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Sample records for carnosine retards tumor

  1. Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model

    PubMed Central

    2010-01-01

    Background It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. Results A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 μl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects proliferation in vivo. Conclusion As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level. PMID:20053283

  2. Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa tumor xenografts.

    PubMed

    Ditte, Zuzana; Ditte, Peter; Labudova, Martina; Simko, Veronika; Iuliano, Filippo; Zatovicova, Miriam; Csaderova, Lucia; Pastorekova, Silvia; Pastorek, Jaromir

    2014-05-22

    Carbonic anhydrase IX (CA IX) is a transmembrane enzyme that is present in many types of solid tumors. Expression of CA IX is driven predominantly by the hypoxia-inducible factor (HIF) pathway and helps to maintain intracellular pH homeostasis under hypoxic conditions, resulting in acidification of the tumor microenvironment. Carnosine (β-alanyl-L-histidine) is an anti-tumorigenic agent that inhibits the proliferation of cancer cells. In this study, we investigated the role of CA IX in carnosine-mediated antitumor activity and whether the underlying mechanism involves transcriptional and translational modulation of HIF-1α and CA IX and/or altered CA IX function. The effect of carnosine was studied using two-dimensional cell monolayers of several cell lines with endogenous CA IX expression as well as Madin Darby canine kidney transfectants, three-dimensional HeLa spheroids, and an in vivo model of HeLa xenografts in nude mice. mRNA and protein expression and protein localization were analyzed by real-time PCR, western blot analysis, and immunofluorescence staining, respectively. Cell viability was measured by a flow cytometric assay. Expression of HIF-1α and CA IX in tumors was assessed by immunohistochemical staining. Real-time measurement of pH was performed using a sensor dish reader. Binding of CA IX to specific antibodies and metabolon partners was investigated by competitive ELISA and proximity ligation assays, respectively. Carnosine increased the expression levels of HIF-1α and HIF targets and increased the extracellular pH, suggesting an inhibitory effect on CA IX-mediated acidosis. Moreover, carnosine significantly inhibited the growth of three-dimensional spheroids and tumor xenografts compared with untreated controls. Competitive ELISA showed that carnosine disrupted binding between CA IX and antibodies specific for its catalytic domain. This finding was supported by reduced formation of the functional metabolon of CA IX and anion exchanger 2 in the

  3. Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa tumor xenografts

    PubMed Central

    2014-01-01

    Background Carbonic anhydrase IX (CA IX) is a transmembrane enzyme that is present in many types of solid tumors. Expression of CA IX is driven predominantly by the hypoxia-inducible factor (HIF) pathway and helps to maintain intracellular pH homeostasis under hypoxic conditions, resulting in acidification of the tumor microenvironment. Carnosine (β-alanyl-L-histidine) is an anti-tumorigenic agent that inhibits the proliferation of cancer cells. In this study, we investigated the role of CA IX in carnosine-mediated antitumor activity and whether the underlying mechanism involves transcriptional and translational modulation of HIF-1α and CA IX and/or altered CA IX function. Methods The effect of carnosine was studied using two-dimensional cell monolayers of several cell lines with endogenous CA IX expression as well as Madin Darby canine kidney transfectants, three-dimensional HeLa spheroids, and an in vivo model of HeLa xenografts in nude mice. mRNA and protein expression and protein localization were analyzed by real-time PCR, western blot analysis, and immunofluorescence staining, respectively. Cell viability was measured by a flow cytometric assay. Expression of HIF-1α and CA IX in tumors was assessed by immunohistochemical staining. Real-time measurement of pH was performed using a sensor dish reader. Binding of CA IX to specific antibodies and metabolon partners was investigated by competitive ELISA and proximity ligation assays, respectively. Results Carnosine increased the expression levels of HIF-1α and HIF targets and increased the extracellular pH, suggesting an inhibitory effect on CA IX-mediated acidosis. Moreover, carnosine significantly inhibited the growth of three-dimensional spheroids and tumor xenografts compared with untreated controls. Competitive ELISA showed that carnosine disrupted binding between CA IX and antibodies specific for its catalytic domain. This finding was supported by reduced formation of the functional metabolon of CA IX

  4. Carnosine Inhibits the Proliferation of Human Gastric Carcinoma Cells by Retarding Akt/mTOR/p70S6K Signaling

    PubMed Central

    Zhang, Zhenwei; Miao, Lei; Wu, Xin; Liu, Guangze; Peng, Yuting; Xin, Xiaoming; Jiao, Binghua; Kong, Xiangping

    2014-01-01

    Carnosine (β-alanyl-L-histidine), described as an enigmatic peptide for its antioxidant, anti-aging and especially antiproliferation properties, has been demonstrated to play an anti-tumorigenic role in certain types of cancer. However, its function in human gastric carcinoma remains unclear. In this study, the effect of carnosine on cell proliferation and its underlying mechanisms were investigated in the cultured human gastric carcinoma cells. The mTOR signaling axis molecules were analyzed in carnosine treated cells. The results showed that treatment with carnosine led to proliferation inhibition, cell cycle arrest in the G0/G1 phase, apoptosis increase, and inhibition of mTOR signaling activation by decreasing the phosphorylation of Akt, mTOR and p70S6K, suggesting that proliferation inhibition of carnosine in human gastric carcinoma was through the inhibition of Akt/mTOR/p70S6K pathway, and carnosine would be a mimic of rapamycin. PMID:24799956

  5. [Carnosine, carnosinase and kidney diseases].

    PubMed

    Kiliś-Pstrusińska, Katarzyna

    2012-04-20

     Carnosine (beta-alanyl-L-histidine) is an endogenously synthesized dipeptide which is present in different human tissues, including the kidney. Carnosine is hydrolyzed by the enzyme carnosinase. There are two carnosinase homologues: serum secreted carnosinase and non-specific cytosolic dipeptidase, encoded by the genes CNDP1 and CNDP2 respectively and located on chromosome 18q22.3. Carnosine functions as a radical oxygen species scavenger and as a natural angiotensin converting enzyme inhibitor. Carnosine inhibits advanced glycation end product formation and reduces the synthesis of matrix proteins such as fibronectin and collagen type VI of podocytes and mesangial cells. In experimental studies it was shown that carnosine reduces the level of proinflammatory and profibrotic cytokines. It is suggested that carnosine is a naturally occurring anti-aging substance in human organisms with a beneficial effect on the cardiovascular system. This paper reports the results of studies concerning carnosine's role in kidney diseases, particularly in ischemia/reperfusion induced acute renal failure, diabetic nephropathy, gentamicin-induced nephrotoxicity and also in blood pressure regulation. The correlations between serum carnosine and serum carnosinase activity and polymorphism in the CNDP1 gene are analyzed. The role of CNDP1 gene polymorphism in the development of diabetic nephropathy and non-diabetic chronic kidney disease is discussed. Carnosine is engaged in different metabolic pathways. It has nephroprotective features. Further studies of carnosine metabolism and its biological properties, particularly those concerning the human organism, are required.

  6. L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

    PubMed

    Cartwright, Stephanie P; Bill, Roslyn M; Hipkiss, Alan R

    2012-01-01

    The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

  7. Physiology and pathophysiology of carnosine.

    PubMed

    Boldyrev, Alexander A; Aldini, Giancarlo; Derave, Wim

    2013-10-01

    Carnosine (β-alanyl-l-histidine) was discovered in 1900 as an abundant non-protein nitrogen-containing compound of meat. The dipeptide is not only found in skeletal muscle, but also in other excitable tissues. Most animals, except humans, also possess a methylated variant of carnosine, either anserine or ophidine/balenine, collectively called the histidine-containing dipeptides. This review aims to decipher the physiological roles of carnosine, based on its biochemical properties. The latter include pH-buffering, metal-ion chelation, and antioxidant capacity as well as the capacity to protect against formation of advanced glycation and lipoxidation end-products. For these reasons, the therapeutic potential of carnosine supplementation has been tested in numerous diseases in which ischemic or oxidative stress are involved. For several pathologies, such as diabetes and its complications, ocular disease, aging, and neurological disorders, promising preclinical and clinical results have been obtained. Also the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into l-histidine and β-alanine, is discussed. The carnosine system has evolved as a pluripotent solution to a number of homeostatic challenges. l-Histidine, and more specifically its imidazole moiety, appears to be the prime bioactive component, whereas β-alanine is mainly regulating the synthesis of the dipeptide. This paper summarizes a century of scientific exploration on the (patho)physiological role of carnosine and related compounds. However, far more experiments in the fields of physiology and related disciplines (biology, pharmacology, genetics, molecular biology, etc.) are required to gain a full understanding of the function and applications of this intriguing molecule.

  8. L-Carnosine Prevents the Pro-cancerogenic Activity of Senescent Peritoneal Mesothelium Towards Ovarian Cancer Cells.

    PubMed

    Mikuła-Pietrasik, Justyna; Książek, Krzysztof

    2016-02-01

    L-Carnosine inhibits senescence of somatic cells and displays anticancer activity. Here we analyzed if L-carnosine (20 mM) retards senescence of human peritoneal mesothelial cells (HPMCs) and inhibits progression of ovarian cancer cells. Experiments were performed with primary HPMCs established from patients undergoing abdominal surgery and with three ovarian cancer cell lines: A2780, OVCAR-3 and SKOV-3. L-Carnosine retards senescence of HPMCs plausibly via inhibition of mitochondria-related oxidative stress. Prolonged exposure of HPMCs to L-carnosine prevented senescent HPMC-dependent exacerbation of cancer cell adhesion, migration, invasion and proliferation, which may be linked with decreased secretion of various pro-cancerogenic agents by HPMCs. Cancer cells exposed directly to L-carnosine displayed reduced viability, increased frequency of apoptosis and unaltered proliferation. L-carnosine may be a valuable anticancer drug, especially in the context of prevention and therapy of intraperitoneal ovarian cancer metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Radiochemical synthesis and preliminary in vivo evaluation of new radioactive platinum complexes with carnosine.

    PubMed

    Maurin, Michał; Garnuszek, Piotr

    2010-02-01

    Application of cross-linking agents such as SATA and 2-iminothiolane (2-IT) for radiochemical synthesis of new radioactive Pt(II) and Pt(IV) complexes with carnosine was investigated. The mixed-ligand Pt(II)([(125)I]Hist)(Carnosine) complex has been synthesized in a multi-step reaction. First, carnosine was modified by the attachment of SATA. After chromatographic purification, the conjugate was unprotected to form a reactive sulfhydryl functional group, and then the modified carnosine was substituted to PtCl(2)[(125)I]Hist complex. The Pt(II)(IT-[(125)I]Carnosine) and Pt(IV)(IT-[(131)I]Carnosine) complexes were synthesized in a three-step reaction. First, carnosine was labeled with iodine radionuclide ((125)I or (131)I), followed by conjugation with 2-IT. The modified IT-[*I]Carnosine was complexed with tetrachloroplatinate or hexachloroplatinate. Comparative biodistribution studies were performed in normal Wistar rats and in Lewis rats with implanted (s.c.) rat pancreatic tumor cells (AR42J). The HPLC analysis showed a relatively fast formation of the new mixed-ligand Pt([(125)I]Hist)(Carnosine) complex (yield ca. 50% after 20h). Reaction of K(2)PtCl(4) with [(125)I]Carnosine modified by 2-IT proceeded rapidly and with a high yield (>95% after 2h). The synthesis of the Pt(IV)IT-[*I]Carnosine complex was the slower reaction in comparison to the analogous synthesis of the Pt(II) complex (yield ca. 70% after 12h), thus a purification step was necessary. The biodistribution study proved the in vivo stability of the newly synthesized complexes (a low accumulation in thyroid gland and in GIT) and showed that the conjugation of the modified carnosine changes significantly biodistribution scheme of the Pt complexes comparing to the reference Pt(II)[*I]Hist and Pt(IV)([*I]Hist)(2) complexes. The mixed-ligand complex was rapidly excreted in urine and revealed the highest accumulation in kidneys (>5%ID/g). A very high concentration in blood and in liver was observed for the

  10. Organophosphate Flame Retardants Act as Endocrine-Disrupting Chemicals in MA-10 Mouse Tumor Leydig Cells.

    PubMed

    Schang, Gauthier; Robaire, Bernard; Hales, Barbara F

    2016-04-01

    The organophosphate flame retardants (OPFRs) have emerged as alternatives to banned brominated flame retardants but little is known about their possible activity as endocrine disruptors. Our goal was to compare the effects of 7 commonly used OPFRsin vitroon MA-10 mouse Leydig tumor cells to those of a major brominated flame retardant, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). The effects of OPFRs and BDE-47 on mitochondrial activity, cell counts, oxidative stress, steroid secretion and gene expression were investigated. BDE-47 and all 7 OPFRs tested significantly reduced MA-10 cell mitochondrial activity (concentrations ≥50 μM) and cell number (concentrations ≥10 μM). All of the OPFRs significantly increased (10 μM, 1.7-4.4-fold) superoxide production whereas BDE-47 had no significant effect. Basal progesterone production was significantly increased (10 μM, 1.5 to 3-fold) by 2-ethylhexyl diphenyl phosphate, isodecyl diphenyl phosphate, isopropylated triphenyl phosphate, tert-butylphenyl diphenyl phosphate, and tricresyl phosphate, while BDE-47, triphenyl phosphate and tri-o-cresyl phosphate had no effect. Interestingly, isopropylated triphenyl phosphate enhanced dbcAMP-stimulated steroid production (∼2-fold), while tri-o-cresyl phosphate decreased (∼2/3) LH-stimulated steroid production. Several OPFRs affected the expression of genes involved in the biosynthesis of progesterone. In conclusion, all the OPFRs tested affected mitochondrial activity, cell survival, and superoxide production. Basal or stimulated steroid secretion was affected by all of the OPFRs except triphenyl phosphate; BDE-47 had no effect. Hence, the OPFRs currently used as alternatives affect Leydig cells to a greater extent than the brominated flame retardants that they have replaced.

  11. Carnosine Inhibits the Proliferation of Human Gastric Cancer SGC-7901 Cells through Both of the Mitochondrial Respiration and Glycolysis Pathways

    PubMed Central

    Shen, Yao; Yang, Jianbo; Li, Juan; Shi, Xiaojie; Ouyang, Li; Tian, Yueyang; Lu, Jianxin

    2014-01-01

    Carnosine, a naturally occurring dipeptide, has been recently demonstrated to possess anti-tumor activity. However, its underlying mechanism is unclear. In this study, we investigated the effect and mechanism of carnosine on the cell viability and proliferation of the cultured human gastric cancer SGC-7901 cells. Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells cultured with pyruvate have active mitochondria, and depend on mitochondrial oxidative phosphorylation more than glycolysis pathway for generation of ATP. Carnosine markedly decreased the absolute value of mitochondrial ATP-linked respiration, and reduced the maximal oxygen consumption and spare respiratory capacity, which may reduce mitochondrial function correlated with proliferative potential. Simultaneously, carnosine also reduced the extracellular acidification rate and glycolysis of SGC-7901 cells. Our results suggested that carnosine is a potential regulator of energy metabolism of SGC-7901 cells both in the anaerobic and aerobic pathways, and provided a clue for preclinical and clinical evaluation of carnosine for gastric cancer therapy. PMID:25115854

  12. Carnosine inhibits the proliferation of human gastric cancer SGC-7901 cells through both of the mitochondrial respiration and glycolysis pathways.

    PubMed

    Shen, Yao; Yang, Jianbo; Li, Juan; Shi, Xiaojie; Ouyang, Li; Tian, Yueyang; Lu, Jianxin

    2014-01-01

    Carnosine, a naturally occurring dipeptide, has been recently demonstrated to possess anti-tumor activity. However, its underlying mechanism is unclear. In this study, we investigated the effect and mechanism of carnosine on the cell viability and proliferation of the cultured human gastric cancer SGC-7901 cells. Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells cultured with pyruvate have active mitochondria, and depend on mitochondrial oxidative phosphorylation more than glycolysis pathway for generation of ATP. Carnosine markedly decreased the absolute value of mitochondrial ATP-linked respiration, and reduced the maximal oxygen consumption and spare respiratory capacity, which may reduce mitochondrial function correlated with proliferative potential. Simultaneously, carnosine also reduced the extracellular acidification rate and glycolysis of SGC-7901 cells. Our results suggested that carnosine is a potential regulator of energy metabolism of SGC-7901 cells both in the anaerobic and aerobic pathways, and provided a clue for preclinical and clinical evaluation of carnosine for gastric cancer therapy.

  13. The antineoplastic effect of carnosine is accompanied by induction of PDK4 and can be mimicked by L-histidine.

    PubMed

    Letzien, Ulrike; Oppermann, Henry; Meixensberger, Jürgen; Gaunitz, Frank

    2014-04-01

    Carnosine (β-alanyl-L-histidine) is a naturally occurring dipeptide that shows antineoplastic effects in cell culture as well as in animal experiments. Since its mode of action and the targets at the molecular level have not yet been elucidated, we performed qRT-PCR experiments with RNA isolated from glioblastoma cell lines treated with carnosine, β-alanine, L-alanine, L-histidine and the dipeptide L-alanine-L-histidine. The experiments identified a strong induction of expression of the gene encoding pyruvate dehydrogenase 4 (PDK4) under the influence of carnosine and L-histidine, but not by the other substances employed. In addition, inhibition of cell viability was only detected in cells treated with carnosine and L-histidine, with the latter showing a significantly stronger effect than carnosine. Since the tumor cells expressed the tissue form of carnosinase (CN2) but almost no serum carnosinase (CN1), we conclude that cleavage by CN2 is a prerequisite for the antineoplastic effect of carnosine. In addition, enhanced expression of PDK4 under the influence of carnosine/L-histidine opens a new perspective for the interpretation of the ergogenic potential of dietary β-alanine supplementation and adds a new contribution to a growing body of evidence that single amino acids can regulate key metabolic pathways important in health and disease.

  14. Identification of hydrazine in commercial preparations of carnosine and its influence on carnosine's antioxidative properties.

    PubMed

    Zhou, S; Dickinson, L C; Yang, L; Decker, E A

    1998-07-15

    Commercial preparations of synthetic carnosine are commonly used by researchers to investigate carnosine's biological functions and potential applications. Our studies on the interaction of synthetic carnosine and aldehydic lipid oxidation products have led to the detection and structural identification of hydrazine, a strong reducing agent. The concentrations of hydrazine in various sources of commercial carnosine were in the range of 0.01-0.20% (w/w). The levels of contaminating hydrazine in commercial carnosine were capable of interfering with the analyses of headspace aldehydes, malonaldehyde, and thiobarbituric acid-reactive substances. Since hydrazine can potentially interfere with lipid oxidation reactions and measurement of lipid oxidation products, it will be necessary to use purified carnosine to reevaluate carnosine's biological and chemical properties. Copyright 1998 Academic Press.

  15. Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress.

    PubMed

    Stegen, Sanne; Stegen, Bram; Aldini, Giancarlo; Altomare, Alessandra; Cannizzaro, Luca; Orioli, Marica; Gerlo, Sarah; Deldicque, Louise; Ramaekers, Monique; Hespel, Peter; Derave, Wim

    2015-09-01

    There is growing in vivo evidence that the dipeptide carnosine has protective effects in metabolic diseases. A critical unanswered question is whether its site of action is tissues or plasma. This was investigated using oral carnosine versus β-alanine supplementation in a high-fat diet rat model. Thirty-six male Sprague-Dawley rats received a control diet (CON), a high-fat diet (HF; 60% of energy from fat), the HF diet with 1.8% carnosine (HFcar), or the HF diet with 1% β-alanine (HFba), as β-alanine can increase muscle carnosine without increasing plasma carnosine. Insulin sensitivity, inflammatory signaling, and lipoxidative stress were determined in skeletal muscle and blood. In a pilot study, urine was collected. The 3 HF groups were significantly heavier than the CON group. Muscle carnosine concentrations increased equally in the HFcar and HFba groups, while elevated plasma carnosine levels and carnosine-4-hydroxy-2-nonenal adducts were detected only in the HFcar group. Elevated plasma and urine N(ε)-(carboxymethyl)lysine in HF rats was reduced by ∼50% in the HFcar group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA was decreased by 47% (p < 0.05) in the HFcar group, but not in the HFba group, compared with HF rats. We conclude that plasma carnosine, but not muscle carnosine, is involved in preventing early-stage lipoxidation in the circulation and inflammatory signaling in the muscle of rats.

  16. Mitochondrial deficiency impairs hypoxic induction of HIF-1 transcriptional activity and retards tumor growth

    PubMed Central

    Koido, Masaru; Haga, Naomi; Furuno, Aki; Tsukahara, Satomi; Sakurai, Junko; Tani, Yuri; Sato, Shigeo; Tomida, Akihiro

    2017-01-01

    Mitochondria can be involved in regulating cellular stress response to hypoxia and tumor growth, but little is known about that mechanistic relationship. Here, we show that mitochondrial deficiency severely retards tumor xenograft growth with impairing hypoxic induction of HIF-1 transcriptional activity. Using mtDNA-deficient ρ0 cells, we found that HIF-1 pathway activation was comparable in slow-growing ρ0 xenografts and rapid-growing parental xenografts. Interestingly, we found that ex vivo ρ0 cells derived from ρ0 xenografts exhibited slightly increased HIF-1α expression and modest HIF-1 pathway activation regardless of oxygen concentration. Surprisingly, ρ0 cells, as well as parental cells treated with oxidative phosphorylation inhibitors, were unable to boost HIF-1 transcriptional activity during hypoxia, although HIF-1α protein levels were ordinarily increased in these cells under hypoxic conditions. These findings indicate that mitochondrial deficiency causes loss of hypoxia-induced HIF-1 transcriptional activity and thereby might lead to a constitutive HIF-1 pathway activation as a cellular adaptation mechanism in tumor microenvironment. PMID:28060746

  17. Effects of carnosine on cyclophosphamide-induced hematopoietic suppression in mice.

    PubMed

    Xu, Meng; He, Rong-Rong; Zhai, Yu-Jia; Abe, Keiichi; Kurihara, Hiroshi

    2014-01-01

    Cyclophosphamide is one of the most widely used chemotherapeutic agents in treating cancers. Chemotherapy drug-induced oxidative stress produces side effects. The severity of myelosuppression increases with a high dose of cyclophosphamide. Chicken soup or chicken essence, a traditional Chinese aliment, is a popular health supplement for patients with cancers or other diseases in Asia. As a major functional component of chicken meat extract, carnosine (beta-alanyl-L-histidine), a dipeptide of the amino acids beta-alanine and histidine, has been shown to have strong antioxidant activities. In the present study, we investigated the effects of carnosine on hematopoietic suppression in mice treated with cyclophosphamide. As expected, we found that cyclophosphamide administration (with a single dose of 150 mg/kg) induced a rapid (within 24 hours) and severe hematopoietic suppression in mice. We further showed that carnosine administration (100 mg/kg/day or 200 mg/kg/day for continuous seven days) could substantially improve suppressed hematopoietic functions and accelerate the recovery of leukocyte counts, bone marrow spontaneous proliferation, colony stimulating activity (CSA) in serum, and production of endogenous cytokines such as interleukin-3 (IL-3) and stem cell factor (SCF). These results indicate that carnosine has the potential to promote the recovery from hematopoietic suppression induced by cyclophosphamide. Our data suggest that carnosine holds a potential in clinical application to minimize the side effects induced by chemotherapeutic agents such as cyclophosphamide and thus will substantially improve the overall anti-tumor effects of the standard chemotherapies.

  18. Efficacy of carnosine on activation of caspase 3 and human renal carcinoma cell inhibition.

    PubMed

    Pandurangan, Muthuraman; Mistry, Bhupendra; Enkhataivan, Gansukh; Kim, Doo Hwan

    2016-11-01

    Carnosine is a natural antioxidant dipeptide that is highly concentrated in muscles and brain. The present study investigated the effect of carnosine cell growth inhibition and activation of the caspase-3 enzyme under cell co-culture system. Renal carcinoma and normal cells were co-cultured to provide three-dimensional views for the experimental analyses. Carnosine inhibited renal cancer cell growth up to 40%, whereas it was 25% in normal cells. Caspase-3 enzyme activity corresponded to the appearance of immunofluorescence in the cytoplasm using the caspase-3 antibody. Caspase-3 enzyme activity gradually increased in renal carcinoma cells in a concentration-dependent manner. The increased immunofluorescence and fluorescent detection of caspase-3 indicated the occurrence of apoptosis. The binding affinity of carnosine with caspase-3 subunit was confirmed by In silico docking study and glide energy was -5.2kcal/mol. Taking all these data together, it is suggested that the carnosine may be a potential antiproliferative agent in renal carcinoma tumor. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. New derivative of carnosine for nanoparticle assemblies.

    PubMed

    Bellia, Francesco; Oliveri, Valentina; Rizzarelli, Enrico; Vecchio, Graziella

    2013-01-01

    Carnosine (β-alanyl-l-histidine) is an endogenous dipeptide, extensively studied owing to its multifunctional activity exhibited in tissues of several animal species. This natural compound may act as a physiological buffer, ion-chelating agent (especially for copper(II) and zinc(II)), antioxidant and antiglycating agent. The main limit for the therapeutical uses of carnosine is the rapid hydrolysis mostly in human plasma by carnosinase. The chemical derivatization of carnosine is a promising strategy to improve the bioavailability of the dipeptide and facilitating the site-specific transport to different tissues. On this basis, a new carnosine derivative with biotin was synthesized and structurally characterized by NMR and MS measurements, with aim of exploiting the avidin-biotin technology that offers a universal system for selective delivery of any biotinylated agent. The stability of the new carnosine derivative towards the hydrolytic action of serum carnosinase as well as the copper(II) binding ability of the carnosine-biotin conjugate were also assessed. The binding affinity of the new molecular entity to avidin and streptavidin, investigated by a spectrophotometric assay, was exploited to functionalize avidin- and streptavidin-gold nanoparticles with the carnosine-biotin conjugate. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. Intrinsic carnosine metabolism in the human kidney.

    PubMed

    Peters, Verena; Klessens, Celine Q F; Baelde, Hans J; Singler, Benjamin; Veraar, Kimberley A M; Zutinic, Ana; Drozak, Jakub; Zschocke, Johannes; Schmitt, Claus P; de Heer, Emile

    2015-12-01

    Histidine-containing dipeptides like carnosine and anserine have protective functions in both health and disease. Animal studies suggest that carnosine can be metabolized within the kidney. The goal of this study was to obtain evidence of carnosine metabolism in the human kidney and to provide insight with regards to diabetic nephropathy. Expression, distribution, and localization of carnosinase-1 (CNDP1), carnosine synthase (CARNS), and taurine transporters (TauT) were measured in human kidneys. CNDP1 and CARNS activities were measured in vitro. CNDP1 and CARNS were located primarily in distal and proximal tubules, respectively. Specifically, CNDP1 levels were high in tubular cells and podocytes (20.3 ± 3.4 and 15 ± 3.2 ng/mg, respectively) and considerably lower in endothelial cells (0.5 ± 0.1 ng/mg). CNDP1 expression was correlated with the degradation of carnosine and anserine (r = 0.88 and 0.81, respectively). Anserine and carnosine were also detectable by HPLC in the renal cortex. Finally, TauT mRNA and protein were found in all renal epithelial cells. In diabetic patients, CNDP1 seemed to be reallocated to proximal tubules. We report compelling evidence that the kidney has an intrinsic capacity to metabolize carnosine. Both CNDP1 and CARNS are expressed in glomeruli and tubular cells. Carnosine-synthesizing and carnosine-hydrolyzing enzymes are localized in distinct compartments in the nephron and increased CNDP1 levels suggest a higher CNDP1 activity in diabetic kidneys.

  1. Plant-Made Trastuzumab (Herceptin) Inhibits HER2/Neu+ Cell Proliferation and Retards Tumor Growth

    PubMed Central

    Komarova, Tatiana V.; Kosorukov, Vyacheslav S.; Frolova, Olga Y.; Petrunia, Igor V.; Skrypnik, Ksenia A.; Gleba, Yuri Y.; Dorokhov, Yuri L.

    2011-01-01

    Background Plant biotechnology provides a valuable contribution to global health, in part because it can decrease the cost of pharmaceutical products. Breast cancer can now be successfully treated by a humanized monoclonal antibody (mAb), trastuzumab (Herceptin). A course of treatment, however, is expensive and requires repeated administrations of the mAb. Here we used an Agrobacterium-mediated transient expression system to produce trastuzumab in plant cells. Methodology/Principal Findings We describe the cloning and expression of gene constructs in Nicotiana benthamiana plants using intron-optimized Tobacco mosaic virus- and Potato virus X-based vectors encoding, respectively, the heavy and light chains of trastuzumab. Full-size antibodies extracted and purified from plant tissues were tested for functionality and specificity by (i) binding to HER2/neu on the surface of a human mammary gland adenocarcinoma cell line, SK-BR-3, in fluorescence-activated cell sorting assay and (ii) testing the in vitro and in vivo inhibition of HER-2-expressing cancer cell proliferation. We show that plant-made trastuzumab (PMT) bound to the Her2/neu oncoprotein of SK-BR-3 cells and efficiently inhibited SK-BR-3 cell proliferation. Furthermore, mouse intraperitoneal PMT administration retarded the growth of xenografted tumors derived from human ovarian cancer SKOV3 Her2+ cells. Conclusions/Significance We conclude that PMT is active in suppression of cell proliferation and tumor growth. PMID:21390232

  2. Carnosine attenuates early brain injury through its antioxidative and anti-apoptotic effects in a rat experimental subarachnoid hemorrhage model.

    PubMed

    Zhang, Zong-yong; Sun, Bao-liang; Yang, Ming-feng; Li, Da-wei; Fang, Jie; Zhang, Shuai

    2015-03-01

    Carnosine (β-alanyl-L-histidine) has been demonstrated to provide antioxidative and anti-apoptotic roles in the animal of ischemic brain injuries and neurodegenerative diseases. The aim of this study was to examine whether carnosine prevents subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) in rats. We found that intraperitoneal administration of carnosine improved neurobehavioral deficits, attenuated brain edema and blood-brain barrier permeability, and decreased reactive oxygen species level at 48 h following SAH in rat models. Carnosine treatment increased tissue copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) enzymatic activities, and reduced post-SAH elevated lactate dehydrogenase (LDH) activity, the concentration of malondialdehyde (MDA), 3-nitrotyrosine (3-NT), 8-hydroxydeoxyguanosine (8-OHDG), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in rats. Furthermore, carnosine treatment attenuated SAH-induced microglia activation and cortical neuron apoptosis. These results indicated that administration of carnosine may provide neuroprotection in EBI following SAH in rat models.

  3. Differential neuroprotective effects of carnosine, anserine, and N-acetyl carnosine against permanent focal ischemia.

    PubMed

    Min, Jiangyong; Senut, Marie-Claude; Rajanikant, Krishnamurthy; Greenberg, Eric; Bandagi, Ram; Zemke, Daniel; Mousa, Ahmad; Kassab, Mounzer; Farooq, Muhammad U; Gupta, Rishi; Majid, Arshad

    2008-10-01

    Carnosine (beta-alanyl-L-histidine) has been shown to exhibit neuroprotection in rodent models of cerebral ischemia. In the present study, we further characterized the effects of carnosine treatment in a mouse model of permanent focal cerebral ischemia and compared them with its related peptides anserine and N-acetylated carnosine. We also evaluated the efficacy of bestatin, a carnosinase inhibitor, in ameliorating ischemic brain damage. Permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery (pMCAO). Mice were subsequently randomly assigned to receive an intraperitoneal injection of vehicle (0.9% saline), carnosine, N-acetyl carnosine, anserine, bestatin alone, or bestatin with carnosine. Infarct size was examined using 2,3,5-triphenyltetrazolium chloride staining 1, 3, and 7 days following pMCAO, and neurological function was evaluated using an 18-point-based scale. Brain levels of carnosine were measured in treated mice using high-performance liquid chromatography 1 day following pMCAO. We demonstrated that treatment with carnosine, but not its analogues, was able to significantly reduce infarct volume and improve neurological function compared with those in vehicle-treated mice. These beneficial effects were maintained for 7 days post-pMCAO. In contrast, compared with the vehicle-treated group, bestatin-treated mice displayed an increase in the severity of ischemic lesion, which was prevented by the addition of carnosine. These new data further characterize the neuroprotective effects of carnosine and suggest that carnosine may be an attractive candidate for testing as a stroke therapy.

  4. Differential Neuroprotective Effects of Carnosine, Anserine, and N-Acetyl Carnosine against Permanent Focal Ischemia

    PubMed Central

    Min, Jiangyong; Senut, Marie-Claude; Rajanikant, Krishnamurthy; Greenberg, Eric; Bandagi, Ram; Zemke, Daniel; Mousa, Ahmad; Kassab, Mounzer; Farooq, Muhammad U.; Gupta, Rishi; Majid, Arshad

    2009-01-01

    Carnosine (β-alanyl-L-histidine) has been shown to exhibit neuroprotection in rodent models of cerebral ischemia. In the present study, we further characterized the effects of carnosine treatment in a mouse model of permanent focal cerebral ischemia and compared them with its related peptides anserine and N-acetylated carnosine. We also evaluated the efficacy of bestatin, a carnosinase inhibitor, in ameliorating ischemic brain damage. Permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery (pMCAO). Mice were subsequently randomly assigned to receive an intraperitoneal injection of vehicle (0.9% saline), carnosine, N-acetyl carnosine, anserine, bestatin alone, or bestatin with carnosine. Infarct size was examined using 2,3,5-triphenyltetrazolium chloride staining 1, 3, and 7 days following pMCAO, and neurological function was evaluated using an 18-point-based scale. Brain levels of carnosine were measured in treated mice using high-performance liquid chromatography 1 day following pMCAO. We demonstrated that treatment with carnosine, but not its analogues, was able to significantly reduce infarct volume and improve neurological function compared with those in vehicle-treated mice. These beneficial effects were maintained for 7 days post-pMCAO. In contrast, compared with the vehicle-treated group, bestatin-treated mice displayed an increase in the severity of ischemic lesion, which was prevented by the addition of carnosine. These new data further characterize the neuroprotective effects of carnosine and suggest that carnosine may be an attractive candidate for testing as a stroke therapy. PMID:18543335

  5. Determinants of muscle carnosine content.

    PubMed

    Harris, R C; Wise, J A; Price, K A; Kim, H J; Kim, C K; Sale, C

    2012-07-01

    The main determinant of muscle carnosine (M-Carn) content is undoubtedly species, with, for example, aerobically trained female vegetarian athletes [with circa 13 mmol/kg dry muscle (dm)] having just 1/10th of that found in trained thoroughbred horses. Muscle fibre type is another key determinant, as type II fibres have a higher M-Carn or muscle histidine containing dipeptide (M-HCD) content than type I fibres. In vegetarians, M-Carn is limited by hepatic synthesis of β-alanine, whereas in omnivores this is augmented by the hydrolysis of dietary supplied HCD's resulting in muscle levels two or more times higher. β-alanine supplementation will increase M-Carn. The same increase in M-Carn occurs with administration of an equal molar quantity of carnosine as an alternative source of β-alanine. Following the cessation of supplementation, M-Carn returns to pre-supplementation levels, with an estimated t1/2 of 5-9 weeks. Higher than normal M-Carn contents have been noted in some chronically weight-trained subjects, but it is unclear if this is due to the training per se, or secondary to changes in muscle fibre composition, an increase in β-alanine intake or even anabolic steroid use. There is no measureable loss of M-Carn with acute exercise, although exercise-induced muscle damage may result in raised plasma concentrations in equines. Animal studies indicate effects of gender and age, but human studies lack sufficient control of the effects of diet and changes in muscle fibre composition.

  6. Carnosine and the processes of ageing.

    PubMed

    Hipkiss, Alan R; Baye, Estifanos; de Courten, Barbora

    2016-11-01

    The causes of ageing are usually regarded as multifactorial; thus effective regulation might be achieved by intervention at multiple sites. It has been suggested that the endogenous dipeptide carnosine, also available as a food supplement, possesses anti-ageing activity and may achieve its reported age-alleviating effects via a number of mechanisms. Carnosine's possible anti-ageing mechanisms are therefore discussed; the evidence suggests that inhibition of the mechanistic target of rapamycin and carbonyl scavenging may be involved. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Hydroxyl radical scavenging by carnosine and Cu(II)-carnosine complexes: a pulse-radiolysis and spectroscopic study.

    PubMed

    Tamba, M; Torreggiani, A

    1999-09-01

    To obtain a wider insight into the general properties of carnosine and to provide support to its anti-oxidative role. This property is hypothesized to be linked to various mechanisms including free-radical scavenging and metal chelation (i.e. Cu(II)). Pulse-radiolysis experiments were performed by a 12 MeV electron linear accelerator (LINAC) on carnosine/copper(II) (2:1) and carnosine aqueous solutions at different pH. Raman spectra of solid samples were obtained by a Bruker IFS 66 spectrometer. As well as for free carnosine, in the presence of copper ions the interaction of carnosine with *OH radicals involves the imidazole group of the molecule. The oxidation of copper (II)-carnosine system by *OH radicals is related to the pH-dependent structure of the copper(II)-carnosine complex. Raman spectra indicate that at alkaline pH the formation of a dimeric species containing two carnosine molecules complexed to two Cu2+ ions takes place. This structure can address the *OH attack more selectively than carnosine itself to different sites of the imidazole ring. The formation of at least two different *OH-radical adducts occurs and positions C(2) and C(5) of the imidazole ring are the preferential sites for the *OH attack, as the heterocyclic ring is mainly present as its N(1)-protonated tautomeric form. These studies provide further evidence about the formation of carnosine-copper complexes and the predominance of a dimeric structure at slightly basic pH. The chelation of Cu(II) is not detrimental to the scavenging ability of carnosine. Raman spectra are helpful in identifying the structure of the copper(II)-carnosine complexes and in predicting the preferential sites for the *OH attack to the carnosine-copper system.

  8. Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity.

    PubMed

    Garofalo, Mariangela; Iovine, Barbara; Kuryk, Lukasz; Capasso, Cristian; Hirvinen, Mari; Vitale, Andrea; Yliperttula, Marjo; Bevilacqua, Maria Assunta; Cerullo, Vincenzo

    2016-04-01

    Oncolytic viruses are able to specifically replicate, infect, and kill only cancer cells. Their combination with chemotherapeutic drugs has shown promising results due to the synergistic action of virus and drugs; the combinatorial therapy is considered a potential clinically relevant approach for cancer. In this study, we optimized a strategy to absorb peptides on the viral capsid, based on electrostatic interaction, and used this strategy to deliver an active antitumor drug. We used L-carnosine, a naturally occurring histidine dipeptide with a significant antiproliferative activity. An ad hoc modified, positively charged L-carnosine was combined with the capsid of an oncolytic adenovirus to generate an electrostatic virus-carnosine complex. This complex showed enhanced antitumor efficacy in vitro and in vivo in different tumor models. In HCT-116 colorectal and A549 lung cancer cell lines, the complex showed higher transduction ratio and infectious titer compared with an uncoated oncolytic adenovirus. The in vivo efficacy of the complex was tested in lung and colon cancer xenograft models, showing a significant reduction in tumor growth. Importantly, we investigated the molecular mechanisms underlying the effects of complex on tumor growth reduction. We found that complex induces apoptosis in both cell lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in future studies also for delivery of other bioactive drugs. Mol Cancer Ther; 15(4); 651-60. ©2016 AACR. ©2016 American Association for Cancer Research.

  9. [Stimulation of proliferation by carnosine: cellular and transcriptome approaches].

    PubMed

    Vishniakova, Kh S; Babizhaev, M A; Aliper, A M; Buzdin, A A; Kudriavtseva, A V; Egorov, E E

    2014-01-01

    Concentration of endogenous dipeptide carnosine in human muscle tissue reaches tens of millimoles. For more than 100 years of research, a lot of data concerning carnosine functions were accumulated, among which anti-aging effects are regarded most important. Heire, effect of carnosine in cell cultures was studied. It has been found that apart from the known action--an increase of the Hayflick limit and morphological rejuvenation--carnosine stimulates cell division in colony-forming assays and in the course of transition of cells to the quiescent state. The analysis of the transcriptome showed that carnosine-induced changes are mainly related to positive regulation of the cell cycle at all levels, from the onset of the DNA synthesis to chromosome condensation. One can suppose that the revealed stimulation of the cell cycle account for the carnosine-induced rejuvenation processes and a high concentration ofcarnosine in muscle tissue is required for the muscle recovery (regeneration) after excess loads.

  10. Free radical scavenging and radioprotective effects of carnosine and anserine

    NASA Astrophysics Data System (ADS)

    Fu, Haiying; Katsumura, Yosuke; Lin, Mingzhang; Muroya, Yusa; Hata, Kuniki; Fujii, Kentaro; Yokoya, Akinari; Hatano, Yoshihiko

    2009-12-01

    Two histidine-containing natural dipeptides, carnosine and anserine (β-alanyl-1-methyl- L-histidine), have been examined for their antioxidant and radioprotective abilities. Pulse radiolysis studies indicated the antioxidative properties of carnosine and anserine aqueous solutions at different pH. The rate constants for the reaction OH radical with carnosine at neutral pH were determined to be 5.3×10 9 M -1 s -1 at 300 nm, and 4.1×10 9 M -1 s -1 at 400 nm, respectively. Carnosine and anserine also protected plasmid pUC18 DNA from X-ray radiation-induced strand breaks as evidenced from the studies by agarose gel electrophoresis. Carnosine showed higher protective efficiency under the experimental conditions. Our data demonstrated that carnosine and anserine may play an important role in the maintenance of the antioxidant system.

  11. Metabolite Proofreading in Carnosine and Homocarnosine Synthesis

    PubMed Central

    Veiga-da-Cunha, Maria; Chevalier, Nathalie; Stroobant, Vincent; Vertommen, Didier; Van Schaftingen, Emile

    2014-01-01

    Carnosine synthase is the ATP-dependent ligase responsible for carnosine (β-alanyl-histidine) and homocarnosine (γ-aminobutyryl-histidine) synthesis in skeletal muscle and brain, respectively. This enzyme uses, also at substantial rates, lysine, ornithine, and arginine instead of histidine, yet the resulting dipeptides are virtually absent from muscle or brain, suggesting that they are removed by a “metabolite repair” enzyme. Using a radiolabeled substrate, we found that rat skeletal muscle, heart, and brain contained a cytosolic β-alanyl-lysine dipeptidase activity. This enzyme, which has the characteristics of a metalloenzyme, was purified ≈200-fold from rat skeletal muscle. Mass spectrometry analysis of the fractions obtained at different purification stages indicated parallel enrichment of PM20D2, a peptidase of unknown function belonging to the metallopeptidase 20 family. Western blotting showed coelution of PM20D2 with β-alanyl-lysine dipeptidase activity. Recombinant mouse PM20D2 hydrolyzed β-alanyl-lysine, β-alanyl-ornithine, γ-aminobutyryl-lysine, and γ-aminobutyryl-ornithine as its best substrates. It also acted at lower rates on β-alanyl-arginine and γ-aminobutyryl-arginine but virtually not on carnosine or homocarnosine. Although acting preferentially on basic dipeptides derived from β-alanine or γ-aminobutyrate, PM20D2 also acted at lower rates on some “classic dipeptides” like α-alanyl-lysine and α-lysyl-lysine. The same activity profile was observed with human PM20D2, yet this enzyme was ∼100–200-fold less active on all substrates tested than the mouse enzyme. Cotransfection in HEK293T cells of mouse or human PM20D2 together with carnosine synthase prevented the accumulation of abnormal dipeptides (β-alanyl-lysine, β-alanyl-ornithine, γ-aminobutyryl-lysine), thus favoring the synthesis of carnosine and homocarnosine and confirming the metabolite repair role of PM20D2. PMID:24891507

  12. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies

    PubMed Central

    Prokopieva, V. D.; Yarygina, E. G.; Bokhan, N. A.; Ivanova, S. A.

    2016-01-01

    The main properties and biological effects of the antioxidant carnosine, the natural dipeptide β-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free-radical processes and formation of oxidative stress. PMID:26904160

  13. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies.

    PubMed

    Prokopieva, V D; Yarygina, E G; Bokhan, N A; Ivanova, S A

    2016-01-01

    The main properties and biological effects of the antioxidant carnosine, the natural dipeptide β-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free-radical processes and formation of oxidative stress.

  14. Effects of carnosine supplementation on glucose metabolism: Pilot clinical trial.

    PubMed

    de Courten, Barbora; Jakubova, Michaela; de Courten, Maximilian Pj; Kukurova, Ivica Just; Vallova, Silvia; Krumpolec, Patrik; Valkovic, Ladislav; Kurdiova, Timea; Garzon, Davide; Barbaresi, Silvia; Teede, Helena J; Derave, Wim; Krssak, Martin; Aldini, Giancarlo; Ukropec, Jozef; Ukropcova, Barbara

    2016-05-01

    Carnosine is a naturally present dipeptide in humans and an over-the counter food additive. Evidence from animal studies supports the role for carnosine in the prevention and treatment of diabetes and cardiovascular disease, yet there is limited human data. This study investigated whether carnosine supplementation in individuals with overweight or obesity improves diabetes and cardiovascular risk factors. In a double-blind randomized pilot trial in nondiabetic individuals with overweight and obesity (age 43 ± 8 years; body mass index 31 ± 4 kg/m(2) ), 15 individuals were randomly assigned to 2 g carnosine daily and 15 individuals to placebo for 12 weeks. Insulin sensitivity and secretion, glucose tolerance (oral glucose tolerance test), blood pressure, plasma lipid profile, skeletal muscle ((1) H-MRS), and urinary carnosine levels were measured. Carnosine concentrations increased in urine after supplementation (P < 0.05). An increase in fasting insulin and insulin resistance was hampered in individuals receiving carnosine compared to placebo, and this remained significant after adjustment for age, sex, and change in body weight (P = 0.02, P = 0.04, respectively). Two-hour glucose and insulin were both lower after carnosine supplementation compared to placebo in individuals with impaired glucose tolerance (P < 0.05). These pilot intervention data suggest that carnosine supplementation may be an effective strategy for prevention of type 2 diabetes. © 2016 The Obesity Society.

  15. Carnosine induced formation of silver nanochains: A radiolytic study

    NASA Astrophysics Data System (ADS)

    Malkar, Vishwabharati V.; Mukherjee, Tulsi; Kapoor, Sudhir

    2015-02-01

    Interaction of carnosine with silver clusters and its nanoparticles is studied at pH 8.2 and 9.2. Using time resolved kinetic measurements we show that carnosine interacts with the charged silver clusters. Using ionizing radiation silver particles are also produced in aqueous solution. In the presence of carnosine distinct differences in the surface plasmon absorption band of Ag nanoparticles is observed with change in pH. The results suggest that silver nanochains get formed through dipole-dipole interaction due to weak interaction with carnosine. UV-Vis spectrophotometry and transmission electron microscopy are used to characterize the nanoparticles.

  16. Inhibitory effect of carnosine and N-acetyl carnosine on LPS-induced microglial oxidative stress and inflammation.

    PubMed

    Fleisher-Berkovich, Sigal; Abramovitch-Dahan, Chen; Ben-Shabat, Shimon; Apte, Ron; Beit-Yannai, Elie

    2009-07-01

    Chronic inflammation and oxidative stress have been implicated in the pathogenesis of neurodegenerative diseases. A growing body of research focuses on the role of microglia, the primary immune cells in the brain, in modulating brain inflammation and oxidative stress. One of the most abundant antioxidants in the brain, particularly in glia, is the dipeptide carnosine, beta-alanyl-L-histidine. Carnosine is believed to be involved in cellular defense such as free radical detoxification and inhibition of protein cross-linking. The more stable N-acetyl derivative of carnosine has also been identified in the brain. The aim of the present study was to examine the role of carnosine and N-acetyl carnosine in the regulation of lipopolysaccharide (LPS)-induced microglial inflammation and oxidative damage. In this study, BV2 microglial cells were stimulated with bacterial LPS, a potent inflammatory stimulus. The data shows that both carnosine and N-acetyl carnosine significantly attenuated the LPS-induced nitric oxide synthesis and the expression of inducible nitric oxide synthase by 60% and 70%, respectively. By competitive spectrophotometric measurement and electrospray mass spectrometry analysis, we demonstrated a direct interaction of N-acetyl carnosine with nitric oxide. LPS-induced TNFalpha secretion and carbonyl formation were also significantly attenuated by both compounds. N-acetyl carnosine was more potent than carnosine in inhibiting the release of the inflammatory and oxidative stress mediators. These observations suggest the presence of a novel regulatory pathway through which carnosine and N-acetyl carnosine inhibit the synthesis of microglial inflammatory and oxidative stress mediators, and thus may prove to play a role in brain inflammation.

  17. Transport characteristics of L-carnosine and the anticancer derivative 4-toluenesulfonylureido-carnosine in a human epithelial cell line.

    PubMed

    Nielsen, Carsten Uhd; Supuran, Claudiu T; Scozzafava, Andrea; Frokjaer, Sven; Steffansen, Bente; Brodin, Birger

    2002-09-01

    The aim of the present study was to evaluate whether the transepithelial transport of the anticancer compound 4-toluenesulfonylureido-carnosine (Ts-carnosine) and the dipeptide moiety L-carnosine was due to a hPepT1 carrier-mediated flux. Transport experiments were conducted using Caco-2 cell monolayers and either reversed-phase HPLC-UV or liquid scintillation counting methods for quantification. pKa, LogD, and LogP were determined using the Sirius GlpKa meter. L-carnosine was transported across the apical membrane with a Km,app of 2.48 +/- 1.16 mM and a Vmax of 2.08 +/- 0.34 nmol x cm(-2) x min(-1) and across the basolateral membrane with a Km,app of 7.21 +/- 3.17 mM and a Vmax of 0.54 +/- 0.10 nmol x cm(-2) x min(-1), and transepithelially with a Papp of 4.46 x 10(-2) +/- 6.4 x 10(-6) cm x min(-10). Ts-carnosine had an affinity (Ki) for hPepT1 of 2.33 +/- 0.54 mM; however, the transepithelial transport was low as compared to that of L-carnosine. L-carnosine was transported across both the apical and basolateral membrane of Caco-2 cell monolayers in a carrier-mediated manner however, the transepithelial transport followed apparent simple non-saturable kinetics. Ts-carnosine had an affinity for hPepT1 but a relatively low transepithelial transport. This indicates that the transepithelial transport of L-carnosine and Ts-carnosine is not hPepT1 carrier-mediated and that L-carnosine is not a suitable dipeptide moiety for hPepT1-mediated absorption of sulfonamide-type anticancer compounds.

  18. Salmonella typhimurium peptidase active on carnosine.

    PubMed Central

    Kirsh, M; Dembinski, D R; Hartman, P E; Miller, C G

    1978-01-01

    Wild-type Salmonella typhimurium can use carnosine (beta-alanyl-L-histidine) as a source of histidine, but carnosine utilization is blocked in particular mutants defective in the constitutive enzyme peptidase D, the product of the pepD gene. Biochemical evidence for assigning carnosinase activity to peptidase D (a broad-specificity dipeptidase) includes: (i) coelution of carnosinase and dipeptidase activity from diethylaminoethyl-cellulose and Bio-Gel P-300 columns; (ii) coelectrophoresis of carnosinase and dipeptidase on polyacrylamide gels; and (iii) inactivation of carnosinase and dipeptidase activities at identical rates at both 4 and 42 degrees C. Genetic evidence indicates that mutations leading to loss of carnosinase activity map at pepD. Several independent pepD mutants have been isolated by different selection procedures, and the patterns of peptide utilization of strains carrying various pepD alleles have been studied. Many pepD mutations lead to the production of partially active peptidase D enzymes with substrate specificities that differ strikingly from those of the wild-type enzyme. The growth yields of carnosinase-deficient strains growing in Difco nutrient broth indicate that carnosine is the major utilizable source of histidine in this medium. PMID:26655

  19. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

    PubMed Central

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle. PMID:27190533

  20. Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle.

    PubMed

    Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Peng, Mi; Li, Hanyun; Song, Yonggui

    2016-01-01

    A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL(-1) for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL(-1). The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle.

  1. Preventive Effects of Carnosine on Lipopolysaccharide-induced Lung Injury

    PubMed Central

    Tanaka, Ken-Ichiro; Sugizaki, Toshifumi; Kanda, Yuki; Tamura, Fumiya; Niino, Tomomi; Kawahara, Masahiro

    2017-01-01

    Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute lung injury, which involves neutrophilic inflammation and pulmonary cell death. Reactive oxygen species (ROS) play important roles in ARDS development. New compounds for inhibiting the onset and progression of ARDS are required. Carnosine (β-alanyl-L-histidine) is a small di-peptide with numerous activities, including antioxidant effects, metal chelation, proton buffering capacity and the inhibition of protein carbonylation and glycoxidation. We have examined the preventive effects of carnosine on tissue injury, oedema and inflammation in a murine model for ARDS. Oral administration of carnosine suppressed lipopolysaccharide (LPS)-induced vascular permeability, tissue injury and inflammation in the lung. In vivo imaging analysis revealed that LPS administration increased the level of ROS and that this increase was inhibited by carnosine administration. Carnosine also suppressed LPS-induced neutrophilic inflammation (evaluated by activation of myeloperoxidase in the lung and increased extracellular DNA in bronchoalveolar lavage fluid). Furthermore, carnosine administration suppressed the LPS-induced endoplasmic reticulum stress response in vivo. These results suggest that the oral administration of carnosine suppresses LPS-induced lung injury via carnosine’s ROS-reducing activity. Therefore, carnosine may be beneficial for suppressing the onset and progression of ARDS. PMID:28205623

  2. New dinitrosyl iron complexes bound with physiologically active dipeptide carnosine.

    PubMed

    Shumaev, Konstantin B; Kosmachevskaya, Olga V; Nasybullina, Elvira I; Gromov, Sergey V; Novikov, Alexander A; Topunov, Alexey F

    2017-01-01

    Dinitrosyl iron complexes (DNICs) are physiological NO derivatives and account for many NO functions in biology. Polyfunctional dipeptide carnosine (beta-alanyl-L-histidine) is considered to be a very promising pharmacological agent. It was shown that in the system containing carnosine, iron ions and Angeli's salt, a new type of DNICs bound with carnosine as ligand {(carnosine)2-Fe-(NO)2}, was formed. We studied how the carbonyl compound methylglyoxal influenced this process. Carnosine-bound DNICs appear to be one of the cell's adaptation mechanisms when the amount of reactive carbonyl compounds increases at hyperglycemia. These complexes can also participate in signal and regulatory ways of NO and can act as protectors at oxidative and carbonyl stress conditions.

  3. EFFECTS OF 3-METHYLCHOLANTHRENE ON THE ENDOCRINE SYSTEM AND METABOLISM OF THE RAT AND ITS INFLUENCE TO RETARD GROWTH OF MAMMARY TUMORS HITHERTO REFRACTORY

    PubMed Central

    Huggins, Charles; Pollice, Lucio

    1958-01-01

    The repeated administration of 3-methylcholanthrene to adolescent rats resulted in (a) a profound, incomplete, and selective depression of certain hypophyseal functions; (b) decreased growth of transplanted mammary tumors; and (c) a retardation of body growth. Only the last mentioned effect was reversed by forced feeding. The retarded rate of body growth induced by 3-methylcholanthrene was prevented by the concurrent administration of dihydrotestosterone or progesterone, or by ovariectomy; rats so treated became overweight despite the injection of 3-methylcholanthrene. Phenolic estrogens intensified the retardation of body growth induced by 3-methylcholanthrene and emaciation resulted. The administration of 3-methylcholanthrene resulted in decreased gonadotrophin production by the pituitary and the ovaries were more drastically affected by the depression of pituitary activity than the adrenals were. The compound exerted differential effects on the pituitary glands of males and females respectively. Hormonal functions of both ovary and testis were decreased in rats treated with 3-methylcholanthrene but, whilst ovarian weight was much reduced, the size of the testis was not decreased and the germinal epithelium of the male was little affected by the treatment in most instances. There was a considerable reduction of the content of alkaline phosphatase in the breast of intact rats treated with 3-methylcholanthrene but atrophy of the mammary epithelium did not occur and hyperplasia of the mammary tree was often observed. The administration of 3-methylcholanthrene considerably slowed the growth of transplanted mammary tumors characterized by high dependence on hormones and the concurrent administration of gonadotrophin restored the growth rate of the tumors. The administration of 3-methylcholanthrene or androstan-17β-ol-3-one was only moderately effective in controlling the growth of transplanted mammary tumors characterized by low hormonal dependence; the combined

  4. Protective effect of carnosine on febrile seizures in immature mice.

    PubMed

    Dai, Yun-Jian; Wu, Deng-Chang; Feng, Bo; Hou, Wei-wei; Xu, Ceng-Lin; Ohtsu, Hiroshi; Chen, Zhong; Hu, Wei-Wei

    2015-02-19

    Febrile seizures (FSs) are the most common type of convulsions in childhood and complex FSs represent an increased risk for development of temporal lobe epilepsy. The aim of this study was to analyze the anticonvulsant effects of carnosine, an endogenous dipeptide composed of alanine and histidine, on hyperthermia induced seizure in immature mice. Injection of carnosine significantly increased the latency and decreased the duration of FSs in a dose-dependent manner. In addition, histidine had similar effects on FSs as carnosine. The protective effect of carnosine or histidine was completely abolished by α-fluoromethylhistidine (α-FMH), a selective and irreversible histidine decarboxylase inhibitor, or in histidine decarboxylase deficient (HDC-KO) mice. Peripheral carnosine administration increased the level of carnosine, histidine and histamine in the cortex and hippocampus of mice pups, but decreased glutamate contents in the cortex and hippocampus. These results indicate that carnosine can protect against FSs in mice pups through its conversion to histamine, suggesting that it may serve as an efficient anti-FSs drug in the future. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Carnosine and its possible roles in nutrition and health.

    PubMed

    Hipkiss, Alan R

    2009-01-01

    The dipeptide carnosine has been observed to exert antiaging activity at cellular and whole animal levels. This review discusses the possible mechanisms by which carnosine may exert antiaging action and considers whether the dipeptide could be beneficial to humans. Carnosine's possible biological activities include scavenger of reactive oxygen species (ROS) and reactive nitrogen species (RNS), chelator of zinc and copper ions, and antiglycating and anticross-linking activities. Carnosine's ability to react with deleterious aldehydes such as malondialdehyde, methylglyoxal, hydroxynonenal, and acetaldehyde may also contribute to its protective functions. Physiologically carnosine may help to suppress some secondary complications of diabetes, and the deleterious consequences of ischemic-reperfusion injury, most likely due to antioxidation and carbonyl-scavenging functions. Other, and much more speculative, possible functions of carnosine considered include transglutaminase inhibition, stimulation of proteolysis mediated via effects on proteasome activity or induction of protease and stress-protein gene expression, upregulation of corticosteroid synthesis, stimulation of protein repair, and effects on ADP-ribose metabolism associated with sirtuin and poly-ADP-ribose polymerase (PARP) activities. Evidence for carnosine's possible protective action against secondary diabetic complications, neurodegeneration, cancer, and other age-related pathologies is briefly discussed.

