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Introduction: Advanced glycation end-products (AGEs) are contributing factors to diabetes complications. The antigenic nature of AGEs established the theory of incessant accumulation of AGEs can incite an autoimmune response in a diabetic patient. Glycating agents like 3-deoxyglucosone are increased in diabetic patients, leading to the high formation of AGEs aggravating the pathophysiological conditions in diabetes. We aimed to study the immunogenicity of glycated histone H1 protein and AGEs (N-carboxymethyl-lysine and pentosidine) as well as detection of autoantibodies in the sera of type 2 diabetic subjects. Materials and Methods: Female rabbits were injected with native H1 and glycated-H1 to discern its immunogenicity. Diabetic subjects’ sera were also scanned for the detection of autoantibodies against glycated-H1 and AGEs using immunochemical assay technique. Results: Glycated-H1 was highly immunogenic, unlike the native analog. Diabetic sera showed 48% (72 of 150 samples) significantly strong binding with glycated-H1, further sera also showed 40% (60 of 150 samples), and 36% (54 of 150 samples) strong binding with CML, and pentosidine, respectively. Conclusion: The findings support modified H1 as well AGEs are highly immunogenic in nature. The presence of autoantibodies against glycated-H1 and AGEs may be utilized in the assessment of diabetes or its complications. [ABSTRACT FROM AUTHOR]

Non-enzymatic glycation is the addition of a free carbonyl group of a reducing sugar to the free amino groups of proteins, which results in the formation of early and advanced glycation end-products (AGEs). Glycation reaction is profoundly associated with diabetes and its secondary complications, such as nephropathy and neuropathy. Glyoxal is a carbonyl species that reacts rapidly with the free amino groups of proteins to form AGEs. While the formation of AGEs with various glycating agents has previously been demonstrated, no extensive studies have been conducted to assess the role of quercetin in all three stages of glycation (early, intermediate and late). In this study, we report the glycation of HSA (human serum albumin) and its characterization by several spectroscopic techniques. Furthermore, inhibition of products at all stages of glycation was studied by various assays. Spectroscopic analysis suggests structural perturbations in the HSA macromolecule as a result of modification, which might be due to the generation of free radicals and the formation of AGEs. Inhibition in the formation of glycation has established that quercetin is a better and a more potent antiglycating agent than aminoguanidine at all stages of glycation. [ABSTRACT FROM AUTHOR]

Nonenzymatic glycation of amino groups of DNA bases by reducing sugars can generate advanced glycation end products (AGEs). Cellular formation of AGEs under normal physiology is continuously scanned and removed by efficient system in the cells. However, excess formation and accumulation of AGEs may be cause or consequence of some human diseases. Mammalian DNA incubated with d -glucose for 28 days at 37 °C showed structural changes in DNA as confirmed by UV, fluorescence, CD, melting temperature, S1 nuclease sensitivity and gel electrophoresis. Formation of DNA-AGE was confirmed by HPLC and LC–MS. Enzyme immunoassay and electrophoretic mobility shift assay of autoantibodies in type 2 diabetes patients’ sera with disease duration of 5–15 years exhibited significantly high binding with DNA-AGE as compared to patients with 1–5 years of disease duration. Autoantibodies against aberrant DNA-AGE may be important in the assessment of initiation/progression of secondary complications in type 2 diabetes mellitus patients. [ABSTRACT FROM AUTHOR]

Advanced glycation end-products (AGEs) are heterogeneous group of compounds, known to be implicated in diabetic complications. One of the consequences of the Maillard reaction is attributed to the production of reactive intermediate products such as α-oxoaldehydes. 3-deoxyglucosone (3-DG), an α-oxoaldehyde has been found to be involved in accelerating vascular damage during diabetes. In the present study, calf thymus histone H3 was treated with 3-deoxyglucosone to investigate the generation of AGEs (Nε-carboxymethyllysine, pentosidine), by examining the degree of side chain modifications and formation of different intermediates and employing various physicochemical techniques. The results clearly indicate the formation of AGEs and structural changes upon glycation of H3 by 3-deoxyglucosone, which may hamper the normal functioning of H3 histone, that may compromise the veracity of chromatin structures and function in secondary complications of diabetes. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is characterized by inflammation of the knee joint, which is caused by accumulation of cytokines and C-reactive protein (CRP) in the extracellular matrix as an early immune response to infection. The articular cartilage destruction is discernible by elevated tumour necrosis factor-α (TNF-α). In this study, blood samples of knee osteoarthritis patients were analyzed for biochemical and physiological parameters based on the lipid profile, uric acid, total leukocyte count (TLC), hemoglobin percentage (Hb%) and absolute lymphocyte count (ALC). Furthermore, immunological parameters including TNF-α, interleukin-6 (IL-6) and CRP were analyzed. The presence of antibodies against hydroxyl radical modified collagen-II (•OH-collagen-II) was also investigated in arthritis patients using direct binding ELISA. The uric acid and lipid profiles changed extensively. Specifically, increased uric acid levels were associated with OA in both genders, as were enhanced immunological parameters. The TNF-α level also increased in both genders suffering from OA. Finally, auto-antibodies against OH-collagen II antigen were found in the sera of arthritis patients. These results indicated that immunological parameters are better predictors or indexes for diagnosis of OA than biochemical parameters. [ABSTRACT FROM AUTHOR]

