogen starved media was 61% which is 2.34 folds higher than nutrient sufficient TAP medium. Glucose supplementation has lead to proportional increase in biomass productivity with the increasing concentration of glucose whereas vitamin B12 supplementations had not shown any influence in lipid and biomass production. Further, fatty acid methyl ester (FAME) profiling of C. reinhardtii, CC 1010 has revealed more than 80% of total SFA (saturated fatty acid) and MUFA (mono unsaturated fatty acid) content. Quality checking parameters of biodiesel like cetane number, saponification value, iodine number and degree of unsaturation were analyzed and the biodiesel fuel properties were found to be appropriate as per the international standards, EN 14214 and ASTM D6751. Conclusively, among all the treatments, nitrogen starvation with 0.1% glucose supplementation had yielded high lipid content in C. reinhardtii, CC 1010.


Subject(s)
Biofuels , Biotechnology/methods , Chlamydomonas reinhardtii/growth & development , Chlamydomonas reinhardtii/metabolism , Fatty Acids/biosynthesis , Biofuels/standards , Biomass , Fatty Acids/analysis , Gas Chromatography-Mass Spectrometry , Glucose/metabolism , Lipids/analysis , Lipids/biosynthesis , Microalgae/growth & development , Microalgae/metabolism , Microscopy, Confocal , Nitrogen/metabolism , Phosphorus/metabolism
8.
Mol Cell Biochem ; 317(1-2): 11-20, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18563536

ABSTRACT

The association between hypercholesterolemia and kidney damage has been well known for last few decades. The oxidative stress and inflammatory responses are involved in renal injury, which is upregulated in hypercholesterolemic condition. The present study is aimed to evaluate the possible effect of lupeol and its ester derivative, lupeol linoleate in renal damage associated with hypercholesterolemic rats. Hypercholesterolemia was induced in male Wistar rats by feeding them with a high cholesterol diet (HCD) comprising normal rat chow supplemented with 4% cholesterol and 1% cholic acid for 30 days. Lupeol and lupeol linoleate were supplemented (50 mg/kg body wt/day) to HCD fed rats during the last 15 days. Increased levels of renal total cholesterol, triglycerides and phospholipids, along with altered serum biochemical parameters of tissue injury indices and elevated activities of renal marker enzymes (lactate dehydrogenase and alkaline phosphatase) were noted in HCD fed rats. Elevated lipid peroxidation levels coupled with decreased antioxidant status (enzymatic and non enzymatic antioxidants) were observed in hypercholesterolemic rats, which indicate the onset of oxidative changes in the renal tissue. Renal lysosomal acid hydrolase activities (ACP, beta-Glu, beta-Gal, NAG and Cat-D) and acute phase proteins like C-Reactive protein and fibrinogen were significantly increased in HCD fed rats, which further indicates the heightening of inflammation. In addition, histopathological findings also confirmed the renal damage in hypercholesterolemic condition. Lupeol and lupeol linoleate effectively reverted the above abnormalities and was comparable with that of the control. These observations highlight the protective effect of lupeol and its ester derivative in ameliorating the renal injury associated with hypercholesterolemia.


Subject(s)
Hypercholesterolemia/complications , Hypercholesterolemia/drug therapy , Kidney Diseases/complications , Kidney Diseases/drug therapy , Protective Agents/therapeutic use , Triterpenes/therapeutic use , Animals , Antioxidants/metabolism , C-Reactive Protein/metabolism , Dietary Fats , Hydrolases/metabolism , Hypercholesterolemia/blood , Kidney Diseases/blood , Kidney Diseases/pathology , Lipid Peroxidation/drug effects , Lipids/analysis , Lysosomes/drug effects , Lysosomes/enzymology , Male , Pentacyclic Triterpenes , Phytotherapy , Rats , Rats, Wistar , Triterpenes/pharmacology
9.
Life Sci ; 80(21): 1993-8, 2007 May 01.
Article in English | MEDLINE | ID: mdl-17418239