  6. Fragmentation pathways analysis for the gas phase dissociation of protonated carnosine-oxaliplatin complexes.

    PubMed

    Ritacco, Ida; Moustafa, Eslam M; Sicilia, Emilia; Russo, Nino; Shoeib, Tamer

    2015-03-14

    Collision-induced dissociation (CID) experiments on the protonated carnosine-oxaliplatin complex, [Carnosine + OxPt + H](+) using several collision energies were shown to yield nine different fragment ions. Energy-resolved CID experiments on [Carnosine + OxPt + H](+) showed that the generation of the product ion [Carnosine - H + Pt(dach)](+) (where dach is 1,2-diaminocyclohexane) is the lowest energy process. At slightly higher collision energies, the loss of neutral carnosine from [Carnosine + OxPt + H](+) to produce [OxPt + H](+) was observed, followed by the loss of oxaliplatin from the same precursor ion to produce [Carnosine + H](+). At significantly higher energies, the ion [OxPt - CO2 + H](+) was shown to be formed, while the last two investigated ions [Carnosine + OxPt - CO2 + H](+) and [Carnosine - NH3 - H + Pt(dach)](+) did not attain any significant relative abundance. Density functional calculations at the B3LYP/LANL2DZ level were employed to probe the fragmentation mechanisms that account for all experimental data. The lowest free energy barriers for the generation of each of the ions [Carnosine - H + Pt(dach)](+), [OxPt + H](+), [Carnosine + H](+), [Carnosine + OxPt - CO2 + H](+) and [Carnosine - NH3 - H + Pt(dach)](+) from [Carnosine + OxPt + H](+) according to the fragmentation mechanisms offered here were calculated to be 31.9, 38.8, 49.3, 75.2, and 85.6 kcal mol(-1), respectively.

  7. Experimental and Theoretical Study of Carnosine in THz Range

    NASA Astrophysics Data System (ADS)

    Yan, Hai-Tao; Wang, Wei-Ning

    2005-12-01

    The characteristic fingerprints of carnosine from 0.2 to 2.6 THz are first measured by terahertz time-domain spectroscopy at room temperature. For the pure carnosine, the refractive index varies between 1.79 and 1.85 with the average value 1.84, while for the carnosine-polyethylene mixture, four absorption peaks centred at 1.37, 1.56, 1.85 and 2.49 THz are detected. A comparison of the theoretical predictions using the density functional theory with the experimental results shows satisfactory agreement except somewhat blue shift.

  8. Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy

    PubMed Central

    Lee, Changhan; Raffaghello, Lizzia; Brandhorst, Sebastian; Safdie, Fernando M.; Bianchi, Giovanna; Martin-Montalvo, Alejandro; Pistoia, Vito; Wei, Min; Hwang, Saewon; Merlino, Annalisa; Emionite, Laura; de Cabo, Rafael; Longo, Valter D.

    2013-01-01

    Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2val19 to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs—but not either treatment alone—resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers. PMID:22323820

  9. Quantitation of carnosine in humans plasma after dietary consumption of beef.

    PubMed

    Park, Young Joon; Volpe, Stella L; Decker, Eric A

    2005-06-15

    Carnosine (beta-alanyl-L-histidine) is a dipeptide found in the muscle foods that has been postulated to be a bioactive food component. The objective of this research was to determine the concentration of carnosine in human plasma after ingestion of beef. Nine males and nine females were recruited for the study. Food devoid of meat products was given to the subjects so that they did not consume carnosine for 48 h prior to the test. Subjects fasted for 12 h and then had blood withdrawn prior to a meal containing 200 g of ground beef. Additional blood samples were collected over the following 24 h and carnosine concentrations were determined by HPLC. The cooked ground beef used in the study contained 52% water, 24% protein, 22% fat, and 124 mg of carnosine/100 g of beef. No plasma carnosine was detected in subjects before the consumption of the beef. Carnosine was detected in plasma 15 min after beef consumption. Plasma carnosine concentrations continued to increase with a maximum (32.7 mg of carnosine/L of plasma) being recorded 2.5 h after consumption. Carnosine concentrations then decreased until no carnosine could be detected at 5.5 h postconsumption. These results indicate that dietary carnosine is absorbed into human plasma after the consumption of beef. Since carnosine has several potential health benefits, evidence of its bioavailability suggests that it could be a bioactive food component.

  10. Possible Benefit of Dietary Carnosine towards Depressive Disorders

    PubMed Central

    Hipkiss, Alan R

    2015-01-01

    Many stress-related and depressive disorders have been shown to be associated with one or more of the following; shortened telomeres, raised cortisol levels and increased susceptibility to age-related dysfunction. It is suggested here that insufficient availability of the neurological peptide, carnosine, may provide a biochemical link between stress- and depression-associated phenomena: there is evidence that carnosine can enhance cortisol metabolism, suppress telomere shortening and exert anti-aging activity in model systems. Dietary supplementation with carnosine has been shown to suppress stress in animals, and improve behaviour, cognition and well-being in human subjects. It is therefore proposed that the therapeutic potential of carnosine dietary supplementation towards stress-related and depressive disorders should be examined. PMID:26425385

  11. Carnosine protects against NMDA-induced neurotoxicity in differentiated rat PC12 cells through carnosine-histidine-histamine pathway and H(1)/H(3) receptors.

    PubMed

    Shen, Yao; Hu, Wei-Wei; Fan, Yan-Yin; Dai, Hai-Bing; Fu, Qiu-Li; Wei, Er-Qing; Luo, Jian-Hong; Chen, Zhong

    2007-03-01

    Since the histidine-containing dipeptide carnosine (beta-alanyl-L-histidine) is believed to have many physiological functions in the brain, we investigated the neuroprotective effects of carnosine and its mechanisms of action in an in vitro model of neurotoxicity induced by N-methyl-d-aspartate (NMDA) in differentiated PC12 cells. Pretreatment with carnosine increased the viability and decreased the number of apoptotic and necrotic cells measured by MTT and Hoechst 33342 and propidium iodide (PI) double staining assays. Carnosine also can inhibit the glutamate release and increase HDC activity and the intracellular and extracellular contents of carnosine, histidine and histamine detected by high-performance liquid chromatography (HPLC). The protection by carnosine was reversed by alpha- fluoromethylhistidine, a selective and irreversible inhibitor of histidine decarboxylase (HDC). Pyrilamine and thioperamide, selective central histamine H(1) and H(3) antagonists also significantly reversed the protection of carnosine. Further, the inhibition of glutamate release by carnosine was reversed by thioperamide. Therefore, the protective mechanism of carnosine may not only involve the carnosine-histidine-histamine pathway, but also H(1)/H(3) receptors and the effective inhibition of glutamate release. This study indicates that carnosine may be an endogenous protective factor and calls for its further study as a new antiexcitotoxic agent.

  12. Glycation, ageing and carnosine: are carnivorous diets beneficial?

    PubMed

    Hipkiss, Alan R

    2005-10-01

    Non-enzymic protein glycosylation (glycation) plays important roles in ageing and in diabetes and its secondary complications. Dietary constituents may play important roles in accelerating or suppressing glycation. It is suggested that carnivorous diets contain a potential anti-glycating agent, carnosine (beta-alanyl-histidine), whilst vegetarians may lack intake of the dipeptide. The possible beneficial effects of carnosine and related structures on protein carbonyl stress, AGE formation, secondary diabetic complications and age-related neuropathology are discussed.

  13. On the enigma of carnosine's anti-ageing actions.

    PubMed

    Hipkiss, Alan R

    2009-04-01

    Carnosine (beta-alanyl-L-histidine) has described as a forgotten and enigmatic dipeptide. Carnosine's enigma is particularly exemplified by its apparent anti-ageing actions; it suppresses cultured human fibroblast senescence and delays ageing in senescence-accelerated mice and Drosophila, but the mechanisms responsible remain uncertain. In addition to carnosine's well-documented anti-oxidant, anti-glycating, aldehyde-scavenging and toxic metal-ion chelating properties, its ability to influence the metabolism of altered polypeptides, whose accumulation characterises the senescent phenotype, should also be considered. When added to cultured cells, carnosine was found in a recent study to suppress phosphorylation of the translational initiation factor eIF4E resulting in decreased translation frequency of certain mRNA species. Mutations in the gene coding for eIF4E in nematodes extend organism lifespan, hence carnosine's anti-ageing effects may be a consequence of decreased error-protein synthesis which in turn lowers formation of protein carbonyls and increases protease availability for degradation of polypeptides altered postsynthetically. Other studies have revealed carnosine-induced upregulation of stress protein expression and nitric oxide synthesis, both of which may stimulate proteasomal elimination of altered proteins. Some anti-convulsants can enhance nematode longevity and suppress the effects of a protein repair defect in mice, and as carnosine exerts anti-convulsant effects in rodents, it is speculated that the dipeptide may participate in the repair of protein isoaspartyl groups. These new observations only add to the enigma of carnosine's real in vivo functions. More experimentation is clearly required.

  14. Carnosine treatment in combination with ACE inhibition in diabetic rats.

    PubMed

    Peters, V; Riedl, E; Braunagel, M; Höger, S; Hauske, S; Pfister, F; Zschocke, J; Lanthaler, B; Benck, U; Hammes, H-P; Krämer, B K; Schmitt, C P; Yard, B A; Köppel, H

    2014-11-01

    In humans, we reported an association of a certain allele of carnosinase gene with reduced carnosinase activity and absence of nephropathy in diabetic patients. CN1 degrades histidine dipeptides such as carnosine and anserine. Further, we and others showed that treatment with carnosine improves renal function and wound healing in diabetic mice and rats. We now investigated the effects of carnosine treatment alone and in combination with ACE inhibition, a clinically established nephroprotective drug in diabetic nephropathy. Male Sprague-Dawley rats were injected i.v. with streptozotocin (STZ) to induce diabetes. After 4 weeks, rats were unilaterally nephrectomized and randomized for 24 weeks of treatment with carnosine, lisinopril or both. Renal CN1 protein concentrations were increased under diabetic conditions which correlated with decreased anserine levels. Carnosine treatment normalized CN1 abundance and reduced glucosuria, blood concentrations of glycosylated hemoglobin (HbA1c), carboxyl-methyl lysine (CML), N-acetylglucosamine (GlcNac; all p<0.05 vs. non-treated STZ rats), reduced cataract formation (p<0.05) and urinary albumin excretion (p<0.05), preserved podocyte number (p<0.05) and normalized the increased renal tissue CN1 protein concentration. Treatment with lisinopril had no effect on HbA1C, glucosuria, cataract formation and CN1 concentration, but reduced albumin excretion rate more effectively than carnosine treatment (p<0.05). Treatment with both carnosine and lisinopril combined the effects of single treatment, albeit without additive effect on podocyte number or albuminuria. Increased CN1 amount resulted in decreased anserine levels in the kidney. Both carnosine and lisinopril exert distinct beneficial effects in a standard model of diabetic nephropathy. Both drugs administered together combine the respective effects of single treatment, albeit without exerting additive nephroprotection. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. [Taurine and carnosine in tissues of Pacific mollusks].

    PubMed

    Aiushin, N B; Petrova, I Iu; Epshteĭn, L M

    1997-01-01

    The containing of taurine and carnosine (low-molecular biologically active substances) was studied in tissues of molluscs (Gastropodae, Brahiopodae and Cephalopodae) by 38 species. The highest concentration of taurine found in the octopus and 5 species of shells (Gastropodae). The containing of carnosine in mollusks is highly lower than in bovine muscles. Organoleptic quality of lyophilized water-spirit extracts by soft tissues of molluscs allow to use it as a taurine-enriching food addition.

  16. Structural Elucidation of a Carnosine-Acrolein Adduct and its Quantification in Human Urine Samples.

    PubMed

    Bispo, Vanderson S; de Arruda Campos, Ivan P; Di Mascio, Paolo; Medeiros, Marisa H G

    2016-01-19

    Aldehydes accumulate in inflammation, during myocardial infarction and have been associated with pain symptoms. One pathway of aldehyde detoxification is the conjugation with carnosine. A 3-methylpyridinium carnosine adduct from the reaction of carnosine and acrolein was characterized using extensive spectroscopic measurements. The adduct with urinary concentrations of 1.82 ± 0.68 nmol/mg of creatinine is one of the most abundant acrolein metabolites in urine and opens promising therapeutic strategies for carnosine.

  17. Structural Elucidation of a Carnosine-Acrolein Adduct and its Quantification in Human Urine Samples

    PubMed Central

    Bispo, Vanderson S.; de Arruda Campos, Ivan P.; Di Mascio, Paolo; Medeiros, Marisa H. G.

    2016-01-01

    Aldehydes accumulate in inflammation, during myocardial infarction and have been associated with pain symptoms. One pathway of aldehyde detoxification is the conjugation with carnosine. A 3-methylpyridinium carnosine adduct from the reaction of carnosine and acrolein was characterized using extensive spectroscopic measurements. The adduct with urinary concentrations of 1.82 ± 0.68 nmol/mg of creatinine is one of the most abundant acrolein metabolites in urine and opens promising therapeutic strategies for carnosine. PMID:26783107

  18. Effects of carnosine and related compounds on the stability and morphology of erythrocytes from alcoholics.

    PubMed

    Prokopieva, V D; Bohan, N A; Johnson, P; Abe, H; Boldyrev, A A

    2000-01-01

    The effects of carnosine and related compounds on erythrocytes from alcoholics were studied. In their presence, erythrocytes showed an increased ability to resist haemolysis and showed a more normal morphology, with carnosine and N-acetyl-carnosine being the most effective compounds. These beneficial properties of the dipeptides do not appear to be directly related to their antioxidant or buffering properties.

  19. Carnosine content in the porcine longissimus thoracis muscle and its association with meat quality attributes and carnosine-related gene expression.

    PubMed

    D'Astous-Pagé, Joël; Gariépy, Claude; Blouin, Richard; Cliche, Simon; Sullivan, Brian; Fortin, Frédéric; Palin, Marie-France

    2017-02-01

    Muscle carnosine has pH-buffering, antioxidant and carbonyl scavenging properties, which may affect pork quality attributes. Study objectives were to: (1) compare muscle carnosine content and carnosine-related gene mRNA abundance in purebred pigs (n=282), (2) study the effect of muscle carnosine content on pork quality attributes and gene expression across breeds, and (3) study transcript abundance of carnosine-related genes in various tissues. Pigs were raised under similar conditions and slaughtered at 120±4.5kg. Longissimus thoracis muscles were sampled on the dressing line for gene expression and at 24h for meat quality measurements. Muscle carnosine content and carnosine-related gene mRNA abundance were modulated according to pig breeds. Greater pH24h, better water holding capacity and improved meat color values were found in pigs with high muscle carnosine content. Data suggest that high muscle carnosine is associated with improved pork meat quality attributes. The pig genetic background may be a key determinant for muscle carnosine content regulation. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  20. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.

    PubMed

    de Courten, Barbora; Kurdiova, Timea; de Courten, Maximilian P J; Belan, Vitazoslav; Everaert, Inge; Vician, Marek; Teede, Helena; Gasperikova, Daniela; Aldini, Giancarlo; Derave, Wim; Ukropec, Jozef; Ukropcova, Barbara

    2015-01-01

    Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists. Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography), % body fat (bioimpedance), abdominal subcutaneous and visceral adiposity (magnetic resonance imaging), insulin sensitivity (euglycaemic hyperinsulinemic clamp), resting energy expenditure (REE, indirect calorimetry), free-living ambulatory physical activity (accelerometers) and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years) with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04) and subcutaneous (r = 0.38, p = 0.02) but not visceral fat (r = 0.17, p = 0.33). Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008), REE (r = -0.58, p<0.001) and HDL-cholesterol levels (r = -0.34, p = 0.048). Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity. Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

  1. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans

    PubMed Central

    de Courten, Barbora; Kurdiova, Timea; de Courten, Maximilian P. J.; Belan, Vitazoslav; Everaert, Inge; Vician, Marek; Teede, Helena; Gasperikova, Daniela; Aldini, Giancarlo; Derave, Wim; Ukropec, Jozef; Ukropcova, Barbara

    2015-01-01

    Background Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists. Methods and Results Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography), % body fat (bioimpedance), abdominal subcutaneous and visceral adiposity (magnetic resonance imaging), insulin sensitivity (euglycaemic hyperinsulinemic clamp), resting energy expenditure (REE, indirect calorimetry), free-living ambulatory physical activity (accelerometers) and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years) with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04) and subcutaneous (r = 0.38, p = 0.02) but not visceral fat (r = 0.17, p = 0.33). Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008), REE (r = -0.58, p<0.001) and HDL-cholesterol levels (r = -0.34, p = 0.048). Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity. Conclusion Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease. PMID:26439389

  2. Effect of carnosine on rats under experimental brain ischemia.

    PubMed

    Gallant, S; Kukley, M; Stvolinsky, S; Bulygina, E; Boldyrev, A

    2000-06-01

    The effect of dietary carnosine on the behavioral and biochemical characteristics of rats under experimental ischemia was studied. Carnosine was shown to improve the animals orientation and learning in "Open Field" and "T-Maze" tests, and this effect was accompanied with an increase in glutamate binding to N-methyl-D-aspartate (NMDA) receptors in brain synaptosomes. Long-term brain ischemia induced by both sides' occlusion of common carotid arteries resulted in 55% mortality of experimental rats, and those who survived were characterized by partial suppression of orientation in T-maze. In the group of rats treated with carnosine, mortality after ischemic attack was decreased (from 55% to 17%) and most of the learning parameters were kept at the pre-ischemic level. Monoamine oxidase B (MAO B) activity in brain of the carnosine treated rats was not changed by ischemia significantly (compared to that of ischemic untreated rats) but NMDA binding to brain synaptosomal membranes being increased by ischemic attack was significantly suppressed and reached the level characteristic of normal brain. The suggestion was made that carnosine possesses a dual effect on NMDA receptors resulting in increase in their amount after long-term treatment but decrease the capacity to bind NMDA after ischemic attack.

  3. Beta-alanine supplementation, muscle carnosine and exercise performance.

    PubMed

    Blancquaert, Laura; Everaert, Inge; Derave, Wim

    2015-01-01

    The use of dietary supplements in sports is widespread as athletes are continuously searching for strategies to increase performance at the highest level. Beta-alanine is such a supplement that became increasingly popular during the past years. This review examines the available evidence regarding the optimization of supplementation, the link between beta-alanine and exercise performance and the underlying ergogenic mechanism. It has been repeatedly demonstrated that chronic beta-alanine supplementation can augment intramuscular carnosine content. Yet, the factors that determine the loading process, as well as the mechanism by which this has an ergogenic effect, are still debated. On the basis of its biochemical properties, several functions are ascribed to carnosine, of which intramuscular pH buffer and calcium regulator are the most cited ones. In addition, carnosine has antiglycation and antioxidant properties, suggesting it could have a therapeutic potential. On the basis of the millimolar presence of carnosine in mammalian muscles, it must play a critical role in skeletal muscle physiology. The recent number of studies shows that this is related to an improved exercise homeostasis and excitation-contraction coupling. Recent developments have led to the optimization of the beta-alanine supplementation strategies to elevate muscle carnosine content, which are helpful in its application in sports and to potential future therapeutic applications.

  4. Carnosine Treatment for Gulf War Illness: A Randomized Controlled Trial

    PubMed Central

    Baraniuk, James N.; El-Amin, Suliman; Corey, Rebecca; Rayhan, Rakib U.; Timbol, Christian R.

    2013-01-01

    About 25% of 1990-1991 Persian Gulf War veterans experience disabling fatigue, widespread pain, and cognitive dysfunction termed Gulf War illness (GWI) or Chronic Multisymptom Illness (CMI). A leading theory proposes that wartime exposures initiated prolonged production of reactive oxygen species (ROS) and central nervous system injury. The endogenous antioxidant L-carnosine (β-alanyl-L-histidine) is a potential treatment since it is a free radical scavenger in nervous tissue. To determine if nutritional supplementation with L-carnosine would significantly improve pain, cognition and fatigue in GWI, a randomized double blind placebo controlled 12 week dose escalation study involving 25 GWI subjects was employed. L-carnosine was given as 500, 1000, and 1500 mg increasing at 4 week intervals. Outcomes included subjective fatigue, pain and psychosocial questionnaires, and instantaneous fatigue and activity levels recorded by ActiWatch Score devices. Cognitive function was evaluated by WAIS-R digit symbol substitution test. Carnosine had 2 potentially beneficial effects: WAIS-R scores increased significantly, and there was a decrease in diarrhea associated with irritable bowel syndrome. No other significant incremental changes were found. Therefore, 12 weeks of carnosine (1500 mg) may have beneficial cognitive effects in GWI. Fatigue, pain, hyperalgesia, activity and other outcomes were resistant to treatment. PMID:23618477

  5. Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose.

    PubMed Central

    Gardner, M L; Illingworth, K M; Kelleher, J; Wood, D

    1991-01-01

    1. Healthy humans ingested the dipeptide carnosine (L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of carnosine and beta-alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post-absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption. PMID:1910085

  6. Effects of carnosine on the evoked potentials in hippocampal CA1 region*

    PubMed Central

    Feng, Zhou-yan; Zheng, Xiao-jing; Wang, Jing

    2009-01-01

    Objective: To directly examine the effects of carnosine on neuronal excitation and inhibition in rat hippocampus in vivo. Methods: Artificial cerebrospinal fluid with carnosine was directly administrated over the exposed rat hippocampus. The changes of neuron activity in the CA1 region of hippocampus were evaluated by orthodromically- and antidromically-evoked potentials, as well as paired-pulse stimulation paradigm. Results: In both orthodromic and antidromic response potentials, carnosine transformed population spikes (PSs) with single spike into epileptiform multiple spikes. In addition, similar to the effect of γ-aminobutyric acidA (GABAA) antagonist picrotoxin, carnosine decreased paired-pulse stimulating depression significantly. However, no significant change was observed in the spontaneous field potentials during the application of carnosine. Conclusion: The results indicate a disinhibition-induced excitation effect of carnosine on the CA1 pyramidal neurons. It provides important information against the application of carnosine as a potential anticonvulsant in clinical treatment. PMID:19585668

  7. Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure

    PubMed Central

    Azher, Seema; Margolis, Frank L.; Patel, Kamakshi; Mousa, Ahmad; Majid, Arshad

    2013-01-01

    Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an excellent vertebrate model for studying development and disease, we have examined the distribution pattern of carnosine-LP in the adult and developing zebrafish. In the adult, immunoreactivity for carnosine-LP is specifically concentrated in sensory neurons and non-sensory cells of the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Robust staining has also been observed in the retinal outer nuclear layer and the corneal epithelium. Developmental studies have revealed immunostaining for carnosine-LP as early as 18 h, 24 h, and 7 days post-fertilization in, respectively, the olfactory, corneal, and retinal primordia. These data suggest that carnosine-LP are involved in olfactory and visual function. We have also investigated the effects of chronic (7 days) exposure to carnosine on embryonic development and show that 0.01 μM to 10 mM concentrations of carnosine do not elicit significant deleterious effects. Conversely, treatment with 100 mM carnosine results in developmental delay and compromised larval survival. These results indicate that, at lower concentrations, exogenously administered carnosine can be used to explore the role of carnosine in development and developmental disorders of the nervous system. PMID:19440736

  8. [Effect of carnosine and its N-acetyl derivative on the stability of erythrocytes in patients with alcoholism during abstinence].

    PubMed

    Prokop'eva, V D; Bohan, N A; Johnson, P; Boldyrev, A A

    1998-01-01

    The effects of carnosine, a natural dipeptide, and its derivative, N- acetyl-carnosine (Ac-carnosine), on the stability and shape of red blood cells obtained from abstinent alcoholics was studied. In the presence of both carnosine and Ac-carnosine, the erythrocytes of abstinent alcoholics show a statistically significant increase in their ability to resist acidic hemolysis. Investigations of microscope pictures also show that carnosine and Ac-carnosine have beneficial effects on the pathological state of abstinent alcoholic erythrocytes. The addition of carnosine and Ac-carnosine resulted in the normalization of cell morphology (in 12 and 17 out of 30 cases, respectively). These results may be due to the stabilizing and regenerating ability of these compounds on alcoholic erythrocytes.

  9. Chelating effects of carnosine in ameliorating nickel-induced nephrotoxicity in rats.

    PubMed

    Hasanein, Parisa; Felegari, Zhila

    2017-07-04

    The kidney is one of the main organs affected by nickel (Ni) toxicity. We investigated the protective effects of carnosine on Ni- induced oxidative stress in kidney of rats. Animals received NiSO4 (20 mg/kg/day i.g.) and/or carnosine (10 mg/kg/day, i.g.) for 21 days and then were evaluated for biochemical, molecular and histopathological alterations. Ni caused an increase in renal levels of malondialdehydes and a decrease in reduced glutathione, catalase and superoxide dismutase levels and total antioxidant capacity. Carnosine prevented the prooxidant and antioxidant imbalance induced by Ni. Ni-treated rats showed an increase in serum creatinine, urea and uric acid with a concomitant decrease in albumin. Ni markedly accumulated in kidney of Ni-exposed rats and its concentration was effectively reduced by carnosine treatment. Carnosine corrected the biochemical abnormalities and the elevated renal TNF-α and IL-6 levels in Ni group. It also attenuated Ni-induced abnormalities in renal architecture. Although carnosine showed antioxidant and anti-inflammatory effects in renal tissue of Ni-exposed rats, we cannot clearly attribute the protective effect of carnosine to its antioxidant and anti-inflammatory effects. Instead, the beneficial effect of carnosine observed in the current study can be due to the chelation between Ni and carnosine. Thus, carnosine may represent a therapeutic option to protect against Ni-induced nephrotoxicity that deserves consideration and further examination.

  10. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage.

    PubMed

    Bae, Ok-Nam; Majid, Arshad

    2013-08-21

    Urgent need exists for new therapeutic options in ischemic stroke. We recently demonstrated that carnosine, an endogenous dipeptide consisting of alanine and histidine, is robustly neuroprotective in ischemic brain injury and has a wide clinically relevant therapeutic time window. The precise mechanistic pathways that mediate this neuroprotective effect are not known. Following in vivo administration, carnosine is hydrolyzed into histidine, a precursor of histamine. It has been hypothesized that carnosine may exert its neuroprotective activities through the histidine/histamine pathway. Herein, we investigated whether the neuroprotective effect of carnosine is mediated by the histidine/histamine pathway using in vitro primary astrocytes and cortical neurons, and an in vivo rat model of ischemic stroke. In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death. In primary neuronal cultures, carnosine was found to be neuroprotective but histamine receptor antagonists had no effect on the extent of neuroprotection. The in vivo effect of histidine and carnosine was compared using a rat model of ischemic stroke; only carnosine exhibited neuroprotection. Taken together, our data demonstrate that although the protective effects of carnosine may be partially mediated by activity at the histamine type 1 receptor on astrocytes, the histidine/histamine pathway does not appear to play a critical role in carnosine induced neuroprotection.

  11. A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect

    NASA Astrophysics Data System (ADS)

    Regazzoni, Luca; de Courten, Barbora; Garzon, Davide; Altomare, Alessandra; Marinello, Cristina; Jakubova, Michaela; Vallova, Silvia; Krumpolec, Patrik; Carini, Marina; Ukropec, Jozef; Ukropcova, Barbara; Aldini, Giancarlo

    2016-06-01

    Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species.

  12. A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect

    PubMed Central

    Regazzoni, Luca; de Courten, Barbora; Garzon, Davide; Altomare, Alessandra; Marinello, Cristina; Jakubova, Michaela; Vallova, Silvia; Krumpolec, Patrik; Carini, Marina; Ukropec, Jozef; Ukropcova, Barbara; Aldini, Giancarlo

    2016-01-01

    Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species. PMID:27265207

  13. Peculiarities of carnosine metabolism in a patient with pronounced homocarnosinemia.

    PubMed

    Kramarenko, G G; Markova, E D; Ivanova-Smolenskaya, I A; Boldyrev, A A

    2001-10-01

    The article describes a case of homocarnosinemia with increased liquor and plasma content of homocarnosine, increased urinary excretion of homocarnosine, and low activity of serum carnosinase. These metabolic disturbances were accompanied by moderate neurological disorders. Changes in carnosine metabolism in family members were less pronounced and not accompanied by neuropathological symptoms.

  14. The distribution of carnosine and related dipeptides in rat and human tissues.

    PubMed

    Jackson, M C; Lenney, J F

    1996-03-01

    Carnosine and anserine are present in high concentrations in most skeletal muscles. In addition, carnosine and homocarnosine have been detected in brain and cardiac muscle. Other tissues have been found to be devoid of these histidine-containing dipeptides. However, Flancbaum et al. reported that carnosine was present in every rodent and human tissue analyzed. These authors postulated that carnosine serves as a non-mast cell reservoir for histidine which becomes available for histamine synthesis during periods of physiological stress. We have analyzed many rat and human tissues using an immunohistochemical procedure. Carnosine and related dipeptides were detected in skeletal muscle, cardiac muscle and brain, but not in kidney, liver, lung or several other organs. These negative results seem valid since the immunoassay gave positive staining in the tissues generally known to contain carnosine.

  15. Antioxidant effect of carnosine treatment on renal oxidative stress in streptozotocin-induced diabetic rats.

    PubMed

    Yay, A; Akkuş, D; Yapıslar, H; Balcıoglu, E; Sonmez, M F; Ozdamar, S

    2014-11-01

    Nitric oxide (NO) plays a significant role in the development of diabetic nephropathy. We investigated the effects of an antioxidant, carnosine, on streptozotocin (STZ)-induced renal injury in diabetic rats. We used four groups of eight rats: group 1, control; group 2, carnosine treated; group 3, untreated diabetic; group 4, carnosine treated diabetic. Kidneys were removed and processed, and sections were stained with periodic acid-Schiff (PAS) and subjected to eNOS immunohistochemistry. Examination by light microscopy revealed degenerated glomeruli, thickened basement membrane and glycogen accumulation in the tubules of diabetic kidneys. Carnosine treatment prevented the renal morphological damage caused by diabetes. Moreover, administration of carnosine decreased somewhat the oxidative damage of diabetic nephropathy. Appropriate doses of carnosine might be a useful therapeutic option to reduce oxidative stress and associated renal injury in diabetes mellitus.

  16. Neuroprotective Effect of Carnosine on Primary Culture of Rat Cerebellar Cells under Oxidative Stress.

    PubMed

    Lopachev, A V; Lopacheva, O M; Abaimov, D A; Koroleva, O V; Vladychenskaya, E A; Erukhimovich, A A; Fedorova, T N

    2016-05-01

    Dipeptide carnosine (β-alanyl-L-histidine) is a natural antioxidant, but its protective effect under oxidative stress induced by neurotoxins is studied insufficiently. In this work, we show the neuroprotective effect of carnosine in primary cultures of rat cerebellar cells under oxidative stress induced by 1 mM 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH), which directly generates free radicals both in the medium and in the cells, and 20 nM rotenone, which increases the amount of intracellular reactive oxygen species (ROS). In both models, adding 2 mM carnosine to the incubation medium decreased cell death calculated using fluorescence microscopy and enhanced cell viability estimated by the MTT assay. The antioxidant effect of carnosine inside cultured cells was demonstrated using the fluorescence probe dichlorofluorescein. Carnosine reduced by half the increase in the number of ROS in neurons induced by 20 nM rotenone. Using iron-induced chemiluminescence, we showed that preincubation of primary neuronal cultures with 2 mM carnosine prevents the decrease in endogenous antioxidant potential of cells induced by 1 mM AAPH and 20 nM rotenone. Using liquid chromatography-mass spectrometry, we showed that a 10-min incubation of neuronal cultures with 2 mM carnosine leads to a 14.5-fold increase in carnosine content in cell lysates. Thus, carnosine is able to penetrate neurons and exerts an antioxidant effect. Western blot analysis revealed the presence of the peptide transporter PEPT2 in rat cerebellar cells, which suggests the possibility of carnosine transport into the cells. At the same time, Western blot analysis showed no carnosine-induced changes in the level of apoptosis regulating proteins of the Bcl-2 family and in the phosphorylation of MAP kinases, which suggests that carnosine could have minimal or no side effects on proliferation and apoptosis control systems in normal cells.

  17. Role of Aldose Reductase in the Metabolism and Detoxification of Carnosine-Acrolein Conjugates*

    PubMed Central

    Baba, Shahid P.; Hoetker, Joseph David; Merchant, Michael; Klein, Jon B.; Cai, Jian; Barski, Oleg A.; Conklin, Daniel J.; Bhatnagar, Aruni

    2013-01-01

    Oxidation of unsaturated lipids generates reactive aldehydes that accumulate in tissues during inflammation, ischemia, or aging. These aldehydes form covalent adducts with histidine-containing dipeptides such as carnosine and anserine, which are present in high concentration in skeletal muscle, heart, and brain. The metabolic pathways involved in the detoxification and elimination of these conjugates are, however, poorly defined, and their significance in regulating oxidative stress is unclear. Here we report that conjugates of carnosine with aldehydes such as acrolein are produced during normal metabolism and excreted in the urine of mice and adult human non-smokers as carnosine-propanols. Our studies show that the reduction of carnosine-propanals is catalyzed by the enzyme aldose reductase (AR). Carnosine-propanals were converted to carnosine-propanols in the lysates of heart, skeletal muscle, and brain tissue from wild-type (WT) but not AR-null mice. In comparison with WT mice, the urinary excretion of carnosine-propanols was decreased in AR-null mice. Carnosine-propanals formed covalent adducts with nucleophilic amino acids leading to the generation of carnosinylated proteins. Deletion of AR increased the abundance of proteins bound to carnosine in skeletal muscle, brain, and heart of aged mice and promoted the accumulation of carnosinylated proteins in hearts subjected to global ischemia ex vivo. Perfusion with carnosine promoted post-ischemic functional recovery in WT but not in AR-null mouse hearts. Collectively, these findings reveal a previously unknown metabolic pathway for the removal of carnosine-propanal conjugates and suggest a new role of AR as a critical regulator of protein carnosinylation and carnosine-mediated tissue protection. PMID:23928303

  18. Role of aldose reductase in the metabolism and detoxification of carnosine-acrolein conjugates.

    PubMed

    Baba, Shahid P; Hoetker, Joseph David; Merchant, Michael; Klein, Jon B; Cai, Jian; Barski, Oleg A; Conklin, Daniel J; Bhatnagar, Aruni

    2013-09-27

    Oxidation of unsaturated lipids generates reactive aldehydes that accumulate in tissues during inflammation, ischemia, or aging. These aldehydes form covalent adducts with histidine-containing dipeptides such as carnosine and anserine, which are present in high concentration in skeletal muscle, heart, and brain. The metabolic pathways involved in the detoxification and elimination of these conjugates are, however, poorly defined, and their significance in regulating oxidative stress is unclear. Here we report that conjugates of carnosine with aldehydes such as acrolein are produced during normal metabolism and excreted in the urine of mice and adult human non-smokers as carnosine-propanols. Our studies show that the reduction of carnosine-propanals is catalyzed by the enzyme aldose reductase (AR). Carnosine-propanals were converted to carnosine-propanols in the lysates of heart, skeletal muscle, and brain tissue from wild-type (WT) but not AR-null mice. In comparison with WT mice, the urinary excretion of carnosine-propanols was decreased in AR-null mice. Carnosine-propanals formed covalent adducts with nucleophilic amino acids leading to the generation of carnosinylated proteins. Deletion of AR increased the abundance of proteins bound to carnosine in skeletal muscle, brain, and heart of aged mice and promoted the accumulation of carnosinylated proteins in hearts subjected to global ischemia ex vivo. Perfusion with carnosine promoted post-ischemic functional recovery in WT but not in AR-null mouse hearts. Collectively, these findings reveal a previously unknown metabolic pathway for the removal of carnosine-propanal conjugates and suggest a new role of AR as a critical regulator of protein carnosinylation and carnosine-mediated tissue protection.

  19. Gene expression of carnosine-related enzymes and transporters in skeletal muscle.

    PubMed

    Everaert, Inge; De Naeyer, Hélène; Taes, Youri; Derave, Wim

    2013-05-01

    Chronic oral beta-alanine supplementation can elevate muscle carnosine (beta-alanyl-L-histidine) content and improve high-intensity exercise performance. However, the regulation of muscle carnosine levels is poorly understood. The uptake of the rate-limiting precursor beta-alanine and the enzyme catalyzing the dipeptide synthesis are thought to be key steps. The aims of this study were to investigate the expression of possible carnosine-related enzymes and transporters in both human and mouse skeletal muscle in response to carnosine-altering stimuli. Human gastrocnemius lateralis and mouse tibialis anterior muscle samples were subjected to HPLC and qPCR analysis. Mice were subjected to chronic oral supplementation of beta-alanine and carnosine or to orchidectomy (7 and 30 days, with or without testosterone replacement), stimuli known to, respectively, increase and decrease muscle carnosine and anserine. The following carnosine-related enzymes and transporters were expressed in human and/or mouse muscles: carnosine synthase (CARNS), carnosinase-2 (CNDP2), the carnosine/histidine transporters PHT1 and PHT2, the beta-alanine transporters TauT and PAT1, beta-alanine transaminase (ABAT) and histidine decarboxylase (HDC). Six of these genes showed altered expression in the investigated interventions. Orchidectomy led to decreased muscle carnosine content, which was paralleled with decreased TauT expression, whereas CARNS expression was surprisingly increased. Beta-alanine supplementation increased both muscle carnosine content and TauT, CARNS and ABAT expression, suggesting that muscles increase beta-alanine utilization through both dipeptide synthesis (CARNS) and deamination (ABAT) and further oxidation, in conditions of excess availability. Collectively, these data show that muscle carnosine homeostasis is regulated by nutritional and hormonal stimuli in a complex interplay between related transporters and enzymes.

  20. The dipeptide carnosine constricts rabbit saphenous vein as a zinc complex apparently via a serotonergic receptor.

    PubMed Central

    O'Dowd, A; O'Dowd, J J; Miller, D J

    1996-01-01

    1. The endogenous dipeptide carnosine (beta-alanyl-L-histidine), at 0.1-10 mM, provokes sustained contractures in rabbit saphenous vein rings with greater efficacy than noradrenaline (NA). 2. The effects of carnosine are specific; anserine and homocarnosine are ineffective, as are carnosine's constituent amino acids histidine and beta-alanine. 3. Maximum carnosine-induced tension is enhanced by Zn ions (e.g. to 127.5 +/- 13.1% of control at 10 microM total Zn concentration, Zntot) and the sensitivity to carnosine potentiated (mean [carnosine] required for half-maximal tension, K1/2, reduced from 1.23 mM to 17.0 microM carnosine with 15 microM Zntot). 4. The dipeptide apparently acts as a zinc-carnosine complex. The effects of carnosine at concentrations of 1 microM to 10 mM in the presence of 1-100 microM Zntot, can be described as a unique function of the concentration of Zn-carnosine, with an apparent K1/2 for the complex of 7.4 x 10(-8) M. 5. Contractures are reduced at low [Ca2+], unaffected by adrenoceptor antagonists, but can be blocked by serotonergic receptor antagonists including ketanserin and methiothepin. 6. Competition between albumin and carnosine for Zn ions, as might occur in plasma, can be demonstrated experimentally. 7. The mode of action of carnosine is virtually unique: a vascular muscle receptor apparently transduces the action of a dipeptide in the form of a metal chelate. PMID:8887763

  1. L-carnosine alters some hemorheologic and lipid peroxidation parameters in nephrectomized rats.

    PubMed

    Yapislar, Hande; Taskin, Eylem

    2014-03-11

    Chronic kidney disease (CKD) is a major health problem worldwide. Oxidative stress is one of the mediators of this disease. Systemic complications of oxidative stress are involved in the pathogenesis of hypertension, endothelial dysfunction, shortened erythrocyte lifespan, deformability, and nitric oxide (NO) dysfunction. L-carnosine is known as an antioxidant. In this study, our aim was to investigate the effect of carnosine on hemorheologic and cardiovascular parameters in CKD-induced rats. We used 4-month-old male Sprague-Dawley rats divided into 4 groups of 6 rats each. Three days after subtotal nephrectomy and sham operations, the surviving rats were divided into the 4 groups; 1) Sham (S), 2) Sham+Carnosine (S-C), 3) Subtotal nephrectomy (Nx), and 4) Subtotal nephrectomy + Carnosine (N-C). Carnosine was injected intraperitoneally (i.p.) (50 mg/kg) for 15 days. The control group received the same volume of physiological saline. In CKD rats, malondialdehyde (MDA) levels were increased, and NO and RBC deformability were decreased compared to Sham. Carnosine treatment decreased MDA levels, improved RBC (red blood cell) ability to deform, and increased NO levels. However, carnosine did not affect blood pressure levels in these rats. We found that carnosine has beneficial effects on CKD in terms of lipid peroxidation and RBC deformability. Carnosine may have a healing effect in microcirculation level, but may not have any effect on systemic blood pressure in CKD-induced rats.

  2. Dietary carnosine prevents early atherosclerotic lesion formation in apolipoprotein E-null mice.

    PubMed

    Barski, Oleg A; Xie, Zhengzhi; Baba, Shahid P; Sithu, Srinivas D; Agarwal, Abhinav; Cai, Jian; Bhatnagar, Aruni; Srivastava, Sanjay

    2013-06-01

    Atherosclerotic lesions are associated with the accumulation of reactive aldehydes derived from oxidized lipids. Although inhibition of aldehyde metabolism has been shown to exacerbate atherosclerosis and enhance the accumulation of aldehyde-modified proteins in atherosclerotic plaques, no therapeutic interventions have been devised to prevent aldehyde accumulation in atherosclerotic lesions. We examined the efficacy of carnosine, a naturally occurring β-alanyl-histidine dipeptide, in preventing aldehyde toxicity and atherogenesis in apolipoprotein E-null mice. In vitro, carnosine reacted rapidly with lipid peroxidation-derived unsaturated aldehydes. Gas chromatography mass-spectrometry analysis showed that carnosine inhibits the formation of free aldehydes 4-hydroxynonenal and malonaldialdehyde in Cu(2+)-oxidized low-density lipoprotein. Preloading bone marrow-derived macrophages with cell-permeable carnosine analogs reduced 4-hydroxynonenal-induced apoptosis. Oral supplementation with octyl-D-carnosine decreased atherosclerotic lesion formation in aortic valves of apolipoprotein E-null mice and attenuated the accumulation of protein-acrolein, protein-4-hydroxyhexenal, and protein-4-hydroxynonenal adducts in atherosclerotic lesions, whereas urinary excretion of aldehydes as carnosine conjugates was increased. The results of this study suggest that carnosine inhibits atherogenesis by facilitating aldehyde removal from atherosclerotic lesions. Endogenous levels of carnosine may be important determinants of atherosclerotic lesion formation, and treatment with carnosine or related peptides could be a useful therapy for the prevention or the treatment of atherosclerosis.

  3. Dietary Carnosine Prevents Early Atherosclerotic Lesion Formation in ApoE-null Mice

    PubMed Central

    Barski, Oleg A.; Xie, Zhengzhi; Baba, Shahid P.; Sithu, Srinivas D.; Agarwal, Abhinav; Cai, Jian; Bhatnagar, Aruni; Srivastava, Sanjay

    2013-01-01

    Objective Atherosclerotic lesions are associated with the accumulation of reactive aldehydes derived from oxidized lipids. Although inhibition of aldehyde metabolism has been shown to exacerbate atherosclerosis and enhance the accumulation of aldehyde-modified proteins in atherosclerotic plaques, no therapeutic interventions have been devised to prevent aldehyde accumulation in atherosclerotic lesions. Approach and Results We examined the efficacy of carnosine, a naturally occurring β-alanyl-histidine dipeptide in preventing aldehyde toxicity and atherogenesis in apoE-null mice. In vitro, carnosine reacted rapidly with lipid peroxidation-derived unsaturated aldehydes. Gas chromatography mass-spectrometry analysis showed that carnosine inhibits the formation of free aldehydes - HNE and malonaldialdehyde in Cu2+-oxidized LDL. Preloading bone marrow-derived macrophages with cell-permeable carnosine analogs reduced HNE-induced apoptosis. Oral supplementation with octyl-D-carnosine decreased atherosclerotic lesion formation in aortic valves of apoE-null mice and attenuated the accumulation of protein-acrolein, protein-HHE and protein-HNE adducts in atherosclerotic lesions, while urinary excretion of aldehydes as carnosine conjugates was increased. Conclusions The results of this study suggest that carnosine inhibits atherogenesis by facilitating aldehyde removal from atherosclerotic lesions. Endogenous levels of carnosine may be important determinants of atherosclerotic lesion formation and treatment with carnosine or related peptides could be a useful therapy for the prevention or the treatment of atherosclerosis. PMID:23559625

  4. Inhibitory effect of the carnosine-gallic acid synthetic peptide on MMP-2 and MMP-9 in human fibrosarcoma HT1080 cells.

    PubMed

    Kim, Sung-Rae; Eom, Tae-Kil; Byun, Hee-Guk

    2014-09-01

    Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade extracellular matrix components and play important roles in a variety of biological and pathological processes such as malignant tumor metastasis and invasion. In this study, we constructed carnosine-gallic acid peptide (CGP) to identify a better MMP inhibitor than carnosine. The inhibitory effects of CGP on MMP-2 and MMP-9 were investigated in the human fibrosarcoma (HT1080) cell line. As a result, CGP significantly decreased MMP-2 and MMP-9 expression levels without a cytotoxic effect. Moreover, CGP may inhibit migration and invasion in HT1080 cells through the urokinase plasminogen activator (uPA)-uPA receptor signaling pathways to inhibit MMP-2 and MMP-9. Based on these results, it appears that CGP may play an important role in preventing and treating several MMP-2 and MMP-9-mediated health problems such as metastasis. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

  5. Fabrication and Intracellular Delivery of Doxorubicin/Carbonate Apatite Nanocomposites: Effect on Growth Retardation of Established Colon Tumor

    PubMed Central

    Chowdhury, Ezharul Hoque; Wu, Xin; Hirose, Hajime; Haque, Amranul; Doki, Yuichiro; Mori, Masaki; Akaike, Toshihiro

    2013-01-01

    In continuing search for effective treatments of cancer, the emerging model aims at efficient intracellular delivery of therapeutics into tumor cells in order to increase the drug concentration. However, the implementation of this strategy suffers from inefficient cellular uptake and drug resistance. Therefore, pH-sensitive nanosystems have recently been developed to target slightly acidic extracellular pH environment of solid tumors. The pH targeting approach is regarded as a more general strategy than conventional specific tumor cell surface targeting approaches, because the acidic tumor microclimate is most common in solid tumors. When nanosystems are combined with triggered release mechanisms in endosomal or lysosomal acidic pH along with endosomolytic capability, the nanocarriers demonstrated to overcome multidrug resistance of various tumors. Here, novel pH sensitive carbonate apatite has been fabricated to efficiently deliver anticancer drug Doxorubicin (DOX) to cancer cells, by virtue of its pH sensitivity being quite unstable under an acidic condition in endosomes and the desirable size of the resulting apatite-DOX for efficient cellular uptake as revealed by scanning electron microscopy. Florescence microscopy and flow cytometry analyses demonstrated significant uptake of drug (92%) when complexed with apatite nanoparticles. In vitro chemosensitivity assay revealed that apatite-DOX nanoparticles executed high cytotoxicity in several human cancer cell lines compared to free drugs and consequently apatite-DOX-facilitated enhanced tumor inhibitory effect was observed in colorectal tumor model within BALB/cA nude mice, thereby shedding light on their potential applications in cancer therapy. PMID:23613726

  6. Mental Retardation.

    ERIC Educational Resources Information Center

    Baumeister, Alfred A., Ed.

    Thirteen papers by different authors consider the application of research findings and theoretical formulations to the practical appraisal and treatment of mental retardation. All suggest methods for shaping appropriate and adaptive behaviors in retarded individuals. The papers include "Definition, Diagnosis, and Classification" by D.W. Brison,…

  7. Mental Retardation.

    ERIC Educational Resources Information Center

    Baumeister, Alfred A., Ed.

    Thirteen papers by different authors consider the application of research findings and theoretical formulations to the practical appraisal and treatment of mental retardation. All suggest methods for shaping appropriate and adaptive behaviors in retarded individuals. The papers include "Definition, Diagnosis, and Classification" by D.W. Brison,…

  8. Muscle carnosine loading by beta-alanine supplementation is more pronounced in trained vs. untrained muscles.

    PubMed

    Bex, T; Chung, W; Baguet, A; Stegen, S; Stautemas, J; Achten, E; Derave, W

    2014-01-15

    Carnosine occurs in high concentrations in human skeletal muscle and assists working capacity during high-intensity exercise. Chronic beta-alanine (BA) supplementation has consistently been shown to augment muscle carnosine concentration, but the effect of training on the carnosine loading efficiency is poorly understood. The aim of the present study was to compare muscle carnosine loading between trained and untrained arm and leg muscles. In a first study (n = 17), reliability of carnosine quantification by proton magnetic resonance spectroscopy ((1)H-MRS) was evaluated in deltoid and triceps brachii muscles. In a second study, participants (n = 35; 10 nonathletes, 10 cyclists, 10 swimmers, and 5 kayakers) were supplemented with 6.4 g/day of slow-release BA for 23 days. Carnosine content was evaluated in soleus, gastrocnemius medialis, and deltoid muscles by (1)H-MRS. All the results are reported as arbitrary units. In the nonathletes, BA supplementation increased carnosine content by 47% in the arm and 33% in the leg muscles (not significant). In kayakers, the increase was more pronounced in arm (deltoid) vs. leg (soleus + gastrocnemius) muscles (0.089 vs. 0.049), whereas the reverse pattern was observed in cyclists (0.065 vs. 0.084). Swimmers had significantly higher increase in carnosine in both deltoid (0.107 vs. 0.065) and gastrocnemius muscle (0.082 vs. 0.051) compared with nonathletes. We showed that 1) carnosine content can be reliably measured by (1)H-MRS in deltoid muscle, 2) carnosine loading is equally effective in arm vs. leg muscles of nonathletes, and 3) carnosine loading is more pronounced in trained vs. untrained muscles.

  9. L-Carnosine: multifunctional dipeptide buffer for sustained-duration topical ophthalmic formulations.

    PubMed

    Singh, Swita R; Carreiro, Samantha T; Chu, Jessie; Prasanna, Ganesh; Niesman, Michael R; Collette Iii, Walter W; Younis, Husam S; Sartnurak, Soisurin; Gukasyan, Hovhannes J

    2009-06-01

    The use of l-carnosine as an excipient in topical ophthalmic formulations containing gellan gum, a carbohydrate polymer with in-situ gelling properties upon mixing with mammalian tear fluid, was developed as a novel platform to extend precorneal duration. Specific utilisation of l-carnosine as a buffer in gellan gum carrying vehicles was characterised. Buffer capacity was evaluated using 7.5, 13.3, and 44.2 mm l-carnosine in a pH range of 5.5-7.5. Accelerated chemical stability was determined by HPLC at l-carnosine concentrations of 5-100 mm. Combinations of 7.5 mm l-carnosine with 0.06-0.6% (w/v) gellan gum were characterised rheologically. l-Carnosine-buffered solutions of gellan gum were tested for acute topical ocular tolerance in vivo in pigmented rabbits. A unique formulation combining timolol (which lowers intraocular pressure) in l-carnosine-buffered gellan gum was compared with Timoptic-XE in normotensive dogs. l-Carnosine exhibited optimal pharmaceutical characteristics for use as a buffer in chronically administered topical ocular formulations. Enhancement trends were observed in solution-to-gel transition of l-carnosine-buffered vehicles containing gellan gum vs comparators. Topical tolerability of l-carnosine-buffered gellan gum formulations and lowering of intraocular pressure were equivalent with timolol and Timoptic-XE. Functional synergy between excipients in gellan gum formulations buffered with l-carnosine has potential for topical ocular dosage forms with sustained precorneal residence.

  10. Low plasma carnosinase activity promotes carnosinemia after carnosine ingestion in humans.

    PubMed

    Everaert, Inge; Taes, Youri; De Heer, Emile; Baelde, Hans; Zutinic, Ana; Yard, Benito; Sauerhöfer, Sibylle; Vanhee, Lander; Delanghe, Joris; Aldini, Giancarlo; Derave, Wim

    2012-06-15

    A polymorphism in the carnosine dipeptidase-1 gene (CNDP1), resulting in decreased plasma carnosinase activity, is associated with a reduced risk for diabetic nephropathy. Because carnosine, a natural scavenger/suppressor of ROS, advanced glycation end products, and reactive aldehydes, is readily degraded in blood by the highly active carnosinase enzyme, it has been postulated that low serum carnosinase activity might be advantageous to reduce diabetic complications. The aim of this study was to examine whether low carnosinase activity promotes circulating carnosine levels after carnosine supplementation in humans. Blood and urine were sampled in 25 healthy subjects after acute supplementation with 60 mg/kg body wt carnosine. Precooled EDTA-containing tubes were used for blood withdrawal, and plasma samples were immediately deproteinized and analyzed for carnosine and β-alanine by HPLC. CNDP1 genotype, baseline plasma carnosinase activity, and protein content were assessed. Upon carnosine ingestion, 8 of the 25 subjects (responders) displayed a measurable increase in plasma carnosine up to 1 h after supplementation. Subjects with no measurable increment in plasma carnosine (nonresponders) had ∼2-fold higher plasma carnosinase protein content and ∼1.5-fold higher activity compared with responders. Urinary carnosine recovery was 2.6-fold higher in responders versus nonresponders and was negatively dependent on both the activity and protein content of the plasma carnosinase enzyme. In conclusion, low plasma carnosinase activity promotes the presence of circulating carnosine upon an oral challenge. These data may further clarify the link among CNDP1 genotype, carnosinase, and diabetic nephropathy.

  11. Studies on adsorption of carnosine on silver nanoparticles by SERS

    NASA Astrophysics Data System (ADS)

    Thomas, S.; Biswas, N.; Malkar, V. V.; Mukherjee, T.; Kapoor, S.

    2010-05-01

    The surface-enhanced Raman scattering (SERS) studies of L-carnosine was carried out in aqueous silver sol at pH ˜ 9 and compared with the normal Raman spectrum of the molecule. The experimentally observed Raman bands were assigned based on the results of DFT calculations. Significant changes in the relative intensity are seen in the SERS spectrum when compared to the normal Raman spectrum. The studies suggest that the interaction of carnosine is primarily through the carboxylate group with the imidazole ring in an upright position with respect to the silver surface and the alanine moiety assuming a parallel orientation with the surface where NH 2 group is close to the silver surface.

  12. Hydrophilic chromatographic determination of carnosine, anserine, balenine, creatine, and creatinine.

    PubMed

    Mora, Leticia; Sentandreu, Miguel Angel; Toldrá, Fidel

    2007-06-13

    A new HPLC procedure based on hydrophilic interaction chromatography (HILIC) has been developed for the simultaneous determination of carnosine, anserine, balenine, creatine, and creatinine in meat. This is the first time that HILIC has been directly applied to the study of meat components, having the advantage of not requiring complex cleanup and/or sample derivatization procedures. The chromatographic separation has been developed using a silica column (4.6 x 150 mm, 3 microm), and the proposed methodology is simple, reliable, and fast (<13 min per sample). The method has been validated in terms of linearity, repeatability, reproducibility, and recovery and represents an interesting alternative to methods currently in use for determining the mentioned compounds and other polar substances. The detection limits are 5.64, 8.23, 3.66, 3.99, and 0.06 microg/mL for carnosine, anserine, balenine, creatine, and creatinine, respectively.

  13. Would carnosine or a carnivorous diet help suppress aging and associated pathologies?

    PubMed

    Hipkiss, Alan R

    2006-05-01

    Carnosine (beta-alanyl-L-histidine) is found exclusively in animal tissues. Carnosine has the potential to suppress many of the biochemical changes (e.g., protein oxidation, glycation, AGE formation, and cross-linking) that accompany aging and associated pathologies. Glycation, generation of advanced glycosylation end-products (AGEs), and formation of protein carbonyl groups play important roles in aging, diabetes, its secondary complications, and neurodegenerative conditions. Due to carnosine's antiglycating activity, reactivity toward deleterious carbonyls, zinc- and copper-chelating activity and low toxicity, carnosine and related structures could be effective against age-related protein carbonyl stress. It is suggested that carnivorous diets could be beneficial because of their carnosine content, as the dipeptide has been shown to suppress some diabetic complications in mice. It is also suggested that carnosine's therapeutic potential should be explored with respect to neurodegeneration. Olfactory tissue is normally enriched in carnosine, but olfactory dysfunction is frequently associated with neurodegeneration. Olfactory administration of carnosine could provide a direct route to compromised tissue, avoiding serum carnosinases.

  14. Net release or uptake of histidine and carnosine in kidney of dogs.

    PubMed

    Cianciaruso, B; Fukuda, S; Jones, M R; Kopple, J D

    1985-01-01

    Previous studies are equivocal as to whether the dog kidney produces histidine. Because one possible source of renal histidine is carnosine (beta-alanyl-L-histidine), we investigated net renal production (release) or utilization (uptake) (Qmet) of histidine and carnosine in 19 female dogs after they were fed histidine-free (9 dogs) or histidine-containing diets (10 dogs). Diets were fed in short-(2-11 days) or long-term (52-57 days) studies. Dogs were infused with half-normal saline for 120 min followed by an infusion of half-normal saline containing carnosine, 50 mumol/min. Renal Qmet histidine, calculated from either plasma or whole blood values, was positive during infusion of half-normal saline. During carnosine infusion, Qmet histidine increased markedly, and there was net renal uptake of carnosine. The Qmet histidine and carnosine were not different in the dogs fed histidine-free vs. histidine-containing diets. Thus there is net renal release of histidine in female dogs that increases when carnosine is administered. Qmet histidine or carnosine do not change adaptively when dogs are fed histidine-free diets.

  15. Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat model.

    PubMed

    Zhang, Huizhen; Guo, Shang; Zhang, Linlin; Jia, Liting; Zhang, Zhan; Duan, Hongbao; Zhang, Jingbin; Liu, Jingyan; Zhang, Weidong

    2014-03-15

    Perinatal hypoxia-ischemia brain damage (HIBD) is a major cause of mortality and morbidity in neonates, and there is currently no effective therapy for HIBD. Carnosine plays a neuroprotective role in adult brain damage. We have previously demonstrated that carnosine pretreatment protects against HIBD in a neonatal rat model. Therefore, we hypothesized that treatment with carnosine would also have neuroprotective effects. Hypoxia-ischemia was induced in rats on postnatal days 7-9 (P7-9). Carnosine was administered intraperitoneally at a dose of 250mg/kg at 0h, 24h, and 48h after hypoxia-ischemia was induced. The biochemical markers of oxidative stress and apoptosis were evaluated at 72h after hypoxia-ischemia was induced, Brain learning and memory function performance were observed using the Morris water maze test on postnatal days 28-33 (P28-33). Treatment with carnosine post-HIBD significantly reduced the concentration of 8-iso-prostaglandinF2alpha in brain tissue and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region and cortex as well as the mitochondria caspase-3 protein expression. Furthermore, carnosine also improved the cognitive function of P28-33 rats, whose cognitive function decline was due to HIBD. These results demonstrate that carnosine treatment after HIBD can reduce the brain injury, improving brain function. Carnosine could be an attractive candidate for treating HIBD.