Advanced glycation end-products comprise a complex and heterogeneous group of compounds that have been implicated in diabetes-related complications. The importance of the Maillard reaction is depicted by the formation of reactive intermediate products known as α-oxoaldehydes, such as 3-deoxyglucosone (3-DG). This product has been found to be involved in accelerated vascular damage in diabetes. In the present study, calf thymus histone H2A was reacted with 3-DG, and the generation of advanced glycation end products was investigated by determining the degree of side chain modifications (lysine and arginine residues), Amadori products, carbonyl content, Nε-carboxymethyl lysine, and pentosidine using various physicochemical techniques. Moreover, fluorescence, absorbance as well as structural characteristics of glycated-H2A were comprehensively investigated. Overall, this study demonstrates structural perturbation, formation of different intermediates, and AGEs that are believed to hamper the normal functioning of H2A histone, compromising the integrity of chromatin structures and function in secondary complications of diabetes. © 2014 IUBMB Life, 66(10):686-693, 2014 [ABSTRACT FROM AUTHOR]

Nonenzymatic glycosylation of proteins finally generates advanced glycation end products (AGEs). The Schiff's base and Amadori adduct are stages of early glycation. AGE-modified IgG may undergo conformational alterations and the final entity of the process may be involved in the pathogenesis of Rheumatoid Arthritis (RA). In this study, glycation of human IgG was carried out with varying concentrations of glucose. Effect of incubation period on glycation of IgG has also been studied. Amadori adduct was detected by nitroblue tetrazolium (NBT) dye. The glucose mediated structural alterations in IgG were studied by UV, fluorescence, CD, FT-IR, DLS and DSC spectroscopy, and SDS-PAGE. Glycation-induced aggregation in AGE-IgG was reported in the form of binding of thioflavin T and congo red. Furthermore, AGE-modified IgG exhibited hyperchromicity, decrease of tryptophan fluorescence accompanied by increase in AGE specific fluorescence, loss of β-sheet, appearance of new peak in FT-IR, increase in hydrodynamic size and melting temperature. SDS-PAGE results showed decrease in the band intensity of glycosylated-IgG compared to native IgG. Glycation-induced modifications and aggregation of IgG might be important in the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HN- SCC) and other oral lesions. Oral infections (such as mucosal and endodontic infections, periodontal diseases, caries, and peri-implantitis) are among the specific targets where PDT can be applied Photodynamic therapy (PDT) efficacy depends on the local dose deposited in the lesion as well as oxygen availability in the lesion. Further long-term clinical studies are necessary in establishing a more specific place of the technique in the field of dentistry. [ABSTRACT FROM AUTHOR]

Abstract: Reactions of reducing sugars with free amino groups of proteins can form advanced glycation end products (AGEs). While the formation of nucleoside AGEs has been studied in detail, no extensive work has been carried out to assess DNA Amadori and DNA advanced glycation end products. In this study, we report biophysical/chemical characterization of glucose-induced changes in DNA, as well as DNA Amadori and DNA advanced glycation end products. Glucose treated DNA exhibited hyperchromicity, decrease in melting temperature, and enhanced emission intensity in a time dependent manner. Formation of DNA Amadori product and DNA advanced glycation end products, mainly CEdG (N 2-carboxyethyl-2′-deoxyguanosine), were the major outcome of the study. [Copyright &y& Elsevier]