ABSTRACT

Cyclophosphamide (CP), one of the widely prescribed antineoplastic drugs can cause fatal cardiotoxicity. The present study is aimed at evaluating the cardioprotective role of lipoic acid in CP induced toxicity. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I served as control, Group II received a single dose of CP (200 mg/kg b.wt., i.p.), Group III received lipoic acid (25 mg/kg b.wt., orally) for 10 days, and Group IV received CP immediately followed by lipoic acid for 10 days. In CP administered rats, the levels of protein carbonyl and 8-hydroxy-2-deoxyguanosine were increased significantly (P<0.001) indicating oxidative changes in the heart tissue. The activities of lysosomal acid hydrolases, beta-Glu, beta-Gal, NAG, Cat-D and ACP increased significantly (P<0.001) in the serum as well as in the heart tissue after CP administration. An increase in hydroxyproline was observed in CP induced rats. Lipoic acid effectively reverted these abnormal biochemical changes to near normalcy. These observations highlight the protective role of lipoic acid in CP induced cardiotoxicity.


Subject(s)
Antineoplastic Agents, Alkylating/toxicity , Cyclophosphamide/toxicity , Heart/drug effects , Myocardium/metabolism , Oxidative Stress/drug effects , Protective Agents/pharmacology , Thioctic Acid/pharmacology , 8-Hydroxy-2'-Deoxyguanosine , Analysis of Variance , Animals , Chromatography, High Pressure Liquid , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Hydroxyproline/metabolism , Male , Protein Carbonylation/drug effects , Rats
10.
Fundam Clin Pharmacol ; 21(2): 157-64, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17391288

ABSTRACT

The present investigation was carried out to evaluate the protective effect of Withania somnifera Linn. Dunal (family-Solanaceae), commonly known as Ashwagandha, on adjuvant-induced arthritic rats. Results were compared with those for Indomethacin, a nonsteroidal anti-inflammatory drug. Arthritis was induced by intradermal injection of complete Freund's adjuvant (0.1 mL) into the right hind paw of Wistar albino rats. Withania somnifera root powder (1000 mg/kg/day) and Indomethacin (3 mg/kg/day) were orally administered for 8 days (from 11th to 18th day) after adjuvant injection. The anti-arthritic effect of W. somnifera root powder was assessed by measuring changes in lipid peroxidation, antioxidant status, and glycoprotein levels in plasma and spleen of arthritic animals. In addition, cartilage degradation was also assessed by estimating bone collagen, and urinary constituents in arthritic animals. Results of the present investigation showed significant increase in the level of lipid peroxides, glycoproteins, and urinary constituents with the depletion of antioxidant status and bone collagen in arthritic animals. These biochemical alterations observed were ameliorated significantly by oral administration of W. somnifera root powder (1000 mg/kg body weight) in arthritic animals. The results of this study clearly indicate that W. somnifera root powder is capable of rectifying the above biochemical changes in adjuvant arthritis.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/pharmacology , Arthritis, Experimental/drug therapy , Phytotherapy , Plant Extracts/pharmacology , Withania/chemistry , Animals , Bone and Bones/drug effects , Bone and Bones/metabolism , Cartilage/drug effects , Cartilage/physiopathology , Collagen/drug effects , Collagen/metabolism , Disease Models, Animal , Female , Glycoproteins/blood , Glycoproteins/drug effects , Indomethacin/pharmacology , Lipid Peroxidation/drug effects , Male , Plant Roots/chemistry , Rats , Rats, Wistar , Spleen/drug effects , Spleen/metabolism
11.
Mol Cell Biochem ; 295(1-2): 189-98, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16933029