  16. Carnosine pretreatment protects against hypoxia-ischemia brain damage in the neonatal rat model.

    PubMed

    Zhang, Xiangmin; Song, Lili; Cheng, Xiuyong; Yang, Yi; Luan, Bin; Jia, Liting; Xu, Falin; Zhang, Zhan

    2011-09-30

    Perinatal hypoxia-ischemia brain injury is a major cause of mortality and morbidity in neonates and lacks an effective treatment thus far. Carnosine has been demonstrated to play a neuroprotective role in the adult brain injuries. However, there is no information available concerning its neuroprotective role in the immature brains after hypoxia-ischemia insults. Therefore, we investigated whether carnosine could also confer neuroprotective effects in a neonatal rat hypoxia-ischemia model. Hypoxia-ischemia was induced in rats on postnatal day 7 (P7). Carnosine (250 mg/kg) was administered intraperitoneally, 30 min prior to hypoxia-ischemia induction. Morphological brain injury and biochemical markers of apoptosis and oxidative stress were evaluated 24 h after hypoxia-ischemia induction. Cognitive performance was evaluated by the Morris Water Maze test on P28-P33. We found that pretreatment with carnosine significantly reduced the infarct volume and the number of terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hypoxia-ischemia brain. Carnosine also inhibited mRNA expression of apoptosis-inducing factor(AIF) and caspase-3, which was accompanied by an increase in superoxide dismutase(SOD)activity and a decrease in the malondialdehyde(MDA)level in carnosine-treated rats. Furthermore, carnosine also improved the spatial learning and memory abilities of rats declined due to hypoxia-ischemia. These results demonstrate that carnosine can protect rats against hypoxia-ischemia-induced brain damage by antioxidation.

  17. Low-level chemiluminescence of N-beta-alanyl-L-histidine (L-carnosine).

    PubMed

    Achyuthan, K E

    1999-01-01

    Oxidized N-beta-Ala-L-His (L-carnosine) emitted low-level CL. The CL specificity was shown by experiments with L-carnosine from six separate vendors, several L-carnosine-like compounds, and nine different oxidizers. Purity of L-carnosine samples was analysed by RP-HPLC-MS, (1)H-NMR, MALDI-TOF-MS and ESI-MS. L-Carnosine CL magnitude varied with source; consequently, detection sensitivity was 5-100 nmol. CL of L-anserine (N-beta-Ala-1-methyl-L-His) was equal to or less than L-carnosine, depending upon oxidizer. H(5)IO(6) (2 mmol/L) in 11 mmol/L NaOH or 20 mmol/L K(3)Fe(CN)(6) + 10 mmol/L H(2)O(2) in 100 mmol/L NaOH were oxidizers of choice. Scavengers of (.)OH(-) radical quenched CL. Kinetic studies revealed a bi-phasic CL comprising a short-lived (<1 s) 'flash' and then prolonged ( approximately 2000 s) 'glow'. A structural basis and mechanism of L-carnosine CL are discussed. L-Carnosine CL could be useful for monitoring its level in biological samples. Copyright 1999 John Wiley & Sons, Ltd.

  18. L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts.

    PubMed

    Shao, Lan; Li, Qing-Huan; Tan, Zheng

    2004-11-12

    Telomere is the repetitive DNA sequence at the end of chromosomes, which shortens progressively with cell division and limits the replicative potential of normal human somatic cells. L-carnosine, a naturally occurring dipeptide, has been reported to delay the replicative senescence, and extend the lifespan of cultured human diploid fibroblasts. In this work, we studied the effect of carnosine on the telomeric DNA of cultured human fetal lung fibroblast cells. Cells continuously grown in 20 mM carnosine exhibited a slower telomere shortening rate and extended lifespan in population doublings. When kept in a long-term nonproliferating state, they accumulated much less damages in the telomeric DNA when cultured in the presence of carnosine. We suggest that the reduction in telomere shortening rate and damages in telomeric DNA made an important contribution to the life-extension effect of carnosine.

  19. Engineered Resistant-Starch (ERS) Diet Shapes Colon Microbiota Profile in Parallel with the Retardation of Tumor Growth in In Vitro and In Vivo Pancreatic Cancer Models.

    PubMed

    Panebianco, Concetta; Adamberg, Kaarel; Adamberg, Signe; Saracino, Chiara; Jaagura, Madis; Kolk, Kaia; Di Chio, Anna Grazia; Graziano, Paolo; Vilu, Raivo; Pazienza, Valerio

    2017-03-27

    Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. We have previously demonstrated that short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. The aim of this study was to assess the effect of an engineered resistant-starch (ERS) mimicking diet on the growth of cancer cell lines in vitro, on the composition of fecal microbiota, and on tumor growth in an in vivo pancreatic cancer mouse xenograft model. BxPC-3, MIA PaCa-2 and PANC-1 cells were cultured in the control, and in the ERS-mimicking diet culturing condition, to evaluate tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to an ERS diet to assess tumor volume and weight as compared to mice fed with a control diet. The composition and activity of fecal microbiota were further analyzed in growth experiments by isothermal microcalorimetry. Pancreatic cancer cells cultured in an ERS diet-mimicking medium showed decreased levels of phospho-ERK1/2 (extracellular signal-regulated kinase proteins) and phospho-mTOR (mammalian target of rapamycin) levels, as compared to those cultured in standard medium. Consistently, xenograft pancreatic cancer mice subjected to an ERS diet displayed significant retardation in tumor growth. In in vitro growth experiments, the fecal microbial cultures from mice fed with an ERS diet showed enhanced growth on residual substrates, higher production of formate and lactate, and decreased amounts of propionate, compared to fecal microbiota from mice fed with the control diet. A positive effect of the ERS diet on composition and metabolism of mouse fecal microbiota shown in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that engineered dietary interventions could be supportive as a

  20. Engineered Resistant-Starch (ERS) Diet Shapes Colon Microbiota Profile in Parallel with the Retardation of Tumor Growth in In Vitro and In Vivo Pancreatic Cancer Models

    PubMed Central

    Panebianco, Concetta; Adamberg, Kaarel; Adamberg, Signe; Saracino, Chiara; Jaagura, Madis; Kolk, Kaia; Di Chio, Anna Grazia; Graziano, Paolo; Vilu, Raivo; Pazienza, Valerio

    2017-01-01

    Background/aims: Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. We have previously demonstrated that short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. The aim of this study was to assess the effect of an engineered resistant-starch (ERS) mimicking diet on the growth of cancer cell lines in vitro, on the composition of fecal microbiota, and on tumor growth in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods: BxPC-3, MIA PaCa-2 and PANC-1 cells were cultured in the control, and in the ERS-mimicking diet culturing condition, to evaluate tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to an ERS diet to assess tumor volume and weight as compared to mice fed with a control diet. The composition and activity of fecal microbiota were further analyzed in growth experiments by isothermal microcalorimetry. Results: Pancreatic cancer cells cultured in an ERS diet-mimicking medium showed decreased levels of phospho-ERK1/2 (extracellular signal-regulated kinase proteins) and phospho-mTOR (mammalian target of rapamycin) levels, as compared to those cultured in standard medium. Consistently, xenograft pancreatic cancer mice subjected to an ERS diet displayed significant retardation in tumor growth. In in vitro growth experiments, the fecal microbial cultures from mice fed with an ERS diet showed enhanced growth on residual substrates, higher production of formate and lactate, and decreased amounts of propionate, compared to fecal microbiota from mice fed with the control diet. Conclusion: A positive effect of the ERS diet on composition and metabolism of mouse fecal microbiota shown in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that

  1. Carnosine protects the brain of rats and Mongolian gerbils against ischemic injury: after-stroke-effect.

    PubMed

    Dobrota, Dusan; Fedorova, Tatiana; Stvolinsky, Sergey; Babusikova, Eva; Likavcanova, Katarina; Drgova, Anna; Strapkova, Adriana; Boldyrev, Alexander

    2005-10-01

    Carnosine, a specific constituent of excitable tissues of vertebrates, exhibits a significant antioxidant protecting effect on the brain damaged by ischemic-reperfusion injury when it was administered to the animals before ischemic episode. In this study, the therapeutic effect of carnosine was estimated on animals when this drug was administered intraperitoneally (100 mg/kg body weight) after ischemic episode induced by experimental global brain ischemia. Treatment of the animals with carnosine after ischemic episode under long-term (7-14 days) reperfusion demonstrated its pronounced protective effect on neurological symptoms and animal mortality. Carnosine also prevented higher lipid peroxidation of brain membrane structures and increased a resistance of neuronal membranes to the in vitro induced oxidation. Measurements of malonyl dialdehyde (MDA) in brain homogenates showed its increase in the after brain stroke animals and decreased MDA level in the after brain stroke animals treated with carnosine. We concluded that carnosine compensates deficit in antioxidant defense system of brain damaged by ischemic injury. The data presented demonstrate that carnosine is effective in protecting the brain in the post-ischemic period.

  2. Investigations on in vitro anti-carcinogenic potential of L-carnosine in liver cancer cells.

    PubMed

    Ding, Minghui; Jiao, Guihua; Shi, Haizhou; Chen, Yanrong

    2017-07-27

    This study was carried out to investigate the anti-carcinogenic effect of L-carnosine in human carcinoma cells (SNU-423). The SNU-423 cancer cells were cultured at a density of 2 × 10(4) cells/well in Dulbecco modified Eagle medium. After 24 h of adherence, the cells were treated with L-carnosine (0.2 and 1 mg/mL) for 48 h. Then, cell viability was assessed by sulforhodamine assay, while mitochondrial dysfunction was measured by fluorescence microscopy using chromatin-specific dye Hoechst 33258. Intracellular levels of ROS were assayed by fluorescence spectroscopy with 2',7'-dichlorofluorescein diacetate (DCFDA). L-Carnosine significantly inhibited the growth of the SNU-423 cells (p < 0.05). The inhibitory effect of L-carnosine was confirmed by results from mitochondrial fragmentation assay. The relative fluorescent unit was increased in a dose-dependent manner by L-carnosine, with values of 79.43, 186.87 and 400.89 for 0.6, 0.8 and 1 mg/mL of L-carnosine, respectively (p < 0.05). These results demonstrate that L-carnosine exerts anti-carcinogenic effects in human liver cancer cells.

  3. Ability of carnosine and other skeletal muscle components to quench unsaturated aldehydic lipid oxidation products.

    PubMed

    Zhou, S; Decker, E A

    1999-01-01

    Breakdown of lipid peroxides results in the formation of aldehydic compounds which are toxic to biological systems and deleterious to food quality. To determine the potential of skeletal muscle compounds to protect biomolecules from lipid oxidation products, the ability of carnosine and various other related compounds to quench monounsaturated and polyunsaturated aldehydes was investigated. Carnosine, the most abundant dipeptide in skeletal muscle, is capable of quenching alpha,beta-monounsaturated aldehydes and 4-hydroxy-2-trans-nonenal (HNE) more effectively than its constituent amino acid. Carnosine (5 mM) reduced 44% of headspace trans-2-hexenal (0.5 mM) after 1 h incubation at 40 degrees C and pH 7.4. Other histidine-containing dipeptides and the amine compounds, spermine and spermidine, had similar or slightly lower quenching activity than carnosine. Glutathione and thioctic acid had superior quenching ability than carnosine, but their overall contribution to aldehyde quenching compared to carnosine is limited due to their lower concentration in skeletal muscle. The results suggest that carnosine could be important for decreasing the toxicity of lipid oxidation products in biological systems and for minimizing rancidity in muscle foods.

  4. Transport Mechanisms of Carnosine in SKPT Cells: Contribution of Apical and Basolateral Membrane Transporters

    PubMed Central

    Jappar, Dilara; Hu, Yongjun; Keep, Richard F.; Smith, David E.

    2010-01-01

    Purpose The aim of this study was to investigate the transport properties of carnosine in kidney using SKPT cell cultures as a model of proximal tubular transport, and to isolate the functional activities of renal apical and basolateral transporters in this process. Methods The membrane transport kinetics of 10 µM [3H]carnosine was studied in SKPT cells as a function of time, pH, potential inhibitors and substrate concentration. A cellular compartment model was constructed in which the influx, efflux and transepithelial clearances of carnosine were determined. Peptide transporter expression was probed by RT-PCR. Results Carnosine uptake was 15-fold greater from the apical than basolateral surface of SKPT cells. However, the apical-to-basolateral transepithelial transport of carnosine was severely rate-limited by its cellular efflux across the basolateral membrane. The high-affinity, proton-dependence, concentration-dependence and inhibitor specificity of carnosine supports the contention that PEPT2 is responsible for its apical uptake. In contrast, the basolateral transporter is saturable, inhibited by PEPT2 substrates but non-concentrative, thereby, suggesting a facilitative carrier. Conclusions Carnosine is expected to have a substantial cellular accumulation in kidney but minimal tubular reabsorption in blood because of its high influx clearance across apical membranes by PEPT2 and very low efflux clearance across basolateral membranes. PMID:18820998

  5. Safety and Efficacy Evaluation of Carnosine, An Endogenous Neuroprotective Agent for Ischemic Stroke

    PubMed Central

    Bae, Ok-Nam; Serfozo, Kelsey; Baek, Seung-Hoon; Lee, Ki Yong; Dorrance, Anne; Rumbeiha, Wilson; Fitzgerald, Scott D.; Farooq, Muhammad U; Naravelta, Bharath; Bhatt, Archit; Majid, Arshad

    2013-01-01

    Background and Purpose An urgent need exists to develop therapies for stroke which have high efficacy, long therapeutic time windows and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. Methods Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. Results Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically-relevant therapeutic time windows of 6 h and 9 h in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained at 14 d post-stroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust anti-excitotoxic, antioxidant, and mitochondria protecting activity. Conclusion In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment. PMID:23250994

  6. Carnosine is a quencher of 4-hydroxy-nonenal: through what mechanism of reaction?

    PubMed

    Aldini, Giancarlo; Carini, Marina; Beretta, Giangiacomo; Bradamante, Silvia; Facino, Roberto Maffei

    2002-11-15

    The aim of this study was to understand the mechanism of action through which carnosine (beta-alanyl-L-histidine) acts as a quencher of cytotoxic alpha,beta-unsaturated aldehydes, using 4-hydroxy-trans-2,3-nonenal (HNE) as a model aldehyde. In phosphate buffer solution (pH 7.4), carnosine was 10 times more active as an HNE quencher than L-histidine and N-acetyl-carnosine while beta-alanine was totally inactive; this indicates that the two constitutive amino acids act synergistically when incorporated as a dipeptide and that the beta-alanyl residue catalyzes the addition reaction of the histidine moiety to HNE. Two reaction products of carnosine were identified, in a pH-dependent equilibrium: (a) the Michael adduct, stabilized as a 5-member cyclic hemi-acetal and (b) an imine macrocyclic derivative. The adduction chemistry of carnosine to HNE thus appears to start with the formation of a reversible alpha,beta-unsaturated imine, followed by ring closure through an intra-molecular Michael addition. The biological role of carnosine as a quencher of alpha,beta-unsaturated aldehydes was verified by detecting carnosine-HNE reaction adducts in oxidized rat skeletal muscle homogenate.

  7. Antioxidant properties of carnosine re-evaluated with oxidizing systems involving iron and copper ions.

    PubMed

    Mozdzan, Monika; Szemraj, Janusz; Rysz, Jacek; Nowak, Dariusz

    2005-05-01

    Carnosine has antioxidant properties and is efficient in the treatment of chemically-induced inflammatory lesions in animals. However, some studies question its biological significance as antioxidant and show lack of protection and even pro-oxidant effect of carnosine in systems containing nickel and iron ions. The ability of carnosine to: (1) reduce Fe(3+) into Fe(2+) ions; (2) protect deoxyribose from oxidation by Fe(2+)-, Fe(3+)-, and Cu(2+)-H(2)O(2)-EDTA systems; (3) protect DNA from damage caused by Cu(2+)-, and Fe(2+)-H(2)O(2)-ascorbate systems; (4) inhibit HClO- and H(2)O(2)-peroxidase-induced luminol dependent chemiluminescence was tested in vitro. At concentration 10 mM carnosine reduced 16.6+/-0.5 nmoles of Fe(3+) into Fe(2+) ions during 20 min. incubation and added to plasma significantly increased its ferric reducing ability. Inhibition of deoxyribose oxidation by 10 mM carnosine reached 56+/-5, 40+/-11 and 30+/-11% for systems containing Fe(2+), Fe(3+) and Cu(2+) ions, respectively. The damage to DNA was decreased by 84+/-9 and 61+/-14% when Cu(2+)-, and Fe(2+)-H(2)O(2)-ascorbate systems were applied. Combination of 10 mM histidine with alanine or histidine alone (but not alanine) enhanced 1.3 and 2.3 times (P<0.05) the DNA damage induced by Fe(2+)-H(2)O(2)-ascorbate. These amino acids added to 10 mM carnosine decreased 3.1-fold (P<0.05) its protective effect on DNA. Carnosine at 10 and 20 mM decreased by more than 90% light emission from both chemiluminescent systems. It is concluded that carnosine has significant antioxidant activity especially in the presence of transition metal ions. However, hydrolysis of carnosine with subsequent histidine release may be responsible for some pro-oxidant effects.

  8. β-Alanine dose for maintaining moderately elevated muscle carnosine levels.

    PubMed

    Stegen, Sanne; Bex, Tine; Vervaet, Chris; Vanhee, Lander; Achten, Eric; Derave, Wim

    2014-07-01

    Chronic β-alanine (BA) supplementation is an increasingly popular nutritional strategy, because it can elevate muscle carnosine content and thereby enhance high-intensity exercise performance. The current study investigated 1) whether sex and body mass are determinants of BA-induced muscle carnosine loading and 2) the optimal maintenance dose for ensuring constantly elevated muscle carnosine stores. During the loading phase, 34 participants (men and women) were supplemented with 3.2 g (4 × 800 mg) BA per day for 46 d (slightly different loading strategies were applied concerning the effect of meal timing and supplementation form). Thereafter, 19 participants (men and women) continued taking free-powder BA for six more weeks (maintenance phase). The participants were matched and redivided into three groups receiving 0.4, 0.8, and 1.2 g·d(-1) BA, respectively. Muscle carnosine content was measured in the soleus and gastrocnemius muscles using proton magnetic resonance spectroscopy. Body mass and sex had only minimal effect on the absolute increase in muscle carnosine. Given the lower baseline values in women, the relative increase for women was higher, indicating that women required less BA for the same relative increase. In addition, a significant negative correlation was observed between body mass and the relative increase in muscle carnosine (r = -0.45, P = 0.007). A maintenance dose of ∼1.2 g·d(-1) BA was the most effective in keeping muscle carnosine content elevated at the postsupplementation level. Sex and body mass did not markedly affect the absolute increase during muscle carnosine loading, although they are determinants for the relative increase. In addition, we established for the first time an effective maintenance dose of ∼1.2 g·d(-1) BA to keep muscle carnosine content elevated at 30%-50% above baseline for a prolonged period.

  9. Influence of l-carnosine on pro-antioxidant status in elite kayakers and canoeists.

    PubMed

    Slowinska-Lisowska, Malgorzata; Zembron-Lacny, A; Rynkiewicz, M; Rynkiewicz, T; Kopec, W

    2014-12-01

    Carnosine is a dipeptide formed from the amino acids β-alanine and histidine and found in large amounts in the brain and muscle, especially fast twitch muscle. Carnosine has an antioxidant role and accounts for about 10% of the muscle's ability to buffer the H+ ions produced by high intensity exercise. Due to the interesting role of carnosine, the aim of the study was observe the effects of carnosine intake on pro-antioxidant status in highly trained athletes exposed to intense exercise.Fourteen male athletes from the Polish national kayak and canoe teams participated in placebo-controlled and cross-over study. The athletes were supplemented with 4 g/d carnosine for 14 days. Blood samples were collected before and 30 min, 24 h and 48 h after 2000 m exercise trial. In blood, hydrogen peroxide (H2O2), nitric oxide (NO), markers of RO/NS activity 8-isoprostanes and 3-nitrotyrosine, total (GSHt) and oxidised glutathione (GSSG), antioxidant status (APO) and superoxide dismutase (SOD) were determined. There were not observed statistically significant differences in exercise-induced changes in H2O2 and NO concentrations and SOD activity after carnosine intake. However, carnosine prevented an increase in 8-isoprostanes, 3-nitrotyrosine and GSSG concentrations as well as elevated redox status (GSHt-2GSSG)/GSSG at post-exercise period.Although, oral supplementation with 4 g carnosine did not affect RO/NS generation, it significantly attenuated exercise-induced glutathione loss, reduced oxidation/nitration markers concentration and SOD activity. These results suggest that carnosine could provide antioxidative protection for highly trained athletes.

  10. Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E(-/-) mice.

    PubMed

    Brown, Bronwyn E; Kim, Christine H J; Torpy, Fraser R; Bursill, Christina A; McRobb, Lucinda S; Heather, Alison K; Davies, Michael J; van Reyk, David M

    2014-02-01

    Carnosine has been shown to modulate triglyceride and glycation levels in cell and animal systems. In this study we investigated whether prolonged supplementation with carnosine inhibits atherosclerosis and markers of lesion stability in hyperglycaemic and hyperlipidaemic mice. Streptozotocin-induced diabetic apo E(-/-) mice were maintained for 20 weeks, post-induction of diabetes. Half of the animals received carnosine (2g/L) in their drinking water. Diabetes was confirmed by significant increases in blood glucose and glycated haemoglobin, plasma triglyceride and total cholesterol levels, brachiocephalic artery and aortic sinus plaque area; and lower body mass. Prolonged carnosine supplementation resulted in a significant (∼20-fold) increase in plasma carnosine levels, and a significant (∼23%) lowering of triglyceride levels in the carnosine-supplemented groups regardless of glycaemic status. Supplementation did not affect glycaemic status, blood cholesterol levels or loss of body mass. In the diabetic mice, carnosine supplementation did not diminish measured plaque area, but reduced the area of plaque occupied by extracellular lipid (∼60%) and increased both macrophage numbers (∼70%) and plaque collagen content (∼50%). The area occupied by α-actin-positive smooth muscle cells was not significantly increased. These data indicate that in a well-established model of diabetes-associated atherosclerosis, prolonged carnosine supplementation enhances plasma levels, and has novel and significant effects on atherosclerotic lesion lipid, collagen and macrophage levels. These data are consistent with greater lesion stability, a key goal in treatment of existing cardiovascular disease. Carnosine supplementation may therefore be of benefit in lowering triglyceride levels and suppressing plaque instability in diabetes-associated atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Mass Spectrometric and Computational Investigation of the Protonated Carnosine-Carboplatin Complex Fragmentation.

    PubMed

    Ritacco, Ida; Sicilia, Emilia; Shoeib, Tamer; Korany, Mohamed; Russo, Nino

    2015-08-17

    Platinum(II)-based anticancer drugs are square-planar d(8) complexes that, activated by hydrolysis, cause cancer cell death by binding to nuclear DNA and distorting its structure. For that reason, interactions of platinum anticancer drugs with DNA have been extensively investigated, aiming at disentangling the mechanism of action and toxicity. Less attention, however, has been devoted to the formation of adducts between platinum drugs with biological ligands other than DNA. These adducts can cause the loss and deactivation of the drug before it arrives at the ultimate target and are also thought to contribute to the drug's toxicity. Here are reported the outcomes of electrospray ionization mass spectrometry experiments and density functional theory (DFT) computations carried out to investigate the fragmentation pathways of the protonated carnosine-carboplatin complex, [Carnosine + CarbPt + H](+). DFT calculations at the B3LYP/LANL2DZ level employed to probe fragmentation mechanisms account for all experimental data. Because of the relative rigidity of the structure of the most stable 1A conformer, stabilized by three strong hydrogen bonds, the first step of all of the examined fragmentation pathways is the interconversion of the 1A conformer into the less stable structure 1B. Formation of the [Carnosine + H](+) fragment from the precursor ion, [Carnosine + CarbPt + H](+), is calculated to be the lowest-energy process. At slightly higher energies, the loss of two amino groups is observed to produce the [Carnosine + (CarbPt - NH3) + H](+) and [Carnosine + (CarbPt - 2NH3) + H](+) ions. At significantly higher energies, the loss of CO2 occurs, yielding the final [Carnosine + (CarbPt - NH3) - CO2 + H](+) and [Carnosine + (CarbPt - 2NH3) - CO2 + H](+) products. Formation of the [CarbPt + H](+) fragment from [Carnosine + CarbPt + H](+), even if not hampered by a high activation barrier, is calculated to be very unfavorable from a thermodynamic point of view.

  12. Molecular Identification of Carnosine Synthase as ATP-grasp Domain-containing Protein 1 (ATPGD1)*

    PubMed Central

    Drozak, Jakub; Veiga-da-Cunha, Maria; Vertommen, Didier; Stroobant, Vincent; Van Schaftingen, Emile

    2010-01-01

    Carnosine (β-alanyl-l-histidine) and homocarnosine (γ-aminobutyryl-l-histidine) are abundant dipeptides in skeletal muscle and brain of most vertebrates and some invertebrates. The formation of both compounds is catalyzed by carnosine synthase, which is thought to convert ATP to AMP and inorganic pyrophosphate, and whose molecular identity is unknown. In the present work, we have purified carnosine synthase from chicken pectoral muscle about 1500-fold until only two major polypeptides of 100 and 90 kDa were present in the preparation. Mass spectrometry analysis of these polypeptides did not yield any meaningful candidate. Carnosine formation catalyzed by the purified enzyme was accompanied by a stoichiometric formation, not of AMP, but of ADP, suggesting that carnosine synthase belongs to the “ATP-grasp family” of ligases. A data base mining approach identified ATPGD1 as a likely candidate. As this protein was absent from chicken protein data bases, we reconstituted its sequence from a PCR-amplified cDNA and found it to fit with the 100-kDa polypeptide of the chicken carnosine synthase preparation. Mouse and human ATPGD1 were expressed in HEK293T cells, purified to homogeneity, and shown to catalyze the formation of carnosine, as confirmed by mass spectrometry, and of homocarnosine. Specificity studies carried out on all three enzymes were in agreement with published data. In particular, they acted with 15–25-fold higher catalytic efficiencies on β-alanine than on γ-aminobutyrate. The identification of the gene encoding carnosine synthase will help for a better understanding of the biological functions of carnosine and related dipeptides, which still remain largely unknown. PMID:20097752

  13. Carnosine metabolism in diabetes is altered by reactive metabolites.

    PubMed

    Peters, Verena; Lanthaler, Barbara; Amberger, Albert; Fleming, Thomas; Forsberg, Elisabete; Hecker, Markus; Wagner, Andreas H; Yue, Wyatt W; Hoffmann, Georg F; Nawroth, Peter; Zschocke, Johannes; Schmitt, Claus P

    2015-11-01

    Carnosinase 1 (CN1) contributes to diabetic nephropathy by cleaving histidine-dipeptides which scavenge reactive oxygen and carbonyl species and increase nitric oxide (NO) production. In diabetic mice renal CN1 activity is increased, the regulatory mechanisms are unknown. We therefore analysed the in vitro and in vivo regulation of CN1 activity using recombinant and human CN1, and the db/db mouse model of diabetes. Glucose, leptin and insulin did not modify recombinant and human CN1 activity in vitro, glucose did not alter renal CN1 activity of WT or db/db mice ex vivo. Reactive metabolite methylglyoxal and Fenton reagent carbonylated recombinant CN1 and doubled CN1 efficiency. NO S-nitrosylated CN1 and decreased CN1 efficiency for carnosine by 70 % (p < 0.01), but not for anserine. Both CN1 cysteine residues were nitrosylated, the cysteine at position 102 but not at position 229 regulated CN1 activities. In db/db mice, renal CN1 mRNA and protein levels were similar as in non-diabetic controls, CN1 efficiency 1.9 and 1.6 fold higher for carnosine and anserine. Renal carbonyl stress was strongly increased and NO production halved, CN1 highly carbonylated and less S-nitrosylated compared to WT mice. GSH and NO2/3 concentrations were reduced and inversely related with carnosine degradation rate (r = -0.82/-0.85). Thus, reactive metabolites of diabetes upregulate CN1 activity by post-translational modifications, and thus decrease the availability of reactive metabolite-scavenging histidine dipeptides in the kidney in a positive feedback loop. Interference with this vicious circle may represent a new therapeutic target for mitigation of DN.

  14. Quantification of Carnosine-Aldehyde Adducts in Human Urine.

    PubMed

    da Silva Bispo, Vanderson; Di Mascio, Paolo; Medeiros, Marisa

    2014-10-01

    Lipid peroxidation generates several reactive carbonyl species, including 4-hydroxy-2-nonenal (HNE), acrolein (ACR), 4-hydroxy-2-hexenal (HHE) and malondialdehyde. One major pathwayof aldehydes detoxification is through conjugation with glutathione catalyzed by glutathione-S-transferases or, alternatively, by conjugation with endogenous histidine containing dipeptides, such as carnosine (CAR). In this study, on-line reverse-phase high-performance liquid chromatography (HPLC) separation with tandem mass spectrometry detection was utilized for the accurate quantification of CAR- ACR, CAR-HHE and CAR-HNE adducts in human urinary samples from non-smokers young adults. Standard adducts were prepared and isolated by HPLC. The results showed the presence of a new product from the reaction of CAR with ACR. This new adduct was completely characterized by HPLC/MS-MSn, 1H RMN, COSY and HSQC. The new HPLC/MS/MS methodology employing stable isotope-labeled internal standards (CAR-HHEd5 and CAR-HNEd11) was developed for adducts quantification. This methodology permits quantification of 10pmol CAR-HHE and 1pmol of CAR-ACR and CAR-HNE. Accurate determinations in human urine sample were performed and showed 4.65±1.71 to CAR-ACR, 5.13±1.76 to CAR-HHE and 5.99±3.19nmol/mg creatinine to CAR-HNE. Our results indicate that carnosine pathways can be an important detoxification route of a, ß -unsaturated aldehydes. Moreover, carnosine adducts may be useful as redox stress indicator. Copyright © 2014. Published by Elsevier Inc.

  15. Effect of carnosine on the immunosuppressive effect of histamine

    SciTech Connect

    Sharpan, Yu. V.

    1985-04-01

    This paper studies the ability of carnosine (beta-imidazole-lactate) to affect histamine-induced immunosuppression of proliferative activity of various lymphocyte subpopulations and the realization of this effect through surface histamine receptors of the cells. The experiments were carried out on mice; lymphocytes were incubated with tritium-labeled thymidine for 4 h, after which their radioactivity was determined on a scintillation counter. The results show that histamine has an inhibitory action on antigen-induced proliferation of T suppressor lymphocytes through H-2 histamine receptors, for this effect was considerably inhibited by the H-2 histamine blockers metiamide, but not by the H-1 histamine blocker mepyramine.

  16. [Protective properties of L-carnosine studied in vitro on a hemorrhagic stroke model].

    PubMed

    Khama-Murad, A Kh

    2009-01-01

    The protective properties of L-carnosine have been studied in vitro on a model of hemorrhagic stroke developed on survival olfactory cortex slices of hypertensive rats after long-term exposure to autoblood. The preliminary application of L-carnosine in a concentration of 5 mg/ml regenerates an activity of glutamatergic and GABAergic components of focal potentials inhibited by autoblood and prevents tissue swelling. L-carnosine protects the bioelectrical activity of nerve cells after their long-term exposure to autoblood and produces an antiedematic effect.

  17. Carnosine protects neurons against oxidative stress and modulates the time profile of MAPK cascade signaling.

    PubMed

    Kulebyakin, Konstantin; Karpova, Larisa; Lakonsteva, Ekaterina; Krasavin, Mikhail; Boldyrev, Alexander

    2012-07-01

    Carnosine is a known protector of neuronal cells against oxidative injury which prevents both apoptotic and necrotic cellular death. It was shown earlier that carnosine serves as an intracellular buffer of free radicals. Using the model of ligand-dependent oxidative stress in neurons, we have shown that homocysteine (HC) initiates long-term activation of extracellular signal regulated kinase, isoforms 1 and 2 (ERK 1/2) and Jun N-terminal kinase (JNK) which corresponds to exitotoxic effect resulting in cellular death. L-carnosine (β-alanyl-L-histidine) protects neurons from both excitotoxic effect of homocysteine and cellular death. Its analogs, β-alanyl-D-histidine (D-carnosine) and L-histidyl-β-alanine, restricted accumulation of free radicals and delayed activation of ERK1/2 and JNK in neuronal cells, but did not promote neuronal viability.

  18. Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain.

    PubMed

    Kohen, R; Yamamoto, Y; Cundy, K C; Ames, B N

    1988-05-01

    Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. However, their exact function is not clear. The antioxidant activity of these compounds has been examined by testing their peroxyl radical-trapping ability at physiological concentrations. Carnosine, homocarnosine, anserine, and other histidine derivatives all showed antioxidant activity. All of these compounds showing peroxyl radical-trapping activity were also electrochemically active as reducing agents in cyclic voltammetric measurements. Furthermore, carnosine inhibited the oxidative hydroxylation of deoxyguanosine induced by ascorbic acid and copper ions. Other roles of carnosine, such as chelation of metal ions, quenching of singlet oxygen, and binding of hydroperoxides, are also discussed. The data suggest a role for these histidine-related compounds as endogenous antioxidants in brain and muscle.

  19. Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain.

    PubMed Central

    Kohen, R; Yamamoto, Y; Cundy, K C; Ames, B N

    1988-01-01

    Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. However, their exact function is not clear. The antioxidant activity of these compounds has been examined by testing their peroxyl radical-trapping ability at physiological concentrations. Carnosine, homocarnosine, anserine, and other histidine derivatives all showed antioxidant activity. All of these compounds showing peroxyl radical-trapping activity were also electrochemically active as reducing agents in cyclic voltammetric measurements. Furthermore, carnosine inhibited the oxidative hydroxylation of deoxyguanosine induced by ascorbic acid and copper ions. Other roles of carnosine, such as chelation of metal ions, quenching of singlet oxygen, and binding of hydroperoxides, are also discussed. The data suggest a role for these histidine-related compounds as endogenous antioxidants in brain and muscle. PMID:3362866

  20. Prevention of peroxynitrite-dependent damage by carnosine and related sulphonamido pseudodipeptides.

    PubMed

    Fontana, M; Pinnen, F; Lucente, G; Pecci, L

    2002-03-01

    The naturally occurring dipeptides carnosine and anserine have been proposed to act as antioxidants in vivo. We investigated whether these compounds can act as protective agents able to counteract peroxynitrite-dependent reactions. The results showed that the dipeptides efficiently protect tyrosine against nitration, alpha1-antiproteinase against inactivation and human low-density lipoprotein against modification by peroxynitrite. Carnosine exerts its protective effect at concentrations similar to those found in human tissues. In addition, some synthetic pseudodipeptides, stucturally related to carnosine but stable to hydrolytic enzymes, possess protective properties against peroxynitrite-dependent damage similar to the natural dipeptides. These pseudodipeptides may represent stable mimics of the biologically active carnosine suitable for pharmacological applications.

  1. Carnosine inhibits KRAS-mediated HCT116 proliferation by affecting ATP and ROS production.

    PubMed

    Iovine, Barbara; Iannella, Maria Luigia; Nocella, Francesca; Pricolo, Maria Rosaria; Bevilacqua, Maria Assunta

    2012-02-28

    Carnosine is a natural dipeptide that has generated particular interest for its antioxidant, anti-aging and especially for its antiproliferative properties. In this study, we demonstrate that carnosine inhibits the proliferation of human HCT116 colon cancer cells. In this cell line, the activating KRAS mutation induces mitochondrial ROS, the signaling molecules for cell proliferation. We observed that 50-100 mM carnosine decreases ATP and ROS concentration and induces cell cycle arrest in G1 phase. In HCT116 cells these effects are related to decreased ERK1/2 phosphorylation and increased p21waf1 protein. Our findings support the concept that carnosine could inhibit HCT116 cell growth via its antioxidant activity and its ability to affect glycolysis.

  2. Effects of sprint training combined with vegetarian or mixed diet on muscle carnosine content and buffering capacity.

    PubMed

    Baguet, Audrey; Everaert, Inge; De Naeyer, Hélène; Reyngoudt, Harmen; Stegen, Sanne; Beeckman, Sam; Achten, Eric; Vanhee, Lander; Volkaert, Anneke; Petrovic, Mirko; Taes, Youri; Derave, Wim

    2011-10-01

    Carnosine is an abundant dipeptide in human skeletal muscle with proton buffering capacity. There is controversy as to whether training can increase muscle carnosine and thereby provide a mechanism for increased buffering capacity. This study investigated the effects of 5 weeks sprint training combined with a vegetarian or mixed diet on muscle carnosine, carnosine synthase mRNA expression and muscle buffering capacity. Twenty omnivorous subjects participated in a 5 week sprint training intervention (2-3 times per week). They were randomized into a vegetarian and mixed diet group. Measurements (before and after the intervention period) included carnosine content in soleus, gastrocnemius lateralis and tibialis anterior by proton magnetic resonance spectroscopy ((1)H-MRS), true-cut biopsy of the gastrocnemius lateralis to determine in vitro non-bicarbonate muscle buffering capacity, carnosine content (HPLC method) and carnosine synthase (CARNS) mRNA expression and 6 × 6 s repeated sprint ability (RSA) test. There was a significant diet × training interaction in soleus carnosine content, which was non-significantly increased (+11%) with mixed diet and non-significantly decreased (-9%) with vegetarian diet. Carnosine content in other muscles and gastrocnemius buffer capacity were not influenced by training. CARNS mRNA expression was independent of training, but decreased significantly in the vegetarian group. The performance during the RSA test improved by training, without difference between groups. We found a positive correlation (r = 0.517; p = 0.002) between an invasive and non-invasive method for muscle carnosine quantification. In conclusion, this study shows that 5 weeks sprint training has no effect on the muscle carnosine content and carnosine synthase mRNA.

  3. Effect of beta-alanine and carnosine supplementation on muscle contractility in mice.

    PubMed

    Everaert, Inge; Stegen, Sanne; Vanheel, Bert; Taes, Youri; Derave, Wim

    2013-01-01

    Enhanced carnosine levels have been shown to be ergogenic for high-intensity exercise performances, although the role of carnosine in the control of muscle function is poorly understood. Therefore, the aim of this study was to investigate the effect of long-term supplementation with increasing doses of carnosine and beta-alanine on muscle carnosine, anserine, and taurine levels and on in vitro contractility and fatigue in mice. Male Naval Medical Research Institute mice (n = 66) were control fed or supplemented with either carnosine (0.1%, 0.5%, or 1.8%) or beta-alanine (0.6 or 1.2%) in their drinking water for 8-12 wk. Soleus and extensor digitorum longus (EDL) were tested for in vitro contractile properties, and carnosine, anserine, and taurine content were measured in EDL and tibialis anterior by high-performance liquid chromatography. Only supplementation with 1.8% carnosine and 1.2% beta-alanine resulted in markedly higher carnosine (up to +160%) and anserine levels (up to +46%) compared with control mice. Beta-alanine supplementation (1.2%) resulted in increased fatigue resistance in the beginning of the fatigue protocol in soleus (+2%-4%) and a marked leftward shift of the force-frequency relation in EDL (10%-31% higher relative forces). Comparable with humans, beta-alanine availability seems to be the rate-limiting step for synthesis of muscle histidine-containing dipeptides in mice. Moreover, muscle histidine-containing dipeptides loading in mice moderately and muscle dependently affects excitation-contraction coupling and fatigue.

  4. Inhibition of oxidative stress in brain during rat adjuvant arthritis by carnosine, trolox and novel trolox-carnosine.

    PubMed

    Poništ, S; Slovák, L; Kuncírová, V; Fedorova, T; Logvinenko, A; Muzychuk, O; Mihalová, D; Bauerová, K

    2015-01-01

    Carnosine (CARN) is an anti-glycating agent able to quench superoxide, and to neutralize 4-hydroxynonenal. Trolox-carnosine (CARN-T) was synthesized because of its resistance against degradation and to improve CARN antioxidant capacity. We evaluated the impact of trolox (TRO), CARN and its derivative CARN-T on oxidative stress (OS) in brain during rat adjuvant arthritis (AA). The experiments were done on healthy, control arthritic and arthritic animals with administration of CARN 150 mg/kg b.w., TRO 41 mg/kg b.w. and CARN-T 75 mg/kg b.w. in a daily dose during 28 days. Antioxidants did not affect the body weight on day 14, but on day 28 TRO enhanced the weight reduction. On day 14 and 28 CARN-T and TRO reduced arthritic score. IL-1beta, MCP-1 and MMP-9 were measured in plasma on day 14. MCP-1 was decreased by CARN-T and TRO. All antioxidants reduced IL-1beta and MMP-9 levels. Malondialdehyde, 4-hydroxynonenal and protein carbonyls were increased in brain. CARN, CARN-T and TRO prevented higher lipid and protein oxidation in brain. CARN and CARN-T caused no weight reduction like TRO that has an advantage in inflammatory arthritis. Moreover the antioxidants administered had a similar therapeutic effects on arthritic score, markers of inflammation in plasma and OS in brain.

  5. Carnosine modulates glutamine synthetase expression in senescent astrocytes exposed to oxygen-glucose deprivation/recovery.

    PubMed

    Shi, Xiaojie; Wang, Bingyu; Liu, Yuan; Zhang, Jingjing; Huang, Yuyan; Cao, Pei; Shen, Yao; Lyu, Jianxin

    2017-01-20

    Carnosine is believed to be neuroprotective in cerebral ischemia. However, few reports concern its function on senescent astrocytes during cerebral ischemia. The aim of this study was to investigate the effects of carnosine on cell damage and glutamine synthetase (GS) expression in D-galactose-induced senescent astrocytes exposed to oxygen-glucose deprivation/recovery (OGD/R). The results showed that OGD/R caused massive cell damage and a significant decrease in GS expression both in the young and senescent astrocytes. The GS expression level was partly recovered whereas it continued to decline in the recovery stage in the young and senescent astrocytes, respectively. Decreased GS expression significantly inhibited glutamate uptake and glutamine production and release. Carnosine prevented the cell damage, rescued the expression of GS and reversed the glutamate uptake activity and glutamine production in the senescent astrocytes exposed to OGD/R. The modulatory effect of carnosine on GS expression was partly antagonized by pyrilamine, a selective histamine H1 receptors antagonist, but not bestatin. Bisindolylmaleimide II, a broad-spectrum inhibitor of PKC could also reverse the action of carnosine on GS expression. Thus, histamine H1 receptors and PKC pathway may be involved in the modulatory action of carnosine in GS expression in the senescent astrocytes exposed to OGD/R.

  6. Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes.

    PubMed

    Ansurudeen, Ishrath; Sunkari, Vivekananda Gupta; Grünler, Jacob; Peters, Verena; Schmitt, Claus Peter; Catrina, Sergiu-Bogdan; Brismar, Kerstin; Forsberg, Elisabete Alcantara

    2012-07-01

    Diabetes mellitus (DM) is a progressive disorder with severe late complications. Normal wound healing involves a series of complex and well-orchestrated molecular events dictated by multiple factors. In diabetes, wound healing is grossly impaired due to defective, and dysregulated cellular and molecular events at all phases of wound healing resulting in chronic wounds that fail to heal. Carnosine, a dipeptide of alanine and histidine and an endogenous antioxidant is documented to accelerate healing of wounds and ulcers. However, not much is known about its role in wound healing in diabetes. Therefore, we studied the effect of carnosine in wound healing in db/db mice, a mice model of Type 2 DM. Six millimeter circular wounds were made in db/db mice and analyzed for wound healing every other day. Carnosine (100 mg/kg) was injected (I.P.) every day and also applied locally. Treatment with carnosine enhanced wound healing significantly, and wound tissue analysis showed increased expression of growth factors and cytokines genes involved in wound healing. In vitro studies with human dermal fibroblasts and microvascular-endothelial cells showed that carnosine increases cell viability in presence of high glucose. These effects, in addition to its known role as an antioxidant and a precursor for histamine synthesis, provide evidence for a possible therapeutic use of carnosine in diabetic wound healing.

  7. Protective effects of carnosine on white matter damage induced by chronic cerebral hypoperfusion.

    PubMed

    Ma, Jing; Bo, Shu-Hong; Lu, Xiao-Tong; Xu, A-Jing; Zhang, Jian

    2016-09-01

    Carnosine is a dipeptide that scavenges free radicals, inhibits inflammation in the central nervous system, and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions. Therefore, we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury. White matter damage was induced by right unilateral common carotid artery occlusion in mice. The animals were treated with 200, 500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury. Then, 37 days later, Klüver-Barrera staining, toluidine blue staining and immunofluorescence staining were performed. Carnosine (200, 500 mg/kg) substantially reduced damage to the white matter in the corpus callosum, internal capsule and optic tract, and it rescued expression of myelin basic protein, and alleviated the loss of oligodendrocytes. However, carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses. These findings show that carnosine, at a particular dose range, protects against white matter damage caused by chronic cerebral ischemia in mice, likely by reducing oligodendroglial cell loss.

  8. The effects of carnosine in an experimental rat model of septic shock

    PubMed Central

    Sahin, Sabiha; Oter, Serdar; Burukoglu, Dilek; Sutken, Emine

    2013-01-01

    Background To examine the effect of carnosine on liver function and histological findings in experimental septic shock model, 24 Sprague-Dawley rats were used. Material/Methods Rats were divided into control, septic shock, and carnosine-treated septic shock groups. Femoral vein and artery catheterization were performed on all rats. Rats in the control group underwent laparotomy and catheterization; in the test groups, cecal ligation-perforation and bladder cannulation were added. Rats in the treatment group received a single intraperitoneal (IP) injection of 250 mg/kg carnosine 60 minutes after cecal ligation-perforation. Rats were monitored for blood pressure, heart rate, and body temperature to assess the postoperative septic response, and body fluids were replaced as necessary. At the end of 24 hours, rats were sacrificed and liver samples were collected. Results Statistically significant improvements were observed in liver function, tissue and serum MDA levels, and histological findings in rats treated with carnosine, compared to rats with untreated sepsis. HB and HCT values did not change significantly during the course of the experiment. Rats exposed to septic shock and treated with carnosine exhibited decreased sinusoidal dilatation and cellular inflammation into the portal region, compared to the sepsis group; the livers of rats in this group had near-normal histological structure. Conclusions We conclude that carnosine may be an effective treatment for oxidative damage due to liver tissue perfusion defects in cases of septic shock. PMID:23396325

  9. Dual effects of carnosine on energy metabolism of cultured cortical astrocytes under normal and ischemic conditions.

    PubMed

    Shen, Yao; Tian, Yueyang; Yang, Jianbo; Shi, Xiaojie; Ouyang, Li; Gao, Jieqiong; Lu, Jianxin

    2014-01-01

    The aim of this study was to investigate the effects of carnosine on the bioenergetic profile of cultured cortical astrocytes under normal and ischemic conditions. The Seahorse Bioscience XF96 Extracellular Flux Analyzer was used to measure the oxygen consumption rates (OCRs) and extracellular acidification rates (ECARs) of cultured cortical astrocytes treated with and without carnosine under normal and ischemic conditions. Under the normal growth condition, the basal OCRs and ECARs of astrocytes were 21.72±1.59 pmol/min/μg protein and 3.95±0.28 mpH/min/μg protein respectively. Mitochondrial respiration accounted for ~80% of the total cellular respiration and 85% of this coupled to ATP synthesis. Carnosine significantly reduced basal OCRs and ECARs and ATP-linked respiration, but it strikingly increased the spare respiratory capacity of astrocytes. The cellular ATP level in carnosine-treated astrocytes was reduced to ~42% of the control. However, under the ischemic condition, carnosine upregulated the mitochondrial respiratory and cellular ATP content of astrocytes exposed to 8h of oxygen-glucose deprivation (OGD) followed by 24 h of recovery under the normal growth condition. Carnosine may be an endogenous regulator of astrocyte energy metabolism and a clinically safe therapeutic agent for promoting brain energy metabolism recovery after ischemia/reperfusion injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Impairment of Electron Transfer Chain Induced by Acute Carnosine Administration in Skeletal Muscle of Young Rats

    PubMed Central

    Macarini, José Roberto; Maravai, Soliany Grassi; Cararo, José Henrique; Dimer, Nádia Webber; Gonçalves, Cinara Ludvig; Kist, Luiza Wilges; Bogo, Mauricio Reis; Schuck, Patrícia Fernanda; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2014-01-01

    Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain complexes (I–III, II, and II-III), malate dehydrogenase, succinate dehydrogenase, and creatine kinase activities and the expression of mitochondrial-specific transcription factors (NRF-1, PGC-1α, and TFAM) in skeletal muscle of young Wistar rats. We observed a significant decrease of complexes I–III and II activities in animals receiving carnosine acutely, as compared to control group. However, no significant alterations in respiratory chain complexes, citric acid cycle enzymes, and creatine kinase activities were found between rats receiving carnosine chronically and control group animals. As compared to control group, mRNA levels of NRF-1, PGC-1α, and TFAM were unchanged. The present findings indicate that electron transfer through the respiratory chain is impaired in skeletal muscle of rats receiving carnosine acutely. In case these findings are confirmed by further studies and ATP depletion is also observed, impairment of bioenergetics could be considered a putative mechanism responsible for the muscle damage observed in serum carnosinase-deficient patients. PMID:24877122

  11. Carnosine mitigates apoptosis and protects testicular seminiferous tubules from gamma-radiation-induced injury in mice.

    PubMed

    Haeri, S A; Rajabi, H; Fazelipour, S; Hosseinimehr, S J

    2014-01-01

    This study investigated the radioprotective effects of a naturally occurring dipeptide, carnosine, on testicular damage. Carnosine was administered (10, 50 and 100 mg kg(-1) body weight) to male mice via intraperitoneal injection for 4 days prior to gamma irradiation (2 Gy). Apoptosis with the TUNEL assay and histopathological parameters were evaluated 12-h and 14-day post-irradiation. Pre-treatment with carnosine before irradiation significantly reduced the frequency of TUNEL-positive cells induced by radiation treatment at all doses by reduction factors of 1.8, 2.47 and 2.23 for carnosine at 10, 50 and 100 mg kg(-1) bw, respectively, unlike that observed in the radiation alone group. Exposure to ionising radiation decreased sperm count and reduced the height and diameter of seminiferous epithelial tubules. Pre-treatment with all doses of carnosine significantly augmented seminiferous epithelial height and tubule diameter and also increased the number of germinal cells in comparison to the group treated with radiation only. These results indicate that carnosine prevents testicular dysfunction induced by gamma-irradiation via an anti-apoptotic effect; this restoration of proper testicular function ultimately leads to the recovery of spermatogenesis. © 2013 Blackwell Verlag GmbH.

  12. Impairment of electron transfer chain induced by acute carnosine administration in skeletal muscle of young rats.

    PubMed

    Macarini, José Roberto; Maravai, Soliany Grassi; Cararo, José Henrique; Dimer, Nádia Webber; Gonçalves, Cinara Ludvig; Kist, Luiza Wilges; Bogo, Mauricio Reis; Schuck, Patrícia Fernanda; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2014-01-01

    Serum carnosinase deficiency is an inherited disorder that leads to an accumulation of carnosine in the brain tissue, cerebrospinal fluid, skeletal muscle, and other tissues of affected patients. Considering that high levels of carnosine are associated with neurological dysfunction and that the pathophysiological mechanisms involved in serum carnosinase deficiency remain poorly understood, we investigated the in vivo effects of carnosine on bioenergetics parameters, namely, respiratory chain complexes (I-III, II, and II-III), malate dehydrogenase, succinate dehydrogenase, and creatine kinase activities and the expression of mitochondrial-specific transcription factors (NRF-1, PGC-1α , and TFAM) in skeletal muscle of young Wistar rats. We observed a significant decrease of complexes I-III and II activities in animals receiving carnosine acutely, as compared to control group. However, no significant alterations in respiratory chain complexes, citric acid cycle enzymes, and creatine kinase activities were found between rats receiving carnosine chronically and control group animals. As compared to control group, mRNA levels of NRF-1, PGC-1α , and TFAM were unchanged. The present findings indicate that electron transfer through the respiratory chain is impaired in skeletal muscle of rats receiving carnosine acutely. In case these findings are confirmed by further studies and ATP depletion is also observed, impairment of bioenergetics could be considered a putative mechanism responsible for the muscle damage observed in serum carnosinase-deficient patients.

  13. Protective effect of bioactive peptide carnosine against lead-induced oxidative stress in kidney of rats.

    PubMed

    Hasanein, P; Teimuri-Far, M

    2015-08-05

    Oxidative stress is among the mechanisms involved in renal injury. We aimed to investigate the protective effects of bioactive peptide carnosine on lead induced oxidative stress and nephrotoxicity in rats. Animals received an aqueous solution of lead acetate (500 mg Pb/L in the drinking water) and/or carnosine (10 mg/kg, i.g.) for eight weeks. Then rats were weighed and used for biochemical, histological and oxidant/antioxidant evaluations. Lead-induced oxidative stress in renal tissue was indicated by a significant increase in the renal contents of malondialdehyde (MDA) as well as decrease in the levels of reduced glutathione (GSH), total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD) (P's < 0.001). Carnosine treatment decreased MDA whereas it increased the contents of GSH, TAC, CAT and SOD in both lead and control groups. Carnosine prevented the increased kidney weight and lead-induced deleterious effects on serum creatinine, urea, uric acid, albumin and total protein in lead group. It also attenuated lead induced abnormal renal structure. The present study showed that carnosine protected against lead induced oxidative stress and renal injury in rat. Therefore, carnosine represents a potential therapeutic option against the deleterious effect of lead induced nephrotoxicity which deserves consideration and further examination.

  14. Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation

    PubMed Central

    Meixensberger, Jürgen; Gaunitz, Frank

    2016-01-01

    Here we analyzed whether the anti-neoplastic effect of carnosine, which inhibits glycolytic ATP production, can be antagonized by ATP production via oxidative phosphorylation fueled by pyruvate. Therefore, glioblastoma cells were cultivated in medium supplemented with glucose, galactose or pyruvate and in the presence or absence of carnosine. CPI-613 was employed to inhibit the entry of pyruvate into the tricarboxylic acid cycle and 2,4-dinitrophenol to inhibit oxidative phosphorylation. Energy metabolism and viability were assessed by cell based assays and histochemistry. ATP in cell lysates and dehydrogenase activity in living cells revealed a strong reduction of viability under the influence of carnosine when cells received glucose or galactose but not in the presence of pyruvate. CPI-613 and 2,4-dinitrophenol reduced viability of cells cultivated in pyruvate, but no effect was seen in the presence of glucose. No effect of carnosine on viability was observed in the presence of glucose and pyruvate even in the presence of 2,4-dinitrophenol or CPI-613. In conclusion, glioblastoma cells produce ATP from pyruvate via the tricarboxylic acid cycle and oxidative phosphorylation in the absence of a glycolytic substrate. In addition, pyruvate attenuates the anti-neoplastic effect of carnosine, even when ATP production via tricarboxylic acid cycle and oxidative phosphorylation is blocked. We also observed an inhibitory effect of carnosine on the tricarboxylic acid cycle and a stimulating effect of 2,4-dinitrophenol on glycolytic ATP production. PMID:27811375

  15. Protective effects of carnosine on white matter damage induced by chronic cerebral hypoperfusion

    PubMed Central

    Ma, Jing; Bo, Shu-hong; Lu, Xiao-tong; Xu, A-jing; Zhang, Jian

    2016-01-01

    Carnosine is a dipeptide that scavenges free radicals, inhibits inflammation in the central nervous system, and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions. Therefore, we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury. White matter damage was induced by right unilateral common carotid artery occlusion in mice. The animals were treated with 200, 500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury. Then, 37 days later, Klüver-Barrera staining, toluidine blue staining and immunofluorescence staining were performed. Carnosine (200, 500 mg/kg) substantially reduced damage to the white matter in the corpus callosum, internal capsule and optic tract, and it rescued expression of myelin basic protein, and alleviated the loss of oligodendrocytes. However, carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses. These findings show that carnosine, at a particular dose range, protects against white matter damage caused by chronic cerebral ischemia in mice, likely by reducing oligodendroglial cell loss. PMID:27857746

  16. Quantification of carnosine- related peptides by microchip electrophoresis with chemiluminescence detection

    PubMed Central

    Zhao, Shulin; Huang, Yong; Shi, Ming; Huang, Junming; Liu, Yi-Ming

    2009-01-01

    A microchip electrophoresis (MCE) method with chemiluminescence (CL) detection was developed for the determination of carnosine-related peptides including carnosine, homocarnosine and anserine in biological samples. A simple integrated MCE-CL system was built to perform the assays. The highly sensitive CL detection was achieved by means of the CL reaction between hydrogen peroxide and N-(4-aminobutyl)- N-ethylisoluminol-tagged peptides in the presence of adenine as a CL enhancer and Co2+ as a catalyst. Experimental conditions for analyte labeling, MCE separation, and CL detection were studied. MCE separation of the above said three peptides took less than 120 s. Detection limits (S/N=3) of 3.0×10−8, 2.8×10−8 and 3.4×10−8 M were obtained for carnosine, anserine and homocarnosine, respectively. The present MCE-CL method was applied for the determination of carnosine, anserine and homocarnosine in human cerebrospinal fluid (CSF) and canine plasma. Homocarnosine was detected at the µM level in the CSF samples analyzed while the levels of carnosine and anserine in these samples were below the detection limit of the assay. Interestingly, both carnosine and anserine were detected in the canine plasma samples, but not homocarnosine. PMID:19538931

  17. The Neuroprotective Effects of Carnosine in Early Stage of Focal Ischemia Rodent Model

    PubMed Central

    Park, Hui-Seung; Han, Kyung-Hoon; Shin, Jeoung-A; Park, Joo-Hyun; Song, Kwan-Young

    2014-01-01

    Objective This study was conducted to elucidate neuroprotective effect of carnosine in early stage of stroke. Methods Early stage of rodent stroke model and neuroblastoma chemical hypoxia model was established by middle cerebral artery occlusion and antimycin A. Neuroprotective effect of carnosine was investigated with 100, 250, and 500 mg of carnosine treatment. And antioxidant expression was analyzed by enzyme linked immunosorbent assay (ELISA) and western blot in brain and blood. Results Intraperitoneal injection of 500 mg carnosine induced significant decrease of infarct volume and expansion of penumbra (p<0.05). The expression of superoxide dismutase (SOD) showed significant increase than in saline group in blood and brain (p<0.05). In the analysis of chemical hypoxia, carnosine induced increase of neuronal cell viability and decrease of reactive oxygen species (ROS) production. Conclusion Carnosine has neuroprotective property which was related to antioxidant capacity in early stage of stroke. And, the oxidative stress should be considered one of major factor in early ischemic stroke. PMID:24851146

  18. Protective effect of carnosine after chronic cerebral hypoperfusion possibly through suppressing astrocyte activation

    PubMed Central

    Ma, Jing; Chen, Jihui; Bo, Shuhong; Lu, Xiaotong; Zhang, Jian

    2015-01-01

    Aim: Subcortical ischemic vascular dementia (SIVD) induced by chronic hypoperfusion is a common cause of vascular dementia. The aim of this study was to determine whether the protective effect of carnosine on white matter lesion after chronic cerebral hypoperfusion through suppressing astrocyte activation. Methods: Adult male mice (C57BL/6 strain) were subjected to permanent occlusion of the right unilateral common carotid arteries (rUCCAO) and treated with carnosine or histidine. Open field test, freezing test, Klüver-Barrera staining, immunohistochemical analyses and western blot were performed after rUCCAO. Results: We found that carnosine ameliorated white matter lesion and cognitive impairment after rUCCAO. Carnosine suppressed the activation of astrocyte in both wide type mice and histidine decarboxylase knockout mice. However, administration of histidine did not show the same effect. We found that there were no differences between rUCCAO group and sham group for the expression of glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST). Furthermore, carnosine significantly attenuated the increase of inflammatory cytokine interferon gama. Conclusion: These data suggest carnosine induced neuroprotection during SIVD in mice is not dependent on the histaminergic pathway or the regulation of the expression of GLT-1 and GLAST, but may be due to a suppression of astrocyte activation and inflammatory cytokine release. PMID:26885268

  19. Investigation of dose-related effects of carnosine on anxiety with sympathetic skin response and T-maze.

    PubMed

    Dolu, Nazan; Acer, Hale; Kara, Ali Yucel

    2014-01-01

    Carnosine is a dipeptide formed of the amino acids β-alanine and histidine. Only a limited number of studies have examined the effects of carnosine on sympathetic nerve activation and anxiety. The present study was undertaken to determine the dose-related effects of carnosine on anxiety in the elevated T-maze test (ETM) with electrodermal activity (EDA). Carnosine was injected in three groups of rats with doses of 10 (low dose), 100 (medium dose) and 1000 (high dose) mg/kg i.p. Physiological saline was injected in the sham group. The anxiety scores of the rats were measured with ETM 20 minutes after injection. Then, SCL was measured. The decreased number of entries into the open arm (NEOA), the percentage of time spent in the open arm (% TSOA) and higher EDA [shown by skin conductance level (SCL)] indicate higher anxiety. The NEOA and % TSOA were lower in the high-dose group than in the other groups. SCL was lower in the medium-dose carnosine group than in the high-dose carnosine and sham groups. SCL was higher in the high-dose group than in the medium-dose and sham groups. Our results suggest that high-dose carnosine produced anxiety-like effects as assessed in the SCL and ETM. Medium-dose carnosine acted as an anxiolytic. The anxiety-related responses of carnosine depend on its dose-related effect.