Abstract: Proteins modifications in diabetes may lead to early glycation products (EGPs) as well as advanced glycation end products (AGEs). Whereas no extensive studies have been carried out to assess the role of EGPs in secondary complications of diabetes, numerous investigators have demonstrated the role of AGEs. Early glycation involves attachment of glucose on ε-NH2 of lysine residues of proteins leading to generation of the Amadori product (an early glycation species). This study reports the structural and immunological characterization of EGPs of HSA because we believe that during persistent hyperglycemia the HSA, one of the major blood proteins, can undergo fast glycation. Glucose mediated generation of EGPs of HSA was quantitated as Amadori products by NBT assay and authenticated by boronate affinity chromatography and LC/MS. Compared to native HSA changes in glycated-HSA were characterized by hyperchromicity, loss in fluorescence intensity and a new peak in the FTIR profile. Immunogenicity of native- and glycated-HSA was evaluated by inducing antibodies in rabbits. Results suggest generation of neo-epitopes on glycated-HSA rendering it highly immunogenic compared to native HSA. Quantization of EGPs of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes. [Copyright &y& Elsevier]

Sweetpotato leaves contain biologically active anthocyanins that have significant medicinal value for certain human diseases and may also be used as natural food colorants. Foliar anthocyanins and their relative abundance were investigated in leaves of sweetpotato cultivars 'Shimon-1', 'Kyushu-119', and 'Elegant Summer' grown under artificial shading and different temperature conditions. High-performance liquid chromatography profiles of the cultivars tested showed similar peaks but with peak areas differing with cultivar, temperature and shading. The relative quantity of individual anthocyanin was YGM (Yamagawamurashaki)-la> YGM-4b> YGM-1b> YGM-5a> YGM-0d> YGM-0a> YGM-2> YGM-0c> YGM-3> YGM-6> YGM-5b> YGM-0b> YGM-0f> YGM-0e> YGM0g. Seven were peonidin and eight cyanidin derivatives. The highest anthocyanin contents were found in plants grown at a moderate temperature (20 °C) with lower levels at 25 and 30 °C. The leaves of plants grown in full sun accumulated significantly more total as well as the major individual anthocyanins than plants grown in 40% and 80% shade. The results indicate that growing sweetpotatoes at moderate temperatures and without shading facilitates the accumulation of anthocyanins in the leaves. The anthocyanin composition of the leaves is discussed relative to their physiological function in human health. [ABSTRACT FROM AUTHOR]

Three separate experiments showed that wheat tissue infected with the cereal eyespot fungus, Pseudocercosporella herpotrichoides, produced fewer spores in the presence of chopped wheat straw than when it was absent. This provides a possible explanation for earlier observations that there was often less eyespot in plots where straw had been incorporated than where it had been burnt. Sporulation on eyespot infected wheat tissue was not closely correlated with the viability of P. herpotrichoides, which could usually be isolated from infected tissue for some time after it had apparently lost the ability to produce spores. Many of the colonies that were isolated from such tissue also failed to sporulate under the conditions used but non sporulating colonies were less common amongst those isolated from tissue that had been mixed with chopped straw than from tissue that had not. [ABSTRACT FROM AUTHOR]

Background: Loss of functional independence occurs frequently with hospitalization. In community-dwelling elders, lower extremity disability is an important predictor of functional loss. Ambulation assistive devices (canes, walkers), as markers of lower extremity disability, may predict functional decline associated with hospitalization, but this has not been evaluated previously. We sought to determine the association of mobility impairment, as indicated by cane or walker use prehospitalization, with adverse outcomes at hospital discharge and 3 months post discharge.Methods: Subjects were community-dwelling adults (N = 1212) aged 70 and older, hospitalized for acute medical illness. The study was a secondary analysis of the Hospital Outcomes Project for the Elderly, a prospective randomized trial at three university and two private acute-care hospitals, which randomized patients to usual care or an intervention group designed to maintain functional abilities.Results: After controlling for demographic and illness-related characteristics and prehospital function, mobility impairment was significantly associated with functional decline. Use of a walker was associated with 2.8 times increased risk for decline in ADL function by hospital discharge (p = .0002). Three months after discharge, patients who used assistive devices prior to hospitalization were more likely to have declined in both ADLs (p = .02) and IADLs (p = .003).Conclusions: Hospitalized patients with mobility impairment, as indicated by use of a cane or a walker, are at high risk for functional decline. Such patients may benefit from more intensive in-hospital and post-hospital rehabilitative therapy to maintain function. [ABSTRACT FROM AUTHOR]

The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70–80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses. [ABSTRACT FROM AUTHOR]