ABSTRACT

In the present study, the role of pentacyclic triterpenes, lupeol and its ester lupeol linoleate, was studied in relation to hepatic oxidative abnormalities and lipoprotein peroxidation in hypercholesterolemic rats. Hypercholesterolemia was induced in male Wistar rats by feeding them with high cholesterol diet (4% cholesterol + 1% cholic acid; HCD) for 30 days. Pentacyclic triterpenes, lupeol and lupeol linoleate were supplemented (50 mg/kg body wt/day) during the last 15 days. After the experimental period, there was a significant depression in hepatic activities of antioxidant enzymes, SOD (38.39%), CAT (25.03%) and GPx (30.26%) along with a marked fall in the levels of non-enzymic antioxidant molecules GSH (31.39%), vitamin C (46.07%) and vitamin E (42.28%), with a concomitant increase (p<0.001) in lipid peroxidation and in the activities of serum alkaline phosphatase, lactate dehydrogenase and aminotransferases when compared to controls. Treatment with triterpenes decreased lipid peroxidation and reverted the activities of antioxidants (p<0.001 and p<0.01) and marker enzymes to near control. Histopathological findings further confirmed the hepatoprotective nature of triterpenes by showing the normal architecture in treated rats, as against the fatty cellular changes in HCD fed rats. Further, the susceptibility of apo-B containing lipoprotein to oxidation by copper and Fenton's reagent was increased in in vitro condition in HCD fed rats, whereas the lipoproteins were less susceptible to oxidation in triterpenes treated animals. Therefore, it may be concluded that lupeol and its ester afford protection against the hepatic abnormalities and lipoprotein peroxidation in hypercholesterolemic rats.


Subject(s)
Hypercholesterolemia/pathology , Lipid Peroxidation/drug effects , Lipoproteins/metabolism , Liver/drug effects , Oxidative Stress/drug effects , Triterpenes/pharmacology , Animals , Antioxidants/metabolism , Copper/pharmacology , Enzymes/blood , Hydrogen Peroxide/pharmacology , Hypercholesterolemia/chemically induced , Iron/pharmacology , Liver/enzymology , Liver/pathology , Male , Pentacyclic Triterpenes , Rats , Rats, Wistar
12.
Hum Exp Toxicol ; 26(12): 923-32, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18375635

ABSTRACT

Kidney stones are known to haunt humanity for centuries and increase in oxalate is a predominant risk factor for stone formation. The present study was initiated with a notion to study the oxidative and nitrosative stress on erythrocytes under oxalate stress and the putative role of sulphated polysaccharides. Hyperoxaluria was induced in two groups by the administration of 0.75% ethylene glycol in drinking water for 28 days and one of them was treated with sulphated polysaccharides from Fucus vesiculosus from the 8th day to the end of the experimental period of 28 days at a dose of 5 mg/kg body weight subcutaneously. Control and drug control (sulphated polysaccharides alone) were also included in the study. Glycolic and glyoxylic acid levels of urine were analyzed as an index of hyperoxaluria. The plasma enzymic markers of cellular integrity, redox status of red blood cells, osmotic fragility, and (14)C-oxalate binding were investigated. Urine and plasma nitric oxide metabolites, expression of inducible nitric oxide synthase protein, and mRNA were assessed in kidney to evaluate the nitrosative stress. Increased levels of glycolic and glyoxylic acid in urine indicated the prevalence of hyperoxaluria in ethylene glycol-administered groups. Plasma aspartate and alanine transaminase were not altered, but alkaline phosphatase and lactate dehydrogenase of hyperoxaluric group were increased indicating tissue damage. Activities of antioxidant enzymes were decreased, whereas erythrocyte membrane lipid peroxidation was increased in hyperoxaluric rats. Moreover, an altered fragility with an increase in oxalate binding activity was observed in hyperoxaluric group. Increase in nitric oxide metabolites levels in urine and plasma along with an increase in expression of inducible nitric oxide synthase protein and mRNA in kidney were observed in hyperoxaluric rats. Administration of sulphated polysaccharides to hyperoxaluric rats averted the abnormal increase in urinary glycolic and glyoxylic acid levels and enzyme activities, decreased lipid peroxidation, and increased the activities of antioxidant enzymes. Furthermore, increased nitrosative stress accompanying hyperoxaluria was also normalized on sulphated polysaccharides treatment. To conclude, sulphated polysaccharide administration was able to maintain the integrity of erythrocyte membrane and decrease the damage to erythrocytes in hyperoxaluria.