  20. Protective effects of L-carnosine on CCl4 -induced hepatic injury in rats.

    PubMed

    Alsheblak, Mehyar Mohammad; Elsherbiny, Nehal M; El-Karef, Amro; El-Shishtawy, Mamdouh M

    2016-03-01

    The present study was undertaken to investigate the possible protective effect of L-carnosine (CAR), an endogenous dipeptide of alanine and histidine, on carbon tetrachloride (CCl4)-induced hepatic injury. Liver injury was induced in male Sprague-Dawley rats by intraperitoneal (i.p.) injections of CCl4, twice weekly for six weeks. CAR was administered to rats daily, at dose of 250 mg/kg, i.p. At the end of six weeks, blood and liver tissue specimens were collected. Results show that CAR treatment attenuated the hepatic morphological changes, necroinflammation and fibrosis induced by CCl4, as indicated by hepatic histopathology scoring. In addition, CAR treatment significantly reduced the CCl4-induced elevation of liver-injury parameters in serum. CAR treatment also combatted oxidative stress; possibly by restoring hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) levels. Moreover, CAR treatment prevented the activation of hepatic stellate cells (HSCs), as indicated by reduced α-smooth muscle actin (α-SMA) expression in the liver, and decreased hepatic inflammation as demonstrated by a reduction in hepatic tumor necrosis factor-α (TNF-α) and restoration of interleukin-10 (IL-10) levels. In conclusion, CCl4-induced hepatic injury was alleviated by CAR treatment. The results suggest that these beneficial, protective effects are due, at least in part, to its anti-oxidant, anti-inflammatory and anti-fibrotic activities.

  1. β-Alanine ingestion increases muscle carnosine content and combat specific performance in soldiers.

    PubMed

    Hoffman, Jay R; Landau, Geva; Stout, Jeffrey R; Hoffman, Mattan W; Shavit, Nurit; Rosen, Philip; Moran, Daniel S; Fukuda, David H; Shelef, Ilan; Carmom, Erez; Ostfeld, Ishay

    2015-03-01

    The purpose of this study was to examine the effect of β-alanine (BA) ingestion on tissue carnosine levels and the impact such changes would have on combat specific activity. Eighteen soldiers (19.9 ± 0.8 year) from an elite combat unit were randomly assigned to either a BA or placebo (PL) group. Before and following a 30-day supplementation period carnosine content of the gastrocnemius muscle and brain was determined by proton magnetic resonance spectroscopy. During each testing session, participants performed military relevant tasks that included a 2.5 km run, a 1-min sprint, 50-m casualty carry, repeated 30-m sprints with target shooting, and a 2-min serial subtraction test (SST) to assess cognitive function under stressful conditions. A significant elevation (p = 0.048) in muscle carnosine content was noted in BA compared to PL. Changes in muscle carnosine content was correlated to changes in fatigue rate (r = 0.633, p = 0.06). No changes (p = 0.607) were observed in brain carnosine content. Following supplementation, no differences were noted in 2.5 km run, 1-min sprint, repeated sprint, or marksmanship performance, but participants in BA significantly (p = 0.044) improved their time for the 50-m casualty carry and increased their performance (p = 0.022) in the SST compared to PL. In summary, 30-days of BA ingestion can increase muscle carnosine content and improve aspects of military specific performance. Although cognitive performance was significantly greater in participants consuming BA compared to placebo, current study methods were unable to detect any change in brain carnosine levels, thus, the precise mechanism underlying these effects remains elusive.

  2. Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine

    PubMed Central

    Abdelkader, Hamdy; Longman, Michael R; Alany, Raid G; Pierscionek, Barbara

    2016-01-01

    This study reports on L-carnosine phytosomes as an alternative for the prodrug N-acetyl-L-carnosine as a novel delivery system to the lens. L-carnosine was loaded into lipid-based phytosomes and hyaluronic acid (HA)-dispersed phytosomes. L-carnosine-phospholipid complexes (PC) of different molar ratios, 1:1 and 1:2, were prepared by the solvent evaporation method. These complexes were characterized with thermal and spectral analyses. PC were dispersed in either phosphate buffered saline pH 7.4 or HA (0.1% w/v) in phosphate buffered saline to form phytosomes PC1:1, PC1:2, and PC1:2 HA, respectively. These phytosomal formulations were studied for size, zeta potential, morphology, contact angle, spreading coefficient, viscosity, ex vivo transcorneal permeation, and cytotoxicity using primary human corneal cells. L-carnosine-phospholipid formed a complex at a 1:2 molar ratio and phytosomes were in the size range of 380–450 nm, polydispersity index of 0.12–0.2. The viscosity of PC1:2 HA increased by 2.4 to 5-fold compared with HA solution and PC 1:2, respectively; significantly lower surface tension, contact angle, and greater spreading ability for phytosomes were also recorded. Ex vivo transcorneal permeation parameters showed significantly controlled corneal permeation of L-carnosine with the novel carrier systems without any significant impact on primary human corneal cell viability. Ex vivo porcine lenses incubated in high sugar media without and with L-carnosine showed concentration-dependent marked inhibition of lens brunescence indicative of the potential for delaying changes that underlie cataractogenesis that may be linked to diabetic processes. PMID:27366062

  3. Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine.

    PubMed

    Abdelkader, Hamdy; Longman, Michael R; Alany, Raid G; Pierscionek, Barbara

    2016-01-01

    This study reports on L-carnosine phytosomes as an alternative for the prodrug N-acetyl-L-carnosine as a novel delivery system to the lens. L-carnosine was loaded into lipid-based phytosomes and hyaluronic acid (HA)-dispersed phytosomes. L-carnosine-phospholipid complexes (PC) of different molar ratios, 1:1 and 1:2, were prepared by the solvent evaporation method. These complexes were characterized with thermal and spectral analyses. PC were dispersed in either phosphate buffered saline pH 7.4 or HA (0.1% w/v) in phosphate buffered saline to form phytosomes PC1:1, PC1:2, and PC1:2 HA, respectively. These phytosomal formulations were studied for size, zeta potential, morphology, contact angle, spreading coefficient, viscosity, ex vivo transcorneal permeation, and cytotoxicity using primary human corneal cells. L-carnosine-phospholipid formed a complex at a 1:2 molar ratio and phytosomes were in the size range of 380-450 nm, polydispersity index of 0.12-0.2. The viscosity of PC1:2 HA increased by 2.4 to 5-fold compared with HA solution and PC 1:2, respectively; significantly lower surface tension, contact angle, and greater spreading ability for phytosomes were also recorded. Ex vivo transcorneal permeation parameters showed significantly controlled corneal permeation of L-carnosine with the novel carrier systems without any significant impact on primary human corneal cell viability. Ex vivo porcine lenses incubated in high sugar media without and with L-carnosine showed concentration-dependent marked inhibition of lens brunescence indicative of the potential for delaying changes that underlie cataractogenesis that may be linked to diabetic processes.

  4. Neurotropic effect of exogenous L-carnosine in cultured slices of the olfactory cortex from rat brain.

    PubMed

    Khama-Murad, A X; Pavlinova, L I; Mokrushin, A A

    2008-07-01

    Incubation of cultured slices of the olfactory cortex from rat brain with L-carnosine in concentrations of 50, 250, and 500 M induced activation of glutamatergic and GABAB-ergic mechanisms and facilitated long-term posttetanic potentiation. The effect of L-carnosine is mediated by its effect on AMPA- and NMDA-related glutamatergic receptors and on inhibitory GABAB receptors.

  5. Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice

    PubMed Central

    Albrecht, Thomas; Schilperoort, Maaike; Zhang, Shiqi; Braun, Jana D.; Qiu, Jiedong; Rodriguez, Angelica; Pastene, Diego O.; Krämer, Bernhard K.; Köppel, Hannes; Baelde, Hans; de Heer, Emile; Anna Altomare, Alessandra; Regazzoni, Luca; Denisi, Alessandra; Aldini, Giancarlo; van den Born, Jacob; Yard, Benito A.; Hauske, Sibylle J.

    2017-01-01

    We previously demonstrated that polymorphisms in the carnosinase-1 gene (CNDP1) determine the risk of nephropathy in type 2 diabetic patients. Carnosine, the substrate of the enzyme encoded by this gene, is considered renoprotective and could possibly be used to treat diabetic nephropathy (DN). In this study, we examined the effect of carnosine treatment in vivo in BTBR (Black and Tan, BRachyuric) ob/ob mice, a type 2 diabetes model which develops a phenotype that closely resembles advanced human DN. Treatment of BTBR ob/ob mice with 4 mM carnosine for 18 weeks reduced plasma glucose and HbA1c, concomitant with elevated insulin and C-peptide levels. Also, albuminuria and kidney weights were reduced in carnosine-treated mice, which showed less glomerular hypertrophy due to a decrease in the surface area of Bowman’s capsule and space. Carnosine treatment restored the glomerular ultrastructure without affecting podocyte number, resulted in a modified molecular composition of the expanded mesangial matrix and led to the formation of carnosine-acrolein adducts. Our results demonstrate that treatment with carnosine improves glucose metabolism, albuminuria and pathology in BTBR ob/ob mice. Hence, carnosine could be a novel therapeutic strategy to treat patients with DN and/or be used to prevent DN in patients with diabetes. PMID:28281693

  6. Protective activity of carnosine and anserine against zinc-induced neurotoxicity: a possible treatment for vascular dementia.

    PubMed

    Mizuno, Dai; Konoha-Mizuno, Keiko; Mori, Miwako; Sadakane, Yutaka; Koyama, Hironari; Ohkawara, Susumu; Kawahara, Masahiro

    2015-08-01

    Carnosine (β-alanyl-L-histidine) is a small dipeptide with numerous beneficial effects, including the maintenance of the acid-base balance, antioxidant properties, chelating agent, anti-crosslinking, and anti-glycation activities. High levels of carnosine and its analogue anserine (1-methyl carnosine) are found in skeletal muscle and the brain. Zinc (Zn)-induced neurotoxicity plays a crucial role in the pathogenesis of vascular dementia (VD), and carnosine inhibits Zn-induced neuronal death. Here, the protective activity of carnosine against Zn-induced neurotoxicity and its molecular mechanisms such as cellular Zn influx and Zn-induced gene expression were investigated using immortalised hypothalamic neurons (GT1-7 cells). Carnosine and anserine protected against Zn-induced neurotoxicity not by preventing increases in intracellular Zn(2+) but by participating in the regulation of the endoplasmic reticulum (ER) stress pathway and the activity-regulated cytoskeletal protein (Arc). Accordingly, carnosine and anserine protected against neurotoxicity induced by ER-stress inducers thapsigargin and tunicamycin. Hence, carnosine and anserine are expected to have future therapeutic potential for VD and other neurodegenerative diseases.

  7. Twenty-four Weeks of β-Alanine Supplementation on Carnosine Content, Related Genes, and Exercise.

    PubMed

    Saunders, Bryan; DE Salles Painelli, Vitor; DE Oliveira, Luana Farias; DA Eira Silva, Vinicius; DA Silva, Rafael Pires; Riani, Luiz; Franchi, Mariana; Gonçalves, Lívia DE Souza; Harris, Roger Charles; Roschel, Hamilton; Artioli, Guilherme Giannini; Sale, Craig; Gualano, Bruno

    2017-05-01

    Skeletal muscle carnosine content can be increased through β-alanine (BA) supplementation, but the maximum increase achievable with supplementation is unknown. No study has investigated the effects of prolonged supplementation on carnosine-related genes or exercise capacity. This study aimed to investigate the effects of 24 wk of BA supplementation on muscle carnosine content, gene expression, and high-intensity cycling capacity (CCT110%). Twenty-five active males were supplemented with 6.4 g·d of sustained release BA or placebo for a 24 wk period. Every 4 wk participants provided a muscle biopsy and performed the CCT110%. Biopsies were analyzed for muscle carnosine content and gene expression (CARNS, TauT, ABAT, CNDP2, PHT1, PEPT2, and PAT1). Carnosine content was increased from baseline at every time point in BA (all P < 0.0001; week 4 = +11.37 ± 7.03 mmol·kg dm, week 8 = +13.88 ± 7.84 mmol·kg dm, week 12 = +16.95 ± 8.54 mmol·kg dm, week 16 = +17.63 ± 8.42 mmol·kg dm, week 20 = +21.20 ± 7.86 mmol·kg dm, and week 24 = +20.15 ± 7.63 mmol·kg dm) but not placebo (all P > 0.05). Maximal increases were +25.66 ± 7.63 mmol·kg dm (range = +17.13 to +41.32 mmol·kg dm), and absolute maximal content was 48.03 ± 8.97 mmol·kg dm (range = 31.79 to 63.92 mmol·kg dm). There was an effect of supplement (P = 0.002) on TauT; no further differences in gene expression were shown. Exercise capacity was improved in BA (P = 0.05) with possible to almost certain improvements across all weeks. Twenty-four weeks of BA supplementation increased muscle carnosine content and improved high-intensity cycling capacity. The downregulation of TauT suggests it plays an important role in muscle carnosine accumulation with BA supplementation, whereas the variability in changes in muscle carnosine content between individuals suggests that other determinants other than the availability of BA may also bear a major influence on muscle carnosine content.

  8. [Increased manganese superoxide dismutase and cyclin B1 expression in carnosine-induced inhibition of glioblastoma cell proliferation].

    PubMed

    Rybakova, Yu S; Kalen, A L; Eckers, J C; Fedorova, T N; Goswami, P C; Sarsour, E H

    2015-01-01

    Carnosine is an endogenous dipeptide with antiproliferative properties. Here we show that carnosine selectively inhibits proliferation of human glioblastoma cells (U-118-MG) compared to breast (MB231) and oral (Cal27 and FaDu) cancer cells. Carnosine-induced inhibition of U-118-MG proliferation is associated with a significant: decrease in cellular reactive oxygen species levels, increase in manganese superoxide dismutase (MnSOD) and increase in cyclin B1 expression resulting in G2-block. We conclude that the antiproliferative property of carnosine is due to its ability to enhance MnSOD and cyclin B1 expression. These results will be of significance to the potential application of carnosine in brain cancer therapy.

  9. Carnosine in the brain and olfactory system of amphibia and reptilia: a comparative study using immunocytochemical and biochemical methods.

    PubMed

    Artero, C; Martì, E; Biffo, S; Mulatero, B; Andreone, C; Margolis, F L; Fasolo, A

    1991-09-16

    The pattern of distribution of carnosine-like immunoreactivity and its relation to glial fibrillary acidic protein immunoreactivity have been studied in two lizards (Gallotia galloti and Tarentola delalandii) and in two anuran amphibians (Rana esculenta and Xenopus laevis) using immunocytochemical techniques. Biochemical data obtained by paper electrophoresis show that the dipeptides carnosine and homocarnosine are both present in the brain of all the species examined. In the central nervous system of both anurans and reptilians, carnosine immunoreactivity is localized in glial cells. An important species difference is, however, seen in the olfactory system since primary olfactory neurons and their processes extending to the olfactory bulb are carnosine positive in reptiles, whereas they are not immunostained in anurans. Thus, the cellular distribution of carnosine immunoreactivity in reptilians is very similar to that observed in birds and mammals and is distinct from that seen in amphibia.

  10. Carnosine's Effect on Amyloid Fibril Formation and Induced Cytotoxicity of Lysozyme

    PubMed Central

    Wu, Josephine W.; Liu, Kuan-Nan; How, Su-Chun; Chen, Wei-An; Lai, Chia-Min; Liu, Hwai-Shen; Hu, Chaur-Jong; Wang, Steven S. -S.

    2013-01-01

    Carnosine, a common dipeptide in mammals, has previously been shown to dissemble alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis effect has not been thoroughly characterized in other proteins. For a more complete understanding of carnosine's mechanism of action in amyloid fibril inhibition, we have investigated the effect of the dipeptide on lysozyme fibril formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our study demonstrates a positive correlation between the concentration and inhibitory effect of carnosine against lysozyme fibril formation. Molecular docking results show carnosine's mechanism of fibrillogenesis inhibition may be initiated by binding with the aggregation-prone region of the protein. The dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal cells by reducing both apoptotic and necrotic cell deaths. Our study provides solid support for carnosine's amyloid fibril inhibitory property and its effect against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights gained herein may pave way to the discovery of other small molecules that may exert similar effects against amyloid fibril formation and its associated neurodegenerative diseases. PMID:24349167

  11. Computational design of bio-inspired carnosine-based HOBr antioxidants

    NASA Astrophysics Data System (ADS)

    Sarrami, Farzaneh; Yu, Li-Juan; Karton, Amir

    2017-09-01

    During a respiratory burst the enzyme myeloperoxidase generates significant amounts of hypohalous acids (HOX, X = Cl and Br) in order to inflict oxidative damage upon invading pathogens. However, excessive production of these potent oxidants is associated with numerous inflammatory diseases. It has been suggested that the endogenous antioxidant carnosine is an effective HOCl scavenger. Recent computational and experimental studies suggested that an intramolecular Cl+ transfer from the imidazole ring to the terminal amine might play an important role in the antioxidant activity of carnosine. Based on high-level ab initio calculations, we propose a similar reaction mechanism for the intramolecular Br+ transfer in carnosine. These results suggest that carnosine may be an effective HOBr scavenger. On the basis of the proposed reaction mechanism, we proceed to design systems that share similar structural features to carnosine but with enhanced HOX scavenging capabilities for X = Cl and Br. We find that (i) elongating the β-alanyl-glycyl side chain by one carbon reduces the reaction barriers by up to 44%, and (ii) substituting the imidazole ring with strong electron-donating groups reduces the reaction barriers by similar amounts. We also show that the above structural and electronic effects are largely additive. In an antioxidant candidate that involves both of these effects the reaction barriers are reduced by 71%.

  12. Theoretical and experimental investigation of carnosine and its oxygenated adducts. The reaction with the nickel ion

    NASA Astrophysics Data System (ADS)

    Pavlos, Dimitrios; Petropouleas, Panayiotis; Hatzipanayioti, Despina

    2015-11-01

    DFT theoretical calculations at B3LYP/TZVP or LANL2DZ level of theory, for neutral, zwitterions, protonated and anionic carnosine, were performed. Energies, the structural and spectroscopic parameters were calculated in the gas phase and aqueous medium. Additional H-bonds stabilize the ionized forms of carnosine, creating ;nests; into which metal ions or bio-molecules may be sheltered. Based on Fukui functions, the reactivity of the abovementioned forms of carnosine, with 1O2, may lead to oxygenated species. The theoretical spectroscopic parameters have been correlated to our experimental results. The effect of H2O2 and the electrochemistry of aqueous carnosine solutions were examined. Theoretical models containing Ni(II), carnosine and water were constructed. In the isolated mauve solid, formulated [Ni(carn)2(H2O)5], the COOsbnd , Nπ and/or NH2 were bonded. When H2O2 was added, the imidazole NMR signals disappeared. A redox couple clearly indicates one electron process, the electron coming from either the oxidation of imidazole ring or the nickel(II)/Ni(III) couple.

  13. Carnosine's effect on amyloid fibril formation and induced cytotoxicity of lysozyme.

    PubMed

    Wu, Josephine W; Liu, Kuan-Nan; How, Su-Chun; Chen, Wei-An; Lai, Chia-Min; Liu, Hwai-Shen; Hu, Chaur-Jong; Wang, Steven S-S

    2013-01-01

    Carnosine, a common dipeptide in mammals, has previously been shown to dissemble alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis effect has not been thoroughly characterized in other proteins. For a more complete understanding of carnosine's mechanism of action in amyloid fibril inhibition, we have investigated the effect of the dipeptide on lysozyme fibril formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our study demonstrates a positive correlation between the concentration and inhibitory effect of carnosine against lysozyme fibril formation. Molecular docking results show carnosine's mechanism of fibrillogenesis inhibition may be initiated by binding with the aggregation-prone region of the protein. The dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal cells by reducing both apoptotic and necrotic cell deaths. Our study provides solid support for carnosine's amyloid fibril inhibitory property and its effect against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights gained herein may pave way to the discovery of other small molecules that may exert similar effects against amyloid fibril formation and its associated neurodegenerative diseases.

  14. Carbon nanotube as a carrier in drug delivery system for carnosine dipeptide: A computer simulation study.

    PubMed

    Ketabi, Sepideh; Rahmani, Leila

    2017-04-01

    Biological application of carbon nanotube in drug delivery is our main concern in this investigation. For this purpose interaction of carnosine and carbon nanotube was studied in both gas phase and separately in aqueous media. Three possible interactions of carnosine dipeptide with (5,5) carbon nanotube in physiological media were considered. At first step each species were modeled using quantum mechanical calculations, in the next step, their properties in aqueous solution were studied by applying Monte Carlo simulations. The results of density functional calculations in gas phase showed that interaction of zwitterion of carnosine with carbon nanotube via NH3(+) had relatively higher interaction energy than the other complexes. Computation of solvation free energies in water showed functionalization with carnosine enhanced the solubility of carbon nanotube significantly that improve the medicinal applications of these materials. Calculation of complexation free energies indicated that zwitterion of carnosine with carbon nanotube via NH3(+) produced the most stable complex in aqueous solution. This tendency could be observed in gas and liquid phase similarly. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. The biological role of carnosine and its possible applications in medicine.

    PubMed

    Budzeń, Sandra; Rymaszewska, Joanna

    2013-01-01

    The article reviews current literature on the biological role of carnosine, its properties and use as a supplement in periods of intense physical activity. Studies carried out on laboratory animals and humans have shown that carnosine can have a beneficial influence on the organism. Carnosine is found naturally mainly in the skeletal muscles, central nervous system, olfactory neurons and in the lens of the eye in some vertebrates, including humans. Due to its antioxidant, protective, chelating, anti-glycation activity, this dipeptide can be used to prevent and treat diseases such as diabetes, neurodegenerative diseases, diseases of the sense organs and cancers. It may also cure or alleviate many other disorders thanks to its wide spectrum of activity. Carnosine is already used by athletes to achieve better results, due to its buffering feature, which contributes to the maintenance of the acid-base balance in the muscles. Future studies on the influence of carnosine on the human organism may lead to the therapeutic use of this dipeptide for many diseases, in addition to improving both amateur and professional athletes' results.

  16. Effects of dietary supplementation with carnosine on meat quality and antioxidant capacity in broiler chickens.

    PubMed

    Cong, J; Zhang, L; Li, J; Wang, S; Gao, F; Zhou, G

    2017-02-01

    1. This study aimed to investigate the effects of carnosine supplementation on meat quality, antioxidant capacity and lipid peroxidation status in broiler chickens. 2. A total of 256 1-d-old male Arbor Acres broilers were randomly assigned to 4 treatments consisting of 8 replicates of 8 chickens each. The birds were supplied with 4 different diets: a basal diet or a basal diet supplemented with 100, 200 or 400 mg/kg carnosine, respectively. The whole experiment lasted 42 d. 3. The results showed that dietary supplementation with carnosine linearly increased the values of pH45 min and redness and reduced drip loss of breast meat. Dietary carnosine increased the activity of antioxidant enzymes in liver, serum and breast meat and decreased the contents of lipid peroxides at 21 and 42 d of age. 4. These findings indicated that dietary supplementation with carnosine was beneficial to enhance meat quality, antioxidant capacity and decrease lipid peroxidation status of breast meat.

  17. Amide proton transfer of carnosine in aqueous solution studied in vitro by WEX and CEST experiments.

    PubMed

    Bodet, Olga; Goerke, Steffen; Behl, Nicolas G R; Roeloffs, Volkert; Zaiss, Moritz; Bachert, Peter

    2015-09-01

    Amide protons of peptide bonds induce an important chemical exchange saturation transfer (CEST) contrast in vivo. As a simple in vitro model for a peptide amide proton CEST effect, we suggest herein the dipeptide carnosine. We show that the metabolite carnosine creates a CEST effect and we study the properties of the exchange of the amide proton (-NH) of the carnosine peptide bond (NHCPB) in model solutions for a pH range from 6 to 8.3 and a temperature range from T = 5 °C to 43 °C by means of CEST and water exchange spectroscopy (WEX) experiments on a 3 T whole-body MR tomograph. The dependence of the NHCPB chemical exchange rate k(sw) on pH and temperature T was determined using WEX. For physiological conditions (T = 37 °C, pH = 7.10) we obtained k(sw) = (47.07 ± 7.90)/s. With similar chemical shift and exchange properties to amide protons in vivo, carnosine forms a simple model system for optimization of CEST pulse sequences in vitro. The potential for direct detection of the metabolite carnosine in vivo is discussed. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage.

    PubMed

    Baek, Seung-Hoon; Noh, Ah Reum; Kim, Kyeong-A; Akram, Muhammad; Shin, Young-Jun; Kim, Eun-Sun; Yu, Seong Woon; Majid, Arshad; Bae, Ok-Nam

    2014-08-01

    Despite the rapidly increasing global burden of ischemic stroke, no therapeutic options for neuroprotection against stroke currently exist. Recent studies have shown that autophagy plays a key role in ischemic neuronal death, and treatments that target autophagy may represent a novel strategy in neuroprotection. We investigated whether autophagy is regulated by carnosine, an endogenous pleiotropic dipeptide that has robust neuroprotective activity against ischemic brain damage. We examined the effect of carnosine on mitochondrial dysfunction and autophagic processes in rat focal ischemia and in neuronal cultures. Autophagic pathways such as reduction of phosphorylated mammalian target of rapamycin (mTOR)/p70S6K and the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II were enhanced in the ischemic brain. However, treatment with carnosine significantly attenuated autophagic signaling in the ischemic brain, with improvement of brain mitochondrial function and mitophagy signaling. The protective effect of carnosine against autophagy was also confirmed in primary cortical neurons. Taken together, our data suggest that the neuroprotective effect of carnosine is at least partially mediated by mitochondrial protection and attenuation of deleterious autophagic processes. Our findings shed new light on the mechanistic pathways that this exciting neuroprotective agent influences. © 2014 American Heart Association, Inc.

  19. Carnosine attenuates mast cell degranulation and histamine release induced by oxygen-glucose deprivation.

    PubMed

    Shen, Yao; Zhang, Shihong; Fu, Lin; Hu, Weiwei; Chen, Zhong

    2008-04-01

    Carnosine (beta-alanyl-histidine) is a naturally occurring dipeptide that has been characterized as a putative hydrophilic antioxidant. The protective function of carnosine has been demonstrated in neuronal cells under ischemic injury. The purpose of this study was to investigate the effects of carnosine on oxygen-glucose deprivation (OGD)-induced degranulation and histamine release from mast cells. Cultured mast cells were exposed to OGD for 4 h, and then the degranulation was observed immediately by microscopy. Histamine release was analyzed by high-performance liquid chromatography (HPLC). OGD caused degranulation of mast cells, and increased histamine and lactate dehydrogenase (LDH) release. Carnosine (at a concentration of 5 mM) alone did not produce any appreciable effect on degranulation, histamine, and LDH release from mast cells under normal condition, but significantly inhibited the degranulation, histamine, and LDH release of mast cells induced by OGD. These results indicate that carnosine can protect mast cells from degranulation and histamine release and it may be an endogenous mast cell stabilizer in the pathological processes induced by ischemia.

  20. Carnosine, anserine and taurine contents in individual fibres from the middle gluteal muscle of the camel.

    PubMed

    Dunnett, M; Harris, R C; Soliman, M Z; Suwar, A A

    1997-01-01

    High muscle carnosine und anserine contents contribute significantly to intra-cellular physico-chemical buffering. Our aim was to measure carnosine, anserine and taurine contents directly in individual type I, IIA and IIB fibres from the middle gluteus muscle of the camel. Mean carnosine contents in type I, IIA and IIB were 24.6 +/- 9.2, 39.4 +/- 11.4 and 42.8 +/- 18.8 mmol kg-1 dry weight (dw), respectively. Mean anserine contents in type I, IIA and IIB fibres were 30.0 +/- 8.4, 37.3 +/- 10.1 and 34.5 +/- 9.7 mmol kg-1 dw, respectively. Mean taurine contents in type I, IIA and IIB fibres were 42.4 +/- 15.9, 20.3 +/- 12.9 and 24.7 +/- 15.9 mmol kg-1 dw, respectively. Higher carnosine contents in type II fibres emphasise the importance of carnosine to intra-muscular acid-base regulation. A specific role for taurine in type I fibres in unclear.

  1. Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage

    PubMed Central

    Kim, Kyeong-A; Akram, Muhammad; Shin, Young-Jun; Kim, Eun-Sun; Yu, Seong Woon; Majid, Arshad; Bae, Ok-Nam

    2014-01-01

    Background and Purpose Despite the rapidly increasing global burden of ischemic stroke, no therapeutic options for neuroprotection against stroke currently exist. Recent studies have shown that autophagy plays a key role in ischemic neuronal death and treatments that target autophagy may represent a novel strategy in neuroprotection. We investigated whether autophagy is regulated by carnosine, an endogenous pleiotropic dipeptide which has robust neuroprotective activity against ischemic brain damage. Methods We examined the effect of carnosine on mitochondrial dysfunction and autophagic processes in rat focal ischemia and in neuronal cultures. Results Autophagic pathways such as reduction of phosphorylated mTOR/p70S6K and the conversion of LC3-I to LC3-II were enhanced in the ischemic brain. However, treatment with carnosine significantly attenuated autophagic signaling in the ischemic brain, with improvement of brain mitochondrial function and mitophagy signaling. The protective effect of carnosine against autophagy was also confirmed in primary cortical neurons. Conclusion Taken together, our data suggest that the neuroprotective effect of carnosine is at least partially mediated by mitochondrial protection, and attenuation of deleterious autophagic processes. Our findings shed new light on the mechanistic pathways that this exciting neuroprotective agent influences. PMID:24938837

  2. Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

    NASA Astrophysics Data System (ADS)

    Özdemir, Mahir S.; Reyngoudt, Harmen; DeDeene, Yves; Sazak, Hakan S.; Fieremans, Els; Delputte, Steven; D'Asseler, Yves; Derave, Wim; Lemahieu, Ignace; Achten, Eric

    2007-12-01

    Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pHi range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy (1H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 ± 0.57/4.8 ± 1.59 mM (mean ± SD) for athletes and 2.58 ± 0.65/3.3 ± 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that 1H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo.

  3. Protective effect of carnosine during nitrosative stress in astroglial cell cultures.

    PubMed

    Calabrese, V; Colombrita, C; Guagliano, E; Sapienza, M; Ravagna, A; Cardile, V; Scapagnini, G; Santoro, A M; Mangiameli, A; Butterfield, D A; Giuffrida Stella, A M; Rizzarelli, E

    2005-01-01

    Formation of nitric oxide by astrocytes has been suggested to contribute, via impairment of mitochondrial function, to the neurodegenerative process. Mitochondria under oxidative stress are thought to play a key role in various neurodegenerative disorders; therefore protection by antioxidants against oxidative stress to mitochondria may prove to be beneficial in delaying the onset or progression of these diseases. Carnosine has been recently proposed to act as antioxidant in vivo. In the present study, we demonstrate its neuroprotective effect in astrocytes exposed to LPS- and INFgamma-induced nitrosative stress. Carnosine protected against nitric oxide-induced impairment of mitochondrial function. This effect was associated with decreased formation of oxidatively modified proteins and with decreased up-regulation oxidative stress-responsive genes, such as Hsp32, Hsp70 and mt-SOD. Our results sustain the possibility that carnosine might have anti-ageing effects to brain cells under pathophysiological conditions leading to degenerative damage, such as aging and neurodegenerative disorders.

  4. Carnosine and its (S)-Trolox™ derivative protect animals against oxidative stress.

    PubMed

    Stvolinsky, S; Toropova, K; Gordeeva, M; Kazey, V; Sato, T; Meguro, K; Boldyrev, A

    2012-07-01

    The novel synthetic derivative of carnosine, (S)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carbonyl-β-alanyl-L-histidine (S-Trolox™-Carnosine, STC) increases the resistance of rats to experimental acute hypobaric hypoxia (AHH) thus protecting brain from the oxidative damage. This effect is accompanied by better preservation of the acquired skills in Morris water maze possibly by increasing efficiency of the brain antioxidant system. In addition, STC caused an increase in life span of both male and female fruit fly Drosophila melanogaster whereas carnosine increased life span only in male fruit flies. The results indicate that development of the drug based on STC could be beneficial in neurology and gerontology.

  5. Influence of lipid composition on physicochemical properties of nanoliposomes encapsulating natural dipeptide antioxidant l-carnosine.

    PubMed

    Maherani, Behnoush; Arab-Tehrany, Elmira; Kheirolomoom, Azadeh; Cleymand, Franck; Linder, Michel

    2012-09-15

    Natural dipeptide antioxidants (l-carnosine) are recieving increasing attention because of their noticeable potential as biopreservatives in food recent technology. Encapsulation of antioxidants by nanoliposomes could represent an ameliorative approach to overcome the problems related to the direct application of these antioxidant peptides in food. In this study, nanoliposomes prepared from different lipids (DOPC, POPC and DPPC) by thin film hydration method, were assessed by considering their size, ζ-potential, phase transition temperature and fluidity. One important parameter of interest in this article was to compare the encapsulation efficacy of l-carnosine in three different nanoliposomes using a rapid and precise approach (1)H NMR without the need for physical separation of entrapped and non-entrapped l-carnosine. Furthermore, the morphology of small unilamellar nanoliposomes with different compositions on mica surface was investigated using Atomic Force Microscopy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Carnosine markedly ameliorates H9N2 swine influenza virus-induced acute lung injury.

    PubMed

    Xu, Tong; Wang, Cunlian; Zhang, Ruihua; Xu, Mingju; Liu, Baojian; Wei, Dong; Wang, Guohua; Tian, Shufei

    2015-10-01

    Oxidative stress injury is an important pathogenesis of influenza virus in critically ill patients. The present study investigated the efficacy of carnosine, an antioxidant and free radical scavenger, on a model of acute lung injury (ALI) induced by H9N2 swine influenza virus. Female specific-pathogen-free BALB/c mice were randomized into four groups and treated as follows: (1) H9N2 group, (2) mock control group, (3) H9N2+carnosine group and (4) carnosine control group. The H9N2 group mice were inoculated intranasally with A/Swine/Hebei/012/2008/ (H9N2) virus (100 μl) in allantoic fluid (AF), whilst mock-infected animals were intranasally inoculated with non-infectious AF. Carnosine [10 mg (kg body mass)- 1] was administered orally (100 μl) for 7 days consecutively. The survival rate, lung water content, TNF-α and IL-1β levels, lung histopathology, myeloperoxidase (MPO) activity, and Toll-like receptor (TLR)-4 levels were determined at 2, 4, 6, 8 and 14 days after inoculation. Carnosine treatment effectively decreased the mortality (43 versus 75 %, P < 0.05), significantly ameliorated pathological lesions in lungs and decreased the lung wet/dry mass ratio (P < 0.05). It also inhibited MPO activity, suppressed TNF-α and IL-1β release, decreased the H9N2 viral titre, and markedly inhibited levels of TLR-4 mRNA and protein in the lungs of infected mice (P < 0.05), which supported the use of carnosine for managing severe influenza cases.

  7. Carnosine markedly ameliorates H9N2 swine influenza virus-induced acute lung injury

    PubMed Central

    Wang, Cunlian; Zhang, Ruihua; Xu, Mingju; Liu, Baojian; Wei, Dong; Wang, Guohua; Tian, Shufei

    2015-01-01

    Oxidative stress injury is an important pathogenesis of influenza virus in critically ill patients. The present study investigated the efficacy of carnosine, an antioxidant and free radical scavenger, on a model of acute lung injury (ALI) induced by H9N2 swine influenza virus. Female specific-pathogen-free BALB/c mice were randomized into four groups and treated as follows: (1) H9N2 group, (2) mock control group, (3) H9N2+carnosine group and (4) carnosine control group. The H9N2 group mice were inoculated intranasally with A/Swine/Hebei/012/2008/ (H9N2) virus (100 μl) in allantoic fluid (AF), whilst mock-infected animals were intranasally inoculated with non-infectious AF. Carnosine [10 mg (kg body mass)− 1] was administered orally (100 μl) for 7 days consecutively. The survival rate, lung water content, TNF-α and IL-1β levels, lung histopathology, myeloperoxidase (MPO) activity, and Toll-like receptor (TLR)-4 levels were determined at 2, 4, 6, 8 and 14 days after inoculation. Carnosine treatment effectively decreased the mortality (43 versus 75 %, P < 0.05), significantly ameliorated pathological lesions in lungs and decreased the lung wet/dry mass ratio (P < 0.05). It also inhibited MPO activity, suppressed TNF-α and IL-1β release, decreased the H9N2 viral titre, and markedly inhibited levels of TLR-4 mRNA and protein in the lungs of infected mice (P < 0.05), which supported the use of carnosine for managing severe influenza cases. PMID:26233716

  8. Carnosine decreases IGFBP1 production in db/db mice through suppression of HIF-1.

    PubMed

    Forsberg, Elisabete A; Botusan, Ileana R; Wang, Jing; Peters, Verena; Ansurudeen, Ishrath; Brismar, Kerstin; Catrina, Sergiu Bogdan

    2015-06-01

    IGF binding protein 1 (IGFBP1) is a member of the binding proteins for the IGF with an important role in glucose homeostasis. Circulating IGFBP1 is derived essentially from the liver where it is mainly regulated negatively by insulin. Carnosine, a natural antioxidant, has been shown to improve metabolic control in different animal models of diabetes but its mechanisms of action are still not completely unraveled. We therefore investigate the effect of carnosine treatment on the IGFBP1 regulation in db/db mice. Db/db mice and heterozygous non-diabetic mice received for 4 weeks regular water or water supplemented with carnosine. Igfbp1 mRNA expression in the liver was evaluated using qPCR and the protein levels in plasma by western blot. Plasma IGF1 and insulin were analyzed using immunoassays. HepG2 cells were used to study the in vitro effect of carnosine on IGFBP1. The modulation of hypoxia inducible factor-1 alpha (HIF-1α) which is the central mediator of hypoxia-induction of IGFBP1 was analyzed using: WB, reporter gene assay and qPCR. Carnosine decreased the circulating IGFBP1 levels and the liver expression Igfbp1, through a complex mechanism acting both directly by suppressing the HIF-1α-mediated IGFBP1 induction and indirectly through increasing circulating insulin level followed by a decrease in the blood glucose levels and increased the plasma levels or IGF1. Reduction of IGFBP1 in diabetes through insulin-dependent and insulin-independent pathways is a novel mechanism by which carnosine contributes to the improvement of the metabolic control in diabetes. © 2015 Society for Endocrinology.

  9. Intestinal absorption of carnosine and its constituent amino acids in man 1

    PubMed Central

    Asatoor, A. M.; Bandoh, J. K.; Lant, A. F.; Milne, M. D.; Navab, F.

    1970-01-01

    Serum concentrations of β-alanine and l-histidine are compared in five normal adults after ingestion of the dipeptide carnosine (β-alanyl-l-histidine) and after equivalent amounts of the constituent free amino acids. The results indicate that absorption is significantly more rapid after the ingestion of the amino acids than after the dipeptide. The use of the test in a case of Hartnup disease suggests that carnosine is taken up by intestinal cells as the dipeptide, but subsequent hydrolysis and delivery of the constituent amino acids to the portal blood is a slower process than transport of the free amino acids themselves. PMID:5423906

  10. Vibrational study on the cobalt binding mode of Carnosine

    NASA Astrophysics Data System (ADS)

    Torreggiani, Armida; Taddei, Paola; Tinti, Anna; Fini, Giancarlo

    2002-10-01

    The Co(II)- L-Carnosine (Carnos) system was investigated at different pH and metal/ligand molar ratios by Raman and IR spectroscopy. Raman spectra present some marker bands yielding information on the ability of the Co(II)/Carnos system to bind molecular oxygen and to identify the metal co-ordination site of the imidazole ring (N π or N τ atom) of Carnos. The existence of different oxygenated species is greatly affected by pH and the structure of the predominant complexes depends on the available nitrogen atoms. Under basic conditions, binuclear complexes binding molecular oxygen are the predominant species and two forms (monobridged and dibridged) were identified by the Raman νO-O band (750-850 cm -1). Decreasing pH to 7, the species present in the system are less able to bind oxygen. Hydrogen peroxide and a Co(III) chelate not binding O 2, were formed with a significant conversion of peroxo into superoxo complexes. A slight excess of Carnos does not enhance metal chelation. In slightly acidic conditions, the formation of H 2O 2 and superoxo species is more enhanced than at pH 7 and another Co(III) chelate is probably formed.

  11. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    PubMed

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders.

  12. [Experimental study of the basic pharmacokinetic characteristics of dipeptide carnosine and its efficiency of penetration into brain tissues].

    PubMed

    Sariev, A K; Abaimov, D A; Tankevich, M V; Pantyukhova, E Yu; Prokhorov, D I; Fedorova, T N; Lopachev, A V; Stvolinskii, S L; Konovalova, E V; Seifulla, R D

    2015-01-01

    We have used an original chromatography/mass spectrometry technique to study the pharmacokinetics of dipeptide carnosine in C57 Black/6 mice after intra-peritoneal administration of the drug at a dose of 1 g/kg. The basic pharmacokinetic characteristics of carnosine were measured the in the blood and brain. The obtained concentration-time curve has a biexponential character. It is shown that the maximum concentration of carnosine in the blood plasma is Cmax = 1081.75 ± 124.24 μg/mL and it is achieved in a time interval of Tmax = 0.25 h. We showed that i.p. administration of exogenous carnosine could significantly increase the concentration of that substance in the brain. Tissue availability of dipeptide carnosine for brain tissue is relatively good and constitutes 59% from the total amount of blood carnosine. It was found that the maximum concentration of carnosine in the brain occurs at the sixth hour after i.p. administration when the concentration of drug in the blood is minimal.

  13. The neuroprotective effect of carnosine (β-alanyl-L-histidine) on retinal ganglion cell following ischemia-reperfusion injury.

    PubMed

    Ji, Yong-Sok; Park, Jung-Won; Heo, Hwan; Park, Jong-Seong; Park, Sang-Woo

    2014-06-01

    To investigate whether carnosine can increase retinal ganglion cell (RGC) survival in ischemic mouse retina. Retinal ischemia was induced by constant elevation of intraocular pressure (100-110 mmHg) for 60 min in C57BL/6 J mice pretreated with carnosine (1000 mg/kg) or saline. Hypoxia inducing factor-1 alpha (HIF-1α), glial fibrillary acidic protein (GFAP), and dynamin-related protein-1 (Drp-1) expressions were assessed at 6, 12, and 24 h after retinal ischemia. Bax and Bcl-2 expressions were also analyzed at 12 h after retinal ischemia. RGC survival was assessed by retrograde FluoroGold labeling at 2 weeks after retinal ischemia. The expression of HIF-1α, GFAP, and Drp-1 was increased within 24 h after ischemic injury. Carnosine treatment effectively decreased the elevated expression of HIF-1α, GFAP, and Drp-1 in ischemic mouse retina. In ischemic retina treated with carnosine, Bax expression was decreased, whereas Bcl-2 expression was increased compared with ischemic retina treated with saline. Carnosine treatment also protected against RGC loss in ischemia mouse retina. Our findings showed that carnosine treatment significantly decreased RGC loss through decreased expression of HIF-1α, GFAP, Drp-1, and Bax, and increased expression of Bcl-2 in ischemic mouse retina. We suggest that carnosine can be an effective endogenous neuroprotective molecule in the prevention of RGC loss in ischemic retina.

  14. Electrophysiological evidence of biphasic action of carnosine on long-term potentiation in urethane-anesthetized rats.

    PubMed

    Suer, Cem; Dolu, Nazan; Artis, A Seda; Sahin, Leyla; Aydogan, Sami

    2011-02-01

    Carnosine is a dipeptide synthesized by the carnosine synthetase from β-alanine and l-histidine. The well-known effects of carnosine may be related with mechanisms producing long-term potentiation which is one of the electrophysiological signs of memory. In the present study we aimed to investigate the effect of four different doses of carnosine on long-term potentiation in urethane-anesthetized rat. A bipolar stimulating electrode was placed in the medial perforant path and a double-barrel glass micropipette was placed in the dentate gyrus as the recording electrode. Artificial cerebrospinal fluid (in the control group) or carnosine (0.1, 1, 10, and 100μg/μL) was infused into the dentate gyrus. Our results showed that the I/O curve of the excitatory postsynaptic potential slope or population spike amplitude was not significantly shifted by carnosine. We found that population spike amplitude increased to 244% and 287% at the dose of 100μg/μL in the post-tetanic and induction phases, respectively, but decreased to 163% and 186% at the dose of 0.1μg/μL and to 145% and 162% at the dose of 1μg/μL when compared with 203% and 232% of the control values. However, there were no significant differences for the slope of excitatory postsynaptic potential. Carnosine had no effect on the EPSP slope or PS amplitude recorded from the dentate gyrus in response to test stimuli when high-frequency stimulation was not delivered. In the present study, we speculated that the effects of carnosine in lower or higher doses could be explained by its effect on different processes, such as soluble guanylyl cyclase inhibition or the conversion of carnosine into histamine.

  15. Muscle Carnosine Concentration with the Co-Ingestion of Carbohydrate with β-alanine in Male Rats.

    PubMed

    Naderi, Alireza; Sadeghi, Mehdi; Sarshin, Amir; Imanipour, Vahid; Nazeri, Seyed Ali; Farkhayi, Fatemeh; Willems, Mark E T

    2017-07-04

    Muscle carnosine is an intracellular buffer. The intake of β-alanine, combined with carbohydrate and protein, enhanced carnosine loading in human muscle. The aim of the present study was to examine if muscle carnosine loading was enhanced by β-alanine intake and co-ingestion of glucose in male rats. Thirty-six male rats were divided into three groups and supplemented for four weeks: β-alanine (βA group, 1.8% β-alanine in drinking water), β-alanine and glucose (βAGL group, 1.8% β-alanine and 5% glucose in drinking water), and control (C group, drinking water). During the supplementation period, rats were exercised (20 m·min(-1), 10 min·day(-1), 4 days·week(-1) for 4 weeks). Muscle carnosine concentration was quantified in soleus (n = 12) and rectus femoris (n = 6) muscles using high-performance liquid chromatography. In soleus muscle, carnosine concentration was 2.24 ± 1.10, 6.12 ± 1.08, and 6.93 ± 2.56 mmol/kg dw for control, βA, and βAGL, respectively. In rectus femoris, carnosine concentration was 2.26 ± 1.31, 7.90 ± 1.66, and 8.59 ± 2.33 mmol/kg dw for control, βA, and βAGL respectively. In each muscle, βA and βAGL resulted in similar carnosine increases compared to the control. In conclusion, β-alanine intake for four weeks, either alone or with glucose co-ingestion, equally increased muscle carnosine content. It appears that the potential insulin response to fluid glucose intake does not affect muscle carnosine loading in male rats.

  16. Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent.

    PubMed

    Hipkiss, A R; Michaelis, J; Syrris, P

    1995-08-28

    The dipeptide carnosine (beta-alanyl-L-histidine) was readily glycosylated non-enzymatically upon incubation with the sugars glucose, galactose, deoxyribose and the triose dihydroxyacetone. Carnosine inhibited glycation of actyl-Lys-His-amide by dihydroxyacetone and it protected alpha-crystallin, superoxide dismutase and catalise against glycation and cross-linking mediated by ribose, deoxyribose, dihydroxyacetone, dihydroxyacetone phosphate and fructose. Unlike certain glycated amino acids, glycated carnosine was non-mutagenic. The potential biological and therapeutic significance of these observations are discussed.

  17. Carnosine Attenuates Brain Oxidative Stress and Apoptosis After Intracerebral Hemorrhage in Rats.

    PubMed

    Xie, Rong-Xia; Li, Da-Wei; Liu, Xi-Chang; Yang, Ming-Feng; Fang, Jie; Sun, Bao-Liang; Zhang, Zong-Yong; Yang, Xiao-Yi

    2017-02-01

    Carnosine, an endogenous dipeptide (β-alanyl-L-histidine), exerts multiple neuroprotective properties, but its role in intracerebral hemorrhage (ICH) remains unclear. This study investigates the effect of Carnosine on brain injury using the rat ICH model, which is established by type IV collagenase caudatum infusion. The results indicate that intraperitoneal administration of Carnosine (1000 mg/kg) significantly attenuates brain edema, blood-brain barrier (BBB) disruption, oxidative stress, microglia activation and neuronal apoptosis of perihematoma at 72 h following ICH in rats models, as convinced by preventing the disruption of tight junction protein ZO-1, occludin and claudin-5, followed by the decrease of ROS, MDA, 3-NT, 8-OHDG level and the increase of GSH-Px and SOD activity, then followed by the decline of Iba-1, ED-1, active caspase-3 and TUNEL positive cells and the decrease of IL-1β, IL-6, TNF-α, active caspase-3 and cytochrome c level. Our results suggest that Carnosine may provide neuroprotective effect after experimental ICH in rat models.

  18. Physiological and therapeutic effects of carnosine on cardiometabolic risk and disease.

    PubMed

    Baye, Estifanos; Ukropcova, Barbara; Ukropec, Jozef; Hipkiss, Alan; Aldini, Giancarlo; de Courten, Barbora

    2016-05-01

    Obesity, type 2 diabetes (T2DM) and cardiovascular disease (CVD) are the most common preventable causes of morbidity and mortality worldwide. They represent major public health threat to our society. Increasing prevalence of obesity and T2DM contributes to escalating morbidity and mortality from CVD and stroke. Carnosine (β-alanyl-L-histidine) is a dipeptide with anti-inflammatory, antioxidant, anti-glycation, anti-ischaemic and chelating roles and is available as an over-the-counter food supplement. Animal evidence suggests that carnosine may offer many promising therapeutic benefits for multiple chronic diseases due to these properties. Carnosine, traditionally used in exercise physiology to increase exercise performance, has potential preventative and therapeutic benefits in obesity, insulin resistance, T2DM and diabetic microvascular and macrovascular complications (CVD and stroke) as well as number of neurological and mental health conditions. However, relatively little evidence is available in humans. Thus, future studies should focus on well-designed clinical trials to confirm or refute a potential role of carnosine in the prevention and treatment of chronic diseases in humans, in addition to advancing knowledge from the basic science and animal studies.

  19. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    PubMed

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. The carnosine content of vastus lateralis is elevated in resistance-trained bodybuilders.

    PubMed

    Tallon, Mark J; Harris, Roger C; Boobis, Les H; Fallowfield, Joanne L; Wise, John A

    2005-11-01

    Resistance training is associated with periods of acute intracellular hypoxia with increased H(+) production and low intramuscular pH. The aim of this study was to investigate the possible adaptive response in muscle carnosine (beta-alanyl-L-histidine) in bodybuilders. Extracts of biopsies of m. vastus lateralis of 6 national-level competitive bodybuilders and 6 age-matched untrained but moderately active healthy subjects were analyzed by high-performance liquid chromatography. Significant differences were shown in carnosine (p < 0.001) and histidine (p < 0.05). Muscle carnosine in bodybuilders was twice that in controls. The carnosine contents measured are the highest recorded in human muscle and represent a 20% contribution to muscle buffering capacity. Taurine was 38% lower in bodybuilders, though the difference was not significant. Possible causes for the changes observed are prolonged repetitive exposure to low muscle pH, change of diet or dietary supplement use, or the use of anabolic steroids. The increase in buffering capacity could influence the ability to carry out intense muscular activity.

  1. Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity.

    PubMed

    Hill, C A; Harris, R C; Kim, H J; Harris, B D; Sale, C; Boobis, L H; Kim, C K; Wise, J A

    2007-02-01

    Muscle carnosine synthesis is limited by the availability of beta-alanine. Thirteen male subjects were supplemented with beta-alanine (CarnoSyn) for 4 wks, 8 of these for 10 wks. A biopsy of the vastus lateralis was obtained from 6 of the 8 at 0, 4 and 10 wks. Subjects undertook a cycle capacity test to determine total work done (TWD) at 110% (CCT(110%)) of their maximum power (Wmax). Twelve matched subjects received a placebo. Eleven of these completed the CCT(110%) at 0 and 4 wks, and 8, 10 wks. Muscle biopsies were obtained from 5 of the 8 and one additional subject. Muscle carnosine was significantly increased by +58.8% and +80.1% after 4 and 10 wks beta-alanine supplementation. Carnosine, initially 1.71 times higher in type IIa fibres, increased equally in both type I and IIa fibres. No increase was seen in control subjects. Taurine was unchanged by 10 wks of supplementation. 4 wks beta-alanine supplementation resulted in a significant increase in TWD (+13.0%); with a further +3.2% increase at 10 wks. TWD was unchanged at 4 and 10 wks in the control subjects. The increase in TWD with supplementation followed the increase in muscle carnosine.

  2. Identification and characterization of a mouse dipeptidase that hydrolyzes L-carnosine.

    PubMed

    Otani, Hiroto; Okumura, Nobuaki; Hashida-Okumura, Akiko; Nagai, Katsuya

    2005-02-01

    L-Carnosine is a bioactive dipeptide present in mammalian tissues including the central nervous system. We have recently shown that L-carnosine is involved in the regulation of energy homeostasis through the autonomic nervous system, but the mechanisms for its biosynthesis and degradation have not yet been fully elucidated. Here we report the biochemical and immunohistochemical characterization of a mammalian protein that has a 17% overall amino acid sequence homology with a Lactobacilus carnosinase, PepV. A recombinant protein expressed in E. coli has the enzymatic ability to digest L-carnosine and various other dipeptides, and this activity is inhibited by bestatin. It requires Mn2+ for enzymatic activity and its effect is reversible. Immunohistochemical analysis showed that a few neuronal populations express this protein at very high levels. It is highly expressed in the parafascicular nucleus of the thalamus, tuberomammillary nucleus of the hypothalamus and the mitral cell layer of the olfactory bulb. In addition, neuronal processes, but not cell bodies, are stained in the striatum. In all these areas, the protein did not colocalize with the glial fibrilary acidic protein. These results suggest that a peptidase that digests L-carnosine is enriched in several specific neuronal populations in the central nervous system.

  3. Simple enzymatic procedure for l‐carnosine synthesis: whole‐cell biocatalysis and efficient biocatalyst recycling

    PubMed Central

    Heyland, Jan; Antweiler, Nicolai; Lutz, Jochen; Heck, Tobias; Geueke, Birgit; Kohler, Hans‐Peter E.; Blank, Lars M.; Schmid, Andreas

    2010-01-01

    Summary β‐Peptides and their derivates are usually stable to proteolysis and have an increased half‐life compared with α‐peptides. Recently, β‐aminopeptidases were described as a new enzyme class that enabled the enzymatic degradation and formation of β‐peptides. As an alternative to the existing chemical synthesis routes, the aim of the present work was to develop a whole‐cell biocatalyst for the synthesis and production of β‐peptides using this enzymatic activity. For the optimization of the reaction system we chose the commercially relevant β,α‐dipeptide l‐carnosine (β‐alanine‐l‐histidine) as model product. We were able to show that different recombinant yeast and bacteria strains, which overexpress a β‐peptidase, could be used directly as whole‐cell biocatalysts for the synthesis of l‐carnosine. By optimizing relevant reaction conditions for the best‐performing recombinant Escherichia coli strain, such as pH and substrate concentrations, we obtained high l‐carnosine yields of up to 71%. Long‐time as well as biocatalyst recycling experiments indicated a high stability of the developed biocatalyst for at least five repeated batches. Application of the recombinant E. coli in a fed‐batch process enabled the accumulation of l‐carnosine to a concentration of 3.7 g l−1. PMID:21255308

  4. Analytical and physicochemical characterisation of the senile cataract drug dipeptide β-alanyl-L-histidine (carnosine).

    PubMed

    Abdelkader, Hamdy; Swinden, Julian; Pierscionek, Barbara K; Alany, Raid G

    2015-10-10

    This study presents a simple but sensitive HPLC chromatographic method with a stability-indicating assay for determination and physicochemical characterisation of L-carnosine, a promising senile cataract prophylactic agent. Chromatographic analysis was conducted using a reverse phase (RP)-HPLC system and an isocratic mobile phase of 98% v/v trifluoroacetic acid (0.1% v/v) and 2% v/v acetonitrile with detection at 220 nm. L-carnosine was subjected to stress conditions to force its degradation using chemical and thermal agents and was subsequently detected from its degradation products using ESI-MS. The lipophilicity of the drug and 1:1 drug to phospholipid complex (PC) mol/mol was determined by estimating the partition coefficient (P). Lipophilicity was greatly enhanced when L-carnosine was formulated as a phospholipid complex using the solvent evaporation method. L-carnosine-phospholipid complex could be a promising approach for effective delivery to the human lens as offers a potential novel treatment for senile cataract. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Mentally Retarded Sex Offenders.

    ERIC Educational Resources Information Center

    Schoen, Jill; Hoover, John H.