Background: The ability to walk independently may become jeopardized during hospitalization. It is unknown which patients are at risk for decline in walking, or to what extent patients will recover. The purpose of this study was to determine the incidence of, risk factors for, and outcomes associated with new walking dependence after hospitalization.Methods: Baseline characteristics and functional outcomes at hospital discharge and 3 months after discharge were measured for 1,181 community-dwelling adults aged 70 and over who were hospitalized for medical illness and who walked independently prior to hospitalization.Results: At discharge, 16.8% of patients were newly dependent in walking. Risk factors included age > 85 (odds ratio [OR] 2.7 vs age <75, 95% confidence interval [CI] 1.5-4.9), functional impairment before hospitalization (OR 1.4 for each impairment, CI 1.1-1.7), Caucasian race (OR 1.9, CI 1.1-3.3), and use of a walker (OR 1.8, CI 1.04-3.2) or wheelchair (OR 3.2, CI 1.3-7.6) before admission. A cancer diagnosis (OR 2.3, CI 1.2-4.6) and more than four comorbid conditions (OR 1.9, CI 1.2-3.0) were also predictive. New walking dependence was associated with discharge to a nursing home (p = .0001) and higher postdischarge mortality (p < .001). Twenty-seven percent of patients who developed new walking dependence and survived 3 months continued to be dependent in walking.Conclusions: New walking dependence occurs frequently with hospitalization, may be predicted by specific risk factors, and portends a poor prognosis. Strategies are needed to help at-risk patients maintain walking independence during and after hospitalization. [ABSTRACT FROM AUTHOR]

Presents the results of a study which was conducted to determine the incidence of, risk factors for, and outcomes associated with new walking dependence after hospitalization of the elderly. How the study was conducted; Results of the study; Study recommendation which suggests that strategies are needed to help at-risk patients maintain walking independence during and after hospitalization.

Protein bound toxins are poorly removed by conventional extracorporeal therapies. Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with cancer. The interaction between tinzaparin, an inhibitor of angiotensin converting enzyme and human serum albumin, a principal plasma protein in the liver has been investigated in vitro under a simulated physiological condition by UV–vis spectrophotometry and fluorescence spectrometry. The intrinsic fluorescence intensity of human serum albumin was strongly quenched by tinzaparin (TP). The binding constants and binding stoichiometry can be calculated from the data obtained from fluorescence quenching experiments. The negative value of ΔG° reveals that the binding process is a spontaneous process. Thermodynamic analysis shows that the HSA-TP complex formation occurs via hydrogen bonds, hydrophobic interactions and undergoes slight structural changes as evident by far-UV CD. It indicated that the hydrophobic interactions play a main role in the binding of TP to human serum albumin. In addition, the distance between TP (acceptor) and tryptophan residues of human serum albumin (donor) was estimated to be 2.21 nm according to the Förster's resonance energy transfer theory. For the deeper understanding of the interaction, thermodynamic, and molecular docking studies were performed as well. Our docking results suggest that TP forms stable complex with HSA (K b ∼ 10 4 ) and its primary binding site is located in subdomain IIA (Sudlow Site I). The results obtained herein will be of biological significance in pharmacology and clinical medicine. [ABSTRACT FROM AUTHOR]

Peroxynitrite is a bifaceted reactive species. It can oxidize and nitrate proteins/nucleic acids/lipids and is involved in inflammation, apoptosis, cytotoxicity and autoimmune disorders of unknown etiology, including SLE. In this study, H3 histone exposed to peroxynitrite caused loss of tertiary structure, nitration of tyrosine residues and dityrosine formation. Experimentally produced antibodies against peroxynitrite-modified H3 histone showed specificity for the immunogen. However, cross-reactions with other nitrated proteins were also observed. We further investigated the binding of SLE autoantibodies with native DNA, native H3 histone and peroxynitrite-modified H3 histone to explore the possible role of modified-H3 histone in the initiation and/or progression of SLE in a sub-group of patients. The results showed preferential binding of SLE anti-nDNA autoantibodies to peroxynitrite-modified H3 histone. The visual detection of immune complex formation with native and peroxynitrite-modified H3 histone reiterated preferential binding of SLE autoantibodies with modified H3 histone. It may be concluded that anti-histone autoantibodies seen in a sub-group of SLE patients might be due to the immunogenicity of peroxynitrite-modified H3 histone. [ABSTRACT FROM AUTHOR]