Subject(s)
Erythrocytes/drug effects , Fucus/chemistry , Hyperoxaluria/drug therapy , Oxidative Stress/drug effects , Polysaccharides/therapeutic use , Animals , Biomarkers/metabolism , Carbon Radioisotopes , Disease Models, Animal , Erythrocytes/enzymology , Erythrocytes/pathology , Ethylene Glycol/toxicity , Glycolates/urine , Glyoxylates/urine , Hyperoxaluria/blood , Hyperoxaluria/chemically induced , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Male , Nitric Oxide Donors , Nitrosation , Osmotic Fragility/drug effects , Oxalates/metabolism , Oxidative Stress/physiology , Plant Extracts/therapeutic use , Rats , Rats, Wistar , Sulfates
13.
Biomarkers ; 11(2): 153-63, 2006.
Article in English | MEDLINE | ID: mdl-16766391

ABSTRACT

The generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in hyperoxaluric condition has been proved experimentally. This may result in the formation of the cytotoxic metabolite peroxynitrite, which is capable of causing lipid peroxidation and protein modification. The presence of nitrotyrosine in proteins has been associated with several pathological conditions. The present study investigated the presence of nitrotyrosine in the stone formers Tamm-Horsfall glycoprotein (THP). In vitro nitration of control THP was carried out using peroxynitrite. New Zealand white rabbits were immunized with peroxynitrated THP at 15-day intervals. Antisera collected following the third immunization were assayed for antibody titres using solid-phase ELISA. Antibodies were purified by affinity chromatography. The carbonyl content of control, stone formers and nitrated THP were determined. Western blotting was carried with control, stone formers and nitrated THPs. Immunodiffusion studies demonstrated cross-reaction with nitrated bovine serum albumin. Significant amounts (p < 0.001) of carbonyl content were present in both stone formers and nitrated THPs. Western blot analysis confirmed the presence of nitrated amino acid 3-nitrotyrosine in stone formers, which could bring about structural and functional modifications of THP in hyperoxaluric patients. A cross-reaction with nitrated bovine serum albumin confirms that the raised antibody has certain paratopes similar to the epitope of nitrated protein molecules. Detection of 3-nitrotyrosine in stone formers THP indicates that it is one of the key factors influencing the conversion of THP to a structurally and immunologically altered form during calcium oxalate stone formation.


Subject(s)
Calcium Oxalate/metabolism , Calculi/metabolism , Enzyme-Linked Immunosorbent Assay/methods , Mucoproteins/analysis , Nitrosation , Animals , Blotting, Western , Chromatography, Affinity , Cross Reactions , Electrophoresis, Polyacrylamide Gel , Humans , Immune Sera , Mucoproteins/metabolism , Rabbits , Uromodulin
14.
Mutat Res ; 606(1-2): 85-91, 2006 Jul 14.
Article in English | MEDLINE | ID: mdl-16697249

ABSTRACT

The aim of the present study was to investigate the protective efficacy of alpha-lipoic acid (LA) on the cyclophosphamide (CP)-induced chromosomal aberrations (CA) and apoptosis in the bone marrow of rats. Male Wistar rats of 140+/-20 g were categorized into eight groups. Five groups were administered CP (40 mg/kg body weight, intraperitoneally) to induce toxicity; four of these groups received a single intraperitoneal injection of LA at a dose of either 100 or 200 mg/kg body weight, and either 30 or 60 min prior to CP administration. A vehicle-treated control group and LA control groups were also included. Twenty-four hours after CP treatment, the frequency of CA in bone marrow cells were significantly increased in comparison with the controls. The CP-induced CA were associated with significant increase in DNA damage in the bone marrow as evidenced by increased single strand breaks, whereas in rats treated with LA and CP, the frequency of CA and single strand breaks were significantly decreased in comparison to those given CP alone. CP administration distinctly triggered the apoptotic and necrotic cell death, and LA pretreatment affected cell death by decreasing the number of apoptotic and necrotic cells. The protective effect of LA was found to be stronger at a dose of 200 mg/kg body weight than 100 mg/kg body weight dosage, indicating the dose dependent protective effect of LA. However, the protection by LA was not dependent on the time intervals between LA and CP administration. The results of this study illustrate the protective effect of LA on the CA and apoptosis induced by CP in the erythropoietic system of rats.