    1990-01-01

    Critically reviews data about the behavioral characteristics of mentally retarded sexual offenders. Discusses possible interactions between mental retardation and the provision of services and directions for future research. (Author)

  6. Ergogenic Effects of β-Alanine and Carnosine: Proposed Future Research to Quantify Their Efficacy

    PubMed Central

    Caruso, John; Charles, Jessica; Unruh, Kayla; Giebel, Rachel; Learmonth, Lexis; Potter, William

    2012-01-01

    β-alanine is an amino acid that, when combined with histidine, forms the dipeptide carnosine within skeletal muscle. Carnosine and β-alanine each have multiple purposes within the human body; this review focuses on their roles as ergogenic aids to exercise performance and suggests how to best quantify the former’s merits as a buffer. Carnosine normally makes a small contribution to a cell’s total buffer capacity; yet β-alanine supplementation raises intracellular carnosine concentrations that in turn improve a muscle’s ability to buffer protons. Numerous studies assessed the impact of oral β-alanine intake on muscle carnosine levels and exercise performance. β-alanine may best act as an ergogenic aid when metabolic acidosis is the primary factor for compromised exercise performance. Blood lactate kinetics, whereby the concentration of the metabolite is measured as it enters and leaves the vasculature over time, affords the best opportunity to assess the merits of β-alanine supplementation’s ergogenic effect. Optimal β-alanine dosages have not been determined for persons of different ages, genders and nutritional/health conditions. Doses as high as 6.4 g day−1, for ten weeks have been administered to healthy subjects. Paraesthesia is to date the only side effect from oral β-alanine ingestion. The severity and duration of paraesthesia episodes are dose-dependent. It may be unwise for persons with a history of paraesthesia to ingest β-alanine. As for any supplement, caution should be exercised with β-alanine supplementation. PMID:22852051

  7. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    PubMed

    Banerjee, S; Poddar, M K

    2016-04-05

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Creatine supplementation augments skeletal muscle carnosine content in senescence-accelerated mice (SAMP8).

    PubMed

    Derave, Wim; Jones, Glenys; Hespel, Peter; Harris, Roger C

    2008-06-01

    The histidine-containing dipeptides (HCD) carnosine and anserine are found in high concentrations in mammalian skeletal muscle. Given its versatile biologic properties, such as antioxidative, antiglycation, and pH buffering capacity, carnosine has been implicated as a protective factor in the aging process. The present study aimed to systematically explore age-related changes in skeletal muscles HCD content in a murine model of accelerated aging. Additionally, we investigated the effect of lifelong creatine supplementation on muscle HCD content and contractile fatiguability. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 weeks. At week 10, 25, and 60, tibialis anterior muscles were dissected and analysed for HCD and taurine content by HPLC. Soleus and EDL muscles were tested for in vitro contractile fatigue and recovery. From 10 to 60 weeks of age, muscular carnosine (-45%), taurine (-24%), and total creatine (-42%) concentrations gradually and significantly decreased. At 25 but not at 60 weeks, oral creatine supplementation significantly increased carnosine (+88%) and anserine (+40%) content compared to age-matched control-fed animals. Taurine and total creatine content were not affected by creatine supplementation at any age. Creatine-treated mice showed attenuated muscle fatigue (soleus) and enhanced force recovery (m. extensor digitorum longus [EDL]) compared to controls at 25 weeks, but not at 60 weeks. From the present study, we can conclude that skeletal muscle tissue exhibits a significant decline in HCD content at old age. Oral creatine supplementation is able to transiently but potently increase muscle carnosine and anserine content, which coincides with improved resistance to contractile fatigue.

  9. Control of the structural stability of α-crystallin under thermal and chemical stress: the role of carnosine.

    PubMed

    Villari, Valentina; Attanasio, Francesco; Micali, Norberto

    2014-11-26

    The structural properties of α-crystallin, the major protein of the eye lens of mammals, in aqueous solution are investigated by means of small angle X-ray and dynamic light scattering. The research interest is devoted in particular to the effect of carnosine in protecting the protein under stress conditions, like temperature increase and presence of denaturant (guanidinium-HCl). The results suggest that carnosine interacts, through mechanisms involving hydrophobic interactions, with α-crystallin and avoids the structural changes in the quaternary structure induced by thermal and chemical stress. It is also shown that, if mediated by carnosine, the self-aggregation of α-crystallin induced by the denaturant at higher temperature can be controlled and even partially reversed. Therefore, carnosine is effective in preserving the structural integrity of the protein, suggesting the possibility of new strategies of intervention for preventing or treating pathologies related to protein aggregation, like cataracts.

  10. A biochemical and immunohistochemical study of the protective effects of carnosine for carbon tetrachloride induced liver injury in rats.

    PubMed

    Kuloglu, N; Sönmez, M F

    2015-01-01

    We investigated the protective effect of carnosine on carbon tetrachloride-induced liver tissue damage. Thirty-two adult male rats were divided into four equal groups. Group 1 was the untreated control, group 2 was injected with 0.2 ml/kg/day carbon tetrachloride, group 3 was injected with with 0.2 ml/kg/day carbon tetrachloride plus 200 mg/kg/day carnosine, and group 4 was injected with 200 mg/kg/day carnosine. Increased serum alanine amino transferase and aspartate amino transferase levels, liver malondialdehyde levels, HSP-70 expression and steatosis were observed following treatment with carbon tetrachloride. Carbon tetrachloride caused severe biochemical and histopathological changes in liver tissue and treatment with carnosine partially prevented the damage. HSP-70 may help control liver damage.

  11. Collision-induced dissociation products of the protonated dipeptide carnosine: structural elucidation, fragmentation pathways and potential energy surface analysis.

    PubMed

    Moustafa, Eslam M; Ritacco, Ida; Sicilia, Emilia; Russo, Nino; Shoeib, Tamer

    2015-05-21

    Collision-induced dissociation (CID) experiments on protonated carnosine, [carnosine + H](+), with several collision energies were shown to yield eleven different fragment ions with the generation of product ions [carnosine-H2O + H](+) and [carnosine-NH3 + H](+) being the lowest energy processes. Energy-resolved CID showed that at slightly higher collision energies the ions [histidine + H](+) and [histidine-H2O-CO + H](+) are formed. At even higher energies four other product ions were observed, however, attained relatively lower abundances. Quantum chemistry calculations, carried out at different levels of theory, were employed to probe fragmentation mechanisms that account for all the experimental data. All the adopted computational protocols give similar energetic trends, and the range of the calculated free energy barrier values for the generation of all the observed product ions is in agreement with the fragmentation mechanisms offered here.

  12. Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance

    PubMed Central

    Tsoi, Bun; Li, Xiao-Di; Li, Wei-Xi; Abe, Keiichi; Kurihara, Hiroshi

    2012-01-01

    Carnosine (β-alanyl-L-histidine), a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Killer (NK) cells were obviously decreased. Results also demonstrated that restraint stress decreased the cytotoxic activity of NK cells per spleen (LU10/spleen) while the activity of a single NK cell (LU10/106 cells) was not changed. However, oral administration of carnosine (150 and 300 mg/kg) increased spleen index and number of spleen lymphocytes (including NK cells), and elevated the cytotoxic activity of NK cells per spleen in restraint-stressed mice. These results indicated that carnosine ameliorated stress-evoked immunocompromise through spleen lymphocyte number maintenance. Carnosine was further found to reduce stress-induced elevation of plasma corticosterone level. On the other hand, results showed that carnosine and RU486 (a glucocorticoids receptor antagonist) treatment prevented the reduction in mitochondrion membrane potential and the release of mitochondrial cytochrome c into cytoplasm, increased Bcl-2/Bax mRNA ratio, as well as decreased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in spleen lymphocytes of stressed mice. The results above suggested that the maintenance of spleen lymphocyte number by carnosine was related with the inhibition of lymphocytes apoptosis caused by glucocorticoids overflow. The stimulation of lymphocyte proliferation by carnosine also contributed to the maintenance of spleen lymphocyte number in stressed mice. In view of the elevated histamine level, the anti-stress effects of

  13. The Successful Retardate.

    ERIC Educational Resources Information Center

    Albizu-Miranda, Carlos; And Others

    To study the prevalence of mental retardation in Puerto Rico, the proportional distribution of successful retardates, and the processes accounting for success and failure, a random sample of 4,771 adults between the ages of 23 and 49 was screened by the Stanford Binet Form L and a vocabulary test. From this sample, the estimated retardation rate…

  14. Depression and Mental Retardation.

    ERIC Educational Resources Information Center

    O'Neil, Marie A.

    Mentally retarded people may be particularly vulnerable to depression and related emotional disturbances due to limited social skills, lack of friends, and negative self-esteem. A therapy group for depressed retarded clients provided an opportunity to collect information about depression in retarded individuals and to evaluate various treatment…

  15. Design, synthesis, and evaluation of carnosine derivatives as selective and efficient sequestering agents of cytotoxic reactive carbonyl species.

    PubMed

    Vistoli, Giulio; Orioli, Marica; Pedretti, Alessandro; Regazzoni, Luca; Canevotti, Renato; Negrisoli, Gianpaolo; Carini, Marina; Aldini, Giancarlo

    2009-06-01

    Carnosine aryl derivatives as sequestering agents of RCS: Reactive carbonyl species (RCS) are cytotoxic mediators representing a novel drug target, as they are presumed to play a pathogenic role in several diseases. Carnosine is a selective RCS-sequestering agent, but is rapidly hydrolyzed by serum carnosinase. Herein we describe the in silico design, synthesis, and evaluation of a set of carnosine aryl derivatives.Reactive carbonyl species (RCS) are important cytotoxic mediators generated by lipid oxidation of polyunsaturated fatty acids (PUFAs) and represent a novel drug target, as they are presumed to play a pathogenic role in several diseases. L-Carnosine (L-CAR, beta-alanyl-L-histidine) is a specific detoxifying agent of RCS, but is rapidly hydrolyzed in human serum by carnosinase, a specific dipeptidase. Herein we describe the in silico design, synthesis, and biological evaluation of carnosine derivatives that are resistant to carnosinase and that have increased quenching efficacy. Stability against carnosinase-mediated turnover was achieved by isomerization of the histidine residue, leading to D-carnosine (D-CAR, beta-alanyl-D-histidine), which maintains the same quenching activity of L-carnosine. A molecular modeling approach was then used to design derivatives characterized by an increased quenching efficacy. The most promising candidates were synthesized, and their stability and quenching activity were evaluated. This study describes a set of aryl derivatives that are characterized by high stability in human plasma and a quenching activity toward 4-hydroxy-trans-2-nonenal (HNE), chosen as a model of RCS, up to threefold greater than D-carnosine.

  16. Carnosine content of the middle gluteal muscle in thoroughbred horses with relation to age, sex and training.

    PubMed

    Marlin, D J; Harris, R C; Gash, S P; Snow, D H

    1989-01-01

    1. Muscle biopsies were collected from 85 thoroughbred horses and analysed for carnosine content by an automated HPLC method. 2. No significant sex difference was found between colts, geldings and fillies. 3. There was a trend towards lower muscle carnosine contents with age, which was only significant between 1-year-old untrained horses and 4+ year-old horses (P less than 0.002).

  17. New glycoside derivatives of carnosine and analogs resistant to carnosinase hydrolysis: synthesis and characterization of their copper(II) complexes.

    PubMed

    Lanza, Valeria; Bellia, Francesco; D'Agata, Roberta; Grasso, Giuseppe; Rizzarelli, Enrico; Vecchio, Graziella

    2011-02-01

    Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide widely and abundantly distributed in muscle and nervous tissues of several animal species. Many functions have been proposed for this compound, such as antioxidant and metal ion-chelator properties. However, the main limitation on therapeutic use of carnosine on pathologies related to increased oxidative stress and/or metal ion dishomeostasis is associated with the hydrolysis by the specific dipeptidase carnosinase. Several attempts have been made to overcome this limitation. On this basis, we functionalized carnosine and its amide derivative with small sugars such as glucose and lactose. The resistance of these derivatives to the carnosinase hydrolysis was tested and compared with that of carnosine. We found that the glycoconjugation protects the dipeptide moiety from carnosinase hydrolysis, thus potentially improving the availability of carnosine. The copper(II) binding properties of all the new synthesized compounds were investigated by spectroscopic (UV-Visible and circular dichroism) and ESI-MS studies. Particularly, the new family of amide derivatives that are not significantly hydrolyzed by carnosinase is a very promising class of carnosine derivatives. The sugar moiety can act as a recognition element. These new derivatives are potentially able to act as chelating agents in the development of clinical approaches for the regulation of metal homeostasis in the field of medicinal inorganic chemistry. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Anti-aggregating effect of the naturally occurring dipeptide carnosine on aβ1-42 fibril formation.

    PubMed

    Aloisi, Alessandra; Barca, Amilcare; Romano, Alessandro; Guerrieri, Sara; Storelli, Carlo; Rinaldi, Rosaria; Verri, Tiziano

    2013-01-01

    Carnosine is an endogenous dipeptide abundant in the central nervous system, where by acting as intracellular pH buffering molecule, Zn/Cu ion chelator, antioxidant and anti-crosslinking agent, it exerts a well-recognized multi-protective homeostatic function for neuronal and non-neuronal cells. Carnosine seems to counteract proteotoxicity and protein accumulation in neurodegenerative conditions, such as Alzheimer's Disease (AD). However, its direct impact on the dynamics of AD-related fibril formation remains uninvestigated. We considered the effects of carnosine on the formation of fibrils/aggregates of the amyloidogenic peptide fragment Aβ1-42, a major hallmark of AD injury. Atomic force microscopy and thioflavin T assays showed inhibition of Aβ1-42 fibrillogenesis in vitro and differences in the aggregation state of Aβ1-42 small pre-fibrillar structures (monomers and small oligomers) in the presence of carnosine. in silico molecular docking supported the experimental data, calculating possible conformational carnosine/Aβ1-42 interactions. Overall, our results suggest an effective role of carnosine against Aβ1-42 aggregation.

  19. Systematic review and stratified meta-analysis of the efficacy of carnosine in animal models of ischemic stroke.

    PubMed

    Davis, Charles K; Laud, Peter J; Bahor, Zsanett; Rajanikant, G K; Majid, Arshad

    2016-10-01

    Carnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies. We included publications describing in vivo models of ischemic stroke where the neuroprotective efficacy of carnosine was being evaluated through the reporting of infarct volume and/or neurological score as outcomes. Overall efficacy was evaluated using weighted mean difference random effects meta-analysis. We also evaluated for study quality and publication bias. We identified eight publications that met our inclusion criteria describing a total of 29 comparisons and 454 animals. Overall methodological quality of studies was moderate (median = 4/9). Carnosine reduced infarct volume by 29.4% (95% confidence interval (CI), 24.0% to 34.9%; 29 comparisons). A clear dose-response effect was observed, and efficacy was reduced when carnosine was administered more than 6 h after ischemia. Our findings suggest that carnosine administered before or after the onset of ischemia exhibits robust efficacy in experimental ischemic stroke. However, the methodological quality of some of the studies was low and testing occurred only in healthy young male animals. © The Author(s) 2016.

  20. Anti-Aggregating Effect of the Naturally Occurring Dipeptide Carnosine on Aβ1-42 Fibril Formation

    PubMed Central

    Romano, Alessandro; Guerrieri, Sara; Storelli, Carlo; Rinaldi, Rosaria; Verri, Tiziano

    2013-01-01

    Carnosine is an endogenous dipeptide abundant in the central nervous system, where by acting as intracellular pH buffering molecule, Zn/Cu ion chelator, antioxidant and anti-crosslinking agent, it exerts a well-recognized multi-protective homeostatic function for neuronal and non-neuronal cells. Carnosine seems to counteract proteotoxicity and protein accumulation in neurodegenerative conditions, such as Alzheimer’s Disease (AD). However, its direct impact on the dynamics of AD-related fibril formation remains uninvestigated. We considered the effects of carnosine on the formation of fibrils/aggregates of the amyloidogenic peptide fragment Aβ1-42, a major hallmark of AD injury. Atomic force microscopy and thioflavin T assays showed inhibition of Aβ1-42 fibrillogenesis in vitro and differences in the aggregation state of Aβ1-42 small pre-fibrillar structures (monomers and small oligomers) in the presence of carnosine. in silico molecular docking supported the experimental data, calculating possible conformational carnosine/Aβ1-42 interactions. Overall, our results suggest an effective role of carnosine against Aβ1-42 aggregation. PMID:23844165

  1. Systematic review and stratified meta-analysis of the efficacy of carnosine in animal models of ischemic stroke

    PubMed Central

    Davis, Charles K; Laud, Peter J; Bahor, Zsanett; Majid, Arshad

    2016-01-01

    Carnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies. We included publications describing in vivo models of ischemic stroke where the neuroprotective efficacy of carnosine was being evaluated through the reporting of infarct volume and/or neurological score as outcomes. Overall efficacy was evaluated using weighted mean difference random effects meta-analysis. We also evaluated for study quality and publication bias. We identified eight publications that met our inclusion criteria describing a total of 29 comparisons and 454 animals. Overall methodological quality of studies was moderate (median = 4/9). Carnosine reduced infarct volume by 29.4% (95% confidence interval (CI), 24.0% to 34.9%; 29 comparisons). A clear dose-response effect was observed, and efficacy was reduced when carnosine was administered more than 6 h after ischemia. Our findings suggest that carnosine administered before or after the onset of ischemia exhibits robust efficacy in experimental ischemic stroke. However, the methodological quality of some of the studies was low and testing occurred only in healthy young male animals. PMID:27401803

  2. Tumor

    MedlinePlus

    ... excessively in the body. Normally, the body controls cell growth and division. New cells are created to replace ... room for healthy replacements. If the balance of cell growth and death is disturbed, a tumor may form. ...

  3. Energy metabolism, proteotoxic stress and age-related dysfunction - protection by carnosine.

    PubMed

    Hipkiss, Alan R

    2011-08-01

    This review will discuss the relationship between energy metabolism, protein dysfunction and the causation and modulation of age-related proteotoxicity and disease. It is proposed that excessive glycolysis, rather than aerobic (mitochondrial) activity, could be causal to proteotoxic stress and age-related pathology, due to the generation of endogenous glycating metabolites: the deleterious role of methylglyoxal (MG) is emphasized. It is suggested that TOR inhibition, exercise, fasting and increased mitochondrial activity suppress formation of MG (and other deleterious low molecular weight carbonyl compounds) which could control onset and progression of proteostatic dysfunction. Possible mechanisms by which the endogenous dipeptide, carnosine, which, by way of its putative aldehyde-scavenging activity, may control age-related proteotoxicity, cellular dysfunction and pathology, including cancer, are also considered. Whether carnosine could be regarded as a rapamycin mimic is briefly discussed.

  4. Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by β-alanine transamination.

    PubMed

    Blancquaert, Laura; Baba, Shahid P; Kwiatkowski, Sebastian; Stautemas, Jan; Stegen, Sanne; Barbaresi, Silvia; Chung, Weiliang; Boakye, Adjoa A; Hoetker, J David; Bhatnagar, Aruni; Delanghe, Joris; Vanheel, Bert; Veiga-da-Cunha, Maria; Derave, Wim; Everaert, Inge

    2016-09-01

    Using recombinant DNA technology, the present study provides the first strong and direct evidence indicating that β-alanine is an efficient substrate for the mammalian transaminating enzymes 4-aminobutyrate-2-oxoglutarate transaminase and alanine-glyoxylate transaminase. The concentration of carnosine and anserine in murine skeletal and heart muscle depends on circulating availability of β-alanine, which is in turn controlled by degradation of β-alanine in liver and kidney. Chronic oral β-alanine supplementation is a popular ergogenic strategy in sports because it can increase the intracellular carnosine concentration and subsequently improve the performance of high-intensity exercises. The present study can partly explain why the β-alanine supplementation protocol is so inefficient, by demonstrating that exogenous β-alanine can be effectively routed toward oxidation. The metabolic fate of orally ingested β-alanine is largely unknown. Chronic β-alanine supplementation is becoming increasingly popular for improving high-intensity exercise performance because it is the rate-limiting precursor of the dipeptide carnosine (β-alanyl-l-histidine) in muscle. However, only a small fraction (3-6%) of the ingested β-alanine is used for carnosine synthesis. Thus, the present study aimed to investigate the putative contribution of two β-alanine transamination enzymes, namely 4-aminobutyrate-2-oxoglutarate transaminase (GABA-T) and alanine-glyoxylate transaminase (AGXT2), to the homeostasis of carnosine and its methylated analogue anserine. We found that, when transfected into HEK293T cells, recombinant mouse and human GABA-T and AGXT2 are able to transaminate β-alanine efficiently. The reaction catalysed by GABA-T is inhibited by vigabatrin, whereas both GABA-T and AGXT2 activity is inhibited by aminooxyacetic acid (AOA). Both GABA-T and AGXT2 are highly expressed in the mouse liver and kidney and the administration of the inhibitors effectively reduced their enzyme

  5. Carnosine prevents necrotic and apoptotic death of rat thymocytes via ouabain sensitive Na/K-ATPase

    PubMed Central

    Smolyaninova, Larisa V.; Dergalev, Alexander A.; Kulebyakin, Konstantin Y.; Carpenter, David O.; Boldyrev, Alexander A.

    2012-01-01

    It is known that ouabain, a selective inhibitor of Na/K-ATPase, can cause not only activation of signal cascades, which regulate the cell viability, but also can cause free radical accumulation, which can evoke the oxidative stress. We have shown that nanomolar concentrations of ouabain result in the temporary increase in the level of intracellular free radicals but the millimolar concentration of ouabain induces a stable intracellular accumulation of free radicals in rat thymocytes. The increasing level of free radicals resulting from both low and high concentrations of ouabain can be attenuated by the antioxidant, carnosine. Moreover the long-term incubation with ouabain leads to the cell death by necrosis and apoptosis. Ouabain-mediated apoptosis and necrosis were also abolished by carnosine. PMID:22763713

  6. Effect of Dietary Supplementation of Blood Meal and Additional Magnesium on Carnosine and Anserine Concentrations of Pig Muscles.

    PubMed

    Park, Se Won; Kim, Chan Ho; Kim, Jong Woong; Shin, Hye Seong; Paik, In Kee; Kil, Dong Yong

    2014-01-01

    The objective of this study was to investigate the effect of dietary supplementation of blood meal as a source of L-histidine, and the addition of magnesium (Mg) as a catalyst of carnosine synthetase for the carnosine and anserine concentrations of pig muscles (longissimus dorsi, LD and vastus intermedius, VI). A total of twenty-four pigs with an average body weight of 60.2±4.2 kg were randomly allotted to one of three dietary treatments (eight replicates), during 56 d of the feeding trial. Dietary treatments included: (1) Basal: basal diet; (2) BM: 95% basal diet + 5% blood meal; and (3) BM+Mg: 94.8% basal diet + 5% blood meal + 0.2% MgO (60% Mg). Results indicated that drip loss in the LD was less (p<0.05) for meat with BM+Mg treatment than that with Basal treatment, but the values for BM treatment did not differ from those of the other two treatment groups. The concentrations of carnosine in the LD were increased by 10.0% in both BM and BM+Mg treatment groups over the Basal treatment group (significance not verified). The concentrations of carnosine and anserine in the VI were not affected by the dietary treatments. Inclusion of additional Mg in diets had no effect on carnosine and anserine concentrations in the LD and VI. In conclusion, dietary supplementation of blood meal could be a potential method of fortifying the pork with carnosine. Inclusion of additional Mg in the diets containing blood meal had no benefit on carnosine and anserine depositions in pig muscles.

  7. Effect of Dietary Supplementation of Blood Meal and Additional Magnesium on Carnosine and Anserine Concentrations of Pig Muscles

    PubMed Central

    2014-01-01

    The objective of this study was to investigate the effect of dietary supplementation of blood meal as a source of L-histidine, and the addition of magnesium (Mg) as a catalyst of carnosine synthetase for the carnosine and anserine concentrations of pig muscles (longissimus dorsi, LD and vastus intermedius, VI). A total of twenty-four pigs with an average body weight of 60.2±4.2 kg were randomly allotted to one of three dietary treatments (eight replicates), during 56 d of the feeding trial. Dietary treatments included: (1) Basal: basal diet; (2) BM: 95% basal diet + 5% blood meal; and (3) BM+Mg: 94.8% basal diet + 5% blood meal + 0.2% MgO (60% Mg). Results indicated that drip loss in the LD was less (p<0.05) for meat with BM+Mg treatment than that with Basal treatment, but the values for BM treatment did not differ from those of the other two treatment groups. The concentrations of carnosine in the LD were increased by 10.0% in both BM and BM+Mg treatment groups over the Basal treatment group (significance not verified). The concentrations of carnosine and anserine in the VI were not affected by the dietary treatments. Inclusion of additional Mg in diets had no effect on carnosine and anserine concentrations in the LD and VI. In conclusion, dietary supplementation of blood meal could be a potential method of fortifying the pork with carnosine. Inclusion of additional Mg in the diets containing blood meal had no benefit on carnosine and anserine depositions in pig muscles. PMID:26760946

  8. Improved survival from compound 48/80-induced lethal stress and inhibition of myocardial histamine and carnosine mobilization by lodoxamide.

    PubMed

    Flancbaum, L; Fitzpatrick, J C; Fisher, H

    1989-02-01

    The precise roles of carnosine and histamine in the physiologic response of the cardiovascular system to stress are unknown. We have previously shown in skeletal and cardiac muscle that carnosine serves as a histidine reservoir available for subsequent histamine synthesis following trauma and sepsis. This study was designed to quantify the effect of histamine-releasing and blocking agents on the myocardial carnosine-histamine pathway as well as on survival during severe stress. Four groups of mature (9-month-old) Sprague-Dawley rats were treated with either (1) saline, (2) lodoxamide (L, mast cell degranulation inhibitor), (3) compound 48/80 (a mast cell degranulator which causes stress), or (4) L followed by 48/80, and observed until agonal or the end of 30 min. When either endpoint was reached the animals were sacrificed and their hearts were removed for tissue analyses of histidine, histamine, 3-methylhistamine, and carnosine via high-pressure liquid chromatography. All five L-pretreated animals survived challenge with 48/80 while all five animals given 48/80 alone died (P less than .005). This mortality correlated well with the increase in the myocardial levels of histidine (P less than or equal to .0005), histamine (P less than or equal to .0077), and 3-methylhistamine (P less than or equal to .0004) and the decrease in carnosine (P less than or equal to .009) experienced by the animals treated with 48/80 alone in comparison to the control, L-only- and L + 48/80-treated groups. A protective effect of L was shown against the deleterious effects of 48/80 which is associated with prevention of myocardial carnosine mobilization to histidine and histamine. These data support the role of carnosine as a nontoxic myocardial histidine reservoir which is mobilized in response to stress-induced increases in histamine requirements.

  9. Carnosine and Homocarnosine Degradation Mechanisms by the Human Carnosinase Enzyme CN1: Insights from Multiscale Simulations.

    PubMed

    Pavlin, Matic; Rossetti, Giulia; De Vivo, Marco; Carloni, Paolo

    2016-05-17

    The endogenous dipeptide l-carnosine, and its derivative homocarnosine, prevent and reduce several pathologies like amytrophic lateral sclerosis (ALS), Alzheimer's disease, and Parkinson's disease. Their beneficial action is severely hampered because of the hydrolysis by carnosinase enzymes, in particular the human carnosinase, hCN1. This belongs to the metallopeptidase M20 family, where a cocatalytic active site is formed by two Zn(2+) ions, bridged by a hydroxide anion. The protein may exist as a monomer and as a dimer in vivo. Here we used hybrid quantum mechanics/molecular mechanics simulations based on the dimeric apoenzyme's structural information to predict the Michaelis complexes with l-carnosine and its derivative homocarnosine. On the basis of our calculations, we suggest that (i) l-carnosine degradation occurs through a nucleophilic attack of a Zn(2+)-coordinated bridging moiety for both monomer and dimer. This mechanistic hypothesis for hCN1 catalysis differs from previous proposals, while it is in agreement with available experimental data. (ii) The experimentally measured higher affinity of homocarnosine for the enzyme relative to l-carnosine might be explained, at least in part, by more extensive interactions inside the monomeric and dimeric hCN1's active site. (iii) Hydrogen bonds at the binding site, present in the dimer but absent in the monomer, might play a role in the experimentally observed higher activity of the dimeric form. Investigations of the enzymatic reaction are required to establish or disprove this hypothesis. Our results may serve as a basis for the design of potent hCN1 inhibitors.

  10. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

    PubMed

    Banerjee, Soumyabrata; Poddar, Mrinal K

    2015-03-01

    Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  11. Doubling of muscle carnosine concentration does not improve laboratory 1-hr cycling time-trial performance.

    PubMed

    Chung, Weiliang; Baguet, Audrey; Bex, Tine; Bishop, David J; Derave, Wim

    2014-06-01

    Muscle carnosine loading through chronic oral beta-alanine supplementation has been shown to be effective for short-duration, high-intensity exercise. This randomized, placebo-controlled study explored whether the ergogenic effect of beta-alanine supplementation is also present for longer duration exercise. Subjects (27 well-trained cyclists/triathletes) were supplemented with either beta-alanine or placebo (6.4 g/day) for 6 weeks. Time to completion and physiological variables for a 1-hr cycling time-trial were compared between preand postsupplementation. Muscle carnosine concentration was also assessed via proton magnetic resonance spectroscopy before and after supplementation. Following beta-alanine supplementation, muscle carnosine concentration was increased by 143 ± 151% (mean ± SD; p < .001) in the gastrocnemius and 161 ± 56% (p < .001) in the soleus. Postsupplementation time trial performance was significantly slower in the placebo group (60.6 ± 4.4-63.0 ± 5.4 min; p < .01) and trended toward a slower performance following beta-alanine supplementation (59.8 ± 2.8-61.7 ± 3.0 min; p = .069). We found an increase in lactate/proton concentration ratio following beta-alanine supplementation during the time-trial (209.0 ± 44.0 (beta-alanine) vs. 161.9 ± 54.4 (placebo); p < .05), indicating that a similar lactate concentration was accompanied by a lower degree of systemic acidosis, even though this acidosis was quite moderate (pH ranging from 7.30 to 7.40). In conclusion, chronic beta-alanine supplementation in well-trained cyclists had a very pronounced effect on muscle carnosine concentration and a moderate attenuating effect on the acidosis associated with lactate accumulation, yet without affecting 1-h time-trial performance under laboratory conditions.

  12. Effect of dietary histidine on contents of carnosine and anserine in muscles of broilers.

    PubMed

    Kai, Shinichi; Watanabe, Genya; Kubota, Masatoshi; Kadowaki, Motoni; Fujimura, Shinobu

    2015-05-01

    Carnosine (β-alanyl-L-histidine) and anserine (β-alanyl-1-methyl-L-histidine) are dipeptides mainly found in skeletal muscle and brain of many vertebrates, and particularly high concentrations are observed in chicken pectoral muscles. It was reported that these peptides have many functions, such as antioxidant activity. In this study, we examined the effect of different levels of dietary histidine on carnosine and anserine contents in broiler muscles. The 14-days-old female Chunky strain broilers were given feeds containing three different levels of histidine; 67% (Low-His), 100% (Control) and 200% (High-His) of histidine requirement according to the NRC (1994). Chicks were fed experimental diets for 10 days. Both dipeptides in muscle were significantly decreased. In particular, carnosine was not detected at all in the Low-His group and was significantly increased in the High-His group. Both dipeptides were not detected in plasma. These results indicated the possibility to produce chicken meat with enhanced amount of these dipeptides by high histidine feeding.

  13. Bioaccessibility of the Bioactive Peptide Carnosine during in Vitro Digestion of Cured Beef Meat.

    PubMed

    Marcolini, Elena; Babini, Elena; Bordoni, Alessandra; Di Nunzio, Mattia; Laghi, Luca; Maczó, Anita; Picone, Gianfranco; Szerdahelyi, Emoke; Valli, Veronica; Capozzi, Francesco

    2015-05-27

    A bioactive compound is a food component that may have an impact on health. Its bioaccessibility, defined as the fraction released from the food matrix into the gastrointestinal tract during digestion, depends on compound stability, interactions with other food components, and supramolecular organization of food. In this study, the effect of pH on the bioaccessibility of the bioactive dipeptide carnosine was evaluated in two commercial samples of the Italian cured beef meat bresaola at two key points of digestion: before the gastric and after the duodenal phases. The digestion process was simulated using an in vitro static system, whereas capillary zone electrophoresis (CZE) and (1)H nuclear magnetic resonance (NMR) were used for quantitative analysis. The gap between the total carnosine content, measured by CZE, and its free diffusible fraction observable by NMR spectroscopy, was 11 and 19% for two independent bresaola products, where such percentages represent the fraction of carnosine not accessible for intestinal absorption because it was adsorbed to the food matrix dispersed in the digestion fluid.

  14. Hormonal responses to resistance exercise after ingestion of carnosine and anserine.

    PubMed

    Goto, Kazushige; Maemura, Hirohiko; Takamatsu, Kaoru; Ishii, Naokata

    2011-02-01

    Intramuscular carnosine buffers protons (H+) in skeletal muscle. We examined the effects of supplementation with chicken breast meat extract (CBEX) containing carnosine and anserine on hormonal responses to resistance exercise. Twenty-two men were assigned to a CBEX drink group (CBEX containing total 2 g of carnosine and anserine) (n = 14) or a placebo drink group (n = 8). The subjects ingested the prescribed drink (100 mL) twice daily for 30 days without physical training. Before and after the supplementation period, the subjects completed 5 sets of bilateral knee extension exercises (with a 90-s rest between sets). The magnitude of the increase in exercise-induced free testosterone did not change significantly after supplementation in either group. The blood lactate response to exercise was attenuated after supplementation in both groups (p < 0.05). In the CBEX group, the plasma epinephrine and norepinephrine concentrations after exercise were significantly lower after supplementation (p < 0.05). The serum growth hormone response to exercise was also reduced in the CBEX group after supplementation (delta value: 5.4 ± 1.9 ng/mL [pre] vs. 1.6 ± 0.5 ng/mL [post], p = 0.05). No significant differences in exercise-induced strength reduction (fatigue index) were observed in the 2 groups after supplementation. These results suggest that short-term supplementation with CBEX attenuates the exercise-induced epinephrine, norepinephrine, and growth hormone responses.

  15. Analysis of carnosine, homocarnosine, and other histidyl derivatives in rat brain.

    PubMed

    O'Dowd, J J; Cairns, M T; Trainor, M; Robins, D J; Miller, D J

    1990-08-01

    Isocratic reverse-phase analytical HPLC has been used to examine naturally occurring imidazoles of rat brain. Elution of brain extracts with a phosphate buffer mobile phase from columns packed with Hypersil ODS (5 microns) resulted in good separation of the well-documented brain imidazole-containing dipeptides carnosine and homocarnosine. Measured concentrations corresponded to published values. Several further peaks observed had properties consistent with those of N-acetyl derivatives of compounds related to carnosine and homocarnosine. N-Acetyl forms not commercially available were prepared and their identities verified by nuclear magnetic resonance spectroscopy. A number of these had chromatographic properties identical to those of compounds in brain extracts. Fractions corresponding to some of the peaks were examined using staining systems specific for certain chemical features and compared with results obtained for commercial or synthetic standards. The results of these tests supported the chromatographic data. Thus, chromatographic and microchemical evidence is presented for the existence of N-acetyl forms of histidine, 1-methylhistidine, carnosine, anserine, and homocarnosine in rat brain.

  16. Detection, characterisation, and quantification of carnosine and other histidyl derivatives in cardiac and skeletal muscle.

    PubMed

    O'Dowd, J J; Robins, D J; Miller, D J

    1988-11-17

    Isocratic reverse phase analytical high performance liquid chromatography (HPLC) has been used to examine naturally occurring imidazoles of cardiac and skeletal muscles. Elution of muscle extracts with a phosphate buffer mobile phase from columns packed with hypersil ODS (5 micron) resulted in good separation of the skeletal muscle imidazole-containing dipeptides carnosine and anserine. Measured concentrations corresponded to published values. N-Acetyl forms that were not commercially available were prepared from their parent compounds and their identities verified by NMR-spectroscopy. Examination of frog cardiac muscle confirmed the presence of N-acetylhistidine and also indicated the presence of its 1-methyl derivative. Extracts of mammalian cardiac muscle were examined by HPLC which indicated the presence of low concentrations of carnosine but substantial amounts of N-acetyl forms of histidine, 1-methylhistidine, carnosine and anserine. Fractions corresponding to the numerous peaks were examined using staining systems specific for certain chemical features and compared to results obtained for commercial or synthetic standards. Results of these tests supported the chromatographic data. The total concentrations in cardiac muscle of these imidazole-containing substances (approx. 10 mM) is sufficient to alter significantly the sensitivity of their contractile apparatus to calcium ions.

  17. Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

    PubMed Central

    2013-01-01

    The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide’s influence on cellular ATP concentrations. Carnosine’s ability to reduce the formation of altered proteins (typically adducts of methylglyoxal) and enhance proteolysis of aberrant polypeptides is indicative of its influence on proteostasis. Furthermore these dual actions might provide a rationale for the use of carnosine in the treatment or prevention of diverse age-related conditions where energy metabolism or proteostasis are compromised. These include cancer, Alzheimer's disease, Parkinson's disease and the complications of type-2 diabetes (nephropathy, cataracts, stroke and pain), which might all benefit from knowledge of carnosine’s mode of action on human cells. PMID:23442334

  18. Antioxidant potential of date (Phoenix dactylifera L.) seed protein hydrolysates and carnosine in food and biological systems.

    PubMed

    Ambigaipalan, Priyatharini; Shahidi, Fereidoon

    2015-01-28

    Date seed protein hydrolysates were evaluated for antioxidant activity as well as solubility and water-holding capacity in food and biological model systems. Date seed protein hydrolysates as well as carnosine exhibited >80% of solubility over a pH range of 2-12. The hydrolysates and carnosine at 0.5% (w/w) were also found to be effective in enhancing water-holding capacity and cooking yield in a fish model system, which was nearly similar to sodium tripolyphosphate (STPP; 0.3%, w/w). Incorporation of hydrolysates (200 ppm) in fish model systems resulted in the highest inhibition (30%) of oxidation in comparison to butylated hydroxytoluene (BHT; 9%). In addition, hydrolysates and carnosine inhibited β-carotene oxidation by 75%. The hydrolysates (0.1 mg/mL) inhibited LDL cholesterol oxidation by 60%, whereas carnosine inhibited oxidation by 80% after 12 h of incubation. Additionally, hydrolysates and carnosine effectively inhibited hydroxyl (6 mg/mL) and peroxyl (0.1 mg/mL) radical-induced DNA scission. Therefore, date seed protein hydrolysates could be used as a potential functional food ingredient for health promotion.

  19. Carnosine and vitamin E--a promising pair in the combat against testicular oxidative stress in aged rats.

    PubMed

    Aydın, A F; Çoban, J; Doğan-Ekici, I; Doğru-Abbasoğlu, S; Uysal, M; Koçak-Toker, N

    2015-12-01

    Oxidative stress is considered to play a key role in ageing. Carnosine alone or together with vitamin E may prove to be helpful in dealing with problems of ageing through its antioxidant activity. Testis, by producing steroids and possessing a poor antioxidant system may become a strong target for the chronic oxidative stress generated during ageing. Therefore we investigated the in vivo effect of carnosine alone or together with vitamin E on testicular oxidative stress in aged rats. In this study, young (5 months) and aged (22 months) Wistar rats were used. Carnosine (250 mg kg(-1); i.p.; 5 days per week) and vitamin E (200 mg kg(-1); i.m.; twice per week) were given to aged rats for 2 months. Increased testicular lipid peroxidation and superoxide dismutase activity in aged rats were declined to the levels of young ones by both treatments. Decreased glutathione peroxidase and glutathione transferase activities returned to the level of young's only by carnosine plus vitamin E treatment. Histopathological evaluation described by Johnsen's score, also showed significant improvement with preserved spermatogenesis. Carnosine plus vitamin E treatment appears to stage a powerful performance by attenuating testicular oxidative stress and sparing the antioxidant system. © 2014 Blackwell Verlag GmbH.

  20. Carnosine, taurine and enzyme activities of human skeletal muscle fibres from elderly subjects with osteoarthritis and young moderately active subjects.

    PubMed

    Tallon, Mark J; Harris, Roger C; Maffulli, Nicola; Tarnopolsky, Mark A

    2007-04-01

    Ageing is associated with a reduction in muscle carnosine (beta-alanyl-L-histidine), but there are no data on the changes specifically in type I and type II muscle fibres. Given the higher carnosine content of type II fibers, changes observed in whole muscle may be secondary to a shift in fibre composition. Carnosine, beta-alanine, histidine, taurine, and citrate synthase (CS) and glycogen phosphorylase (Phos), were measured in pools of single muscle fibres from freeze-dried muscle biopsies of vastus lateralis of nine elderly sedentary subjects (65-80 years) with osteoarthritis of the knee and undergoing total knee replacement, and nine young moderately active healthy subjects (20-35 years). Fibres were characterised as type I or II by myosin ATPase activity. Carnosine was 53.2% lower in type II fibres of older subjects resulting in an estimated 7% (and most probably still higher) decline in intracellular physico-chemical buffering capacity. Younger subjects showed higher CS activities in type I and higher Phos activities in type II fibres. These differences were less apparent in elderly subjects. Possible causes for the change in the carnosine content are reduced physical activity, reduced meat intake, or the result of progressive denervation.

  1. Brominated Flame Retardants

    EPA Science Inventory

    Brominated flame retardants (BFRs) belong to a large class of compounds known as organohalogens. BFRs are currently the largest marketed flame retardant group due to their high performance efficiency and low cost. In the commercial market, more than 75 different BFRs are recogniz...

  2. [Genetics of mental retardation].

    PubMed

    Goldenberg, A; Saugier-Veber, P

    2010-10-01

    Mental retardation affects nearly 3 % of the population. The causes of these disorders are various and are often not identified. Recent advances focused on the molecular basis of mental retardation. Nearly half of mental retardation syndromes have a genetic origin and the description of molecular, cytogenetic and metabolic alterations in these disorders led to the development of diagnostic tools. Indeed, identifying the precise origin of the mental retardation allows to improve patient care and to refine the prognosis. Moreover, these molecular tools will help the geneticist to evaluate the recurrence risk in the family in the genetic counseling step. On a fundamental point of view, the knowledge of molecular basis of mental retardation will help to understand the biological pathway which constitutes the first step before therapeutic strategies. Every patient with mental retardation should be investigated for causal origin of the disease. We will detail the diagnostic methods necessary to investigate a patient presenting with mental retardation. Then different examples of syndromes including a mental retardation will be chosen to illustrate different clinical situations. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  3. Mental Retardation in Perspective.

    ERIC Educational Resources Information Center

    Horvath, Michael; And Others

    This monograph presents a general introduction to the history, classification, and characteristics of mental retardation. It begins with a discussion of the history of mental retardation from ancient Greece and Rome to the present. The beginnings of special education are traced to the early 19th century in Europe. Major influences in treatment of…

  4. Brominated Flame Retardants

    EPA Science Inventory

    Brominated flame retardants (BFRs) belong to a large class of compounds known as organohalogens. BFRs are currently the largest marketed flame retardant group due to their high performance efficiency and low cost. In the commercial market, more than 75 different BFRs are recogniz...

  5. D-carnosine octylester attenuates atherosclerosis and renal disease in ApoE null mice fed a Western diet through reduction of carbonyl stress and inflammation

    PubMed Central

    Menini, Stefano; Iacobini, Carla; Ricci, Carlo; Scipioni, Angela; Fantauzzi, Claudia Blasetti; Giaccari, Andrea; Salomone, Enrica; Canevotti, Renato; Lapolla, Annunziata; Orioli, Marica; Aldini, Giancarlo; Pugliese, Giuseppe

    2012-01-01

    BACKGROUND AND PURPOSE Lipoxidation-derived reactive carbonyl species (RCS) such as 4-hydroxy-2-nonenal (HNE) react with proteins to form advanced lipoxidation end products (ALEs), which have been implicated in both atherosclerosis and renal disease. L-carnosine acts as an endogenous HNE scavenger, but it is rapidly inactivated by carnosinase. This study aimed at assessing the effect of the carnosinase-resistant, D-carnosine, on HNE-induced cellular injury and of its bioavailable prodrug D-carnosine octylester on experimental atherosclerosis and renal disease. EXPERIMENTAL APPROACH Vascular smooth muscle cells (VSMCs) were exposed to HNE or H2O2 plus D-carnosine. ApoE null mice fed a Western, pro-atherogenic diet were treated with D-carnosine octylester for 12 weeks. KEY RESULTS In vitro, D-carnosine attenuated the effect of HNE, but not of H2O2, on VSMCs. In vivo, D-carnosine octylester-treated mice showed reduced lesion area and a more stable plaque phenotype compared with untreated animals, with reduced foam cell accumulation, inflammation and apoptosis and increased clearance of apoptotic bodies and collagen deposition, resulting in decreased necrotic core formation. Likewise, renal lesions were attenuated in D-carnosine octylester-treated versus untreated mice, with lower inflammation, apoptosis and fibrosis. This was associated with increased urinary levels of HNE-carnosine adducts and reduced protein carbonylation, circulating and tissue ALEs, expression of receptors for these products, and systemic and tissue oxidative stress. CONCLUSIONS AND IMPLICATIONS These data indicate RCS quenching with a D-carnosine ester was highly effective in attenuating experimental atherosclerosis and renal disease by reducing carbonyl stress and inflammation and that this may represent a promising therapeutic strategy in humans. PMID:22229552

  6. Fire-Retardant, Decorative Inks

    NASA Technical Reports Server (NTRS)

    Kourtides, D.; Nir, Z.; Mikroyannidis, J.

    1987-01-01

    Effectiveness of fire-retardant additives evaluated. Fire retardance of decorative acrylic printing inks for aircraft interiors enhanced by certain commercial and experimental fire-retardant additives, according to study.

  7. Fire-Retardant, Decorative Inks

    NASA Technical Reports Server (NTRS)

    Kourtides, D.; Nir, Z.; Mikroyannidis, J.

    1987-01-01

    Effectiveness of fire-retardant additives evaluated. Fire retardance of decorative acrylic printing inks for aircraft interiors enhanced by certain commercial and experimental fire-retardant additives, according to study.

  8. Determination of carnosine in feed and meat by high-performance anion-exchange chromatography with integrated pulsed amperometric detection.

    PubMed

    Nardiello, Donatella; Cataldi, Tommaso R I

    2004-05-07

    Carnosine (beta-alanyl-L-histidine) is a dipeptide regarded as an important molecular marker of the presence of processed animal proteins including meat and bone meal in animal feed. For its identification and quantification a sensitive and selective method by high-performance anion-exchange chromatography coupled with integrated pulsed amperometric detection (HPAEC-IPAD) was developed. The assay is based on isocratic elution with 100 mM NaOH as the mobile phase. Interferences of real matrices were efficiently removed; carnosine could be determined at the concentration ranges 0.1-100 microM with a rather low detection limit of 0.23 ng. Unlike feeds for dogs and cats, no carnosine peak was observed in all examined feeds for ruminants. The good analytical characteristics allowed camosine determination down to 5 microg/g of feed.

  9. [Genetic mental retardation].

    PubMed

    Rodríguez-Revenga Bodi, L; Madrigal-Bajo, I; Milà-Racasens, M

    2006-10-10

    Mental retardation is a frequently occurring disorder with a major impact on the life of the affected person, the family and society, with an estimated incidence of 1-3% in developed countries. Among the etiologies that cause mental retardation it would appear that 30% have a genetic origin, 15% have an environmental origin, and the rest have an unknown origin. AIM. To report the genetic causes of mental retardation and the new molecular techniques used in order to reach a diagnosis. The identification of the causes of mental retardation is of great interest due to the consequences it has in the intervention, prognosis, estimation of risk of recurrence and its prevention. Causes of mental retardation are extremely heterogeneous. Genetic causes can be classified as chromosomal alterations (aneuploidies, subtelomeric rearrangements, microdeletion or microduplication syndrome), monogenic, metabolic, or multifactorial alterations. Thanks to the development of high-resolution new techniques -comparative genomic hybridization (CGH) arrays, and multiplex ligation probe amplification (MLPA)- now we are able to detect microdeletions and microduplication all over the genome, which might be related with mental retardation. The genetic causes of mental retardation are highly heterogeneous and complex. Nowadays and thanks to the new molecular techniques we are able to perform several studies, even though almost half of cases remain undiagnosed. In those undiagnosed cases with positive familial history a genetic counseling can be provided. However, in order to perform a prenatal or a preimplantational study a genetic diagnosis is required.

  10. X linked mental retardation.

    PubMed

    Rejeb, Imen; Ben Jemaa, Lamia; Chaabouni, Habiba

    2009-05-01

    Mental retardation (MR) is a group of heterogeneous clinical conditions. There are more than 900 genetic disorders associated with MR and it affects around 3% of the general population. Many MR conditions described are syndromic, fragile X syndrome being the most common clinical entity among them. X linked mental retardation (XLMR) is subdivided in two categories: syndromic XLMR (MRXS) when MR is associated with clinical features and non-syndromic XLMR (MRX) when MR is isolated. The aim of this systematic review of the literature was to join together the results of several studies related to X linked mental retardation and to present various genes implicated in this disease. In this review, focus has been given on genes implicated in mental retardation, the clinical data and on phenotype-genotype correlations. An exhaustive electronic and library research of the recent literature was carried out on the Web sites "Science Direct" and "Interscience Wiley". The key words used were "mental retardation", "X chromosome", "gene", "syndromic mental retardation", "non-syndromic mental retardation". In this review a number of X linked genes, the clinical features associated with the gene abnormality, and the prevalence of the disease gene are discussed. We classified these genes by order of their first implication in MR. A table presented on the XLMR Update Web site who list the 82 known XLMR genes is available as XLMR Genes and corresponding proteins.

  11. Carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury through histamine H₁ and H₂ receptors in vitro.

    PubMed

    Zhang, Luyi; Yao, Ke; Fan, Yanying; He, Ping; Wang, Xiaofen; Hu, Weiwei; Chen, Zhong

    2012-12-01

    Although it is believed that carnosine has protective effects on various cell types, its effect on microvascular endothelial cells has not been well defined. In the present study, we investigated the protective effects of carnosine in microvascular endothelial cells using an in vitro rotenone-induced oxidative stress model. Mouse brain microvascular endothelial cells were exposed to 1 μmol/L rotenone for 18 h. In some experiments, carnosine (100 nmol/L-1 mmol/L) was added 30 min prior to rotenone exposure. When used, histamine receptor antagonists (100 nmol/L-10 μmol/L) were added 15 min before carnosine treatment. After rotenone exposure, apoptosis of microvascular cells was analysed by Hoechst 33342 staining, whereas mitochondrial membrane potential was assessed by JC-1 staining. Intracellular carnosine and histamine levels were determined using HPLC or ultra-HPLC. Over the range 1 μmol/L-1 mmol/L, carnosine concentration-dependently decreased the number of apoptotic cells after 18 h exposure to rotenone. This effect was reversed by the histamine H1 receptor antagonists pyrilamine and diphenhydramine (1 and 10 μmol/L) and the H2 receptor antagonists cimetidine (100 nmol/L-10 μmol/L) and zolatidine (10 μmol/L). α-Fluoromethylhistidine (100 μmol/L), a selective and irreversible inhibitor of histidine decarboxylase, also significantly inhibited the protective effects of carnosine. At 0.1 mmol/L, carnosine restored the decrease in mitochondrial membrane potential after 6 h exposure to 1 μmol/L rotenone and this effect was also reversed by the H1 and H2 receptor antagonists. Moreover, intracellular carnosine levels increased as early as 1 h after carnosine treatment, whereas intracellular histamine levels increased 18 h after carnosine treatment. The results of the present study indicate that carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury via histamine H1 and H2 receptors. The

  12. Molecular identification of carnosine N-methyltransferase as chicken histamine N-methyltransferase-like protein (hnmt-like).

    PubMed

    Drozak, Jakub; Chrobok, Lukasz; Poleszak, Olga; Jagielski, Adam K; Derlacz, Rafal

    2013-01-01

    Anserine (beta-alanyl-N(Pi)-methyl-L-histidine), a naturally occurring derivative of carnosine (beta-alanyl-L-histidine), is an abundant constituent of skeletal muscles and brain of many vertebrates. Although it has long been proposed to serve as a proton buffer, radicals scavenger and transglycating agent, its physiological function remains obscure. The formation of anserine is catalyzed by carnosine N-methyltransferase which exhibits unknown molecular identity. In the present investigation, we have purified carnosine N-methyltransferase from chicken pectoral muscle about 640-fold until three major polypeptides of about 23, 26 and 37 kDa coeluting with the enzyme were identified in the preparation. Mass spectrometry analysis of these polypeptides resulted in an identification of histamine N-methyltransferase-like (HNMT-like) protein as the only meaningful candidate. Analysis of GenBank database records indicated that the hnmt-like gene might be a paralogue of histamine N-methyltransferase gene, while comparison of their protein sequences suggested that HNMT-like protein might have acquired a new activity. Chicken HNMT-like protein was expressed in COS-7 cells, purified to homogeneity, and shown to catalyze the formation of anserine as confirmed by both chromatographic and mass spectrometry analysis. Both specificity and kinetic studies carried out on the native and recombinant enzyme were in agreement with published data. Particularly, several compounds structurally related to carnosine, including histamine and L-histidine, were tested as potential substrates for the enzyme, and carnosine was the only methyl group acceptor. The identification of the gene encoding carnosine N-methyltransferase might be beneficial for estimation of the biological functions of anserine.

  13. Molecular Identification of Carnosine N-Methyltransferase as Chicken Histamine N-Methyltransferase-Like Protein (HNMT-Like)

    PubMed Central

    Drozak, Jakub; Chrobok, Lukasz; Poleszak, Olga; Jagielski, Adam K.; Derlacz, Rafal

    2013-01-01

    Anserine (beta-alanyl-N(Pi)-methyl-L-histidine), a naturally occurring derivative of carnosine (beta-alanyl-L-histidine), is an abundant constituent of skeletal muscles and brain of many vertebrates. Although it has long been proposed to serve as a proton buffer, radicals scavenger and transglycating agent, its physiological function remains obscure. The formation of anserine is catalyzed by carnosine N-methyltransferase which exhibits unknown molecular identity. In the present investigation, we have purified carnosine N-methyltransferase from chicken pectoral muscle about 640-fold until three major polypeptides of about 23, 26 and 37 kDa coeluting with the enzyme were identified in the preparation. Mass spectrometry analysis of these polypeptides resulted in an identification of histamine N-methyltransferase-like (HNMT-like) protein as the only meaningful candidate. Analysis of GenBank database records indicated that the hnmt-like gene might be a paralogue of histamine N-methyltransferase gene, while comparison of their protein sequences suggested that HNMT-like protein might have acquired a new activity. Chicken HNMT-like protein was expressed in COS-7 cells, purified to homogeneity, and shown to catalyze the formation of anserine as confirmed by both chromatographic and mass spectrometry analysis. Both specificity and kinetic studies carried out on the native and recombinant enzyme were in agreement with published data. Particularly, several compounds structurally related to carnosine, including histamine and L-histidine, were tested as potential substrates for the enzyme, and carnosine was the only methyl group acceptor. The identification of the gene encoding carnosine N-methyltransferase might be beneficial for estimation of the biological functions of anserine. PMID:23705015

  14. EPILEPSY AND MENTAL RETARDATION

    PubMed Central

    Madhavan, Thuppal; Narayan, Jayanthi

    1992-01-01

    Epilepsy is one of the most frequently associated conditions with mental retardation which interferes with the learning process. Vie present study investigates the 1207 cases (Male -8I4, Female-393) registered at NIMH, Secunderabad, over a period of two years. Vie factors studied were the prevalence of epilepsy, degree of mental retardation, aetiology and associated factors. Ten mentally retarded persons with epilepsy were followed up longitudinally to study the effect of epilepsy on learning. It was observed that an attack of seizure resulted in a setback in the learning of skills. The results are discussed. PMID:21776089

  15. Bioactive peptide carnosin protects against lead acetate-induced hepatotoxicity by abrogation of oxidative stress in rats.

    PubMed

    Hasanein, Parisa; Kazemian-Mahtaj, Azam; Khodadadi, Iraj

    2016-08-01

    Context Oxidative stress is a common mechanism of liver injury. Carnosine is a dipeptide having strong antioxidant effects. Objectives We investigated the effects of carnosine on lead-induced hepatotoxicity and oxidative stress in rats. Materials and methods Animals received an aqueous solution of lead acetate (500 mg Pb/L in the drinking water) and/or daily oral gavage of carnosine (10 mg/kg) for 8 weeks. Rats were then weighed and used for the biochemical (commercial kits), molecular (standard chemical methods) and histological (microscopic) evaluations. Results Lead-induced oxidative stress in liver tissue was indicated by a significant increase in the level of malondialdehyde (MDA) (8.25 ± 0.15 nmol/mg) as well as decrease in the level of total antioxidant capacity (TAC) (1.72 ± 0.25 μmol/g) and total thiol (SH) groups) 1.9 ± 0.22 μmol/g). Carnosine treatment decreased MDA (4 ± 0.08 nmol/mg), whereas it increased the contents of total thiol (3.25 ± 0.04 μmol/g) and TAC (3.44 ± 0.32 μmol/g) in the lead group. Carnosine also prevented the decreased body weight (p < 0.001), albumin (p < 0.05) and total protein levels (p < 0.001) and increased liver weight (p < 0.05) and activates of hepatic enzymes (p's < 0.001) (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase) in the lead group. Furthermore, histopathological study showed that carnosine attenuates liver damage by decreasing necrosis and infiltration of inflammatory cells. Conclusion Carnosine prevented lead-induced hepatotoxicity, indicated by molecular, biochemical and histopathological analyses through inhibiting lipid peroxidation and enhancing antioxidant defence systems. Therefore, carnosine makes a good candidate to protect against the deleterious effect of chronic lead intoxication.

  16. Synthesis and evaluation of neuroprotective alpha,beta-unsaturated aldehyde scavenger histidyl-containing analogues of carnosine.

    PubMed

    Guiotto, Andrea; Calderan, Andrea; Ruzza, Paolo; Osler, Alessio; Rubini, Chiara; Jo, Dong-Gyu; Mattson, Mark P; Borin, Gianfranco

    2005-09-22

    The synthesis, scavenging activity, and cytoprotective profiles of histidyl-containing carnosine analogues bearing hydrazide or 1,2-diol moieties is reported. Some compounds have demonstrated higher aldehyde-sequestering efficiency than carnosine and were also efficient in protecting SH-SY5Y neuroblastoma cells and rat hippocampal neurons from 4-hydroxy-trans-2,3-nonenal (HNE)-mediated death. The cytoprotective efficacy of these compounds suggests their potential use as therapeutic agents for disorders that involve excessive membrane lipids peroxidation and HNE-mediated neuronal toxicity.

  17. Fire retardant polyisocyanurate foam

    NASA Technical Reports Server (NTRS)

    Riccitiello, S. R.; Parker, J. A.

    1972-01-01

    Fire retardant properties of low density polymer foam are increased. Foam has pendant nitrile groups which form thermally-stable heterocyclic structures at temperature below degradation temperature of urethane linkages.

  18. The effects of carnosine on oxidative DNA damage levels and in vitro lifespan in human peripheral blood derived CD4+T cell clones.