Results from a series of crop sequence and single-year experiments that tested different straw and cultivation treatments in a total of 11 site–season combinations confirmed previous evidence that the development of eyespot disease in cereals can be decreased by debris in the seed bed even if that debris includes eyespot-infected stem bases, which are the principal sources of primary inoculum. Two of the experiments, which followed non-cereal break crops and tested the effects of crop debris applied after ploughing or tining on eyespot in winter wheat that was artificially inoculated with Oculimacula spp., provided convincing evidence that the effects can be attributed to the debris per se, and not to any associated husbandry practices. There were often larger effects on disease in summer than in spring or on severity than on incidence suggesting that the effects of debris cannot be explained solely by effects on inoculum or initial infection, and that debris has a disease-suppressive effect. [ABSTRACT FROM AUTHOR]

BSTRACT: Protein isolate (PI) was prepared from 3 cowpea varieties and 2 soybean varieties in each of 2 y. The protein contents of cowpea PI (CPI) (91.4% to 91.8%) and soy PI (SPI) (93.0% to 93.5%) were significantly different ( P < 0.05). Electrophoretogram showed that CPI was concentrated at 60 and 40 kDa, whereas SPI showed bands at 95, 65, 60, 40, and 35 kDa. The CPI had higher lysine (49.3 to 51.8 mg/g) than SPI (41.9 to 43.4 mg/g). The CPI and SPI had surface hydrophobicities ranging from 387.8 to 572.9 and 640.6 to 643.1, respectively. Denaturation temperature (85.2 to 88.4 °C) and enthalpy (8.42 to 10.33 J/g) of CPI were similar to the 7S fraction of SPI (82.6 °C and 96.0 to 96.3 J/g). These characteristics of CPI might be useful to explain its functionalities for application in food systems. [ABSTRACT FROM AUTHOR]

Background: The study objectives were (a) to describe the occurrence, types, and preventability of adverse drug events (ADEs) in hospitalized patients 70 years of age and older; (b) to examine the association between potential risk factors and ADEs; and (c) to examine the relationship of an ADE occurrence and hospital length of stay (LOS) and functional decline.Method: Consecutive general medical admissions (n = 157) of community-dwelling persons were prospectively monitored daily for ADE occurrence. Admission assessment included demographic factors, cognition, preadmission medication use, and functional status. Discharge assessment included functional status. LOS, discharge diagnoses, and medication use during the hospitalization.Results: Twenty-three patients (14.6%) experienced 28 probable ADEs, of which 54.2% (13/24) were judged to be potentially preventable. Patients experiencing an ADE had a significantly lower mean Mini-Mental State Examination score (23.6 +/- 4.3 vs 25.5 +/- 3.6, p = .039) and were prescribed significantly more new inpatient medications (4.0 +/- 2.3 vs 2.6 +/- 1.7, p = .01) compared to non-ADE patients. Age, gender, functional status prior to admission, percent with more than four active diagnoses, or number of preadmission medications were not associated with ADE status. Upon discharge, 50.0% of ADE patients experienced a decline in one or more activities of daily living (ADLs), compared with 24.1% of non-ADE patients (p = .017). ADE patients had a longer LOS (8.7 +/- 4.9 vs 6.6 +/- 3.0 days, p = .022) compared to non-ADE patients.Conclusions: ADEs were associated with number of new inpatient medications and admission cognitive status, but not demographic, disease, or physical function variables. Patients experiencing an ADE were more likely to experience a longer LOS and to decline in ADL function. ADEs may be one factor contributing to functional decline during hospitalization. Future research in this area should include larger samples and multivariable analyses controlling for potential confounders. [ABSTRACT FROM AUTHOR]

BSTRACT: Functional properties of protein isolates prepared from 3 cowpea varieties and 2 soybean varieties in each of 2 y were determined. Both cowpea protein isolate (CPI) and soy protein isolate (SPI) showed a u-shaped curve for solubility with the minimum solubility occurring at pH 4.5. The CPI had lower emulsifying activity than SPI but was similar in stability. Foaming capacity and foaming stability ranged from 58.6 to 60.2 mL and 63.7 to 64.4 min for CPI and from 31.9 to 33.0 mL and 43.4 to 45.0 min for SPI, respectively. Gels were formed at 70 °C for 40 min and 30 min for CPI (12%) and SPI (10%), respectively. The CPI needs modification to enhance functional properties for potential application in food products. [ABSTRACT FROM AUTHOR]

Provides information on a study of three cases of hereditary haemorrhagic telangiectasia (HHT), focusing on patients who developed cerebral abscesses secondary to pulmonary arteriovenous malformations. Detailed information on each case study; Discussion on the results of the cases.