Subject(s)
Apoptosis/drug effects , Chromosome Aberrations/drug effects , Cyclophosphamide/pharmacology , Thioctic Acid/pharmacology , Animals , Bone Marrow Cells/cytology , Chromosomes, Mammalian/drug effects , DNA/drug effects , Flow Cytometry , Male , Necrosis , Rats , Rats, Wistar
15.
Biochem Biophys Res Commun ; 345(1): 345-54, 2006 Jun 23.
Article in English | MEDLINE | ID: mdl-16690032

ABSTRACT

The rat kidney H1 oxalate binding protein was isolated and purified. Oxalate binds exclusively with H1B fraction of H1 histone. Oxalate binding activity is inhibited by lysine group modifiers such as 4',4'-diisothiostilbene-2,2-disulfonic acid (DIDS) and pyridoxal phosphate and reduced in presence of ATP and ADP. RNA has no effect on oxalate binding activity of H1B whereas DNA inhibits oxalate binding activity. Equilibrium dialysis method showed that H1B oxalate binding protein has two binding sites for oxalate, one with high affinity, other with low affinity. Histone H1B was modeled in silico using Modeller8v1 software tool since experimental structure is not available. In silico interaction studies predict that histone H1B-oxalate interaction take place through lysine121, lysine139, and leucine68. H1B oxalate binding protein is found to be a promoter of calcium oxalate crystal (CaOx) growth. A 10% increase in the promoting activity is observed in hyperoxaluric rat kidney H1B. Interaction of H1B oxalate binding protein with CaOx crystals favors the formation of intertwined calcium oxalate dehydrate (COD) crystals as studied by light microscopy. Intertwined COD crystals and aggregates of COD crystals were more pronounced in the presence of hyperoxalauric H1B.


Subject(s)
Histones/metabolism , Models, Chemical , Models, Molecular , Nucleocytoplasmic Transport Proteins/metabolism , Nucleocytoplasmic Transport Proteins/ultrastructure , Oxalates/metabolism , Urinary Calculi/metabolism , Amino Acid Sequence , Animals , Binding Sites , Computational Biology/methods , Computer Simulation , Disease Models, Animal , Histones/chemistry , Male , Molecular Conformation , Molecular Sequence Data , Nucleocytoplasmic Transport Proteins/chemistry , Oxalates/chemistry , Protein Binding , Protein Interaction Mapping/methods , Rats , Rats, Wistar , Sequence Analysis, Protein , Urinary Calculi/chemistry
16.
Vascul Pharmacol ; 44(6): 406-10, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16713367

ABSTRACT

The aqueous suspension of Withania somnifera root powder was investigated for their in vivo and in vitro immunomodulatory properties. W. somnifera showed potent inhibitory activity towards the complement system, mitogen induced lymphocyte proliferation and delayed-type hypersensitivity reaction. Administration of W. somnifera root powder did not have a significant effect on humoral immune response in rats. Our results report immunosuppressive effect of W. somnifera root powder, thus it could be a candidate for developing as an immunosuppressive drug for the inflammatory diseases.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Complement Inactivating Agents/pharmacology , Plant Extracts/pharmacology , Withania , Animals , Anti-Inflammatory Agents/therapeutic use , Arthritis, Experimental/drug therapy , Arthritis, Experimental/immunology , Cell Proliferation , Cells, Cultured , Complement Activation/drug effects , Complement Inactivating Agents/therapeutic use , Disease Models, Animal , Erythrocytes/immunology , Freund's Adjuvant/immunology , Humans , Hypersensitivity, Delayed/drug therapy , Hypersensitivity, Delayed/immunology , Inflammation/drug therapy , Inflammation/immunology , Lymphocytes/drug effects , Plant Extracts/therapeutic use , Plant Roots , Rats , Rats, Wistar
17.
Article in English | MEDLINE | ID: mdl-16730236