    PubMed

    Hyland, P; Duggan, O; Hipkiss, A; Barnett, C; Barnett, Y

    2000-12-20

    Carnosine (beta-alanyl-L-histidine), an abundant naturally-occurring dipeptide has been shown to exhibit anti-ageing properties towards cultured cells, possibly due in part to its antioxidant/free radical scavenging abilities. In this paper the results of an investigation on the effects of carnosine, at the physiological concentration of 20 mM, on oxidative DNA damage levels and in vitro lifespan in peripheral blood derived human CD4+ T cell clones are reported. Under the culture conditions used (20% O(2)) long term culture with carnosine resulted in a significant increase in the lifespan of a clone derived from a healthy young subject. No such extension was observed when a T cell clone from a healthy old SENIEUR donor was similarly cultured. Culture with carnosine from the midpoint of each clone's lifespan did not have any effect on longevity, independent of donor age. Oxidative DNA damage levels were measured in the clones at various points in their lifespans. Carnosine acted as a weak antioxidant, with levels of oxidative DNA damage being lower in T cells grown long term in the presence of carnosine. The possibility that carnosine might confer anti-ageing effects to T cells under physiological oxygen tensions would appear to be worthy of further investigation.

  19. Litter-Spinning Retarders

    NASA Technical Reports Server (NTRS)

    Wilson, John C.

    1995-01-01

    Aerodynamic plates stop litter from spinning during hoisting by helicopter. Features of proposed litter-spinning retarders include convenience of deployment and independence from ground restraint. Retarder plate(s) folded flat against bottom of litter during storage or while litter is loaded. Plate(s) held in storage position by latch that releases manually or automatically as litter is hoisted. Upon release, springs move plates into deployed position.

  20. Litter-Spinning Retarders

    NASA Technical Reports Server (NTRS)

    Wilson, John C.

    1995-01-01

    Aerodynamic plates stop litter from spinning during hoisting by helicopter. Features of proposed litter-spinning retarders include convenience of deployment and independence from ground restraint. Retarder plate(s) folded flat against bottom of litter during storage or while litter is loaded. Plate(s) held in storage position by latch that releases manually or automatically as litter is hoisted. Upon release, springs move plates into deployed position.

  1. Laccase mediated-synthesis of hydroxycinnamoyl-peptide from ferulic acid and carnosine.

    PubMed

    Aljawish, Abdulhadi; Chevalot, Isabelle; Madad, Nidal; Paris, Cédric; Muniglia, Lionel

    2016-06-10

    Carnosine (CAR) dipeptide was functionalized with ferulic acid (FA) as substrate using laccase from Myceliophtora thermophila as biocatalyst. The enzymatic reaction was performed in aqueous medium under mild conditions (pH 7.5, 30°C) as an eco-friendly procedure. Results showed that this enzymatic process led to the synthesis of two new derivatives (P1, P2), from the coupling between CAR and FA derived products. Conditions allowing a high production of P1, P2 derivatives were determined with an optimal ratio of (FA: CAR) of (1:1.6) at optimal time reaction of 8h. Under these optimal conditions, the coupling between CAR and FA-products was demonstrated, resulting in the decrease of -NH2 groups (almost 50%) as quantified via derivatization. Due to the presence of FA in the structure of these new derivatives, they exhibited higher hydrophobic property than carnosine. Structural analyses by mass spectrometry showed that P1 and P2 (FA-CAR) derivatives exhibited the same molecular mass (MM 770g/mol) containing one CAR-molecule and three FA-molecules but with different chemical structures. Furthermore, these derivatives presented improved antioxidant (almost 10 times) and anti-proliferative (almost 18 times) properties in comparison with CAR. Moreover, P1 derivative exhibited higher antioxidant and anti-proliferative activities than P2 derivative, which confirmed the different structures of P1 and P2. These results suggested that the oxidized phenols coupling with carnosine is a promising process to enhance the CAR-properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Covalent cross-linking of glutathione and carnosine to proteins by 4-oxo-2-nonenal.

    PubMed

    Zhu, Xiaochun; Gallogly, Molly M; Mieyal, John J; Anderson, Vernon E; Sayre, Lawrence M

    2009-06-01

    The lipid oxidation product 4-oxo-2-nonenal (ONE) derived from peroxidation of polyunsaturated fatty acids is a highly reactive protein cross-linking reagent. The major family of cross-links reflects conjugate addition of side chain nucleophiles such as sulfhydryl or imidazole groups to the C triple bond C of ONE to give either a 2- or 3-substituted 4-ketoaldehyde, which then undergoes Paal-Knorr condensation with the primary amine of protein lysine side chains. If ONE is intercepted in biological fluids by antielectrophiles such as glutathione (GSH) or beta-alanylhistidine (carnosine), this would lead to circulating 4-ketoaldehydes that could then bind covalently to the protein Lys residues. This phenomenon was investigated by SDS-PAGE and mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight and LC-ESI-MS/MS with both tryptic and chymotryptic digestion). Under the reaction conditions of 0.25-2 mM ONE, 1 mM GSH or carnosine, 0.25 mM bovine beta-lactoglobulin (beta-LG), and 100 mM phosphate buffer (pH 7.4, 10% ethanol) for 24 h at 37 degrees C, virtually every Lys of beta-LG was found to be fractionally cross-linked to GSH. Cross-linking of Lys to carnosine was less efficient. Using cytochrome c and RNase A, we showed that ONE becomes more protein-reactive in the presence of GSH, whereas protein modification by 4-hydroxy-2-nonenal is inhibited by GSH. Stable antielectrophile-ONE-protein cross-links may serve as biomarkers of oxidative stress and may represent a novel mechanism of irreversible protein glutathionylation.

  3. Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders.

    PubMed

    Cararo, José H; Streck, Emilio L; Schuck, Patricia F; Ferreira, Gustavo da C

    2015-09-01

    Imidazole dipeptides (ID), such as carnosine (β-alanyl-L-histidine), are compounds widely distributed in excitable tissues of vertebrates. ID are also endowed of several biochemical properties in biological tissues, including antioxidant, bivalent metal ion chelating, proton buffering, and carbonyl scavenger activities. Furthermore, remarkable biological effects have been assigned to such compounds in age-related human disorders and in patients whose activity of serum carnosinase is deficient or undetectable. Nevertheless, the precise biological role of ID is still to be unraveled. In the present review we shall discuss some evidences from clinical and basic studies for the utilization of ID as a drug therapy for age-related human disorders.

  4. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine.

    PubMed

    Zhang, Shiqi; Ntasis, Emmanouil; Kabtni, Sarah; van den Born, Jaap; Navis, Gerjan; Bakker, Stephan J L; Krämer, Bernhard K; Yard, Benito A; Hauske, Sibylle J

    2016-01-01

    Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubular epithelial cells (PTECs) more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG) or HG (30 mM), were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1), ferroportin (IREG), and transferrin receptor protein 1 (TFRC). Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity.

  5. Effects of carnosine supplementation to an all-plant protein diet for rainbow trout(Oncorhynchus mykiss)

    USDA-ARS?s Scientific Manuscript database

    Fish meal may contain “unknown growth factors” that have yet to be identified for their physiological role. Carnosine is a histidine-ß-alanine dipeptide found in muscle and nervous system tissue which has been demonstrated to have biological activity, but its physiological role is not well defined. ...

  6. Daily Carnosine and Anserine Supplementation Alters Verbal Episodic Memory and Resting State Network Connectivity in Healthy Elderly Adults

    PubMed Central

    Rokicki, Jaroslav; Li, Lucia; Imabayashi, Etsuko; Kaneko, Jun; Hisatsune, Tatsuhiro; Matsuda, Hiroshi

    2015-01-01

    Carnosine and anserine are strong antioxidants, previously demonstrated to reduce cognitive decline in animal studies. We aimed to investigate their cognitive and neurophysiological effects, using functional MRI, on humans. Thirty-one healthy participants (age 40–78, 10 male/21 female) were recruited to a double-blind placebo-controlled study. Participants were assigned to twice-daily doses of imidazole dipeptide formula (n = 14), containing 500 mg (carnosine/anserine, ratio 1/3) or an identical placebo (n = 17). Functional MRI and neuropsychological assessments were carried out at baseline and after 3 months of supplementation. We analyzed resting state functional connectivity with the FSL fMRI analysis package. There were no differences in neuropsychological scores between the groups at baseline. After 3 months of supplementation, the carnosine/anserine group had better verbal episodic memory performance and decreased connectivity in the default mode network, the posterior cingulate cortex and the right fronto parietal network, as compared with the placebo group. Furthermore, there was a correlation between the extents of cognitive and neuroimaging changes. These results suggest that daily carnosine/anserine supplementation can impact cognitive function and that network connectivity changes are associated with its effects. PMID:26640437

  7. Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People

    PubMed Central

    Hisatsune, Tatsuhiro; Kaneko, Jun; Kurashige, Hiroki; Cao, Yuan; Satsu, Hideo; Totsuka, Mamoru; Katakura, Yoshinori; Imabayashi, Etsuko; Matsuda, Hiroshi

    2015-01-01

    Our goal in this study was to determine whether or not anserine/carnosine supplementation (ACS) is capable of preserving cognitive function of elderly people. In a double-blind randomized controlled trial, volunteers were randomly assigned to an ACS or placebo group at a 1:1 ratio. The ACS group took 1.0 g of an anserine/carnosine (3:1) formula daily for 3 months. Participants were evaluated by psychological tests before and after the 3-month supplementation period. Thirty-nine healthy elderly volunteers (60–78 years old) completed the follow-up tests. Among the tests, delayed recall verbal memory assessed by the Wechsler Memory Scale-Logical Memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0128). Blood analysis revealed a decreased secretion of inflammatory cytokines, including CCL-2 and IL-8, in the ACS group. MRI analysis using arterial spin labeling showed a suppression in the age-related decline in brain blood flow in the posterior cingulate cortex area in the ACS group, compared to the placebo group (p = 0.0248). In another randomized controlled trial, delayed recall verbal memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0202). These results collectively suggest that ACS may preserve verbal episodic memory and brain perfusion in elderly people, although further study is needed. PMID:26682691

  8. Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People.

    PubMed

    Hisatsune, Tatsuhiro; Kaneko, Jun; Kurashige, Hiroki; Cao, Yuan; Satsu, Hideo; Totsuka, Mamoru; Katakura, Yoshinori; Imabayashi, Etsuko; Matsuda, Hiroshi

    2016-01-01

    Our goal in this study was to determine whether or not anserine/carnosine supplementation (ACS) is capable of preserving cognitive function of elderly people. In a double-blind randomized controlled trial, volunteers were randomly assigned to an ACS or placebo group at a 1:1 ratio. The ACS group took 1.0 g of an anserine/carnosine (3:1) formula daily for 3 months. Participants were evaluated by psychological tests before and after the 3-month supplementation period. Thirty-nine healthy elderly volunteers (60-78 years old) completed the follow-up tests. Among the tests, delayed recall verbal memory assessed by the Wechsler Memory Scale-Logical Memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0128). Blood analysis revealed a decreased secretion of inflammatory cytokines, including CCL-2 and IL-8, in the ACS group. MRI analysis using arterial spin labeling showed a suppression in the age-related decline in brain blood flow in the posterior cingulate cortex area in the ACS group, compared to the placebo group (p = 0.0248). In another randomized controlled trial, delayed recall verbal memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0202). These results collectively suggest that ACS may preserve verbal episodic memory and brain perfusion in elderly people, although further study is needed.

  9. Ocular pharmacokinetics of carnosine 5% eye drops following topical application in rabbit.

    PubMed

    Tianyang, Zhou; Ling, Zhu; Liya, Wang; Junjie, Zhang

    2011-02-01

    To evaluated the ocular pharmacokinetics of carnosine (CAR, a biologically active dipeptide which occurs naturally throughout the human body) 5% eye drops following topical application. CAR 5% eye drops were topically applied repeatedly (50 μL × 4) at an interval of 5 min. Aqueous humor and lens were collected after 5, 15, 30, 45, 60, 90, 120, 150, and 180 min. CAR concentration was determined by high performance liquid chromatography-tandem quadrupole mass spectrometer (HPLC-MS/MS). CAR concentration in treated eyes was significantly higher than control eyes. Peak concentration (C(max)) of carnosine in treated aqueous humor occurred 60 min following topical administration, with the administrated concentration (total-endogenous concentration) of 40.9 ± 18.9 μg/mL. The area under the concentration-time curve between 0 and 180 min (AUC(0-180)) was 3,276.8 (μg/mL) × min. CAR concentration in treated lens rises to effective level rapidly and changes slightly with time after topical administration. The administrated concentration of car in lens at the last time point (180 min, 1.92 ± 1.65 μg/mL) was not significantly different with the highest value (15 min, 2.11 ± 1.83 μg/mL). CAR 5% eye drops were likely to be absorbed into aqueous humor efficiently and accumulated in lens. More attention should be put onto enhancing the penetration of CAR into lens capsule.

  10. [Nosology of mental retardation].

    PubMed

    González Castañón, Diego; Aznar, Andrea S; Wahlberg, Ernesto

    2006-01-01

    The classificatory systems used through history. The analysis of their criteria for categorization allowed the authors to deduce the nosologic considerations and the paradigms underlying the conceptions of mental retardation sustained in each time period, not always from psychiatric origins. The effects of considering mental retardation as a disorder or a disability are discussed together with the correlation with the type of interventions and instituted social practices (related to mental health, social participation, education). The characteristics of the supports' paradigm and its consequences in the classifications and intervention plans are analyzed with more detail.

  11. Fire retardant polyetherimide nanocomposites

    SciTech Connect

    Lee, J.; Takekoshi, T.; Giannelis, E.P.

    1997-09-01

    Polyetherimide-layered silicates nanocomposites with increased char yield and fire retardancy are described. The use of nanocomposites is a new, environmentally-benign approach to improve fire resistance of polymers. An increase in the aromaticity yields high char residues that normally correlate with higher oxygen index and lower flammability. The often high cost of these materials and the specialized processing techniques required, however, have limited the use of these polymers to certain specialized applications. The effectiveness of fire retardant fillers is also limited since the large amounts required make processing difficult and might inadvertently affect mechanical properties.

  12. Influence of genetic knockout of Pept2 on the in vivo disposition of endogenous and exogenous carnosine in wild-type and Pept2 null mice

    PubMed Central

    Kamal, Mohamed A.; Jiang, Huidi; Hu, Yongjun; Keep, Richard. F.; Smith, David E.

    2009-01-01

    Carnosine (β-alanyl-l-histidine), an endogenous dipeptide substrate of the proton-coupled oligopeptide transporter PEPT2, plays an important role in many physiological processes. This study examined the effect of PEPT2 on the disposition of endogenous and exogenous carnosine in wild-type and Pept2 null mice. After exogenous dosing of [3H]carnosine (1 nmol/g iv bolus), a marked increase was observed in its systemic clearance in Pept2 null mice (0.50 vs. 0.29 ml/min), resulting in a decreased systemic exposure of dipeptide (area under the curve = 43.7 vs. 73.0 min×μM). Carnosine uptake was substantially reduced in the kidney of Pept2 null mice, and renal clearance increased 18-fold in this genotype (206 vs. 11.5 μl/min). Fractional reabsorption of carnosine in Pept2 null mice was only one-fifth that in wild-type animals (0.20 vs. 0.94). PEPT2 also had a substantial impact in brain where the cerebrospinal fluid (CSF)-to-plasma concentration ratio of carnosine was eightfold greater in Pept2 null mice (0.70 vs. 0.08). With respect to endogenous carnosine levels, significant reductions were observed in Pept2 null compared with wild-type mice for choroid plexus (0.026 vs. 0.20 mmol/kg), olfactory bulb (1.12 vs. 1.79 mmol/kg), and spleen (0.019 vs. 0.029 mmol/kg). In contrast, carnosine levels in the skeletal muscle of Pept2 null mice were significantly increased (1.70 vs. 1.14 mmol/kg), and no differences were observed between genotypes for endogenous carnosine levels in plasma and CSF. These results demonstrate that PEPT2 significantly modulates the disposition of exogenous carnosine. However, endogenous carnosine levels may be under homeostatic control to maintain systemic and central concentrations under physiological in vivo conditions. PMID:19225147

  13. Oxaliplatin complexes with carnosine and its derivatives: in vitro cytotoxicity, mass spectrometric and computational studies with a focus on complex fragmentation.

    PubMed

    Moustafa, Eslam M; Camp, Claire L; Youssef, Ahmed S; Amleh, Asma; Reid, Helen J; Sharp, Barry L; Shoeib, Tamer

    2013-11-01

    The complexation of the Pt-based anti-cancer drug oxaliplatin (OxPt) with biological ligands other than DNA is believed to be a major cellular sink for the drug reducing its therapeutic potential and acting as a potential cause of toxicity. In this paper, the very first hypothesis driven investigation of the role of the naturally abundant cytoplasmic dipeptide ligand β-alanyl-l-histidine dipeptide (carnosine) in OxPt detoxification is presented. In vitro studies on hepatocellular carcinoma HepG2 cells suggest that carnosine may inhibit the cytotoxic action of OxPt most likely through the formation of complexes that are less cytotoxic than OxPt alone. Evidence is provided to suggest that pre-exposure of HepG2 cells to elevated levels of carnosine appears to have a lasting effect on reducing the cytotoxicity of OxPt even after the removal of the externally added carnosine. This effect, however, is likely under kinetic control as its magnitude was shown not to vary significantly with the level of carnosine exposure within the concentration range used in this study. Various mass spectrometry techniques employing electrospray ionization and chip nanospray were employed to study the interaction of oxaliplatin with carnosine as well as two of its derivatives β-alanyl-N-methylhistidine (anserine) and N-acetylcarnosine (NAC). Evidence of complexation between OxPt and each of the three ligands examined is presented. Most species observed were unambiguously assigned and compared to their theoretical isotopic patterns. Common fragmentation products due to the collisionally-activated protonated complexes of each of the ligands examined with OxPt, [M + OxPt + H](+), where M = carnosine, anserine or NAC, were reported. Density functional calculations at the B3LYP/LANL2DZ level were used to obtain structural information and relative free energies of different isomers of the observed precursor [Carnosine + OxPt + H](+) both in the gas phase and in solution as well as to probe its

  14. Zinc carnosine protects against hydrogen peroxide-induced DNA damage in WIL2-NS lymphoblastoid cell line independent of poly (ADP-Ribose) polymerase expression.

    PubMed

    Ooi, Theng Choon; Mohammad, Nur Hafiza; Sharif, Razinah

    2014-12-01

    The aim of this study is to investigate the ability of zinc carnosine to protect the human lymphoblastoid (WIL2-NS) cell line from hydrogen peroxide-induced DNA damage. Cells were cultured with medium containing zinc carnosine at the concentrations of 0.4, 4, 16 and 32 μM for 9 days prior to treatment with 30 μM of hydrogen peroxide (30 min). Zinc carnosine at the concentration 16 μM was optimal in protecting cells from hydrogen peroxide-induced cytotoxicity and gave the lowest percentage of apoptotic and necrotic cells. Results showed that zinc carnosine was able to induce glutathione production and protect cells from hydrogen peroxide-induced oxidative stress at all concentration and the highest protection was observed at 32-μM zinc carnosine culture. Cytokinesis-block micronucleus cytome assay showed that cells cultured with 4-32 μM of zinc carnosine showed significant reduction in micronuclei formation, nucleoplasmic bridges and nuclear bud frequencies (p < 0.05), suggesting that these concentrations maybe optimal in protecting cells from hydrogen peroxide-induced DNA damage. However, after being challenged with hydrogen peroxide, no increase in poly(ADP-ribose) polymerase expression was observed. Thus, results from this study demonstrate that zinc carnosines possess antioxidant properties and are able to reduce hydrogen peroxide-induced DNA damage in vitro independent of poly(ADP-ribose) polymerase. Further studies are warranted to understand the mechanism of protection of zinc carnosine against hydrogen peroxide-induced damage.

  15. On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?

    PubMed Central

    Alany, Raid G.

    2016-01-01

    Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s) behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH) assays. Indirect in vitro and ex vivo antioxidant assays were studied by measuring glutathione bleaching capacity and total sulfhydryl (SH) capacity of bovine lens homogenates as well as hydrogen-peroxide-stress assay using human lens epithelial cells. Whole porcine lenses were incubated in high galactose media to study the anticataract effects of L-carnosine. MTT cytotoxicity assays were conducted on human lens epithelial cells. Results. The results showed that L-carnosine is a highly potent antiglycating agent but with weak metal chelating and antioxidant properties. There were no significant decreases in lens epithelial cell viability compared to negative controls. Whole porcine lenses incubated in high galactose media and treated with 20 mM L-carnosine showed a dramatic inhibition of advanced glycation end product formation as evidenced by NBT and boronate affinity chromatography assays. Conclusion. L-Carnosine offers prospects for investigating new methods of treatment for diabetic cataract and any diseases that are caused by glycation. PMID:27822337

  16. Effects of carnosine on long-term plasticity of medial perforant pathway/dentate gyrus synapses in urethane-anesthetized rats: an in vivo model.

    PubMed

    Süer, Cem; Dolu, Nazan; Artis, Seda; Aydogan, Sami

    2009-08-01

    The objective of this study was to examine the effect of carnosine on the hippocampal-dependent learning in perforant pathway/dentate gyrus synapses. The experiments were carried out on adult rats. A bipolar stimulating electrode was placed to the medial perforant path and a double-barrel glass micropipette was placed in the dentate gyrus as the recording electrode. Artificial cerebrospinal fluid (to control group) or carnosine (0.1, 1 microg/microL) was infused into the dentate gyrus via one of the barrels of the glass electrode. Our results showed that the I/O curve of excitatory postsynaptic potential (EPSP) slope or population spike (PS) amplitude was not significantly shifted by carnosine. Although carnosine infused prior to high-frequency stimulation (HFS) decreased the slope of EPSP and amplitude of PS, when infused after HFS, no effect was observed. In the present study, we speculated that carnosine decreased LTP by inhibiting sGC activation. The present experiment provides the first evidence that carnosine may play a role in synaptic plasticity in dentate gyrus in vivo.

  17. On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?

    PubMed

    Abdelkader, Hamdy; Longman, Michael; Alany, Raid G; Pierscionek, Barbara

    2016-01-01

    Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s) behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH) assays. Indirect in vitro and ex vivo antioxidant assays were studied by measuring glutathione bleaching capacity and total sulfhydryl (SH) capacity of bovine lens homogenates as well as hydrogen-peroxide-stress assay using human lens epithelial cells. Whole porcine lenses were incubated in high galactose media to study the anticataract effects of L-carnosine. MTT cytotoxicity assays were conducted on human lens epithelial cells. Results. The results showed that L-carnosine is a highly potent antiglycating agent but with weak metal chelating and antioxidant properties. There were no significant decreases in lens epithelial cell viability compared to negative controls. Whole porcine lenses incubated in high galactose media and treated with 20 mM L-carnosine showed a dramatic inhibition of advanced glycation end product formation as evidenced by NBT and boronate affinity chromatography assays. Conclusion. L-Carnosine offers prospects for investigating new methods of treatment for diabetic cataract and any diseases that are caused by glycation.

  18. Mental Retardation Film List.

    ERIC Educational Resources Information Center

    National Library of Medicine (DHEW), Bethesda, MD.

    A list of films on mental retardation includes titles, publication information, physical descriptions, language revisions when other than English, series reference, technical description of film content, sale source, and distributor. Films intended for the general public are grouped under the heading Nonprofessional; others are listed as…

  19. Vignettes in Mental Retardation.

    ERIC Educational Resources Information Center

    Crissey, Marie Skodak

    1983-01-01

    Described are turn-of-the-century (1900) efforts of E. Johnstone, Vineland Training School for the mentally retarded; H. Goddard, psychologist (also at Vineland); and C. Davenport, Carnegie Foundation biological laboratory, Coldspring Harbor; to identify the roles of genetic heredity and environmental impact, and thus to eradicate or ameliorate…

  20. Flame retardant polymeric materials

    SciTech Connect

    Lewin, M.; Atlas, S.M.; Pearce, E.M.

    1982-01-01

    The flame retardation of polyolefins is the focus of this volume. Methods for reduction of smoke and experimental evaluation of flammability parameters for polymeric materials are discussed. The flammability evaluation methods for textiles and the use of mass spectrometry for analysis of polymers and their degradation products are also presented.

  1. Monkey Retardate Learning Analysis

    ERIC Educational Resources Information Center

    Chamove, A. S.; Molinaro, T. J.

    1978-01-01

    Seven rhesus monkeys reared on diets high in phenylalanine to induce phenylketonuria (PKU--a metabolic disorder associated with mental retardation if untreated) were compared with normal, pair-fed, and younger controls; frontal brain-lesioned monkeys; and those raised on high-tryptophan diets in three object discrimination tasks. (Author)

  2. Deafness and Mental Retardation.

    ERIC Educational Resources Information Center

    Stewart, Larry G., Ed.

    Nine selected proceedings from a study institute discuss program alternatives for the education of deaf mentally retarded (MR) children along with such related issues as identification, size and scope of the problem, instructional approaches, curricular planning, instructional media, program funding sources, and vocational rehabilitation. The…

  3. Monkey Retardate Learning Analysis

    ERIC Educational Resources Information Center

    Chamove, A. S.; Molinaro, T. J.

    1978-01-01

    Seven rhesus monkeys reared on diets high in phenylalanine to induce phenylketonuria (PKU--a metabolic disorder associated with mental retardation if untreated) were compared with normal, pair-fed, and younger controls; frontal brain-lesioned monkeys; and those raised on high-tryptophan diets in three object discrimination tasks. (Author)

  4. Flame retardant spandex type polyurethanes

    NASA Technical Reports Server (NTRS)

    Howarth, J. T.; Sheth, S.; Sidman, K. R.; Massucco, A. A. (Inventor)

    1978-01-01

    Flame retardant elastomeric compositions were developed, comprised of: (1) spandex type polyurethane having incorporated into the polymer chain, halogen containing polyols; (2) conventional spandex type polyurethanes in physical admixture flame retardant additives; and (3) fluoroelastomeric resins in physical admixture with flame retardant additives. Methods of preparing fibers of the flame retardant elastomeric materials are presented and articles of manufacture comprised of the elastomeric materials are mentioned.

  5. Mental Retardation, Selected Conference Papers.

    ERIC Educational Resources Information Center

    Scheerenberger, R.C., Ed.

    A compilation of selected papers includes the following: comprehensive diagnostic services; pediatric aspects of diagnosis; psychological evaluation of the severely retarded; use of social competency devices; diagnosis of the adult retarded; programing for the severely retarded; nursery school experiences for the trainable; a practical approach to…

  6. Multiband retardation control using multi-twist retarders

    NASA Astrophysics Data System (ADS)

    Hornburg, Kathryn J.; Komanduri, Ravi K.; Escuti, Michael J.

    2014-05-01

    We introduce and demonstrate an approach to create highly chromatic retardation spectra across various wave­ lengths. The design approach is based on Multi-Twist Retarder (MTR) principle where multiple liquid crystal polymer layers are coated on top of each other on a single substrate. Previous MTRs have been applied to develop broadband achromatic retarders, but here we show that MTRs are quite flexible, and their retardation spectrum can be tuned to create arbitrary profiles. As a representative example, we show this tailorability by creating a retarder which produces approximately zero retardation in visible (500-900 nm) and half-wave retardation in near- infrared (1-2.7 μm) wavelength region. This would provide enhancement in remote sensing, telecom, and spectroscopy systems where it is advantageous to have an optical element which affects only one band, but is largely transparent otherwise.

  7. Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders

    PubMed Central

    Cararo, José H; Streck, Emilio L; Schuck, Patricia F; Ferreira, Gustavo da C

    2015-01-01

    Imidazole dipeptides (ID), such as carnosine (β-alanyl-L-histidine), are compounds widely distributed in excitable tissues of vertebrates. ID are also endowed of several biochemical properties in biological tissues, including antioxidant, bivalent metal ion chelating, proton buffering, and carbonyl scavenger activities. Furthermore, remarkable biological effects have been assigned to such compounds in age-related human disorders and in patients whose activity of serum carnosinase is deficient or undetectable. Nevertheless, the precise biological role of ID is still to be unraveled. In the present review we shall discuss some evidences from clinical and basic studies for the utilization of ID as a drug therapy for age-related human disorders. PMID:26425391

  8. Effect of transition metal binding on the tautomeric equilibrium of the carnosine imidazolic ring

    NASA Astrophysics Data System (ADS)

    Torreggiani, A.; Fini, G.; Bottura, G.

    2001-05-01

    A Raman study of carnosine (Carn) and its complexes with Cu(II), Zn(II) and Co(II) at different pH values was carried out. At pH 7 and 9, Carn exists in equilibrium between two tautomeric forms. Raman spectroscopy appears to be a useful tool for analysing the tautomeric equilibrium of the imidazole ring of Carn since the sites involved in metal chelation can be identified by some bands (e.g. νC4C5) that change in wavenumber depending on whether the imidazole ring takes the tautomeric form I or II. Form I (N π-H) is predominant in the free ligand, but the metal coordination can affect the tautomeric equilibrium. Although weak compared to those of aromatic residues, the Raman marker bands may be useful in analysing metal-histidine interaction in proteins.

  9. High-performance liquid chromatographic determination of N-alpha-acetyl-L-carnosine in equine plasma.

    PubMed

    Dunnett, M

    1997-01-10

    N-alpha-Acetyl-L-carnosine (NAcCAR) in perchloric acid extracts of equine plasma was assayed by high-performance liquid chromatography on a 3 microns Hypersil ODS (150 x 4.6 mm I.D.) column eluted with 5 mM phosphoric acid-1 mM triethylamine, pH 2.58. NAcCAR was isolated by solid-phase extraction on Isolute PRS (propylsulphonyl) columns. The HPLC mean retention time for NAcCAR was 5.9 +/- 0.2 min. The recovery from plasma by solid-phase extraction was 93.9-99.7% and lower limit of detection in plasma was 0.18 microM. The normal NAcCAR concentration in equine plasma was 2.4 +/- 0.3 microM. The method was applied to the determination of plasma concentrations following oral and intravenous NAcCAR administration.

  10. Fire and smoke retardants

    NASA Astrophysics Data System (ADS)

    Drews, M. J.

    Despite a reduction in Federal regulatory activity, research concerned with flame retardancy and smoke suppression in the private sector appears to be increasing. This trend seem related to the increased utilization of plastics for end uses which traditionally have employed metal or wood products. As a result, new markets have appeared for thermally stable and fire resistance thermoplastic materials, and this in turn has spurred research and development activity. In addition, public awareness of the dangers associated with fire has increased as a result of several highly publicized hotel and restaurant fires within the past two years. The consumers recognition of flammability characteristics as important materials property considerations has increased. The current status of fire and smoke retardant chemistry and research are summarized.

  11. Flame Retardant Epoxy Resins

    NASA Technical Reports Server (NTRS)

    Thompson, C. M.; Smith, J. G., Jr.; Connell, J. W.; Hergenrother, P. M.; Lyon, R. E.

    2004-01-01

    As part of a program to develop fire resistant exterior composite structures for future subsonic commercial aircraft, flame retardant epoxy resins are under investigation. Epoxies and their curing agents (aromatic diamines) containing phosphorus were synthesized and used to prepare epoxy formulations. Phosphorus was incorporated within the backbone of the epoxy resin and not used as an additive. The resulting cured epoxies were characterized by thermogravimetric analysis, propane torch test, elemental analysis and microscale combustion calorimetry. Several formulations showed excellent flame retardation with phosphorous contents as low as 1.5% by weight. The fracture toughness of plaques of several cured formulations was determined on single-edge notched bend specimens. The chemistry and properties of these new epoxy formulations are discussed.

  12. Fire-retardant foams

    NASA Technical Reports Server (NTRS)

    Gagliani, J.

    1978-01-01

    Family of polyimide resins are being developed as foams with exceptional fire-retardant properties. Foams are potentially useful for seat cushions in aircraft and ground vehicles and for applications such as home furnishings and building-construction materials. Basic formulations can be modified with reinforcing fibers or fillers to produce celular materials for variety of applications. By selecting reactants, polymer structure can be modified to give foams with properties ranging from high resiliency and flexibility to brittleness and rigidity.

  13. Fire-retardant foams

    NASA Technical Reports Server (NTRS)

    Gagliani, J.

    1978-01-01

    Family of polyimide resins are being developed as foams with exceptional fire-retardant properties. Foams are potentially useful for seat cushions in aircraft and ground vehicles and for applications such as home furnishings and building-construction materials. Basic formulations can be modified with reinforcing fibers or fillers to produce celular materials for variety of applications. By selecting reactants, polymer structure can be modified to give foams with properties ranging from high resiliency and flexibility to brittleness and rigidity.

  14. [Enzymetic synthesis and characterization of a carnosine analogue in non-aqueous solvent].

    PubMed

    Zhou, Xiaohua; Su, Xiali; Lu, Yao

    2009-12-01

    Carnosine (beta-Ala-L-His) has high antioxidant activity, and it is widely used in biology, chemical engineering, medicine and other fields. Its analogue syntheised in non-aqueous solvent and catalyzed by enzymes is high-effective but low-price, so it has great prospect. Here, we synthesized a carnosine analogue imidazole 4(5)-alanylamide-5(4)-carboxylic acid with imidazole-4,5-dicarboxylic acid and L-Alanine as substrates, alpha-chymotrypsin as catalyst in tetrahydrofuran (THF) solvent. Based on the orthogonal experiments, the optimized synthetic conditions are 4,5-dicarboxylic acid: L-alanine = 1:3 (m/m), alpha-chymotrypsin: substrates (4,5-dicarboxyl acid and L-alanine) = 1:200 (m/m), pH 8 phosphate buffer:THF = 1.6:10 (V/V), reaction temperature 35 degrees C, time 1.5 h. We separated the product with silica gel G60 thin-layer chromatography (TLC), and a new spot appeared at Rf (ratio to front) = 0.81; then the new spot was purified and characterized with UV spectra, high performance liquid chromatogram (HPLC) and 13C NMR (13C nuclear magnetic resonance). The UV spectra shows a new absorption peak at 310 nm, and the peak in 253 nm is largely strengthened; HPLC reserve times are all 4.5 min at 253 nm, 310 nm, 330 nm; 13C NMR shows 8 carbons. Combing with the catalytic mechanism of alpha-chymotrypsin, structure of the analogue is confirmed, i.e., imidazole 4(5)-alanylamide-5(4)-carboxylic acid.

  15. Retarded gravitation theory

    NASA Astrophysics Data System (ADS)

    Raju, C. K.

    2012-10-01

    We propose a Lorentz-covariant theory of gravity, and explain its theoretical origins in the problem of time in Newtonian physics. In this retarded gravitation theory (RGT), the gravitational force depends upon both retarded position and velocity, and the equations of motion are time-asymmetric retarded functional differential equations. We explicitly solve these equations, under simplifying assumptions, for various NASA spacecraft. This shows that the differences from Newtonian gravity, though tiny within the solar system, are just appropriate to explain the flyby anomaly as a ν/c effect due to earth's rotation. The differences can, however, be large in the case of a spiral galaxy, and we show that the combined velocity drag from a large number of co-rotating stars enormously speeds up a test particle. Thus, the non-Newtonian behaviour of rotation curves in a spiral galaxy may be explained as being due to velocity drag rather than dark matter. RGT can also be tested in the laboratory. It necessitates a reappraisal of current laboratory methods of determining the Newtonian gravitational constant G. Since RGT makes no speculative assumptions, its refutation would have serious implications across physics.

  16. Carnosine prevents necrotic and apoptotic death of rat thymocytes via ouabain-sensitive Na/K-ATPase.

    PubMed

    Smolyaninova, Larisa V; Dergalev, Alexander A; Kulebyakin, Konstantin Y; Carpenter, David O; Boldyrev, Alexander A

    2013-01-01

    It is known that ouabain, a selective inhibitor of Na/K-ATPase, not only can cause the activation of signal cascades, which regulate the cell viability, but also can cause the accumulation of free radicals, which can evoke the oxidative stress. We have shown that the nanomolar concentrations of ouabain result in the temporary increase in the level of intracellular free radicals, but the millimolar concentration of ouabain induces a stable intracellular accumulation of free radicals in rat thymocytes. The increasing level of free radicals resulting from both low and high concentrations of ouabain can be attenuated by the antioxidant, carnosine. Moreover, the long-term incubation with ouabain leads to the cell death by necrosis and apoptosis. Ouabain-mediated apoptosis and necrosis were also abolished by carnosine.

  17. Multitarget trehalose-carnosine conjugates inhibit Aβ aggregation, tune copper(II) activity and decrease acrolein toxicity.

    PubMed

    Grasso, Giuseppa Ida; Bellia, Francesco; Arena, Giuseppe; Satriano, Cristina; Vecchio, Graziella; Rizzarelli, Enrico

    2017-07-28

    Increasing evidence is accumulating, showing that neurodegenerative disorders are somehow associated with the toxicity of amyloid aggregates, metal ion dyshomeostasis as well as with products generated by oxidative stress. Within the biological oxidation products, acrolein does have a prominent role. A promising strategy to deal with the above neurogenerative disorders is to use multi-functions bio-molecules. Herein, we show how a class of bio-conjugates takes advantage of the antiaggregating, antioxidant and antiglycating properties of trehalose and carnosine. Their ability to sequester acrolein and to inhibit both self- and metal-induced aggregation is here reported. The copper(II) coordination properties of a new trehalose-carnosine conjugate and the relative antioxidant effects have also been investigated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by β‐alanine transamination

    PubMed Central

    Blancquaert, Laura; Baba, Shahid P.; Kwiatkowski, Sebastian; Stautemas, Jan; Stegen, Sanne; Barbaresi, Silvia; Chung, Weiliang; Boakye, Adjoa A.; Hoetker, J. David; Bhatnagar, Aruni; Delanghe, Joris; Vanheel, Bert; Veiga‐da‐Cunha, Maria; Derave, Wim

    2016-01-01

    Key points Using recombinant DNA technology, the present study provides the first strong and direct evidence indicating that β‐alanine is an efficient substrate for the mammalian transaminating enzymes 4‐aminobutyrate‐2‐oxoglutarate transaminase and alanine‐glyoxylate transaminase.The concentration of carnosine and anserine in murine skeletal and heart muscle depends on circulating availability of β‐alanine, which is in turn controlled by degradation of β‐alanine in liver and kidney.Chronic oral β‐alanine supplementation is a popular ergogenic strategy in sports because it can increase the intracellular carnosine concentration and subsequently improve the performance of high‐intensity exercises. The present study can partly explain why the β‐alanine supplementation protocol is so inefficient, by demonstrating that exogenous β‐alanine can be effectively routed toward oxidation. Abstract The metabolic fate of orally ingested β‐alanine is largely unknown. Chronic β‐alanine supplementation is becoming increasingly popular for improving high‐intensity exercise performance because it is the rate‐limiting precursor of the dipeptide carnosine (β‐alanyl‐l‐histidine) in muscle. However, only a small fraction (3–6%) of the ingested β‐alanine is used for carnosine synthesis. Thus, the present study aimed to investigate the putative contribution of two β‐alanine transamination enzymes, namely 4‐aminobutyrate‐2‐oxoglutarate transaminase (GABA‐T) and alanine‐glyoxylate transaminase (AGXT2), to the homeostasis of carnosine and its methylated analogue anserine. We found that, when transfected into HEK293T cells, recombinant mouse and human GABA‐T and AGXT2 are able to transaminate β‐alanine efficiently. The reaction catalysed by GABA‐T is inhibited by vigabatrin, whereas both GABA‐T and AGXT2 activity is inhibited by aminooxyacetic acid (AOA). Both GABA‐T and AGXT2 are highly expressed in the mouse liver and

  19. Determination of carnosine, anserine, homocarnosine, pentosidine and thiobarbituric acid reactive substances contents in meat from different animal species.

    PubMed

    Peiretti, Pier Giorgio; Medana, Claudio; Visentin, Sonja; Giancotti, Valeria; Zunino, Valentina; Meineri, Giorgia

    2011-06-15

    The aim of this research was to determine the content of the histidinic antioxidants, advanced glycation end products (pentosidine) and thiobarbituric acid reactive substance (TBARS) in the meat from different animal species. Carnosine, anserine, homocarnosine and pentosidine were quantified by HPLC/MS, while TBARS was determined by photometric measurements. The total CRCs (carnosine+anserine+homocarnosine) content was in the increasing order: beef

  20. Biological activities of the natural imidazole-containing peptidomimetics n-acetylcarnosine, carcinine and L-carnosine in ophthalmic and skin care products.

    PubMed

    Babizhayev, Mark A

    2006-04-11

    Apart from genetically programmed cell aging, different external aggressors related to oxidative stress and lipid peroxidation (LPO) can accelerate the skin aging phenomenon. Oxidative stress associated with the formation of lipid peroxides is suggested to contribute to pathological processes in aging and systemic diseases known as the risk factors for cataract. Despite the fact that L-carnosine-related peptidomimetics N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) (NAC) and carcinine (beta-alanylhistamine) are metabolically related to L-carnosine and have been demonstrated to occur in tissues of many vertebrates, including humans, these compounds were shown resistant toward enzymatic hydrolysis. A series of related biocompatible imidazole-containing peptidomimetics were synthesized in order to confer resistance to enzymatic hydrolysis and ex vivo improvement of protective antioxidative properties related to L-carnosine. The included findings revealed a greater role of N-acetylcarnosine (NAC) and carcinine ex vivo in the prolongation and potentiation of physiological responses to the therapeutical and cosmetics treatments with L-carnosine as antioxidant. 3-D molecular conformation studies proposed the antioxidant activity of peptidomimetics (carcinine, L-prolylhistamine, N-acetylcarnosine, L-carnosine) for metal ion binding, quenching of a number free radicals, and binding of hydroperoxide or aldehyde (including dialdehyde LPO products) in an imidazole-peroxide adducts. NAC can act as a time release (carrier) stable version of L-carnosine during application in ophthalmic pharmaceutical and cosmetics formulations which include lubricants. Carcinine, L-prolylhistamine show efficient deactivation of lipid hydroperoxides monitored by HPLC and protection of membrane phospholipids and water soluble proteins from the lipid peroxides-induced damages. This activity is superior over the lipophilic antioxidant vitamin E. The biologically significant applications of

  1. Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure.

    PubMed

    Lombardi, Carlo; Carubelli, Valentina; Lazzarini, Valentina; Vizzardi, Enrico; Bordonali, Tania; Ciccarese, Camilla; Castrini, Anna Isotta; Dei Cas, Alessandra; Nodari, Savina; Metra, Marco

    2015-01-01

    Chronic heart failure (CHF) is characterized by several micronutrient deficits. Amino acid supplementation may have a positive effect on nutritional and metabolic status in patients with CHF. Levo-carnosine (β-alanyl-L-histidine) is expressed at a high concentration in myocardium and muscle. Preliminary studies with L-carnosine in healthy individuals have suggested a potential role in improving exercise performance. To our knowledge, no study has been conducted in patients with heart failure. The aim of this study was to test the oral supplementation of L-carnosine and its effects on quality of life and exercise performance in patients with stable CHF. Fifty patients with stable CHF and severe left-ventricular systolic dysfunction on optimal medical therapy were randomized 1:1 to receive oral orodispersible L-carnosine (500 mg OD) or standard treatment. Left-ventricular ejection fraction (LVEF) was measured by echocardiography. Cardiopulmonary stress test, 6-minute walking test (6 MWT) and quality-of-life (visual analog scale score and the EuroQOL five dimensions questionnaire [EQ-5D]) were performed at baseline and after 6 mo. Patients receiving orodispersible L-carnosine had an improvement in 6 MWT distance (P = 0.014) and in quality-of-life (VAS score) (P = 0.039) between baseline and follow-up. Compared with controls, diet supplementation with orodispersible L-carnosine was associated with an improvement in peakVO2 (P < 0.0001), VO2 at anaerobic threshold, peak exercise workload, 6 MWT and quality-of-life assessed by the EQ-5D test and the VAS score. This study suggests that L-carnosine, added to conventional therapy, has beneficial effects on exercise performance and quality of life in stable CHF. More data are necessary to evaluate its effects on left-ventricular ejection fraction and prognosis in CHF. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Effect of carnosine supplementation on apoptosis and irisin, total oxidant and antioxidants levels in the serum, liver and lung tissues in rats exposed to formaldehyde inhalation.

    PubMed

    Aydin, Suna; Ogeturk, Murat; Kuloglu, Tuncay; Kavakli, Ahmet; Aydin, Suleyman

    2015-02-01

    The main objective of the study has been to show whether carnosine has positive effects on liver and lung tissues of rats exposed to a range of formaldehyde concentrations, and to explore how irisin expression and antioxidant capacity are altered in these tissues by carnosine supplementation. Sprague-Dawley type male rats were divided into 8 groups with 6 animals in each: (I) Control; no chemical supplementation); (II) sham (100mg/kg/day carnosine); (III) low dose formaldehyde (LDFA) for 5 days/week; (IV) LDFA for 5 days/week and carnosine); (V) moderate dose formaldehyde (MDFA) for 5 days/week); (VI) MDFA for 5 days/week and carnosine; (VII) high dose formaldehyde (HDFA) for 5 days/week; (VIII) and HDFA for 5 days/week and carnosine. Sham and control groups were exposed to normal air. Irisin levels of the serum, liver and lung tissue supernatants were analyzed by ELISA, while the REL method was used to determine total oxidant/antioxidant capacity. Irisin production by the tissues was detected immunohistochemically. Increasing doses of FA decreased serum/tissue irisin and total antioxidant levels relative to the controls, as also to increases in TUNEL expressions, total oxidant level, oxidant and apoptosis index. Irisin expression was detected in hepatocyte and sinusoidal cells of the liver and parenchymal cells of the lung. In conclusion, while FA exposure reduces irisin and total oxidant in the serum, liver and lung tissues in a dose-dependent manner and increases the total antioxidant capacity, carnosine supplementation reduces the oxidative stress and restores the histopathological and biochemical signs. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Intravitreal injection of forskolin, homotaurine, and L-carnosine affords neuroprotection to retinal ganglion cells following retinal ischemic injury

    PubMed Central

    Adornetto, Annagrazia; Cavaliere, Federica; Varano, Giuseppe Pasquale; Rusciano, Dario; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

    2015-01-01

    Purpose Retinal ganglion cell (RGC) death is the final event leading to visual impairment in glaucoma; therefore, identification of neuroprotective strategies able to slow down or prevent the process is one of the main challenges for glaucoma research. The purpose of this study was to evaluate the neuroprotective potential of RGC death induced by the in vivo transient increase in intraocular pressure (IOP) of a combined treatment with forskolin, homotaurine, and L-carnosine. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is an activator of adenylate cyclase that decreases IOP by reducing aqueous humor production and functions as a neuroprotector due to its neurotrophin-stimulating activity. Homotaurine is a natural aminosulfonate compound endowed with neuromodulatory effects, while the dipeptide L-carnosine is known for its antioxidant properties. Methods Retinal ischemia was induced in the right eye of adult male Wistar rats by acutely increasing the IOP. Forskolin, homotaurine, and L-carnosine were intravitreally injected and RGC survival evaluated following retrograde labeling with FluoroGold. Total and phosphorylated Akt and glycogen synthase kinase-3β (GSK-3β) protein levels, as well as calpain activity, were analyzed with western blot. Protein kinase A (PKA) was inhibited by intravitreal injection of H89. Results A synergic neuroprotective effect on RGC survival was observed following the combined treatment with forskolin, homotaurine, and L-carnosine compared to forskolin alone. The observed neuroprotection was associated with reduced calpain activity, upregulation of phosphoinositide 3-kinase (PI3K)/Akt pathway, and inhibition of GSK-3β but was independent from PKA activation and distinct from the hypotensive effects of forskolin. Conclusions A multidrug/multitarget approach, by interfering with several pathways involved in RGC degeneration, may be promising to achieve glaucoma neuroprotection. PMID:26167113

  4. Graphene Oxides Decorated with Carnosine as an Adjuvant To Modulate Innate Immune and Improve Adaptive Immunity in Vivo.

    PubMed

    Meng, Chunchun; Zhi, Xiao; Li, Chao; Li, Chuanfeng; Chen, Zongyan; Qiu, Xusheng; Ding, Chan; Ma, Lijun; Lu, Hongmin; Chen, Di; Liu, Guangqing; Cui, Daxiang

    2016-02-23

    Current studies have revealed the immune effects of graphene oxide (GO) and have utilized them as vaccine carriers and adjuvants. However, GO easily induces strong oxidative stress and inflammatory reaction at the site of injection. It is very necessary to develop an alternative adjuvant based on graphene oxide derivatives for improving immune responses and decreasing side effects. Carnosine (Car) is an outstanding and safe antioxidant. Herein, the feasibility and efficiency of ultrasmall graphene oxide decorated with carnosine as an alternative immune adjuvant were explored. OVA@GO-Car was prepared by simply mixing ovalbumin (OVA, a model antigen) with ultrasmall GO covalently modified with carnosine (GO-Car). We investigated the immunological properties of the GO-Car adjuvant in model mice. Results show that OVA@GO-Car can promote robust and durable OVA-specific antibody response, increase lymphocyte proliferation efficiency, and enhance CD4(+) T and CD8(+) T cell activation. The presence of Car in GO also probably contributes to enhancing the antigen-specific adaptive immune response through modulating the expression of some cytokines, including IL-6, CXCL1, CCL2, and CSF3. In addition, the safety of GO-Car as an adjuvant was evaluated comprehensively. No symptoms such as allergic response, inflammatory redness swelling, raised surface temperatures, physiological anomalies of blood, and remarkable weight changes were observed. Besides, after modification with carnosine, histological damages caused by GO-Car in lung, muscle, kidney, and spleen became weaken significantly. This study sufficiently suggest that GO-Car as a safe adjuvant can effectively enhance humoral and innate immune responses against antigens in vivo.

  5. Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study

    PubMed Central

    Hobson, Ruth M; Artioli, Guilherme G.; Otaduy, Maria C.; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S. Painelli, Vitor; Harris, Roger C.; Gualano, Bruno

    2015-01-01

    Objectives Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P<0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists. PMID:25875297

  6. Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study.

    PubMed

    Solis, Marina Yazigi; Cooper, Simon; Hobson, Ruth M; Artioli, Guilherme G; Otaduy, Maria C; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S Painelli, Vitor; Harris, Roger C; Gualano, Bruno; Sale, Craig

    2015-01-01

    Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d(-1) on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P < 0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. 28 d of beta-alanine supplementation at 6.4 g d(-1) appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

  7. Low taurine, gamma-aminobutyric acid and carnosine levels in plasma of diabetic pregnant rats: consequences for the offspring.

    PubMed

    Aerts, L; Van Assche, F A

    2001-01-01

    Gestational diabetes compromises fetal development and induces a diabetogenic effect in the offspring, including the development of gestational diabetes and the transmission of the effect to the next generation. Changes are not limited to glucose and insulin metabolism, and appear to be modulated by alterations at the hypothalamo-hypophyseal axis. In the present work, serum concentrations are given for the non-protein amino-acids taurine and gamma-aminobutyric acid (GABA), both neurotransmitters essential for normal brain development, and for the endogenous neuroprotector carnosine, a known anti-oxydans. Taurine levels are significantly below normal values in mildly diabetic mothers, in their fetal and adult offspring, virgin and pregnant, and in the fetuses of these pregnant offspring. GABA and carnosine levels are at the limit of detection in the diabetic mothers and their offspring at every stage. It is concluded that the low taurine, GABA and carnosine levels in diabetic mothers and their fetuses might compromise the normal structural and functional development of the fetal brain. When adult, these offspring present a deficiency of the circulating levels of these neurotransmitters involved in the hypothalamo-hypophyseal regulation of insulin secretion. This might contribute to the development of impaired glucose tolerance and gestational diabetes, thereby transmitting the effect to the next generation.

  8. Beneficial effects of carnosine and carnosine plus vitamin E treatments on doxorubicin-induced oxidative stress and cardiac, hepatic, and renal toxicity in rats.

    PubMed

    Kumral, A; Giriş, M; Soluk-Tekkeşin, M; Olgaç, V; Doğru-Abbasoğlu, S; Türkoğlu, Ü; Uysal, M

    2016-06-01

    Oxidative stress plays an important role in doxorubicin (DOX)-induced toxicity. Carnosine (CAR) is a dipeptide with antioxidant properties. The aim of this study was to evaluate the decreasing or preventive effect of CAR alone or combination with vitamin E (CAR + Vit E) on DOX-induced toxicity in heart, liver, and brain of rats. Rats were treated with CAR (250 mg kg(-1) day(-1); intraperitoneally (i.p.)) or CAR + Vit E (equals 200 mg kg(-1) α-tocopherol; once every 3 days; intramuscularly) for 12 consecutive days. On the 8th day of treatment, rats were injected with a single dose of DOX (30 mg kg(-1), i.p.). Serum cardiac troponin I (cTnI), urea, and creatinine levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities; and oxidative stress parameters in tissues were measured. We also determined thiobarbituric acid reactive substances, diene conjugate, protein carbonyl (PC), and glutathione levels and antioxidant enzyme activities. DOX resulted in increased serum cTnI, ALT, AST, urea, and creatinine levels and increased lipid peroxide and PC levels in tissues. CAR or CAR + Vit E treatments led to decreases in serum cTnI levels and ALT and AST activities. These treatments reduced prooxidant status and ameloriated histopathologic findings in the examined tissues. Our results may indicate that CAR alone, especially in combination with Vit E, protect against DOX-induced toxicity in heart, liver, and kidney tissues of rats. This was evidenced by improved cardiac, hepatic, and renal markers and restoration of the prooxidant state and amelioration of histopathologic changes. © The Author(s) 2015.

  9. Sensitive determination of carnosine in urine by high-performance liquid chromatography using 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride as a fluorescent labeling reagent.

    PubMed

    Tsuruta, Yasuto; Maruyama, Kiyoshi; Inoue, Hirofumi; Kosha, Keiko; Date, Yuuko; Okamura, Nobuyuki; Eto, Seiji; Kojima, Eijiro

    2010-02-01

    A simple and highly sensitive high-performance liquid chromatography procedure was developed for the determination of carnosine in urine. Carnosine was derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride at 70 degrees C for 15 min in borate buffer (20 mmol l(-1), pH 9.0) to produce fluorescent sulfonamides. After hydrolysis of the reaction mixture with formic acid at 100 degrees C for 15 min, the fluorescent derivative of carnosine was separated on a reversed-phase column with a linear gradient elution using solvents of (A) acetate buffer (0.1 mmol l(-1), pH 7.0) and (B) acetonitrile at a flow-rate of 1.0 ml/min and was detected at excitation and emission wavelengths of 318 and 400 nm, respectively. The detection limit of carnosine was 4 fmol at a signal-to-noise ratio of 3. The within-day and day-to-day relative standard deviations were 2.7-4.6% and 0.4-5.2%, respectively. The concentration of carnosine in normal human urine was found to be 4.6-125 nmol (mg creatinine)(-1) (mean+/-SD: 21.6+/-26.6 nmol (mg creatinine)(-1), n=20). 2009 Elsevier B.V. All rights reserved.

  10. Metabolite proofreading in carnosine and homocarnosine synthesis: molecular identification of PM20D2 as β-alanyl-lysine dipeptidase.

    PubMed

    Veiga-da-Cunha, Maria; Chevalier, Nathalie; Stroobant, Vincent; Vertommen, Didier; Van Schaftingen, Emile

    2014-07-11

    Carnosine synthase is the ATP-dependent ligase responsible for carnosine (β-alanyl-histidine) and homocarnosine (γ-aminobutyryl-histidine) synthesis in skeletal muscle and brain, respectively. This enzyme uses, also at substantial rates, lysine, ornithine, and arginine instead of histidine, yet the resulting dipeptides are virtually absent from muscle or brain, suggesting that they are removed by a "metabolite repair" enzyme. Using a radiolabeled substrate, we found that rat skeletal muscle, heart, and brain contained a cytosolic β-alanyl-lysine dipeptidase activity. This enzyme, which has the characteristics of a metalloenzyme, was purified ≈ 200-fold from rat skeletal muscle. Mass spectrometry analysis of the fractions obtained at different purification stages indicated parallel enrichment of PM20D2, a peptidase of unknown function belonging to the metallopeptidase 20 family. Western blotting showed coelution of PM20D2 with β-alanyl-lysine dipeptidase activity. Recombinant mouse PM20D2 hydrolyzed β-alanyl-lysine, β-alanyl-ornithine, γ-aminobutyryl-lysine, and γ-aminobutyryl-ornithine as its best substrates. It also acted at lower rates on β-alanyl-arginine and γ-aminobutyryl-arginine but virtually not on carnosine or homocarnosine. Although acting preferentially on basic dipeptides derived from β-alanine or γ-aminobutyrate, PM20D2 also acted at lower rates on some "classic dipeptides" like α-alanyl-lysine and α-lysyl-lysine. The same activity profile was observed with human PM20D2, yet this enzyme was ∼ 100-200-fold less active on all substrates tested than the mouse enzyme. Cotransfection in HEK293T cells of mouse or human PM20D2 together with carnosine synthase prevented the accumulation of abnormal dipeptides (β-alanyl-lysine, β-alanyl-ornithine, γ-aminobutyryl-lysine), thus favoring the synthesis of carnosine and homocarnosine and confirming the metabolite repair role of PM20D2. © 2014 by The American Society for Biochemistry and

  11. Effects of α-lipoic acid and L-carnosine supplementation on antioxidant activities and lipid profiles in rats

    PubMed Central

    Kim, Mi Young; Kim, Eun Jin; Kim, Young-Nam; Choi, Changsun

    2011-01-01

    α-Lipoic acid and L-carnosine are powerful antioxidants and are often used as a health supplement and as an ergogenic aid. The objective of this study was to investigate the effects of α-lipoic acid and/or L-carnosine supplementation on antioxidant activity in serum, skin, and liver of rats and blood lipid profiles for 6 weeks. Four treatment groups received diets containing regular rat chow diet (control, CON), 0.5% α-lipoic acid (ALA), 0.25% α-lipoic acid + 0.25% L-carnosine (ALA + LC), or 0.5% L-carnosine (LC). Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and lipid peroxidation products, malondialdehyde (MDA) concentrations, were analyzed in serum, skin, and liver. Blood lipid profiles were measured, including triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C). Skin and liver SOD activities of the ALA and LC groups were higher than those of the CON group (P < 0.05), but serum SOD activity was higher only in the LC group compared to that in the CON group (P < 0.05). Additionally, only liver GSH-Px activity in the LC group was higher than that of the CON and the other groups. Serum and skin MDA levels in the ALA and LC groups were lower than those in the CON group (P < 0.05). Serum TG and TC in the ALA and ALA + LC groups were lower than those in the CON and LC groups (P < 0.05). The HDL-C level in the LC group was higher than that in any other group (P < 0.05). LDL-C level was lower in the ALA + LC and LC groups than that in the CON group (P < 0.05). Thus, α-lipoic acid and L-carnosine supplementation increased antioxidant activity, decreased lipid peroxidation in the serum, liver, and skin of rats and positively modified blood lipid profiles. PMID:22125679

  12. [Mental retardation and ADHD].

    PubMed

    Hässler, Frank; Thome, Johannes

    2012-03-01

    Hyperactivity syndromes and disorders (ADHD and HKD) include the symptoms of overactivity, inattention, and impulsivity, which occur in many other mental disorders as well, including mental retardation (MR). It is not surprising that symptoms of ADHD occur significantly higher in children with learning disabilities. Dekker and Koot (2003) found a prevalence of 14.8 % for ADHD in Dutch children attending special schools, and Emerson (2003) reported rates of 8.7 % for HKD in children with global learning disability, representing a 10-fold increased risk compared to the prevalence of hyperactivity (0.9 %) in the general population sample. Yet only very few studies have been published concerning ADHD in children with mental retardation. Several features distinguish the diagnoses of ADHD and MR. In contrast to the limited knowledge about the differences and similarities of ADHD and MR, many studies considered stimulant medication as a pharmacological management strategy for children suffering from ADHD, MR, or both. According to these studies, psychostimulants may improve the target symptoms of hyperactivity, impulsivity, disinhibition, and inattention, albeit with caveats: ADHD symptoms in patients with MR may be less responsive to medical treatment than in patients without MR. Moreover, people with MR may be more susceptible to side effects.

  13. Mental Retardation Is Dead: Long Live Mental Retardation!

    ERIC Educational Resources Information Center

    Goode, David

    2002-01-01

    This commentary discusses whether the American Association on Mental Retardation should change its name. The history of the term "mental retardation" is reviewed and it is argued that any new term will take on similar risks. The need to involve self-advocates in any terminology change is stressed. (Contains 5 references.) (CR)

  14. Determination of carnosine and other biogenic imidazoles in equine plasma by isocratic reversed-phase ion-pair high-performance liquid chromatography.

    PubMed

    Dunnett, M; Harris, R C

    1992-08-07

    The isocratic reversed-phase ion-pair high-performance liquid chromatographic technique presented provides a sensitive, rapid and reproducible analytical method for the selective determination of carnosine and other biogenic imidazoles in equine plasma. Plasma was deproteinized with 5-sulphosalicylic acid and the compounds of interest were isolated by sorbent extraction on Bond Elut PRS cartridges. Recoveries were 97-105% and the lowest limits of detection were 58.3-80.1 nM. All compounds of interest were well resolved within a maximum retention time of 9.2 min. The mean equine plasma carnosine level determined by this method was 11.31 microM. Comparative determinations were made in canine and human plasma. Carnosine was not detected in human plasma. Concentrations of imidazole in canine plasma are reported here for the first time.

  15. Effect of carnosine, aminoguanidine, and aspirin drops on the prevention of cataracts in diabetic rats

    PubMed Central

    Guo, Yong; Zhang, Jie; Ding, Zhenghua; Ha, Wenjing; Harding, J.J.

    2008-01-01

    Purpose To investigate the effect of carnosine (CA), aminoguanidine (AG), and aspirin (ASA) drops, all inhibitors of glycation, on the development of diabetic cataract in rat. Methods Rats were made diabetic with streptozotocin, and based on the level of plasma glucose, they were assigned as non-diabetic rats (<14 mmol/l plasma glucose) and diabetic rats (>14 mmol/l plasma glucose). Animals in the treated groups received CA, AG, and ASA as drops to the left eyes starting from the day of streptozotocin injection. Progression of lens opacification was recorded using the slit lamp at regular time intervals. All the rats were killed after the week 13, and the levels of advanced glycation end products (AGE), glutathione reductase (GR), catalase (CAT), and glutathione (GSH) were determined. Results Lens opacification progressed in a biphasic manner in the diabetic rats, an initial slow increase during the first eight weeks of diabetes followed by a steep increase in the next five weeks. Carnosine treatment delayed the progression of cataracts in diabetic rats, and the delay was statistically significant on the fourth week of diabetes (p<0.05, when compared with untreated moderately diabetic rats). A decrease in the antioxidant enzymes of CAT and the level of GSH was found in the lens of the untreated diabetic rats at 13 weeks after injection. Some protection was provided in the treated eyes. The level of glycation in the untreated diabetic rats was significantly higher than that in the normal rats (p<0.001). After treatment with CA, AG, and ASA, those diabetic rats had a lower level of glycated lens protein compared to the untreated diabetic rats (p<0.001). Conclusions These results thus suggest that the effect of CA, AG, and ASA is indeed inhibition of the formation of AGEs. However, the effect of CA, AG, and ASA is overwhelmed by the excessive accumulation of AGEs in the severely diabetic rats. CA compared with AG and ASA treatment can delay the progression of lens

  16. THE PATHOLOGY OF MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    CROME, L.; STERN, J.

    DATA FROM RECENT COMPREHENSIVE STUDIES OF THE PATHOLOGY OF MENTAL RETARDATION ARE ASSEMBLED, INCLUDING MATERIAL ON ETIOLOGY, MORPHOLOGY, BIOCHEMISTRY, AND LABORATORY DIAGNOSIS. AREAS COVERED ARE (1) GENETIC CAUSES OF MENTAL RETARDATION, (2) DISORDERS OF GESTATION, (3) BIRTH INJURY, (4) GENERAL CONSIDERATIONS OF POSTNATAL CAUSES OF MENTAL…

  17. Children's Knowledge of Mental Retardation.

    ERIC Educational Resources Information Center

    Budoff, Milton; And Others

    1979-01-01

    A survey of 1,142 normal students in grades 4 through 12 indicated that they knew very little about mental retardation and the mentally retarded. Only about half of the respondents made reference to "subaverage general intellectual functioning," while references to physical impairment were frequent. (DLS)

  18. The Mentally Retarded in Sweden.

    ERIC Educational Resources Information Center

    Grunewald, Karl

    Described are residential and educational services provided for mentally retarded (MC) children and adults in Sweden. Normalization is the focus of the services which make maximum use of mental and physical capacities to reduce the handicap of mental retardation. Described are general principles, and four stages involving development of services…

  19. Playtherapy with the Mentally Retarded.

    ERIC Educational Resources Information Center

    Broekgaarden, R.; And Others

    The use of play therapy with mentally retarded children and adults is examined. The lack of research on the topic is noted, and information on psychoanalytically oriented play therapy approaches are reviewed. Application of play therapy to mentally retarded clients is explored in terms of two questions: (1) at what level do mentally retarded…

  20. Fire-Retardant Epoxy Adhesives

    NASA Technical Reports Server (NTRS)

    Bilow, N.; Giants, T. W.

    1982-01-01

    Phosphorus-containing epoxy is fire-retardant and translucent. Intended as adhesive for laminated plastic sheets, new material bonds well to titanium dioxide-filled plastic film, which ordinarily shows little surface interaction with adhesives. Fire retardancy has been demonstrated, and smoke density is low enough to avoid smoke obscuration.

  1. Flame retarded asphalt blend composition

    SciTech Connect

    Walters, R.B.

    1987-04-21

    This patent describes a flame retarded asphalt composition consisting essentially of a blend of: (a) thermoplastic elastomer modified bitumen; (b) 20-30 wt % inert filler; (c) 1-20 wt % of at least one halogenated flame retardant; and (d) 1-5 wt % of at least one inorganic phosphorus containing compound selected from the group consisting of ammonium phosphate compounds and red phosphorus.

  2. China's Approach to Mental Retardation.

    ERIC Educational Resources Information Center

    Hittman, Stephan

    History, tradition, culture, and superstition have played significant roles in influencing Chinese attitudes toward the mentally retarded. China's overwhelmingly rural, agricultural society has made it dependent upon a huge force of semi-skilled and unskilled labor, to which the retarded are capable of contribution. The stress on self-reliance,…

  3. THE PATHOLOGY OF MENTAL RETARDATION.

    ERIC Educational Resources Information Center

    CROME, L.; STERN, J.

    DATA FROM RECENT COMPREHENSIVE STUDIES OF THE PATHOLOGY OF MENTAL RETARDATION ARE ASSEMBLED, INCLUDING MATERIAL ON ETIOLOGY, MORPHOLOGY, BIOCHEMISTRY, AND LABORATORY DIAGNOSIS. AREAS COVERED ARE (1) GENETIC CAUSES OF MENTAL RETARDATION, (2) DISORDERS OF GESTATION, (3) BIRTH INJURY, (4) GENERAL CONSIDERATIONS OF POSTNATAL CAUSES OF MENTAL…

  4. Educable Mentally Retarded; Level II.

    ERIC Educational Resources Information Center

    Suo, Minnie A; Willemin, Helen

    An introduction of the curriculum guide for educable retarded children with mental ages from 5.0 to 6.6 discusses the philosophy of educating the retarded, goals, the educable program, the readiness program, use of the guide, and a suggested daily schedule. Suggested units treat the following: citizenship and patriotism, family and school,…

  5. Schizophrenia in the Mentally Retarded.

    ERIC Educational Resources Information Center

    Menolascino, Frank J.

    The relationship between schizophrenia and mental retardation is examined. Historical associations between symptoms of the two disorders are reviewed, and a 3-year study of the incidence (14%) of mental illness in 798 retarded individuals in a community based program is described. Information on the etiological, developmental, and phenomenological…

  6. Educable Mentally Retarded, Level I.

    ERIC Educational Resources Information Center

    Suo, Minnie Alice; Willemin, Helen

    Intended for teachers of special classes of educable mentally retarded children aged 6 to 8 (mental age = 3.5 to 4.9), the guide stresses skills necessary to the development of physical, personal and social, and vocational competency. An introduction defines philosophy and goals, outlines the educable mentally retarded program and the readiness…

  7. L-carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities.

    PubMed Central

    Babizhayev, M A; Seguin, M C; Gueyne, J; Evstigneeva, R P; Ageyeva, E A; Zheltukhina, G A

    1994-01-01

    Carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) are natural imidazole-containing compounds found in the non-protein fraction of mammalian tissues. Carcinine was synthesized by an original procedure and characterized. Both carnosine and carcinine (10-25 mM) are capable of inhibiting the catalysis of linoleic acid and phosphatidylcholine liposomal peroxidation (LPO) by the O2(-.)-dependent iron-ascorbate and lipid-peroxyl-radical-generating linoleic acid 13-monohydroperoxide (LOOH)-activated haemoglobin systems, as measured by thiobarbituric-acid-reactive substance. Carcinine and carnosine are good scavengers of OH. radicals, as detected by iron-dependent radical damage to the sugar deoxyribose. This suggests that carnosine and carcinine are able to scavenge free radicals or donate hydrogen ions. The iodometric, conjugated diene and t.l.c. assessments of lipid hydroperoxides (13-monohydroperoxide linoleic acid and phosphatidylcholine hydroperoxide) showed their efficient reduction and deactivation by carnosine and carcinine (10-25 mM) in the liberated and bound-to-artificial-bilayer states. This suggests that the peroxidase activity exceeded that susceptible to direct reduction with glutathione peroxidase. Imidazole, solutions of beta-alanine, or their mixtures with peptide moieties did not show antioxidant potential. Free L-histidine and especially histamine stimulated iron (II) salt-dependent LPO. Due to the combination of weak metal chelating (abolished by EDTA), OH. and lipid peroxyl radicals scavenging, reducing activities to liberated fatty acid and phospholipid hydroperoxides, carnosine and carcinine appear to be physiological antioxidants able to efficiently protect the lipid phase of biological membranes and aqueous environments. PMID:7998987

  8. The effect of 4 weeks beta-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres.

    PubMed

    Kendrick, Iain P; Kim, Hyo Jeong; Harris, Roger Charles; Kim, Chang Keun; Dang, Viet H; Lam, Thanh Q; Bui, Toai T; Wise, John A

    2009-05-01

    Seven male students were supplemented with beta-alanine (beta-ALG) for 4 weeks (6.4 g day(-1)) and seven with a matching placebo (PLG). Subjects undertook 4 weeks of isokinetic training with the right leg (T) whilst the left leg was untrained (UT), serving as a control. Each training session consisted of 10 x 10 maximal 90 degrees extension and flexion contractions at 180 degrees /s using a Kin-Com isokinetic dynamometer, with 1 min rest between bouts. Muscle biopsies were taken from the vastus lateralis immediately before and at the end of the supplementation period. Following freeze drying muscle fibres were dissected and characterised by their MHC profile, as type I, IIa, IIx, or as hybrids of these. Carnosine was measured by HPLC. There was a significant increase in carnosine in both T and UT legs of the beta-ALG (9.63 +/- 3.92 mmol kg(-1) dry muscle and 6.55 +/- 2.36 mmol kg(-1) dry muscle respectively). There was a significant increase in the carnosine content of all fibre phentotypes, with no significant difference between types. There were no significant differences in the changes in muscle or in fibres between the T and UT legs. In contrast there was no significant change in the carnosine content in either the T or UT legs with placebo. The results indicate that 4 weeks training has no effect on the muscle carnosine content. Whilst an increase was seen with beta-alanine supplementation, this was not further influenced by training. These findings suggest that beta-alanine availability is the main factor regulating muscle carnosine synthesis.

  9. Effect of H1 and H2 receptor blockers on mobilization of myocardial carnosine to histamine during compound 48/80-induced shock in young rats.

    PubMed

    Fitzpatrick, J C; Fisher, H; Flancbaum, L

    1990-02-01

    Histamine exerts profound effects on the cardiovascular system during shock mediated by H1 and H2 receptors. The source of histamine is uncertain. It is our hypothesis that carnosine serves as a nonmast-cell reservoir for histidine, utilized for histamine synthesis during shock. We have shown that treatment of older rats with compound 48/80, a mast cell degranulator, produces age-dependent lethal stress, which is prevented by lodoxamide (LOD), a mast cell degranulation inhibitor, is exacerbated by H2 receptor blockade, and is accompanied by increased mobilization of myocardial carnosine to histidine and histamine. This study was designed to evaluate the effects of H1 and H2 blockers on carnosine mobilization to histamine during 48/80-induced shock in young rats. Fifty male SD rats (125 g) were divided into nine groups: saline; LOD; H1 blocker diphenhydramine (DPH); H2 blocker cimetidine (CIM); 48/80; LOD + 48/80; DPH + 48/80; CIM + 48/80; and DPH + CIM + 48/80. All rats were sacrificed 30 min after final injections and hearts were analyzed via HPLC. There was a reduction in myocardial carnosine (P less than or equal to 0.01) and histidine (P less than or equal to 0.001) and a simultaneous increase in histamine (P less than or equal to 0.01, P less than or equal to 0.001) in animals receiving 48/80 or CIM + 48/80, respectively, compared to controls or groups pretreated with LOD, DPH, or DPH + CIM. These results indicate that 48/80-induced shock increases mobilization of myocardial carnosine and histidine to histamine, which supports a role for carnosine as a nonmast-cell histamine source.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. L-carnosine inhibits neuronal cell apoptosis through signal transducer and activator of transcription 3 signaling pathway after acute focal cerebral ischemia.

    PubMed

    Wang, Jian-Ping; Yang, Zhi-Tang; Liu, Cong; He, Yuan-Hong; Zhao, Shan-Shan

    2013-04-24

    Considerable studies have showed that L-carnosine provides anti-oxidative and anti-apoptotic roles in the animal models of global or focal cerebral ischemia. However, the anti-apoptotic mechanisms of L-carnosine in the focal cerebral ischemia model have yet to be elucidated. To investigate the molecular mechanisms, rat models of permanent middle cerebral artery occlusion (pMCAO) and sham operation were first established and then pMCAO and sham-operated rats were treated with L-carnosine or vehicle alone. After this treatment, neurological deficits were evaluated at 12, 24 and 72 h after operation and the infarct volume was measured at 72 h after treatment. In addition, we also detected the mRNA expression of signal transducer and activator of transcription 3 (STAT3) and Pim-1 and the protein expression of phosphorylated STAT3, Pim-1, bcl-2 and cleaved caspase-3 at 12, 24 and 72 h post-pMCAO. Our results showed that the L-carnosine-treated rats had milder neurological deficits and smaller infarct volume and showed up-regulated expression in mRNA levels of STAT3 and Pim-1 than vehicle-treated rats at 72 h after treatment. Meanwhile, compared with vehicle-treated rats, the L-carnosine-treated rats exhibited higher protein expressions of pSTAT3, Pim-1 and bcl-2 but lower expression of cleaved caspase-3 protein at 72 h following operation. These results indicate that L-carnosine plays an important role in inhibiting neuronal cell apoptosis through STAT3 signaling pathway after acute cerebral ischemia.

  11. 78 SUPPLEMENTATION WITH CARNOSINE DURING IN VITRO CULTURE IMPROVES THE QUALITY OF IN VITRO-PRODUCED BOVINE EMBRYOS.

    PubMed

    Le Bourhis, D; Verachten, M; Salvetti, P; Hochet, M; Schibler, L

    2016-01-01

    The objective of the present study was to determine the effect of supplementation of culture medium with carnosine (β-alanyl-l-histidine; Sigma, St-Quentin Fallavier, France), a reactive oxygen species scavenger, on in vitro bovine embryo development and survival following cryopreservation. Abattoir-derived bovine oocytes (4 replicates) were in vitro matured and fertilized with frozen-thawed semen of one bull, according to our standard procedures. In Experiment 1, 20h after IVF, groups of presumptive zygotes were cultured in 30μL of SOF BSAaa+1% oestrus cow serum with 0 (control; n=205) or 5μgmL(-1) of carnosine (n=209) under humidified air with 5% CO2, 5% O2, and 88% N2. Cleavage rates were determined on Day 2, and the blastocyst rates and grade were assessed on Day 7 according to IETS classification. Day 7 grade 1 expanded blastocysts (n=25 control and n=27 carnosine) were frozen in 1.5M ethylene glycol+0.1M sucrose. Embryos were thawed and then cultured for 72h in SOF-BSAaa+1% oestrus cow serum for re-expansion and hatching rate assessments at +24h, +48h, and +72h post-thawing. In Experiment 2, presumed zygotes were cultured in SOF BSAaa+1% oestrus cow serum with 0 (control; n=48) or 5μgmL(-1) of carnosine (n=48) in a WOW dish and observed with Time Laps Cinematography (Primo Vision®, VitroLife, Göteborg, Sweden). Images were recorded every 15min for up to 168h post-insemination. For embryos that reached the blastocyst stage, mean timing of the first cleavage (C1; 2-cell stage), second cleavage (C2; 4-cell stage), second cleavage to compaction (C3), and blastocoel cavity appearance (B4) were recorded. Chi-square test for Experiment 1 and Student's t-test for Experiment 2 were used, and differences were considered significant at P<0.05. In Experiment 1, no differences were observed in cleavage rate, blastocyst rate on Day 7, and grade 1 blastocyst rate between both control and carnosine groups (84.0±4.2v.85.2±3.8, P=0.7; 46.9±7.1v. 45.0±7.5, P=0.7; 24

  12. The Anti-Proliferative Effect of L-Carnosine Correlates with a Decreased Expression of Hypoxia Inducible Factor 1 alpha in Human Colon Cancer Cells

    PubMed Central

    Iovine, Barbara; Oliviero, Giorgia; Garofalo, Mariangela; Orefice, Maria; Nocella, Francesca; Borbone, Nicola; Piccialli, Vincenzo; Centore, Roberto; Mazzone, Massimiliano; Piccialli, Gennaro; Bevilacqua, Maria Assunta

    2014-01-01

    In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS) production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α) as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively). Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia-related diseases. PMID

  13. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

    PubMed

    Iovine, Barbara; Oliviero, Giorgia; Garofalo, Mariangela; Orefice, Maria; Nocella, Francesca; Borbone, Nicola; Piccialli, Vincenzo; Centore, Roberto; Mazzone, Massimiliano; Piccialli, Gennaro; Bevilacqua, Maria Assunta

    2014-01-01

    In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS) production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α) as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively). Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia-related diseases.

  14. Effect of Carnosine in Experimental Arthritis and on Primary Culture Chondrocytes

    PubMed Central

    Ponist, S.; Drafi, F.; Kuncirova, V.; Mihalova, D.; Rackova, L.; Danisovic, L.; Ondrejickova, O.; Tumova, I.; Trunova, O.; Fedorova, T.; Bauerova, K.

    2016-01-01

    Carnosine's (CARN) anti-inflammatory potential in autoimmune diseases has been but scarcely investigated as yet. The aim of this study was to evaluate the therapeutic potential of CARN in rat adjuvant arthritis, in the model of carrageenan induced hind paw edema (CARA), and also in primary culture of chondrocytes under H2O2 injury. The experiments were done on healthy animals, arthritic animals, and arthritic animals with oral administration of CARN in a daily dose of 150 mg/kg b.w. during 28 days as well as animals with CARA treated by a single administration of CARN in the same dose. CARN beneficially affected hind paw volume and changes in body weight on day 14 and reduced hind paw swelling in CARA. Markers of oxidative stress in plasma and brain (malondialdehyde, 4-hydroxynonenal, protein carbonyls, and lag time of lipid peroxidation) and also activity of gamma-glutamyltransferase were significantly corrected by CARN. CARN also reduced IL-1alpha in plasma. Suppression of intracellular oxidant levels was also observed in chondrocytes pretreated with CARN. Our results obtained on two animal models showed that CARN has systemic anti-inflammatory activity and protected rat brain and chondrocytes from oxidative stress. This finding suggests that CARN might be beneficial for treatment of arthritic diseases. PMID:26885252

  15. Circulating Carnosine Dipeptidase 1 Associates with Weight Loss and Poor Prognosis in Gastrointestinal Cancer

    PubMed Central

    Arner, Peter; Henjes, Frauke; Schwenk, Jochen M.; Darmanis, Spyros; Dahlman, Ingrid; Iresjö, Britt-Marie; Naredi, Peter; Agustsson, Thorhallur; Lundholm, Kent; Nilsson, Peter; Rydén, Mikael

    2015-01-01

    Background Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia. Design/Subjects Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer. Results Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results. Conclusions In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC. PMID:25898255

  16. Antiglycation effects of carnosine and other compounds on the long-term survival of Escherichia coli.

    PubMed

    Pepper, Evan D; Farrell, Michael J; Nord, Gary; Finkel, Steven E

    2010-12-01

    Glycation, or nonenzymatic glycosylation, is a chemical reaction between reactive carbonyl-containing compounds and biomolecules containing free amino groups. Carbonyl-containing compounds include reducing sugars such as glucose or fructose, carbohydrate-derived compounds such as methylglyoxal and glyoxal, and nonsugars such as polyunsaturated fatty acids. The latter group includes molecules such as proteins, DNA, and amino lipids. Glycation-induced damage to these biomolecules has been shown to be a contributing factor in human disorders such as Alzheimer's disease, atherosclerosis, and cataracts and in diabetic complications. Glycation also affects Escherichia coli under standard laboratory conditions, leading to a decline in bacterial population density and long-term survival. Here we have shown that as E. coli aged in batch culture, the amount of carboxymethyl lysine, an advanced glycation end product, accumulated over time and that this accumulation was affected by the addition of glucose to the culture medium. The addition of excess glucose or methylglyoxal to the culture medium resulted in a dose-dependent loss of cell viability. We have also demonstrated that glyoxylase enzyme GloA plays a role in cell survival during glycation stress. In addition, we have provided evidence that carnosine, folic acid, and aminoguanidine inhibit glycation in prokaryotes. These agents may also prove to be beneficial to eukaryotes since the chemical processes of glycation are similar in these two domains of life.

  17. Accurate analysis of taurine, anserine, carnosine and free amino acids in a cattle muscle biopsy sample.

    PubMed

    Imanari, Mai; Higuchi, Mikito; Shiba, Nobuya; Watanabe, Akira

    2010-06-01

    We have established an analysis method for some free amino acids (FAAs), as well as taurine (Tau), anserine (Ans) and carnosine (Car), in a fresh biopsy sample from cattle muscle. A series of model biopsy samples, corresponding to the mixtures of lean meat, fat and connective tissue, was prepared and showed high correlation coefficients between the compound concentration and the 3-methylhistidine (3-MeHis) content derived from hydrolysis of the biopsy sample (r = 0.74-0.95, P < 0.01). Interference from blood contamination could not be neglected, because the concentration of some FAAs in blood was comparable to that in muscle. However, it was possible to control the contamination of Tau, Ans, Car, glutamic acid, glutamine, asparatic acid and alanine to less than 5.0% when the blood contamination was controlled to less than 23%.These results suggest the necessity of measuring 3-MeHis as an index of lean meat and hemoglobin as an index of blood contamination when compounds in muscle biopsy samples are evaluated. We have carried out a series of these analyses using one biopsy sample and reveal differences in Tau, Ans, Car and some FAAs in beef muscle after different feeding regimes.

  18. The detox strategy in smoking comprising nutraceutical formulas of non-hydrolyzed carnosine or carcinine used to protect human health.

    PubMed

    Babizhayev, Mark A

    2014-03-01

    The increased oxidative stress in patients with smoking-associated disease, such as chronic obstructive pulmonary disease, is the result of an increased burden of inhaled oxidants as well as increased amounts of reactive oxygen species generated by various inflammatory, immune and epithelial cells of the airways. Nicotine sustains tobacco addiction, a major cause of disability and premature death. In addition to the neurochemical effects of nicotine, behavioural factors also affect the severity of nicotine withdrawal symptoms. For some people, the feel, smell and sight of a cigarette and the ritual of obtaining, handling, lighting and smoking a cigarette are all associated with the pleasurable effects of smoking. For individuals who are motivated to quit smoking, a combination of pharmacotherapy and behavioural therapy has been shown to be most effective in controlling the symptoms of nicotine withdrawal. In the previous studies, we proposed the viability and versatility of the imidazole-containing dipeptide-based compounds in the nutritional compositions as the telomere protection targeted therapeutic system for smokers in combination with in vitro cellular culture techniques being an investigative tool to study telomere attrition in cells induced by cigarette smoke (CS) and smoke constituents. Our working therapeutic concept is that imidazole-containing dipeptide-based compounds (non-hydrolyzed carnosine and carcinine) can modulate the telomerase activity in the normal cells and can provide the redox regulation of the cellular function under the terms of environmental and oxidative stress and in this way protect the length and the structure of telomeres from attrition. The detoxifying system of non-hydrolyzed carnosine or carcinine can be applied in the therapeutic nutrition formulations or installed in the cigarette filter. Patented specific oral formulations of non-hydrolyzed carnosine and carcinine provide a powerful manipulation tool for targeted therapeutic

  19. X-linked mental retardation.

    PubMed

    Ropers, H-Hilger; Hamel, Ben C J

    2005-01-01

    Genetic factors have an important role in the aetiology of mental retardation. However, their contribution is often underestimated because in developed countries, severely affected patients are mainly sporadic cases and familial cases are rare. X-chromosomal mental retardation is the exception to this rule, and this is one of the reasons why research into the genetic and molecular causes of mental retardation has focused almost entirely on the X-chromosome. Here, we review the remarkable recent progress in this field, its promise for understanding neural function, learning and memory, and the implications of this research for health care.

  20. Covalent Cross-Linking of Glutathione and Carnosine to Proteins by 4-Oxo-2-nonenal§

    PubMed Central

    Zhu, Xiaochun; Gallogly, Molly M.; Mieyal, John J.; Anderson, Vernon E.; Sayre, Lawrence M.

    2010-01-01

    The lipid oxidation product 4-oxo-2-nonenal (ONE) derived from peroxidation of polyunsaturated fatty acids is a highly reactive protein cross-linking reagent. The major family of cross-links reflects conjugate addition of side-chain nucleophiles such as sulfhydryl or imidazole groups to the C=C of ONE to give either a 2- or 3-substituted 4-ketoaldehyde, which then undergoes Paal-Knorr condensation with the primary amine of protein lysine side-chains. If ONE is intercepted in biological fluids by antielectrophiles such as glutathione (GSH) or β-alanylhistidine (carnosine), this would lead to circulating 4-ketoaldehydes that could then bind covalently to the protein Lys residues. This phenomenon was investigated by SDS–PAGE and mass spectrometry (MALDI-TOF and LC-ESI-MS/MS with both tryptic and chymotryptic digestion). Under the reaction conditions of 0.25 mM to 2 mM ONE, 1 mM GSH or carnosine, 0.25 mM bovine β-lactoglobulin (β-LG), 100 mM phosphate buffer (pH 7.4, 10% ethanol), 24 h, 37 °C, virtually every Lys of β-LG was found to be fractionally cross-linked to GSH. Cross-linking of Lys to carnosine was slightly less efficient. Using cytochrome c and RNase A, we showed that ONE becomes more protein-reactive in the presence of GSH, whereas protein modification by 4-hydroxy-2-nonenal is inhibited by GSH. Stable antielectrophile–ONE–protein cross-links may serve as biomarkers of oxidative stress and may represent a novel mechanism of irreversible protein glutathionylation. PMID:19480392

  1. Carnosine, anserine, creatine, and inosine 5'-monophosphate contents in breast and thigh meats from 5 lines of Korean native chicken.

    PubMed

    Jung, Samooel; Bae, Young Sik; Kim, Hyun Joo; Jayasena, Dinesh D; Lee, Jun Heon; Park, Hee Bok; Heo, Kang Nyung; Jo, Cheorun

    2013-12-01

    The aim of this study was to examine the effect of chicken line on the contents of endogenous compounds, including carnosine, anserine, creatine, and inosine 5'-monophosphate (IMP), in breast and thigh meats from 5 lines of Korean native chicken for the development of high-quality meat breeds. Additionally, the effects of sex (male or female) and meat type (breast or thigh meat) were examined. In total, 595 F1 progeny [black: 90 (male: 45, female: 45); gray-brown: 110 (male: 52, female: 58); red-brown: 136 (male: 68, female: 68); white: 126 (male: 63, female: 63); and yellow-brown: 133 (male: 62, female: 71)] from 70 full-sib families were used. The male chicken from the red-brown line and the female chicken from the black line showed the highest BW among the 5 lines. Carnosine content was higher in female chicken and breast meat than in male chicken and thigh meat, respectively. Breast meat contained higher anserine content compared with thigh meat. The sex effect on anserine was not consistent between breast and thigh meat. Creatine content was not consistently influenced by sex between breast and thigh meat, and no meat type effect was observed. The IMP contents were higher in female chicken and breast meat compared with male chicken and thigh meat, respectively. In addition, we clearly observed line effects by the comparison of the contents of carnosine, anserine, creatine, and IMP for each meat type according to each sex. These data are useful for selection and development of high-quality, meat-type chicken breeds.

  2. Can earthworms survive fire retardants?

    USGS Publications Warehouse

    Beyer, W.N.; Olson, A.

    1996-01-01

    Most common fire retardants are foams or are similar to common agricultural fertilizers, such as ammonium sulfate and ammonium phosphate. Although fire retardants are widely applied to soils, we lack basic information about their toxicities to soil organisms. We measured the toxicity of five fire retardants (Firetrol LCG-R, Firetrol GTS-R, Silv-Ex Foam Concentrate, Phos-chek D-75, and Phos-chek WD-881) to earthworms using the pesticide toxicity test developed for earthworms by the European Economic Community. None was lethal at 1,000 ppm in the soil, which was suggested as a relatively high exposure under normal applications. We concluded that the fire retardants tested are relatively nontoxic to soil organisms compared with other environmental chemicals and that they probably do not reduce earthworm populations when applied under usual firefighting conditions.

  3. Neurotoxicity of brominated flame retardants

    EPA Science Inventory

    Polybrominated diphenyl ethers (PBDEs) have been commonly used as commercial flame retardants in a variety of products including plastics and textiles. Despite their decreasing usage worldwide, congeners continue to accumulate in the environment, including soil, dust, food, anima...

  4. Deinstitutionalization of the Mentally Retarded.

    ERIC Educational Resources Information Center

    Cortez, Patricia

    Literature on deinstitutionalization of mentally retarded persons is reviewed. Cited are studies showing positive aspects, including improved communication abilities, increased adaptive behavior and personal satisfaction. Community adjustment findings focus on effects of involuntary relocation to another facility, age differences, and…

  5. Neurotoxicity of brominated flame retardants

    EPA Science Inventory

    Polybrominated diphenyl ethers (PBDEs) have been commonly used as commercial flame retardants in a variety of products including plastics and textiles. Despite their decreasing usage worldwide, congeners continue to accumulate in the environment, including soil, dust, food, anima...

  6. INTRODUCTION TO BROMINATED FLAME RETARDANTS

    EPA Science Inventory

    Brominated flame retardants (BFRs) are a large and diverse class of major industrial products used to provide fire safety. Tetrabromobisphenol A (TBBPA), Hexabromocylocodecane (HBCD), and Polybrominated Diphenyl Ethers (PBDEs) are the major commercial compounds. TBBPA is a react...

  7. Epigenetic mechanisms of mental retardation.

    PubMed

    Schaefer, Anne; Tarakhovsky, Alexander; Greengard, Paul

    2011-01-01

    Mental retardation is a common form of cognitive impairment affecting approximately 3% of the population in industrialized countries. The mental retardation syndrome incorporates a highly diverse group of mental disorders characterized by the combination of cognitive impairment and defective adaptive behavior. The genetic basis of the disease is strongly supported by identification of the genetic lesions associated with impaired cognition, learning, and social adaptation in many mental retardation syndromes. Several of the impaired genes encode epigenetic regulators of gene expression. These regulators exert their function through genome-wide posttranslational modification of histones or by mediating and/or recognizing DNA methylation. In this chapter, we review the most recent advances in the field of epigenetic mechanisms of mental retardation. In particular, we focus on animal models of the human diseases and the mechanism of transcriptional deregulation associated with changes in the cell epigenome.

  8. Intumescent Coatings as Fire Retardants

    NASA Technical Reports Server (NTRS)

    Fish, R. H.; Fohlen, G. M.; Parker, J. A.; Sawko, P. M.

    1970-01-01

    Fire-retardant paint, when activated by the heat of fire, reacts to form a thick, low-density, polymeric coating or char layer. Water vapor and sulphur dioxide are released during the intumescent reaction.

  9. The Mentally Retarded Offender: Annotated Bibliography.

    ERIC Educational Resources Information Center

    Schilit, Jeffrey; And Others

    An annotated bibliography of approximately 150 books and articles on the mentally retarded offender as well as 30 nonannotated entries are provided. Topics covered include such areas as characteristics of mentally retarded delinquents, rehabilitation of the retarded offender, community services for retarded persons, rights of the mentally…

  10. The Mentally Retarded Offender: Annotated Bibliography.

    ERIC Educational Resources Information Center

    Schilit, Jeffrey; And Others

    An annotated bibliography of approximately 150 books and articles on the mentally retarded offender as well as 30 nonannotated entries are provided. Topics covered include such areas as characteristics of mentally retarded delinquents, rehabilitation of the retarded offender, community services for retarded persons, rights of the mentally…

  11. Balanced translocations in mental retardation.

    PubMed

    Vandeweyer, Geert; Kooy, R Frank

    2009-07-01

    Over the past few decades, the knowledge on genetic defects causing mental retardation has dramatically increased. In this review, we discuss the importance of balanced chromosomal translocations in the identification of genes responsible for mental retardation. We present a database-search guided overview of balanced translocations identified in patients with mental retardation. We divide those in four categories: (1) balanced translocations that helped to identify a causative gene within a contiguous gene syndrome, (2) balanced translocations that led to the identification of a mental retardation gene confirmed by independent methods, (3) balanced translocations disrupting candidate genes that have not been confirmed by independent methods and (4) balanced translocations not reported to disrupt protein coding sequences. It can safely be concluded that balanced translocations have been instrumental in the identification of multiple genes that are involved in mental retardation. In addition, many more candidate genes were identified with a suspected but (as yet?) unconfirmed role in mental retardation. Some balanced translocations do not disrupt a protein coding gene and it can be speculated that in the light of recent findings concerning ncRNA's and ultra-conserved regions, such findings are worth further investigation as these potentially may lead us to the discovery of novel disease mechanisms.

  12. X-linked mental retardation.

    PubMed

    Lisik, Małgorzata Zofia; Sieron, Aleksander L

    2008-11-01

    Mental retardation is a serious medical and social problem. The prevalence of mental retardation in Western countries is estimated to be between 2 and 3%. Establishing the cause of mental retardation is essential for prognosis, management, and genetic counseling. It is estimated that 25-35% of mental retardation might have a genetic background. Of these genetic causes, 25-30% are probably due to mutations on the X chromosome (X-linked mental retardation, XLMR). XLMR is a heterogeneous set of conditions involved in a large proportion of inherited mental retardation. More than 200 XLMR conditions have been reported and 76 genes has been linked to them. XLMR conditions are commonly subdivided into syndromic and nonsyndromic forms on the basis of clinical presentation. The distinction between these forms of XLMR is gradually becoming less clear as phenotypes are described for several of the genes. The spectrum of phenotypic variability in XLMR is so large that mutations in several XLMR genes have been found in both syndromic and nonsyndromic (XLMR) pedigrees. About 42% of patients from families with an XLMR history might have mutations in one of the known genes implicated in XLMR. However, in genetic counseling we have to use empiric recurrence risk.

  13. Effect of Four Weeks of β-alanine Supplementation on Muscle Carnosine and Blood Serum Lactate during Exercise in Male Rats.

    PubMed

    Naderi, Alireza; Hemat Far, Ahmad; Willems, Mark E T; Sadeghi, Mehdi

    2016-01-01

    β-alanine (BA) supplementation may increase muscle buffering capacity and affect physiological responses during exercise. We examined the effects of 4 weeks of BA supplementation on muscle carnosine and serum lactate in male rats. Rats (n = 24, age: 2 months, body weight: 265±22 g) were divided into a BA supplementation or control group. Along with aerobic acclimatization exercise (15 m·min(-1), 8-10 min·day(-1), 4 days·week(-1) for 4 weeks), the BA group had access to BA powder in their drinking water (1.8%) with the control group having access to plain water for 4 weeks. After 4 weeks, rats ran on a treadmill at speeds of 15, 20, 25, 30, and 35 m·min(-1), respectively, each for 4 min, in order to measure post-exercise serum lactate. Muscle carnosine and serum lactate levels were measured with high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbant assay (ELISA) procedures, respectively. Following BA supplementation, carnosine content in the m.rectus femoris increased by 117% (p < .01) and serum lactate decreased by 7.4% (p < .01). It was concluded that β-alanine supplementation increases muscle carnosine content and reduces serum lactate; these changes may indicate an adaptation of rat skeletal muscles to postpone peripheral muscle fatigue during high-intensity exercise.

  14. l-carnosine dipeptide overcomes acquired resistance to 5-fluorouracil in HT29 human colon cancer cells via downregulation of HIF1-alpha and induction of apoptosis.

    PubMed

    Iovine, Barbara; Guardia, Francesca; Irace, Carlo; Bevilacqua, Maria Assunta

    2016-08-01

    Hypoxia-inducible factor (HIF-1α) protein is over-expressed in many human cancers and is a major cause of resistance to drugs. HIF-1α up-regulation decreases the effectiveness of several anticancer agents, including 5-fluorouracil (5-FU), because it induces the expression of drug efflux transporters, alters DNA repair mechanisms and modifies the balance between pro- and antiapoptotic factors. These findings suggest that inhibition of HIF-1α activity may sensitize cancer cells to cytotoxic drugs. We previously reported that l-carnosine reduces HIF-1α expression by inhibiting the proliferation of colon cancer cells. In the present study we investigated the effect of l-carnosine on HT29 colon cancer cells with acquired resistance to 5-FU. We found that l-carnosine reduces colon cancer cell viability, decreases HIF-1α and multi-drug resistant protein MDR1-pg expression, and induces apoptosis. Moreover, the l-carnosine/5-FU combination lowers the expression of some chemoresistance markers. The combination index evaluated in vitro on the HT29-5FU cell line by median drug effect analysis reveals a significant synergistic effect. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  15. Effects of Dietary Supplementation of Carnosine on Mitochondrial Dysfunction, Amyloid Pathology, and Cognitive Deficits in 3xTg-AD Mice

    PubMed Central

    Corona, Carlo; Frazzini, Valerio; Silvestri, Elena; Lattanzio, Rossano; La Sorda, Rossana; Piantelli, Mauro; Canzoniero, Lorella M. T.; Ciavardelli, Domenico; Rizzarelli, Enrico; Sensi, Stefano L.

    2011-01-01

    Background The pathogenic road map leading to Alzheimer's disease (AD) is still not completely understood; however, a large body of studies in the last few years supports the idea that beside the classic hallmarks of the disease, namely the accumulation of amyloid-β (Aβ) and neurofibrillary tangles, other factors significantly contribute to the initiation and the progression of the disease. Among them, mitochondria failure, an unbalanced neuronal redox state, and the dyshomeostasis of endogenous metals like copper, iron, and zinc have all been reported to play an important role in exacerbating AD pathology. Given these factors, the endogenous peptide carnosine may be potentially beneficial in the treatment of AD because of its free-radical scavenger and metal chelating properties. Methodology In this study, we explored the effect of L-carnosine supplementation in the 3xTg-AD mouse, an animal model of AD that shows both Aβ- and tau-dependent pathology. Principal Findings We found that carnosine supplementation in 3xTg-AD mice promotes a strong reduction in the hippocampal intraneuronal accumulation of Aβ and completely rescues AD and aging-related mitochondrial dysfunctions. No effects were found on tau pathology and we only observed a trend toward the amelioration of cognitive deficits. Conclusions and Significance Our data indicate that carnosine can be part of a combined therapeutic approach for the treatment of AD. PMID:21423579

  16. The effects of ascorbic acid, taurine, carnosine and rosemary powder on colour and lipid stability of beef patties packaged in modified atmosphere.

    PubMed

    Sánchez-Escalante, A; Djenane, D; Torrescano, G; Beltrán, J A; Roncalés, P

    2001-08-01

    This research was aimed at evaluating the inhibition of oxidative changes of beef patties packaged in modified atmosphere (70% O(2)+20% CO(2)+10% N(2)) by natural antioxidants: ascorbic acid (500 ppm), taurine (50 mM), carnosine (50 mM), rosemary powder (1000 ppm) and their combinations with the first. Beef patties stored at 2±1°C for 20 days were evaluated for colour (L*, a*, b*, C* and H*), TBARS, metmyoglobin formation (% of total myoglobin), psychrotrophic microbial counts and sensory odour and discolouration. Rosemary, either alone or with ascorbic acid, was highly effective in inhibiting both metmyoglobin formation and lipid oxidation; sensory analysis was in agreement with these results. Ascorbic acid, ascorbic acid+taurine and ascorbic acid+carnosine treatments showed a limited inhibitory effect of myoglobin oxidation, while carnosine and carnosine+ascorbic acid were effective in inhibiting lipid oxidation. Taurine alone failed to exert any antioxidant effect. Principal components analysis confirmed these results.

  17. Effects of L-carnosine and its zinc complex (Polaprezinc) on pressure ulcer healing.

    PubMed

    Sakae, Kensaku; Agata, Toshihiko; Kamide, Ryoichi; Yanagisawa, Hiroyuki

    2013-10-01

    L-carnosine (CAR) is an endogenous dipeptide. We aimed to determine the effects of CAR and its zinc complex polaprezinc (PLZ) on pressure ulcer healing in institutionalized long-term care patients. This study was a nonrandomized controlled trial with a maximum 4-week follow-up. Forty-two patients with stage II-IV pressure ulcers for 4 or more weeks were allocated to 1 of 3 groups in order of recruitment: the control group (n = 14) was untreated, the PLZ group (n = 10) orally received 150 mg/d PLZ (containing 116 mg CAR and 34 mg zinc), and the CAR group (n = 18) orally received 116 mg/d CAR. Pressure ulcer severity was measured weekly using the Pressure Ulcer Scale for Healing (PUSH) score. At baseline, no significant differences were found among groups in demographic and nutrition parameters and pressure ulcer characteristics (severity, size, and staging). After 4 weeks, the rate of pressure ulcer healing, assessed by the mean weekly improvement in PUSH score, was significantly greater in the CAR (1.6 ± 0.2, P = .02) and PLZ groups (1.8 ± 0.2, P = .009) than in the control group (0.8 ± 0.2). The difference between the CAR and PLZ groups was not significant (P = .73). Actual dietary intakes over this period did not differ significantly among groups. Our results suggest that CAR and PLZ may almost equally accelerate pressure ulcer healing during 4 weeks. The results need confirmation by randomized controlled trials with larger sample sizes.

  18. The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats.

    PubMed

    Aldini, Giancarlo; Orioli, Marica; Rossoni, Giuseppe; Savi, Federica; Braidotti, Paola; Vistoli, Giulio; Yeum, Kyung-Jin; Negrisoli, Gianpaolo; Carini, Marina

    2011-06-01

    The metabolic syndrome is a risk factor that increases the risk for development of renal and vascular complications. This study addresses the effects of chronic administration of the endogenous dipeptide carnosine (β-alanyl-L-histidine, L-CAR) and of its enantiomer (β-alanyl-D-histidine, D-CAR) on hyperlipidaemia, hypertension, advanced glycation end products, advanced lipoxidation end products formation and development of nephropathy in the non-diabetic, Zucker obese rat. The Zucker rats received a daily dose of L-CAR or D-CAR (30 mg/kg in drinking water) for 24 weeks. Systolic blood pressure was recorded monthly. At the end of the treatment, plasma levels of triglycerides, total cholesterol, glucose, insulin, creatinine and urinary levels of total protein, albumin and creatinine were measured. Several indices of oxidative/carbonyl stress were also measured in plasma, urine and renal tissue. We found that both L- and D-CAR greatly reduced obese-related diseases in obese Zucker rat, by significantly restraining the development of dyslipidaemia, hypertension and renal injury, as demonstrated by both urinary parameters and electron microscopy examinations of renal tissue. Because the protective effect elicited by L- and D-CAR was almost superimposable, we conclude that the pharmacological action of L-CAR is not due to a pro-histaminic effect (D-CAR is not a precursor of histidine, since it is stable to peptidic hydrolysis), and prompted us to propose that some of the biological effects can be mediated by a direct carbonyl quenching mechanism.

  19. The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats

    PubMed Central

    Aldini, Giancarlo; Orioli, Marica; Rossoni, Giuseppe; Savi, Federica; Braidotti, Paola; Vistoli, Giulio; Yeum, Kyung-Jin; Negrisoli, Gianpaolo; Carini, Marina

    2011-01-01

    Abstract The metabolic syndrome is a risk factor that increases the risk for development of renal and vascular complications. This study addresses the effects of chronic administration of the endogenous dipeptide carnosine (β-alanyl-L-histidine, L-CAR) and of its enantiomer (β-alanyl-D-histidine, D-CAR) on hyperlipidaemia, hypertension, advanced glycation end products, advanced lipoxidation end products formation and development of nephropathy in the non-diabetic, Zucker obese rat. The Zucker rats received a daily dose of L-CAR or D-CAR (30 mg/kg in drinking water) for 24 weeks. Systolic blood pressure was recorded monthly. At the end of the treatment, plasma levels of triglycerides, total cholesterol, glucose, insulin, creatinine and urinary levels of total protein, albumin and creatinine were measured. Several indices of oxidative/carbonyl stress were also measured in plasma, urine and renal tissue. We found that both L- and D-CAR greatly reduced obese-related diseases in obese Zucker rat, by significantly restraining the development of dyslipidaemia, hypertension and renal injury, as demonstrated by both urinary parameters and electron microscopy examinations of renal tissue. Because the protective effect elicited by L- and D-CAR was almost superimposable, we conclude that the pharmacological action of L-CAR is not due to a pro-histaminic effect (D-CAR is not a precursor of histidine, since it is stable to peptidic hydrolysis), and prompted us to propose that some of the biological effects can be mediated by a direct carbonyl quenching mechanism. PMID:20518851

  20. N alpha-acetylcarnosine is a prodrug of L-carnosine in ophthalmic application as antioxidant.

    PubMed

    Babizhayev, M A; Yermakova, V N; Sakina, N L; Evstigneeva, R P; Rozhkova, E A; Zheltukhina, G A

    1996-10-15

    The naturally occurring compound N alpha-acetylcarnosine (NAC) is proposed as the prodrug of L-carnosine (C) resistant to enzymatic hydrolysis by human serum carnosinase. Rabbit eyes were treated with 1% NAC, C or placebo and extracts of the aqueous humor from the anterior eye chamber were analyzed for imidazole content by reverse phase analytical high performance liquid chromatography (HPLC), thin-layer (TLC) and ion-exchange chromatographic techniques. The topical administration of pure C to the rabbit eye did not lead to accumulation of this compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eye. NAC showed dose-dependent hydrolysis in its passage from the cornea to the aqueous humor, releasing C after 15. 30 min of ocular administration of prodrug in a series of therapeutical modalities: instillation < or = subconjunctival injection < or = ultrasound induced phoresis. Different treatment techniques showed excellent toleration of 1% NAC by the eye. Once in the aqueous humor, C might act as an antioxidant and enter the lens tissue when present at effective concentrations (5-15 mmol/l). The advantage of the ophthalmic prodrug NAC and its bioactivated principle C as universal antioxidants relates to their ability to give efficient protection against oxidative stress both in the lipid phase of biological membranes and in an aqueous environment. NAC is proposed to treat ocular disorders which have the component of oxidative stress in their genesis (cataracts, glaucoma, retinal degeneration, corneal disorders, ocular inflammation, complications of diabetes mellitus, systemic diseases).

  1. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes

    PubMed Central

    Mahmood, A; FitzGerald, A J; Marchbank, T; Ntatsaki, E; Murray, D; Ghosh, S; Playford, R J

    2007-01-01

    Background Zinc carnosine (ZnC) is a health food product claimed to possess health‐promoting and gastrointestinal supportive activity. Scientific evidence underlying these claims is, however, limited. Aim To examine the effect of ZnC on various models of gut injury and repair, and in a clinical trial. Methods In vitro studies used pro‐migratory (wounded monolayer) and proliferation ([3H]‐thymidine incorporation) assays of human colonic (HT29), rat intestinal epithelial (RIE) and canine kidney (MDCK) epithelial cells. In vivo studies used a rat model of gastric damage (indomethacin/restraint) and a mouse model of small‐intestinal (indomethacin) damage. Healthy volunteers (n = 10) undertook a randomised crossover trial comparing changes in gut permeability (lactulose:rhamnose ratios) before and after 5 days of indomethacin treatment (50 mg three times a day) with ZnC (37.5 mg twice daily) or placebo coadministration. Results ZnC stimulated migration and proliferation of cells in a dose‐dependent manner (maximum effects in both assays at 100 µmol/l using HT29 cells), causing an approximate threefold increase in migration and proliferation (both p<0.01). Oral ZnC decreased gastric (75% reduction at 5 mg/ml) and small‐intestinal injury (50% reduction in villus shortening at 40 mg/ml; both p<0.01). In volunteers, indomethacin caused a threefold increase in gut permeability in the control arm; lactulose:rhamnose ratios were (mean (standard error of mean)) 0.35 (0.035) before indomethacin treatment and 0.88 (0.11) after 5 days of indomethacin treatment (p<0.01), whereas no significant increase in permeability was seen when ZnC was coadministered. Conclusion ZnC, at concentrations likely to be found in the gut lumen, stabilises gut mucosa. Further studies are warranted. PMID:16777920

  2. Effects of Beta-Alanine on Muscle Carnosine and Exercise Performance:A Review of the Current Literature

    PubMed Central

    Culbertson, Julie Y.; Kreider, Richard B.; Greenwood, Mike; Cooke, Matthew

    2010-01-01

    Muscle carnosine has been reported to serve as a physiological buffer, possess antioxidant properties, influence enzyme regulation, and affect sarcoplasmic reticulum calcium regulation. Beta-alanine (β-ALA) is a non-essential amino acid. β-ALA supplementation (e.g., 2-6 grams/day) has been shown to increase carnosine concentrations in skeletal muscle by 20-80%. Several studies have reported that β-ALA supplementation can increase high-intensity intermittent exercise performance and/or training adaptations. Although the specific mechanism remains to be determined, the ergogenicity of β-ALA has been most commonly attributed to an increased muscle buffering capacity. More recently, researchers have investigated the effects of co-ingesting β-ALA with creatine monohydrate to determine whether there may be synergistic and/or additive benefits. This paper overviews the theoretical rationale and potential ergogenic value of β-ALA supplementation with or without creatine as well as provides future research recommendations. PMID:22253993

  3. Anserine inhibits carnosine degradation but in human serum carnosinase (CN1) is not correlated with histidine dipeptide concentration.

    PubMed

    Peters, Verena; Jansen, Erwin E W; Jakobs, Cornelis; Riedl, Eva; Janssen, Bart; Yard, Benito A; Wedel, Johannes; Hoffmann, Georg F; Zschocke, Johannes; Gotthardt, Daniel; Fischer, Christine; Köppel, Hannes

    2011-01-30

    We reported an association of a particular allele of the carnosinase (CNDP1 Mannheim) gene with reduced serum carnosinase (CN1) activity and absence of nephropathy in diabetic patients. Carnosine protects against the adverse effects of high glucose levels but serum carnosine concentration was generally low. We measured the concentration of two further histidine dipeptides, anserine and homocarnosine, via HPLC. CN1 activity was measured fluorometically and for concentration we developed a capture ELISA. We found an association between the CNDP1 Mannheim allele and reduced serum CN1 activity for all three dipeptides but no correlation to serum concentrations although anserine and homocarnosine inhibited carnosinase activity. Patients with liver cirrhosis have low CN1 activity (0.24 ± 0.17 μmol/ml/h, n=7 males; normal range: 3.2 ± 1.1, n=104; p<0.05) and CN1 concentrations (2.3 ± 1.5 μg/ml; normal range: 24.9 ± 8.9, p<0.05) but surprisingly, histidine dipeptide concentrations in serum are not increased compared to controls. Serum histidine dipeptide concentrations are not correlated to CN1 activity. The protective effect of low CN1 activity might be related either to turnover of CN1 substrates or a protective function of dipeptides might be localized in other tissues. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Effect of cooking method on carnosine and its homologues, pentosidine and thiobarbituric acid-reactive substance contents in beef and turkey meat.

    PubMed

    Peiretti, Pier Giorgio; Medana, Claudio; Visentin, Sonja; Dal Bello, Federica; Meineri, Giorgia

    2012-05-01

    Commercial samples of beef and turkey meat were prepared by commonly used cooking methods with standard cooking times: (1) broiled at 200°C for 10min, (2) broiled at a medium temperature (140°C) for 10min, (3) cooked by microwave (MW) for 3min and then grilled (MW/grill) for 7min, (4) cooked in a domestic microwave oven for 10min, and (5) boiled in water for 10min. The raw and cooked meats were then analysed to determine the carnosine, anserine, homocarnosine, pentosidine, and thiobarbituric acid-reactive substance (TBARS) contents. It was observed that boiling beef caused a loss of approximately 50% of the carnosine, probably because of the high water solubility of carnosine and its homologues; cooking by microwave caused a medium loss of the anti-oxidants of approximately 20%; cooking by MW/grill led to a reduction in carnosine of approximately 10%. As far as the anserine and homocarnosine contents were concerned, a greater loss was observed for the boiling method (approximately 70%) while, for the other cooking methods, the value ranged from 30% to 70%. The data oscillate more for the turkey meat: the minimum carnosine decrease was observed in the cases of MW/grill and broiling at high temperature (25%). Analogously, the anserine and homocarnosine contents decreased slightly in the case of MW/grill and broiling at a high temperature (2-7%) and by 10-30% in the other cases. No analysed meat sample showed any traces of pentosidine above the instrumental determination limits. The cooked beef showed an increased TBARS value compared to the raw meat, and the highest values were found when the beef was broiled at a high temperature, cooked by microwave or boiled in water. The TBARS value of the turkey meat decreased for all the cooking methods in comparison to the TBARS value of the fresh meat. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Effect of carnosine, methylprednisolone and their combined application on irisin levels in the plasma and brain of rats with acute spinal cord injury.

    PubMed

    Albayrak, Serdal; Atci, İbrahim Burak; Kalayci, Mehmet; Yilmaz, Musa; Kuloglu, Tuncay; Aydin, Suna; Kom, Mustafa; Ayden, Omer; Aydin, Suleyman

    2015-08-01

    Spinal cord injury (SCI) might occur to anybody at any time and any age. In its treatment, methylprednisolone (MP) is a first choice worldwide, but there is still no significant breakthrough in truly beneficial treatment due to SCI's complex pathophysiology. We investigated the effect of carnosine, methylprednisolone (MP) and its combination on irisin levels in the plasma, brain and medulla spinalis tissues in SCI using a rat model. The rats were divided into 6 groups: I (Control, saline); II (sham animals with laminectomy without cross-clamping); III (SCI); IV (SCI treated with 150mg/kg carnosine); V (SCI treated with 30mg/kg methylprednisolone); and VI (SCI treated with a combination of carnosine and MP). The animals were given traumatic SCI after laminectomy, using 70-g closing force aneurysm clips (Yasargil FE 721). Irisin concentration was measured by ELISA. The distribution of irisin in brain and spinal cord tissues was examined by immunochemistry. Irisin was mainly expressed in the astrocytes and microglia of brain tissues, and multipolar neurones of the anterior horn of spinal cord tissue in rats of all groups, indicating that irisin is physiologically indispensable. MP and carnosine and the combination of the two, significantly increased irisin in plasma and were accompanied by a significant rise in irisin immunoreactivity of brain and spinal cord tissues of the injured rats compared with control and sham. This finding raises the possibility that methylprednisolone and carnosine regulate the brain and spinal cord tissues in SCI by inducing irisin expression, and may therefore offer a better neurological prognosis.

  6. Evidence for rapid inter- and intramolecular chlorine transfer reactions of histamine and carnosine chloramines: implications for the prevention of hypochlorous-acid-mediated damage.

    PubMed

    Pattison, David I; Davies, Michael J

    2006-07-04

    Hypochlorous acid (HOCl) is a powerful oxidant generated from H(2)O(2) and Cl(-) by the heme enzyme myeloperoxidase, which is released from activated leukocytes. HOCl possesses potent antibacterial properties, but excessive production can lead to host tissue damage that is implicated in a wide range of human diseases (e.g., atherosclerosis). Histamine and carnosine have been proposed as protective agents against such damage. However, as recent studies have shown that histidine-containing compounds readily form imidazole chloramines that can rapidly chlorinate other targets, it was hypothesized that similar reactions may occur with histamine and carnosine, leading to propagation, rather than prevention, of HOCl-mediated damage. In this study, the reactions of HOCl with histamine, histidine, carnosine, and other compounds containing imidazole and free amine sites were examined. In all cases, rapid formation (k, 1.6 x 10(5) M(-)(1) s(-)(1)) of imidazole chloramines was observed, followed by chlorine transfer to yield more stable, primary chloramines (R-NHCl). The rates of most of these secondary reactions are dependent upon substrate concentrations, consistent with intermolecular mechanisms (k, 10(3)-10(4) M(-)(1) s(-)(1)). However, for carnosine, the imidazole chloramine transfer rates are independent of the concentration, indicative of intramolecular processes (k, 0.6 s(-)(1)). High-performance liquid chromatography studies show that in all cases the resultant R-NHCl species can slowly chlorinate N-alpha-acetyl-Tyr. Thus, the current data indicate that the chloramines formed on the imidazole and free amine groups of these compounds can oxidize other target molecules but with limited efficiency, suggesting that histamine and particularly carnosine may be able to limit HOCl-mediated oxidation in vivo.