ABSTRACT

Aflatoxins are potent hepatotoxic and hepatocarcinogenic agents. Reactive oxygen species and consequent peroxidative damage caused by aflatoxin are considered to be the main mechanisms leading to hepatotoxicity. The present investigation aims at assessing the hepatoprotective effect of lupeol, a pentacyclic triterpene isolated from the stem bark of Crataeva nurvala, on aflatoxin B(1) (AFB(1))-induced hepatotoxicity in a rat model. The hepatoprotection of lupeol is compared with silymarin, a well known standard hepatoprotectant. Lactate dehydrogenase, alkaline phosphatase, alanine and aspartate aminotransferases were found to be significantly increased in the serum and decreased in the liver of AFB(1) administered (1 mg/kg body mass, orally) rats, suggesting hepatic damage. Marked increase in the lipid peroxide levels and a concomitant decrease in the enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) and nonenzymic (reduced glutathione, vitamin C and vitamin E) antioxidants in the hepatic tissue were observed in AFB(1) administered rats. Pretreatment with lupeol (100 mg/kg body mass, orally) and silymarin (100 mg/kg body mass, orally) for 7 days reverted the condition to near normalcy. Hepatoprotection by lupeol is further substantiated by the normal histologic findings as against degenerative changes in the AFB(1) administered rats. The results of this study indicate that lupeol is a potent hepatoprotectant as silymarin.


Subject(s)
Aflatoxin B1/toxicity , Antioxidants/pharmacology , Liver Diseases/prevention & control , Silymarin/pharmacology , Triterpenes/pharmacology , Animals , Ascorbic Acid/metabolism , Chemical and Drug Induced Liver Injury , Glutathione/metabolism , Glutathione Transferase/metabolism , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/metabolism , Liver/pathology , Liver Diseases/metabolism , Male , Oxidoreductases/metabolism , Pentacyclic Triterpenes , Rats , Rats, Wistar , Vitamin E/metabolism
18.
Mol Cell Biochem ; 289(1-2): 31-7, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16625422

ABSTRACT

Cyclophosphamide (CP), a potent antitumor drug, is known to cause severe cardiotoxicity. The present study is aimed at evaluating the role of DL-alpha-Lipoic acid (LA) on the calcium responsiveness of cardiac myofilaments isolated from CP treated rats. Adult male Wistar rats were divided into four treatment groups. Two groups received single intraperitoneal injection of CP (200 mg/kg b.wt.) to induce cardiotoxicity, one of these groups received LA treatment (25 mg/kg b.wt. for 10 days). A vehicle treated control group and a LA drug control were also included. Cardiotoxicity was evident from increased levels of cardiac Troponin I in serum of CP treated rats. The pCa-actomyosin ATPase relationship of myofilaments demonstrated a rightward shift indicating diminished responsiveness in CP treated rats. The hill coefficient was reduced and the myofibrillar myosin Ca(2+)-ATPase and K(+)-(EDTA) activities were also significantly (P < 0.05) reduced. Ultrastructural observations were also in agreement with the above abnormal changes, wherein loss of myofilaments occurred. LA effectively normalized these abnormalities and restored the cardiac function in CP administered rats.


Subject(s)
Actin Cytoskeleton/drug effects , Calcium/metabolism , Cyclophosphamide/toxicity , Myocardium/metabolism , Thioctic Acid/pharmacology , Animals , Male , Myocardium/ultrastructure , Myosins/metabolism , Rats , Rats, Wistar , Troponin I/blood
19.
Toxicology ; 222(3): 225-32, 2006 May 15.
Article in English | MEDLINE | ID: mdl-16580770

ABSTRACT

Adriamycin (ADR), an anthracycline antibiotic, which is widely used as an antineoplastic drug in the treatment of various solid tumors, has been shown to induce genotoxicity in erythropoietic system. The aim of the present study was to investigate the protective efficacy of DL-alpha-lipoic acid (LA) on ADR-induced clastogenicity and apoptosis in the bone marrow of rats. The animals were randomly divided into eight groups consisting of six rats each. Five groups were administered ADR (20 mg/kg body weight, i.v.) to induce genotoxicity; four of these groups received a single intraperitoneal injection of LA at a dose of either 100 or 200 mg/kg body weight, and either 30 or 60 min prior to ADR administration. A vehicle treated control group and LA control groups were also included. The beneficial effects of LA were monitored by DNA strand breaks, chromosomal aberrations, micronucleus assay and apoptotic studies in the bone marrow cells of rats after 24 h following single dose of ADR treatment. ADR treatment caused significant clastogenicity and apoptosis in rat bone marrow cells. The treatment with LA showed significant reduction in the frequency of chromosomal aberrations, DNA strand breaks and apoptosis in bone marrow cells as well as decreased the micronuclei formation in bone marrow and peripheral blood of rats treated with ADR. The protective effect of LA was found to be stronger at a dose of 200 mg/kg body weight than 100 mg/kg body weight dosage with respect to the above results, indicating the dose dependent effect of LA. However, the protection by LA was not dependent on the time intervals between LA and ADR administration. The results of this study illustrate the protective effect of LA on ADR-induced clastogenicity and apoptosis in the erythropoietic system of rats.


Subject(s)
Antibiotics, Antineoplastic/toxicity , Bone Marrow Cells/drug effects , Chromosome Aberrations/drug effects , Doxorubicin/toxicity , Protective Agents/pharmacology , Thioctic Acid/pharmacology , Animals , Apoptosis/drug effects , Chromosome Aberrations/chemically induced , DNA Damage/drug effects , Male , Micronucleus Tests , Rats , Rats, Wistar
20.
Clin Chim Acta ; 364(1-2): 267-74, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16139257

ABSTRACT

BACKGROUND: Association of macromolecules particularly the role of proteins in urolithiasis has been studied for last few centuries, but still a complete profile of stone matrix proteins that mediate co-precipitation of uric acid and calcium oxalate has not been characterized. We isolated and characterize proteins from uric acid rich stone matrix, which have oxalate binding activity. METHODS: Matrix proteins were isolated from uric acid rich stone matrix using EDTA as a demineralizing agent. The radiolabelled solubilized proteins were fractionated with increasing ionic concentration by DEAE cellulose column chromatography to identify the oxalate binding protein. It was purified using Sephadex G-200 column chromatography. Amino acid composition was determined and monoclonal antibody was produced against the oxalate binding uric acid rich stone matrix protein. Urinary uric acid binding proteins were isolated from stone formers urine, their oxalate binding activity assayed and cross reactivity with the produced monoclonal antibody were checked using ELISA and Western blotting. RESULTS: Matrix on DEAE column chromatography elution yielded 3 protein peaks and they were named as fraction I, II and III among which fraction I had higher oxalate binding activity which was further purified with Sephadex G-200 column which yielded 2 protein peaks designated as Ia and Ib. Fraction Ib with molecular weight 29 kDa exhibited the maximum oxalate binding activity. Forty percent of this 29 kDa protein is comprised of basic amino acids. Monoclonal antibody (IgG1) was produced against the 29 kDa stone matrix protein. Urinary uric acid binding proteins were isolated from stone formers, 4 protein peaks were obtained named as fraction I to IV. Among them, fraction IV having molecular weight of approximately 29 kDa cross reacted up to 85.6% with 29 kDa stone matrix protein. Moreover, urinary 29 kDa protein exhibited oxalate binding activity of 94.16 +/- 6.08 pmol/mg protein at pH 5.5. CONCLUSION: The 29 kDa protein isolated from uric acid rich stone matrix and urine are one and the same, thereby insinuating that 29 kDa protein might play a major role in epitaxial deposition of calcium oxalate over uric acid core, consequently favoring the lithogenic events like uric acid and calcium oxalate nucleation, aggregation and retention.


Subject(s)
Calcium Oxalate/metabolism , Kidney Calculi/metabolism , Proteins/metabolism , Uric Acid/metabolism , Animals , Blotting, Western , Calcium Oxalate/chemistry , Carrier Proteins/chemistry , Carrier Proteins/isolation & purification , Carrier Proteins/metabolism , Crystallization , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay/methods , Humans , Kidney Calculi/chemistry , Kidney Calculi/urine , Mice , Mice, Inbred BALB C , Molecular Weight , Nucleocytoplasmic Transport Proteins/chemistry , Nucleocytoplasmic Transport Proteins/isolation & purification , Nucleocytoplasmic Transport Proteins/metabolism , Protein Binding , Proteins/chemistry , Sequence Analysis, Protein , Uric Acid/chemistry
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