  7. Development of novel fire retardants

    NASA Astrophysics Data System (ADS)

    Sigdel Regmi, Bhawani

    Numerous candidate environmentally-friendly, water-soluble, and non-toxic fire retardants and fire-retarding processes were developed and tested according to the ASTM D 3801 flammability test and the NRL 8093 smoldering test. Flame retardants that passed the ASTM D 3801 flammability test with the highest V0 rating were boron esters of guanidinium hydroxycarboxylate (glycolate, salicylate and dihydroxybenzoate), zinc gluconate borate ester, and cyanoacetate salts of organic bases (melaminium, cyanoguanidinium, and ammonium). Several related compounds pass this test with the lower V1 rating. Two new synergistic flame and smolder retarding systems were developed in which the individual components were incapable of preventing flame spread or smoldering but in combination they were highly effective. These systems were mixtures of either guanyl urea phosphate and boric acid or beta-alanine and boric acid. Compositions leading to the maximum solubility of boron oxides in the ammonium borate/sodium borate system were determined at several temperatures and the formation of mixtures exceeding 50% dissolved boric acid equivalents was found possible. These mixtures were applied as flame retardants for wood, paper, and carbon-loaded polyurethane foam both directly and indirectly by in situ precipitation of boric acid or zinc borate by appropriate chemical treatments. These all passed the ASTM flammability test with V0 rating. The performance of the boron-containing fire retardants is likely due to deposition of protective boron oxide coatings at elevated temperatures except where phosphate was present and a protective boron phosphate was deposited instead. In all cases, the oxidation of carbonaceous char was strongly inhibited. The hydroxycarboxylate groups generally formed intumescent chars during thermal decomposition that also contributed to fire retardancy.

  8. [Search for chaperon-like anticataract drugs, the antiaggregants of lens crystallins. Communication. 1. Chaperon-like activity of N-acetyl carnosine dipeptide: in vitro study on a model of ultraviolet-induced aggregation of betaL-crystallin].

    PubMed

    Muranov, K O; Dizhevskaia, A K; Boldyrev, A A; Karpova, O E; Sheremet, N L; Polunin, G S; Avetisov, S E; Ostrovskiĭ, M A

    2008-01-01

    Aggregation ofcrystallins, the lens proteins, is one of the basic stages of cataract formation. Among the protein aggregation models used to study the molecular mechanisms of the initial stages of lenticular opacity, UV-induced aggregation of betaL-crystallin is most close to the in vivo conditions. The carnosine derivative N-acetyl carnosine has been shown to be effective in inhibiting the UV-induced aggregation of betaL-crystallin. Examination of the accumulation kinetics of carbonyl groups in betaL-crystallin under UV irradiation has indicated that neither carnosine nor N-acetyl carnosine fails to affect this parameter--an indicator of oxidative protein damage. By taking into account also the fact that N-acetyl carnosine is not an antioxidant, it can be believed that the molecular mechanism of action of this compound on UV-induced aggregation of betaL is unassociated with its antioxidative properties. The authors hypothesize that the molecular chaperon-like properties similar to those of alpha-crystallin underlie the mechanism of action of the acetyl derivative carnosine. The prospects for searching anticataract agents of a new chaperon-like class are discussed.

  9. Firefighters and flame retardant activism.

    PubMed

    Cordner, Alissa; Rodgers, Kathryn M; Brown, Phil; Morello-Frosch, Rachel

    2015-02-01

    In the past decade, exposure to flame retardant chemicals has become a pressing health concern and widely discussed topic of public safety for firefighters in the United States. Working through local, state, and national unions and independent health and advocacy organizations, firefighters have made important contributions to efforts to restrict the use of certain flame retardants. Firefighters are key members in advocacy coalitions dedicated to developing new environmental health regulations and reforming flammability standards to reflect the best available fire science. Their involvement has been motivated by substantiated health concerns and critiques of deceptive lobbying practices by the chemical industry. Drawing on observations and interviews with firefighters, fire safety experts, and other involved stakeholders, this article describes why firefighters are increasingly concerned about their exposure to flame retardant chemicals in consumer products, and analyzes their involvement in state and national environmental health coalitions.

  10. The genetics of mental retardation.

    PubMed

    Raymond, F Lucy; Tarpey, Patrick

    2006-10-15

    Genetic abnormalities frequently give rise to a mental retardation phenotype. Recent advances in resolution of comparative genomic hybridization and genomic sequence annotation has identified new syndromes at chromosome 3q29 and 9q34. The finding of a significant number of copy number polymorphisms in the genome in the normal population, means that assigning pathogenicity to deletions and duplications in patients with mental retardation can be difficult but has been identified for duplications of MECP2 and L1CAM. Novel autosomal genes that cause mental retardation have been identified recently including CC2D1A identified by homozygosity mapping. Several new genes and pathways have been identified in the field of X-linked mental retardation but many more still await identification. Analysis of families where only a single male is affected reveals that the chance of this being due to a single X-linked gene abnormality is significantly less than would be expected if the excess of males in the population is entirely due to X-linked disease. Recent identification of novel X-linked mental retardation genes has identified components of the post-synaptic density and multiple zinc finger transcription factors as disease causing suggesting new mechanisms of disease causation. The first therapeutic treatments of animal models of mental retardation have been reported, a Drosophila model of Fragile X syndrome has been treated with lithium or metabotropic glutamate receptor (mGluR) antagonists and a mouse model of NF1 has been treated with the HMG-CoA reductase inhibitor lavastatin, which improves the learning and memory skills in these models.

  11. Concentrations of carnosine, anserine, L-histidine and 3-methyl histidine in boar spermatozoa and sheep milk by a modified HPLC method.

    PubMed

    Ducci, M; Pacchini, S; Niccolini, A; Gazzano, A; Cerri, D; Gadea, J; Bobowiec, R; Sighieri, C; Martelli, F

    2006-01-01

    The present study deals with the application of high-performance-liquid-chromatography (HPLC) method for a quantitative detection of carnosine, anserine, L-histidine and 3-methyl-L-histidine in biological material with o-phthaldialdehyde (OPA) post column derivatisation at the constant temperature of 50 degrees C. For this purpose, some mobile-phases were prepared with scalar acetonitrile concentrations. A complete separation of all molecules, particularly for carnosine and 3-methyl-L-histidine, was obtained with a solution of acetonitrile and 6mM hydrochloric acid with 0.48 M sodium chloride (5%:95% v/v). Post column derivatisation reaction at temperature of 50'C permitted to obtain an increase in sensibility of all molecules. This method has been utilised for detection of histidine dipeptides in boar spermatozoa and in sheep milk. Concentrations (mean +/- S.E. nmol/10(9) spermatozoa) of carnosine (0.96 +/- 0.14) and anserine (0.83 +/- 0.18) in boar spermatozoa were significantly lower than those of L-histidine (52.85 +/- 4.86) and 3-methyl-L-histidine (83.07 +/- 7.1). Positive correlation was found between carnosine and anserine contents (r = 0.740; p < 0.01) and between L-histidine and 3-methyl-L-histidine (r = 0.657; p < 0.01). All histidine dipeptides studied were also present in 40 samples of sheep milk. In a case of samples without unit-forming colonies (UFC) of Staphylococcus coagulase-positive, carnosine concentrations (9.17 +/- 0.89 nmol/ml) were higher than anserine (0.51 +/- 0.02 nmol/ml) and both were significantly lower in respect to L-histidine (49.51 +/- 6.48 nmol/ml) and 3-metyl-L-histidine (81.21 +/- 6.82 nmol/ml). A negative correlation was observed between carnosine milk levels (r = -0.773; p < 0.01) and UFC/ml of Staphylococcus coagulase-positive. In conclusion this very simple and fast method can be used to detect histidine dipeptides in biological compartments where their concentrations are very low.

  12. Transportation and the Mentally Retarded.

    ERIC Educational Resources Information Center

    President's Committee on Mental Retardation, Washington, DC.

    Reported were the results of a contract that involved identification, description, and categorization of the nature of transportation problems for the mentally retarded by means of analysis of existing studies, two surveys, and an inventory of specialized programs and systems operating in the United States. One major problem was found to be…

  13. Genetic Counseling in Mental Retardation.

    ERIC Educational Resources Information Center

    Bowen, Peter

    The task of the genetic counselor who identifies genetic causes of mental retardation and assists families to understand risk of recurrence is described. Considered are chromosomal genetic disorders such as Down's syndrome, inherited disorders such as Tay-Sachs disease, identification by testing the amniotic fluid cells (amniocentresis) in time…

  14. Detection of Malingered Mental Retardation

    ERIC Educational Resources Information Center

    Shandera, Anne L.; Berry, David T. R.; Clark, Jessica A.; Schipper, Lindsey J.; Graue, Lili O.; Harp, Jordan P.

    2010-01-01

    In a cross-validation of results from L. O. Graue et al. (2007), standard psychological assessment instruments, as well as tests of neurocognitive and psychiatric feigning, were administered under standard instructions to 24 participants diagnosed with mild mental retardation (MR) and 10 demographically matched community volunteers (CVH). A 2nd…

  15. Scholarly Productivity in Mental Retardation.

    ERIC Educational Resources Information Center

    Matson, Johnny L.; And Others

    1986-01-01

    The most productive institutions in social, educational, and psychological research in mental retardation were identified by noting the affiliations of authors who have published recently (1978-84) in the field. Thirty of the 35 highest ranked institutions were state-assisted universities in the United States. (Author/DB)

  16. Mental Retardation: Diagnosis and Treatment.

    ERIC Educational Resources Information Center

    Poser, Charles M., Ed.

    A collection of writings by 17 authors, the text includes the following discussions: general principles of diagnosis and management of mental retardation, neurologic evaluation of the infant and child, psychological evaluation, educational information, and treatment of pseudoretardation, communicative disorders, and metabolic and endocrine causes.…

  17. Idiots Savants: Retarded and Gifted.

    ERIC Educational Resources Information Center

    Yewchuk, Carolyn

    The paper reviews the paradoxical nature of idiots savants, persons who, although retarded, have exceptional skills in certain areas. Various explanations for the phenomenon are discussed, such as a specific genetic endowment, a specialized compensatory response to general intellectual deficiency, and possession of an eidetic memory. Various…

  18. HANDBOOK OF MENTAL RETARDATION SYNDROMES.

    ERIC Educational Resources Information Center

    CARTER, CHARLES H.

    THE CLINICAL SYNDROMES WHICH CONTRIBUTE TO THE PRODUCTION OF MENTAL RETARDATION ARE DESCRIBED BY SIGNS, SYMPTOMS, AND ETIOLOGY. SYNDROMES TREATED ARE (1) PRENATAL AND POSTNATAL INFECTIONS, (2) PRENATAL INTOXICATION AND ALLERGIC REACTIONS, (3) PRENATAL TRAUMA, PHYSICAL AGENTS, OR INTOXICATION, (4) BIRTH INJURIES, (5) POSTNATAL POISONS AND ALLERGIC…

  19. Mental Retardation: Diagnosis and Treatment.

    ERIC Educational Resources Information Center

    Poser, Charles M., Ed.

    A collection of writings by 17 authors, the text includes the following discussions: general principles of diagnosis and management of mental retardation, neurologic evaluation of the infant and child, psychological evaluation, educational information, and treatment of pseudoretardation, communicative disorders, and metabolic and endocrine causes.…

  20. Scouting for the Mentally Retarded.

    ERIC Educational Resources Information Center

    Boy Scouts of America, New Brunswick, NJ.

    The handbook for leaders discusses ways in which scouting helps and how the unit serves the boys. Advancement, rank, and the boys are discussed; boy scout tests (tenderfoot and second class interpretation for mentally retarded boys), group activities, and a sample ceremony are detailed. Listings are given of membership provisions, helps for…

  1. Books for Mentally Retarded Children.

    ERIC Educational Resources Information Center

    Cincinnati - Hamilton County Public Library, OH.

    Presented is an annotated list of approximately 300 books for educable (EMR) and trainable mentally retarded (TMR) children and adolescents, 6 to 15 years of age. Books are arranged in the following groups for EMR students: Group I contains approximately 84 entries for students 6 to 9 years of age; Group II lists approximately 81 stories and books…

  2. Fire-retardant epoxy polymers

    NASA Technical Reports Server (NTRS)

    Akawie, R. I.; Bilow, N.; Giants, T. W.

    1978-01-01

    Phosphorus atoms in molecular structure of epoxies make them fire-retardant without degrading their adhesive strength. Moreover, polymers are transparent, unlike compounds that contain arsenic or other inorganics. They have been used to bond polyvinylfluoride and polyether sulfone films onto polyimide glass laminates.

  3. Detection of Malingered Mental Retardation

    ERIC Educational Resources Information Center

    Shandera, Anne L.; Berry, David T. R.; Clark, Jessica A.; Schipper, Lindsey J.; Graue, Lili O.; Harp, Jordan P.

    2010-01-01

    In a cross-validation of results from L. O. Graue et al. (2007), standard psychological assessment instruments, as well as tests of neurocognitive and psychiatric feigning, were administered under standard instructions to 24 participants diagnosed with mild mental retardation (MR) and 10 demographically matched community volunteers (CVH). A 2nd…

  4. HANDBOOK OF MENTAL RETARDATION SYNDROMES.

    ERIC Educational Resources Information Center

    CARTER, CHARLES H.

    THE CLINICAL SYNDROMES WHICH CONTRIBUTE TO THE PRODUCTION OF MENTAL RETARDATION ARE DESCRIBED BY SIGNS, SYMPTOMS, AND ETIOLOGY. SYNDROMES TREATED ARE (1) PRENATAL AND POSTNATAL INFECTIONS, (2) PRENATAL INTOXICATION AND ALLERGIC REACTIONS, (3) PRENATAL TRAUMA, PHYSICAL AGENTS, OR INTOXICATION, (4) BIRTH INJURIES, (5) POSTNATAL POISONS AND ALLERGIC…

  5. Fire-retardant epoxy polymers

    NASA Technical Reports Server (NTRS)

    Akawie, R. I.; Bilow, N.; Giants, T. W.

    1978-01-01

    Phosphorus atoms in molecular structure of epoxies make them fire-retardant without degrading their adhesive strength. Moreover, polymers are transparent, unlike compounds that contain arsenic or other inorganics. They have been used to bond polyvinylfluoride and polyether sulfone films onto polyimide glass laminates.

  6. Dichotic Stimulation and Mental Retardation.

    ERIC Educational Resources Information Center

    Mosley, James L.; Virbancic, Mirna I.

    1990-01-01

    This paper reviews literature on the use of dichotic stimulation in individuals with mental retardation, and examines how noninvasive dichotic stimulation relates to hemisphere lateralization. Common findings are discussed concerning direction and magnitude of ear asymmetries, patterns of intrusion errors, and speech lateralization of Down…

  7. Toilet Training the Retarded Child.

    ERIC Educational Resources Information Center

    Schwartz, Jeffrey K.

    The booklet offers guidelines in both Spanish and English to parents who are toilet training a mentally retarded child. The toilet training process is broken down into tasks that the child must learn, and the importance of positive reinforcement for each successfully accomplished task is emphasized. It is recommended that parents keep charts…

  8. Flame Retardants Used in Flexible Polyurethane Foam

    EPA Pesticide Factsheets

    The partnership project on flame retardants in furniture seeks to update the health and environmental profiles of flame-retardant chemicals that meet fire safety standards for upholstered consumer products with polyurethane foam

  9. Improved spectral resolution and high reliability of in vivo 1H MRS at 7 T allow the characterization of the effect of acute exercise on carnosine in skeletal muscle

    PubMed Central

    Just Kukurová, Ivica; Valkovič, Ladislav; Ukropec, Jozef; de Courten, Barbora; Chmelík, Marek; Ukropcová, Barbara; Trattnig, Siegfried

    2015-01-01

    The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by 1H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T 1 measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute quantification of carnosine were determined in both muscles in five healthy volunteers. For absolute quantification, an internal water reference signal was used. The effect of acute exercise on carnosine levels and resonance lines was tested in eight recreational runners/cyclists. The defined carnosine measurement protocol was applied three times – before and twice after (approximately 20 and 40 min) a 1‐h submaximal street run and additional toe‐hopping. The measured T 1 relaxation times for the C2‐H carnosine peak at 7 T were 2002 ± 94 and 1997 ± 259 ms for GM and SOL, respectively, and the T 2 times were 95.8 ± 9.4 and 81.0 ± 21.8 ms for GM and SOL, respectively. The coefficient of variation of the carnosine quantification measurement was 9.1% for GM and 6.3% for SOL, showing high repeatability, and the intraclass correlation coefficients (ICCs) of 0.93 for GM and 0.98 for SOL indicate the high reliability of the measurement. Acute exercise did not change the concentration of carnosine in the muscle, but affected the shape of the resonance lines, in terms of the shifting and splitting into doublets. Carnosine measurement by 1H MRS at 7 T in skeletal muscle exhibits high repeatability and reliability. The observed effects of acute exercise were more prominent in GM, probably as a result of the larger portion of glycolytic fibers in this muscle and the more pronounced exercise‐induced change in pH. Our results support the application of the MRS‐based assessment

  10. Improved spectral resolution and high reliability of in vivo (1) H MRS at 7 T allow the characterization of the effect of acute exercise on carnosine in skeletal muscle.

    PubMed

    Just Kukurová, Ivica; Valkovič, Ladislav; Ukropec, Jozef; de Courten, Barbora; Chmelík, Marek; Ukropcová, Barbara; Trattnig, Siegfried; Krššák, Martin

    2016-01-01

    The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by (1) H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T1 measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute quantification of carnosine were determined in both muscles in five healthy volunteers. For absolute quantification, an internal water reference signal was used. The effect of acute exercise on carnosine levels and resonance lines was tested in eight recreational runners/cyclists. The defined carnosine measurement protocol was applied three times - before and twice after (approximately 20 and 40 min) a 1-h submaximal street run and additional toe-hopping. The measured T1 relaxation times for the C2-H carnosine peak at 7 T were 2002 ± 94 and 1997 ± 259 ms for GM and SOL, respectively, and the T2 times were 95.8 ± 9.4 and 81.0 ± 21.8 ms for GM and SOL, respectively. The coefficient of variation of the carnosine quantification measurement was 9.1% for GM and 6.3% for SOL, showing high repeatability, and the intraclass correlation coefficients (ICCs) of 0.93 for GM and 0.98 for SOL indicate the high reliability of the measurement. Acute exercise did not change the concentration of carnosine in the muscle, but affected the shape of the resonance lines, in terms of the shifting and splitting into doublets. Carnosine measurement by (1) H MRS at 7 T in skeletal muscle exhibits high repeatability and reliability. The observed effects of acute exercise were more prominent in GM, probably as a result of the larger portion of glycolytic fibers in this muscle and the more pronounced exercise-induced change in pH. Our results support the application of the MRS-based assessment of

  11. Peptide-lanthanide cation equilibria in aqueous phase. I. Bound shifts for L-carnosine-praseodymium complexes

    NASA Astrophysics Data System (ADS)

    Mossoyan, J.; Asso, M.; Benlian, D.

    L-Carnosine complexes of Pr 3+ were characterized in aqueous solution by 1H NMR and potentiometric titration. A rigorous treatment of chemical shifts and pH variation data with lanthanide concentration is presented. Two different forms of the peptide ligand, forming simultaneously two complexes, were taken into account. At low pH values the cation is only coordinated at the carboxylate site of the ligand in a weak complex ( β2 = 6) whereas in neutral solution a stronger complex ( β1 = 37) is present as a consequence of the deprotonation of the imidazole ring. The computation of induced bound shifts † 2 and Δ1 for resonating nuclei of the peptide in both forms yields consistent figures. These provide the experimental basis for a conformational model which is usually not obtainable for labile complexes with low stability constants.

  12. MENTAL RETARDATION--THE PRESENT PROBLEM.

    ERIC Educational Resources Information Center

    SHAFTER, ALBERT J.

    MENTAL RETARDATION IS DEFINED AS A MENTAL DEFECT, NOT A DISEASE. LEVELS OF SEVERITY IN MENTAL RETARDATION ARE CAUSED BY AN INTERRELATIONSHIP BETWEEN HEREDITY AND ENVIRONMENT. ONE OF THE MAJOR PROBLEMS CONCERNS THE LONGER LIFE EXPECTANCY OF THE RETARDATE DUE TO IMPROVEMENTS IN MODERN MEDICINE. THIS IS CREATING A SITUATION WHERE RESIDENTIAL…

  13. International Review of Research in Mental Retardation.

    ERIC Educational Resources Information Center

    Ellis, Norman R., Ed.

    The text of Volume 4 represents an international review of research in mental retardation dealing primarily with human and animal laboratory behavior. The contents range through the following topics: memory processes in retardates and normals by Norman Ellis; a theory of primary and secondary familial mental retardation by Arthur Jensen;…

  14. People with Mental Retardation Are Dying, Legally.

    ERIC Educational Resources Information Center

    Keyes, Denis; And Others

    1997-01-01

    Criticizes the institution of the death penalty for convicted criminals with mental retardation. Examples are given of cases in which juries were not told of the defendant's mental retardation before sentencing, and a list of defendants with mental retardation that have been executed since 1976 is provided. (CR)

  15. People with Mental Retardation Are Dying, Legally.

    ERIC Educational Resources Information Center

    Keyes, Denis; And Others

    1997-01-01

    Criticizes the institution of the death penalty for convicted criminals with mental retardation. Examples are given of cases in which juries were not told of the defendant's mental retardation before sentencing, and a list of defendants with mental retardation that have been executed since 1976 is provided. (CR)

  16. Non-Verbal Communication in Retarded Pupils.

    ERIC Educational Resources Information Center

    Powell, Evan R.; Dennis, Virginia Collier

    Thirty educable mentally retarded (EMR) and 20 trainable mentally retarded (TMR) black or white pupils were observed interacting with classmates and 25 teachers in a retardation center. Multi-modal communicative behavior was noted, with focus on interpersonal spatial distance as one index of relationship and affect between interacting partners.…

  17. Mental Retardation: Prevention Strategies That Work.

    ERIC Educational Resources Information Center

    President's Committee on Mental Retardation, Washington, DC.

    The report by the President's Committee on Mental Retardation reviews the current state of knowledge in the area of biological and environmental prevention of mental retardation and describes programs on the frontiers of research or service delivery. Section I examines programs that are effectively preventing mental retardation through biomedical…

  18. Biological Factors in Mild Mental Retardation.

    ERIC Educational Resources Information Center

    Costeff, H.; And Others

    1983-01-01

    Children (N=434) with nonsyndromic mental retardation were analysed for frequency of prenatal, perinatal and infantile biological disturbances. Mildly retarded individuals of unrelated parentage, both idiopathic and familial, had a strikingly higher prevalence of disturbances than a control group of retarded individuals with consanguineous parents…

  19. Low Elevated Lead Levels and Mental Retardation.

    ERIC Educational Resources Information Center

    Marlowe, Mike; And Others

    The relationship between low elevated lead absorption and mild mental retardation was investigated in 40 rural children (preschool to grade 12) without demonstrable cause for their retardation. Trace mineral analysis of hair samples from Ss and a control group (N=20) indicated the mean hair lead concentrations for the retarded Ss were considerably…

  20. International Review of Research in Mental Retardation.

    ERIC Educational Resources Information Center

    Ellis, Norman R., Ed.

    The text of Volume 4 represents an international review of research in mental retardation dealing primarily with human and animal laboratory behavior. The contents range through the following topics: memory processes in retardates and normals by Norman Ellis; a theory of primary and secondary familial mental retardation by Arthur Jensen;…

  1. Low Elevated Lead Levels and Mental Retardation.

    ERIC Educational Resources Information Center

    Marlowe, Mike; And Others

    The relationship between low elevated lead absorption and mild mental retardation was investigated in 40 rural children (preschool to grade 12) without demonstrable cause for their retardation. Trace mineral analysis of hair samples from Ss and a control group (N=20) indicated the mean hair lead concentrations for the retarded Ss were considerably…

  2. Analysis of products of animal origin in feeds by determination of carnosine and related dipeptides by high-performance liquid chromatography.

    PubMed

    Schönherr, Jens

    2002-03-27

    Products of animal origin such as meat meal were commonly used as sources of protein and amino acids for the production of compound feeds. Because the feeding of such products is prohibited in Germany, the official feedstuff control of the government must evaluate feeds for the forbidden use of products of animal origin. Microscope examination is the official method to prove animal-originated adulterations of feeds. This paper proposes a high-performance liquid chromatography method for the determination of the dipeptide carnosine and related dipeptides (anserine and balenine) and shows the dependence of the contents of anserine, balenine, and carnosine in compound feeds on the content of meat meal in feeds. The presented method can complete and confirm the result of the microscopic method for evidence of components of animal origin in feeds.

  3. Mono- and di-halogenated histamine, histidine and carnosine derivatives are potent carbonic anhydrase I, II, VII, XII and XIV activators.

    PubMed

    Saada, Mohamed-Chiheb; Vullo, Daniela; Montero, Jean-Louis; Scozzafava, Andrea; Supuran, Claudiu T; Winum, Jean-Yves

    2014-09-01

    Mono- and di-halogenated histamines, l-histidine methyl ester derivatives and carnosine derivatives incorporating chlorine, bromine and iodine were prepared and investigated as activators of five carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic hCA I, II and VII, and the transmembrane hCA XII and XIV. All of them were activated in a diverse manner by the investigated compounds, with a distinct activation profile.

  4. Abnormal O-GlcNAcylation of Pax3 Occurring from Hyperglycemia-Induced Neural Tube Defects Is Ameliorated by Carnosine But Not Folic Acid in Chicken Embryos.

    PubMed

    Tan, Rui-Rong; Li, Yi-Fang; Zhang, Shi-Jie; Huang, Wen-Shan; Tsoi, Bun; Hu, Dan; Wan, Xin; Yang, Xuesong; Wang, Qi; Kurihara, Hiroshi; He, Rong-Rong

    2017-01-01

    Neural tube defects (NTDs) are among the most common of the embryonic abnormalities associated with hyperglycemic gestation. In this study, the molecular mechanisms of embryonic neurogenesis influenced by hyperglycemia was investigated using chicken embryo models. High-concentration glucose was administered into chicken eggs and resulted in increased plasma and brain tissue glucose, and suppressed expression of glucose transporters (GLUTs). The rate of NTD positively correlated with hyperglycemia. Furthermore, abnormally increased O-GlcNAcylation, a nutritionally responsive modification, of the key neural tube marker Pax3 protein led to the loss of this protein. This loss was not observed in a folate-deficiency NTD induced by methotrexate. Carnosine, an endogenous dipeptide, showed significant recovery effects on neural tube development. In contrast, folic acid, a well-known periconceptional agent, surprisingly showed relatively minimal effect. Higher expression levels of the Pax3 protein were found in the carnosine-treated groups, while lower expression levels were found in folic acid groups. Furthermore, the abnormal O-GlcNAcylation of the Pax3 protein was restored by carnosine. These results suggest new insights into using endogenous nutrients for the protection of embryonic neurodevelopment affected by diabetes gestation. The abnormal excessive O-GlcNAcylation of Pax3 may be responsible for the neural tube defects associated with hyperglycemia.

  5. Collective excitations and retarded interactions

    NASA Astrophysics Data System (ADS)

    Choi, M. Y.; Huberman, B. A.

    1985-03-01

    We study the dynamics of many-body systems with retarded interactions and show how their non-Markovian character can lead to nonergodic behavior. This nonergodicity is characterized by the appearance of long periods or chaotic wanderings in phase space. We construct the phase diagrams for Ising-type systems with delayed interactions, and show the emergence of non-Gibbsian measures as a function of both interaction strengths and delays.

  6. Fire-Retardant Polymeric Additives

    NASA Technical Reports Server (NTRS)

    Williams, Martha K.; Smith, Trent M.

    2011-01-01

    Polyhydroxyamide (PHA) and polymethoxyamide (PMeOA) are fire-retardant (FR) thermoplastic polymers and have been found to be useful as an additive for imparting fire retardant properties to other compatible, thermoplastic polymers (including some elastomers). Examples of compatible flammable polymers include nylons, polyesters, and acrylics. Unlike most prior additives, PHA and PMeOA do not appreciably degrade the mechanical properties of the matrix polymer; indeed, in some cases, mechanical properties are enhanced. Also, unlike some prior additives, PHA and PMeOA do not decompose into large amounts of corrosive or toxic compounds during combustion and can be processed at elevated temperatures. PMeOA derivative formulations were synthesized and used as an FR additive in the fabrication of polyamide (PA) and polystyrene (PS) composites with notable reduction (>30 percent for PS) in peak heat release rates compared to the neat polymer as measured by a Cone Calorimeter (ASTM E1354). Synergistic effects were noted with nanosilica composites. These nanosilica composites had more than 50-percent reduction in peak heat release rates. In a typical application, a flammable thermoplastic, thermoplastic blend, or elastomer that one seeks to render flame-retardant is first dry-mixed with PHA or PMeOA or derivative thereof. The proportion of PHA or PMeOA or derivative in the mixture is typically chosen to lie between 1 and 20 weight percent. The dry blend can then be melt-extruded. The extruded polymer blend can further be extruded and/or molded into fibers, pipes, or any other of a variety of objects that may be required to be fire-retardant. The physical and chemical mechanisms which impart flame retardancy of the additive include inhibiting free-radical oxidation in the vapor phase, preventing vaporization of fuel (the polymer), and cooling through the formation of chemical bonds in either the vapor or the condensed phase. Under thermal stress, the cyclic hydroxyl/ methoxy

  7. Detoxification of cytotoxic alpha,beta-unsaturated aldehydes by carnosine: characterization of conjugated adducts by electrospray ionization tandem mass spectrometry and detection by liquid chromatography/mass spectrometry in rat skeletal muscle.

    PubMed

    Aldini, Giancarlo; Granata, Paola; Carini, Marina

    2002-12-01

    Oxidation of polyunsaturated fatty acids containing phospholipids in tissue generates lipid hydroperoxides, which are further degraded to several products, among which unsaturated aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) play an important role in mediating the pathological effects of oxidative stress. While the reaction of HNE with glutathione (GSH) is a well recognized pathway of detoxification in biological systems, no data are available on HNE interactions with carnosine, a dipeptide (beta-alanyl-L-histidine) present in high concentration in skeletal muscle. The aim of this work was to study the quenching ability of carnosine towards HNE and to characterize the reaction products by electrospray ionization tandem mass spectrometry (ESI-MS/MS), using GSH as a model peptide. GSH incubation with HNE in 1 mM phosphate buffer (pH 7.4) results in the complete disappearance of HNE within 1 h owing to the formation of a Michael adduct, S-(4-hydroxynonanal-3-yl)glutathione. The reaction of HNE with carnosine was studied in different molar ratios and monitored up to 24 h by high-performance liquid chromatography (HPLC) (HNE consumption), MS/MS (infusion) and liquid chromatography mass spectrometry (LC/MS) experiments. Carnosine, although less reactive than GSH, significantly quenched HNE (48.2 +/- 0.9% HNE consumption after 1 h; carnosine:HNE molar ratio 10 : 1). Two reaction products were identified: the Michael adduct, N-(4-hydroxynonanal-3-yl)carnosine involving the imidazolic nitrogen of histidine, and the imine adduct, involving the amino group of the beta-alanine residue. Definitive structure assignment was achieved by chemical reduction with NaBH(4) and multinuclear magnetic resonance experiments. To understand whether carnosine acts as a quencher of unsaturated aldehydes in biological matrices, rat skeletal muscle homogenate was incubated with HNE and the formation of conjugated adducts was determined by LC/MS analysis. Three main products were detected

  8. Ocular disorder in children with mental retardation.

    PubMed

    Joshi, Rajesh Subhash; Somani, Abhishek Arun Kumar

    2013-04-01

    Ocular problems are common in mentally retarded children. Due to population growth these problems are increasing. Prevalence rate is variable from region to region. Data on ocular problems in mentally retarded school children is lacking in this region. The aim of the present study was to identify the ocular disorders in children with mental retardation attending special schools in a district and to study their relationship with the degree of retardation. A total of 241 mentally retarded school children in the age group of 6-16 years attending special schools for the mentally retarded children in a district in central India were examined by a team of ophthalmologist, psychiatrist, and a resident in ophthalmology department of a medical college. Complete ocular examination was done. Ocular problems were identified and categorized according to the intelligent quotient. One hundred and twenty four children (51.45%) had ocular problems. Strabismus (10.37%) and refractive error (20.75%) were the common ocular problems seen in this study. An association was found between the severity of mental retardation and ocular problems (P<0.005). However, no association was seen between the severity of mental retardation and strabismus and refractive error. A high prevalence of ocular problems was seen in mentally retarded school children. Children with mental retardation should undergo annual ophthalmological check up. Early detection and correction of ocular problems will prevent visual impairment in future.

  9. Fire retardancy using applied materials

    NASA Technical Reports Server (NTRS)

    Feldman, R.

    1971-01-01

    An example of advanced technology transfer from the Little Joe, Surveyor, Comsat, re-entry and Apollo age to everyday fire protection needs is presented. Utilizing the principle of sublimation cooling for thermostatic temperature control, the material meets a wide range of fire retardancy and heat transmission control requirements. Properties vary from flexible tape for conduits and electrical cables to rigid coatings for column protection, with a broad spectrum of sublimation temperatures available. The material can be applied in the field or in the factory, utilizing mass production techniques, yielding a product that is reliable, effective, widely available and low in cost.

  10. Angular Limb Deformities: Growth Retardation.

    PubMed

    McCarrel, Taralyn M

    2017-08-01

    Angular limb deformities are common in foals; however, the importance of the deformity and if treatment is required depend on the degree of deformity relative to normal conformation for stage of growth, the breed and discipline expectations, age, and response to conservative therapies. This article addresses the importance of the foal conformation examination to determine which foals need surgical intervention to correct an angular deformity and when. Techniques for surgical growth retardation include the transphyseal staple, screw and wire transphyseal bridge, and transphyseal screw. Appropriate timing for intervention for each location and complications associated with each procedure are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Orthopaedic Problems of the Mentally Retarded

    ERIC Educational Resources Information Center

    McSweeney, Anthony

    1972-01-01

    Problems encountered by orthopedic surgeons treating the mentally retarded are identified, and cooperation among pediatricians, psychiatrists, psychologists, social workers, physiotherapists, occupational therapists, and orthopedic surgeons is recommended. (GW)

  12. Hyperactive and Nonhyperactive Institutionalized Retarded Residents

    ERIC Educational Resources Information Center

    Talkington, Larry W.; Hutton, W. Oran

    1973-01-01

    Two hundred twenty-one predominantly adolescent institutionalized retarded residents, classified as hyperactive, were compared on 15 variables to a matched group classified as nonhyperactive. (Author/MC)

  13. Orthopaedic Problems of the Mentally Retarded

    ERIC Educational Resources Information Center

    McSweeney, Anthony

    1972-01-01

    Problems encountered by orthopedic surgeons treating the mentally retarded are identified, and cooperation among pediatricians, psychiatrists, psychologists, social workers, physiotherapists, occupational therapists, and orthopedic surgeons is recommended. (GW)

  14. L-carnosine modulates respiratory burst and reactive oxygen species production in neutrophil biochemistry and function: may oral dosage form of non-hydrolized dipeptide L-carnosine complement anti-infective anti-influenza flu treatment, prevention and self-care as an alternative to the conventional vaccination?

    PubMed

    Babizhayev, Mark A; Deyev, Anatoliy I; Yegorov, Yegor E

    2014-05-01

    Influenza A is a viral disease of global dimension, presenting with high morbidity and mortality in annual epidemics, and in pandemics which are of infrequent occurrence but which have very high attack rates. Influenza vaccines of the future must be directed toward use of conserved group-specific viral antigens, such as are present in transitional proteins which are exposed during the fusion of virus to the host cell. Influenza probes revealed a continuing battle for survival between host and parasite in which the host population updates the specificity of its pool of humoral immunity by contact with and response to infection with the most recent viruses which possess altered antigenic specificity in their hemagglutinin (HA) ligand. It is well known that the HA protein is found on the surface of the influenza virus particle and is responsible for binding to receptors on host cells and initiating infection. Polymorphonuclear neutrophils (PMN) have been reported to be involved in the initial host response to influenza A virus (IAV). Early after IAV infection, neutrophils infiltrate the airway probably due to release of chemokines that attract PMN. Clearly, severe IAV infection is characterized by increased neutrophil influx into the lung or upper respiratory tract. Carnosine (β-alanyl-L-histidine) and anserine (N-β-alanyl-1-methyl-L-histidine) are found in skeletal muscle of most vertebrates, including those used for food; for example, 100 g of chicken breast contains 400 mg (17.6 mmol/L) of carnosine and 1020 mg (33.6 mmol/l) of anserine. Carnosine-stimulated respiratory burst in neutrophils is a universal biological mechanism of influenza virus destruction. Our own studies revealed previously unappreciated functional effects of carnosine and related histidine containing compounds as a natural biological prevention and barrier against Influenza virus infection, expand public understanding of the antiviral properties of imidazole-containing dipeptide based

  15. The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats

    SciTech Connect

    Cho, C.H.; Luk, C.T.; Ogle, C.W. )

    1991-01-01

    Zinc compounds have been shown to antagonize various types of gastric ulceration in rats. Zinc carnosine (Z-103), a newly developed agent was, therefore, examined for its antiulcer effect in stress-induced ulceration and also its membrane stabilizing action in rat stomachs. Cold-restraint stress induced severe hemorrhagic lesions together with increased mast cell degranulation and {beta}-glucuronidase release in the gastric glandular mucosa. A-103 pretreatment with a single oral dose reversed these actions in a dose-dependent manner. When the compound was incubated in concentrations of 10{sup {minus}7}, 10{sup {minus}6}, 10{sup {minus}5} or 10{sup {minus}4} M, with isolated hepatic lysosomes, it significantly reduced the spontaneous release of {beta}-glucuronidase in the medium. The present study not only demonstrates the antiulcer effect of Z-103 but also indicates that the protective action is likely to be mediated by its membrane-stabilizing action on mast cells and lysosomes in the gastric glandular mucosa.

  16. Effects of carnosine, taurine, and betaine pretreatments on diethylnitrosamine-induced oxidative stress and tissue injury in rat liver.

    PubMed

    Başaran-Küçükgergin, C; Bingül, I; Tekkeşin, M Soluk; Olgaç, V; Doğru-Abbasoğlu, S; Uysal, M

    2016-08-01

    Several chemicals such as N-diethylnitrosamine (DEN) promote hepatocellular cancer in rodents and induce hepatocyte injury. DEN affects the initiation stage of carcinogenesis together with enhanced cell proliferation accompanied by hepatocellular necrosis. DEN-induced hepatocellular necrosis is reported to be related to enhanced generation of reactive oxygen species. Carnosine (CAR), taurine (TAU), and betaine (BET) are known to have powerful antioxidant properties. We aimed to investigate the effects of CAR, TAU, and BET pretreatments on DEN-induced oxidative stress and liver injury in male rats. Rats were given CAR (2 g L(-1) in drinking water), TAU (2.5% in chow), and BET (2.5% in chow) for 6 weeks and DEN (200 mg kg(-1) intraperitoneally) was given 2 days before the end of this period. Serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and γ-glutamyl transferase activities were determined and a histopathologic evaluation was performed on the liver tissue. Oxidative stress was detected in the liver by measuring malondialdehyde, diene conjugate, protein carbonyl and nitrotyrosine levels, glutathione and glutathione peroxidase levels, and superoxide dismutase and glutathione transferase activities. Pretreatments with CAR, TAU, and BET decreased liver prooxidant status without remarkable changes in antioxidant parameters in DEN-treated rats. Pretreatments with TAU and BET, but not CAR, were also found to be effective to reduce liver damage in DEN-treated rats. In conclusion, TAU, BET, and possibly CAR may have an ameliorating effect on DEN-induced hepatic injury by reducing oxidative stress in rats.

  17. Antioxidant, Anti-inflammatory, and Genomic Stability Enhancement Effects of Zinc l-carnosine: A Potential Cancer Chemopreventive Agent?

    PubMed

    Ooi, Theng Choon; Chan, Kok Meng; Sharif, Razinah

    2017-01-01

    Cancer is one of the major causes of death worldwide, and the incidence and mortality rates of cancer are expected to rise tremendously in the near future. Despite a better understanding of cancer biology and advancement in cancer management, current strategies in cancer treatment remain costly and ineffective. Hence, instead of putting more efforts to search for new cancer cures, attention has now been shifted to the development of cancer chemopreventive agents as a preventive measure for cancer formation. It is well known that neoplastic transformation of cells is multifactorial, and the occurrence of oxidative stress, chronic inflammation, and genomic instability events has been implicated in the carcinogenesis of cells. Zinc l-carnosine (ZnC), which is clinically used as gastric ulcer treatment in Japan, has been suggested to have the potential in preventing cancer development. Multiple studies have revealed that ZnC possesses potent antioxidant, anti-inflammatory, and genomic stability enhancement effects. Thus, this review provides some mechanistic insight into the antioxidant, anti-inflammatory, and genomic stability enhancement effects of ZnC in relevance to its chemopreventive potential.

  18. Chemical relevance of the copper(II)— L-carnosine system in aqueous solution: A thermodynamic and spectrophotometric study

    NASA Astrophysics Data System (ADS)

    Daniele, Pier G.; Prenesti, Enrico; Zelano, Vincenzo; Ostacoli, Giorgio

    1993-08-01

    The copper(II)— L-carnosine (L -) system has been re-investigated in aqueous solution, at I = 0.1 mol dm -1, different temperatures (5⩽ t⩽45°C) and with metal to ligand ratios ranging from 3:1 to 1:3. Both potentiometry and visible spectrophotometry were employed. From an overall consideration of all experiments, [CuLH] 2+, [CuL] +, [CuLH -1]°, [Cu 2L 2H -2]° and [Cu 2LH -1] 2+ were recognized as the species which provide the best interpretation of experimental data. The complex formation constants, determined at different temperatures, allowed us to obtain reliable values of Δ H° and good estimates of Δ C° p. From visible spectrophotometric measurements, carried out at different pH and metal to ligand ratios, it was possible to calculate the electronic spectrum of each complex formed in solution. A structure is also proposed for each species, on the basis of thermodynamic and spectral results.

  19. Differential expression of carnosine, homocarnosine and N-acetyl-L-histidine hydrolytic activities in cultured rat macroglial cells.

    PubMed

    Baslow, M H; Suckow, R F; Berg, M J; Marks, N; Saito, M; Bhakoo, K K

    2001-12-01

    N-acetyl-L-histidine (NAH) and N-acetyl-L-aspartate (NAA) are representatives of two series of substances that are synthesized by neurons and other cells in the vertebrate central nervous system (CNS). Histidine containing homologs of NAH are beta-alanyl-L-histidine or carnosine (Carn) and gamma-aminobutyrl-L-histidine or homocarnosine (Hcarn). A homolog of NAA is N-acetylaspartylglutamate (NAAG). These substances belong to a unique group of osmolytes in that they are synthesized in cells that may not to be able to hydrolyze them, and are released in a regulated fashion to a second compartment where they can be rapidly hydrolyzed. In this investigation, the catabolic activities for NAH, Carn, and Hcarn in cultured macroglial cells and neurons have been measured, and the second compartment for NAH and Hcarn has been identified only with astrocytes. In addition, oligodendrocytes can only hydrolyze Carn, although Carn can also be hydrolyzed by astrocytes. Thus, astrocytes express hydrolytic activity against all three substrates, but oligodendrocytes can only act on Carn. The cellular separation of these hydrolytic enzyme activities, and the possible nature of the enzymes involved are discussed.

  20. Quenching activity of carnosine derivatives towards reactive carbonyl species: Focus on α-(methylglyoxal) and β-(malondialdehyde) dicarbonyls.

    PubMed

    Vistoli, Giulio; Colzani, Mara; Mazzolari, Angelica; Gilardoni, Ettore; Rivaletto, Carola; Carini, Marina; Aldini, Giancarlo

    2017-10-21

    The study combines HPLC-based with MS-based competitive analyses to evaluate the quenching activity of a set of carnosine derivatives towards methylglyoxal (MGO) and malondialdehyde (MDA) chosen as representative of α- and β-dicarbonyls, respectively. The obtained results underline that these derivatives are moderately reactive towards MDA with which they form the corresponding N-propenal adduct via Michael addition. In contrast they proved a rather poor quenching activity towards MGO with which they can condense to give MOLD-like adducts through a concerted mechanism involving more quenchers molecules. Even though both quenching mechanisms involve the amino group in its neutral form, in silico studies revealed that the reported reactivity values depend on different stereo-electronic parameters which are reflected in the different observed quenching mechanism. Finally, the MGO quenching reactivity and the unselective (and unwanted) pyridoxal quenching are found to be influenced by the same parameters thus rationalizing the known difficulty in the design of potent and selective quenchers towards β-dicarbonyls. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. A comparison of the cellular actions of polaprezinc (zinc-L-carnosine) and ZnCl2.

    PubMed

    Seo, Hakaru; Ogata-Ikeda, Ikuko; Ishida, Shiro; Okano, Yoshiro; Oyama, Yasuo

    2012-06-27

    Zinc supplementation has been proven to be beneficial for the prevention of some health problems. Many zinc supplements are used for medical and nutritional purposes. However, it is difficult to distinguish between them in terms of their cellular actions. We compared the cellular actions of polaprezinc (zinc-l-carnosine) with those of ZnCl(2) in order to determine whether polaprezinc has greater zinc-related actions than ZnCl(2). Cellular actions of polaprezinc and ZnCl(2) were estimated by flow-cytometric techniques with appropriate fluorescent probes in rat thymocytes. Both agents had almost equal stimulatory effects on the intracellular Zn(2+) level and cellular level of nonprotein thiol in a similar concentration-dependent manner. However, the increase in cell lethality caused by ZnCl(2) under severe oxidative stress was significantly greater than that caused by polaprezinc. There are various zinc supplements, for example, zinc gluconate, zinc picolinate, and zinc methionine. However, the differences in their cellular actions have not been elucidated to date. Such studies could distinguish between zinc supplements. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Intumescent Coatings as Fire Retardants

    NASA Technical Reports Server (NTRS)

    Parker, J. A.; Fohlen, G. M.; Sawko, P. M.; Fish, R. H.

    1970-01-01

    The development of fire-retardant coatings to protect surfaces which may be exposed to fire or extreme heat is a subject of intense interest to many industries. A fire-retardant paint has been developed which represents a new chemical approach for preparing intumescent coatings, and potentially, is very important to fire-prevention authorities. The requirements for a superior coating include ease of application, suitability to a wide variety of surfaces and finishes, and stability over an extended period of time within a broad range of ambient temperature and humidity conditions. These innovative coatings, when activated by the heat of a fire, react to form a thick, low-density, polymeric coating or char layer. Water vapor and sulphur dioxide are released during the intumescent reaction. Two fire-protection mechanisms thus become available: (1) the char layer retards the flow of heat, due to the extremely low thermal conductivity; and (2) water vapor and sulfur dioxide are released, providing fire quenching properties. Still another mechanism functions in cases where the char, by virtue of its high oxidation resistance and low thermal conductivity, reaches a sufficiently high temperature to re-radiate much of the incident heat load. The coatings consist of dispersions of selective salts of a nitro-amino-arornatic compound. Specifically, para-nitroaniline bisulfate and the ammonium salt of para-nitroaniline-ortho sulphuric acid (2-amino-5-nitrobenzenesulphuric acid) are used. Suitable vehicles are cellulose nitrate of lacquer grade, a nitrite-phenolic modified rubber, or epoxy-polysulfide copolymer. Three separate formulations have been developed. A solvent is usually employed, such as methylethyl ketone, butyl acetate, or toluene, which renders the coatings suitably thin and which evaporates after the coatings are applied. Generally, the intumescent material is treated as insoluble in the vehicle, and is ground and dispersed in the vehicle and solvent like an

  3. Identifying Depression in Students with Mental Retardation.

    ERIC Educational Resources Information Center

    Stough, Laura M.; Baker, Lynn

    1999-01-01

    Offers guidelines to teachers for identifying depression in students with mental retardation. Discusses prevalence and symptoms of depression, causes of depression, difficulty of diagnosis in students with mental retardation, detecting symptoms in the classroom, treatment of depression, and psychological services. Inserts list ideas for helping…

  4. Perceptions of Mental Retardation and Mental Illness.

    ERIC Educational Resources Information Center

    Caruso, David R.; Hodapp, Robert M.

    1988-01-01

    Open-ended questions of college students (N=60) indicated students clearly differentiated between the mentally retarded and mentally ill. Mental retardation was characterized by physical stigmata, brain damage, developmental delays, and cognitive deficits; mental illness by emotional lability due to environmental, hereditary, or mixed factors.…

  5. Recreation for Retarded Teenagers and Young Adults.

    ERIC Educational Resources Information Center

    Carlson, Bernice Wells; Ginglend, David R.

    Intended for recreational leaders, classroom teachers, volunteers, and parents, the text presents guidelines for planning and conducting activities for mentally retarded youth and young adults. Consideration of understanding the maturing retardate and his social needs includes different kinds of beneficial social experiences, the maturing…

  6. Mental Retardation, Mental Illness, and Seizure Diagnosis.

    ERIC Educational Resources Information Center

    Pary, Robert

    1993-01-01

    Review of psychiatric hospital discharge summaries for 247 individuals with mental retardation and psychiatric disorders found that 39 had a seizure diagnosis. The only difference between the groups with and without seizures was level of mental retardation. No differences existed concerning length of stay, transfer to state hospital, psychiatric…

  7. Statistics on Mental Retardation in Indiana.

    ERIC Educational Resources Information Center

    Indiana Association for Retarded Citizens, Indianapolis.

    Presented are 19 tables of statistical data on prevalence of mental retardation, and services provided the estimated 158,724 mentally retarded (MR) persons in Indiana through 1973 by special education classes, vocational rehabilitation units, local organizations, and state hospitals and training centers. Given in tables 1 through 8 are data on…

  8. The Texas Plan to Combat Mental Retardation.

    ERIC Educational Resources Information Center

    Governor's Advisory Committee on Mental Retardation Planning, Austin, TX.

    The Texas state plan of action against mental retardation is presented. Aspects considered include the evolution of the plan, the role of the health services, medical aspects of retardation, education and training, vocational rehabilitation and employment, and social welfare. Also surveyed are the following: residential and day care, manpower,…

  9. Manual Skill Training of Retarded Children.

    ERIC Educational Resources Information Center

    Pomerantz, David J.

    1975-01-01

    In an on-going pilot study, training procedures previously found successful with moderately and severely retarded adolescents and adults have been adapted to teaching trainable retarded children (6-, 8-, and 10-years-old) to assemble a 14-piece coaster brake. Modifications in the carefully detailed task analysis approach have included the need for…

  10. Innovations in Vocational Rehabilitation and Mental Retardation.

    ERIC Educational Resources Information Center

    Ayers, George E., Ed.

    Conference proceedings of the Vocational Rehabilitation Subdivision Meetings held at the American Association on Mental Deficiency contain discussions of innovative aspects of vocational rehabilitation and mental retardation. In the area of training rehabilitation counselors, George Baroff describes the Mental Retardation Training Institute in…

  11. Effects of fire retardant on water quality

    Treesearch

    Logan A. Norris; Warren L. Webb

    1989-01-01

    Ammonium-based fire retardants are important in managing wildfires, but their use can adversely affect water quality. Their entry, fate, and impact were studied in five forest streams. Initial retardant concentrations in water approached levels which could damage fish, but no distressed fish were found. Concentrations decreased sharply with time after application and...

  12. Severe Mental Retardation: From Theory to Practice.

    ERIC Educational Resources Information Center

    Bricker, Diane, Ed.; Filler, John, Ed.

    Fourteen papers examine current issues and practices in the education of students with severe mental retardation (SMR). Papers touch upon the broad context of education for SMR students, programs for the SMR population, and critical issues. The following papers are presented: "The Severely Mentally Retarded Individual: Philosophical and…

  13. Mental Retardation: Update 2002. ERIC Digest.

    ERIC Educational Resources Information Center

    Hourcade, Jack

    This digest provides an overview of mental retardation in children and adults. It begins by discussing the definition of mental retardation and the three components that are required for an accurate diagnosis: an IQ score of approximately 70 or below, a determination of deficits in adaptive behavior, and origins of the disability prior to age 18.…

  14. MR 76. Mental Retardation: Past and Present.

    ERIC Educational Resources Information Center

    President's Committee on Mental Retardation, Washington, DC.

    The tenth annual report of the President's Committee on Mental Retardation reviews the history of America's services for the retarded from the 1850's to the present. Traced is governmental involvement through conferences on children and youth, and reviewed is the role of parents and volunteers in securing appropriate services. Among agencies…

  15. Problems of Psychology of Mentally Retarded Children.

    ERIC Educational Resources Information Center

    Academy of Pedagogical Sciences of the USSR, Moscow. Inst. of Defectology.

    Presented are 18 papers on problems in the psychology of mentally retarded children. Seven of the papers are in English, two in French, and nine in Russian. The English papers are concerned with the following topics: peculiarities of psychic functions in oligophrenic (retarded) children with pronounced underdevelopment of frontal lobes of cerebral…

  16. Interaction between Family Violence and Mental Retardation.

    ERIC Educational Resources Information Center

    Strickler, Heidi

    2001-01-01

    Characteristics that make individuals with mental retardation more vulnerable to family violence are discussed in the areas of child, adult, and sexual abuse. Common psychological effects of this trauma are then explored followed by implications for practice. A case study of a female with mental retardation is presented. (Contains references.)…

  17. Political Philosophy and the Mentally Retarded.

    ERIC Educational Resources Information Center

    Stanovich, Keith E.

    The effects of Social Darwinism, eugenics, and contemporary political conservatism on the status of advocacy efforts for the mentally retarded are reviewed. Provided are historical sketches of Social Darwinism, which viewed the retarded as members of an inferior race, and eugenics, which argued for sterilization of the "genetically…

  18. Defining Mental Retardation from an Instructional Perspective.

    ERIC Educational Resources Information Center

    Dever, R. B.

    1990-01-01

    A definition of mental retardation is presented to clarify perceptions of what should happen to persons with mental retardation after identification and program placement. The definition refers to the need for specific skill training and the development of independence. A rationale and six corollaries to the definition are discussed. (JDD)

  19. Teaching Physical Education to Mentally Retarded Children.

    ERIC Educational Resources Information Center

    Davis, Patricia A.

    Methods for teaching physical education activities and skills to mentally retarded children are presented. General objectives are listed and the physical education program is outlined. Hints are offered for teaching the retarded child; and basic skills and rhythms are described. The following are then described; rhythm games, a volleyball unit and…

  20. Arm Tremor, Tardive Dyskinesia, and Mental Retardation.

    ERIC Educational Resources Information Center

    van Emmerik, R. E. A.; And Others

    1993-01-01

    The arm tremor of adults (n=32) diagnosed as having mental retardation and/or tardive dyskinesia was examined through an analysis of the acceleration properties of several arm postures. The degree of arm acceleration was increased in all subjects compared to a control group without mental retardation. Effects of neuroleptic medication were noted.…

  1. Identifying Depression in Students with Mental Retardation.

    ERIC Educational Resources Information Center

    Stough, Laura M.; Baker, Lynn

    1999-01-01

    Offers guidelines to teachers for identifying depression in students with mental retardation. Discusses prevalence and symptoms of depression, causes of depression, difficulty of diagnosis in students with mental retardation, detecting symptoms in the classroom, treatment of depression, and psychological services. Inserts list ideas for helping…

  2. The Effects of Retardation on Exploration.

    ERIC Educational Resources Information Center

    Vandenberg, Brian R.

    1985-01-01

    Exploratory behavior of educationally mentally retarded 7- to 12-year-old children was compared to that of two independent groups of normal children matched on chronological and mental age. In a multidimensional assessment of exploration, results suggested that delays in exploratory behavior in retarded children are developmental in nature, and…

  3. UNDERSTANDING AND HELPING THE RETARDED READER.

    ERIC Educational Resources Information Center

    STRANG, RUTH, ED.

    THE PROCEEDINGS OF A 1962 STATEWIDE ARIZONA CONFERENCE ON READING DEVELOPMENT AND READING DIFFICULTIES INCLUDE 15 PAPERS. ARTICLES ON THE ABLE RETARDED READER ARE "UNDERSTANDING THE ABLE RETARDED READER" BY HELEN M. ROBINSON, AND "CLASSROOM PROCEDURES" BY ROSEMARY YOAKUM. PAPERS ON EMOTIONALLY DISTURBED CHILDREN ARE "IDENTIFICATION OF EMOTIONAL…

  4. Percutaneous permeation modifiers: enhancement versus retardation.

    PubMed

    Kaushik, Diksha; Batheja, Priya; Kilfoyle, Brian; Rai, Vishwas; Michniak-Kohn, Bozena

    2008-05-01

    The use of permeation enhancers to compromise the barrier properties of skin has been ongoing for decades. However, toxicity associated with certain xenobiotics has led to the development of permeation retardants. Since both enhancers and retardants modify the surface layer of the skin, they can be collectively referred to as penetration modifiers. This review attempts to outline a comparison of two types of penetration modifiers: enhancers and retardants. In addition to reports of enhancement and retardation by modifiers, we also provide evidence as to why we should group these compounds together, since we have found that retardants can become enhancers in different formulation environments. Since modifiers influence drug delivery, further exploration of these compounds is required to understand their modifying action on the properties of skin.

  5. Alternative routes to the retarded potentials

    NASA Astrophysics Data System (ADS)

    Heras, Ricardo

    2017-09-01

    Two procedures to introduce the familiar retarded potentials of Maxwell’s equations are reviewed. The first well-known procedure makes use of the Lorenz-gauge potentials of Maxwell’s equations. The second less-known procedure applies the retarded Helmholtz theorem to Maxwell’s equations. Both procedures are compared in the context of an undergraduate presentation of electrodynamics. The covariant form of both procedures is discussed for completeness. As a related discussion, two procedures to introduce the unfamiliar instantaneous potentials of Maxwell’s equations are also reviewed. The first procedure applies the standard Helmholtz theorem to Maxwell’s equations and the second one uses the Coulomb-gauge potentials of Maxwell’s equations. The retarded and instantaneous forms of the potentials of Maxwell’s equations are briefly commented upon. The retarded Helmholtz theorem is used to introduce the retarded potentials of Maxwell’s equations with magnetic monopoles.

  6. Social development of children with mental retardation

    PubMed Central

    Kumar, Indrabhushan; Singh, Amool R.; Akhtar, S.

    2009-01-01

    Background: Social development of children with mental retardation has implications for prognosis. The present study evaluated whether the social maturity scale alone can reflect on the social maturity, intellectual level and consequent adjustment in family and society of children with mental retardation. Materials and Methods: Thirty-five mentally retarded children were administered Vineland Social Maturity Scale and Stanford Binet Intelligence Scale. Results: It was found that there was significant relationship between the measures of social maturity scale and the IQ of the subjects. Further it was found that with increasing severity of retardation, social development also decreases and age does not have any effect on social development. Conclusion: Social quotient increases from profound to mild level of retardation. PMID:21234165

  7. Aetiology of mild mental retardation.

    PubMed Central

    Lamont, M A; Dennis, N R

    1988-01-01

    A clinical and family study was carried out in 169 children attending schools for the mildly mentally retarded in Southampton to assess the prevalence of recognised medical risk factors; 71 children (42%) had such risk factors. These were prenatal in 22, perinatal in 41, and postnatal in eight. Risk factors of possible, but less certain, significance were found in a further 63 children (37%). In 86 families (51%) there was a history of serious educational problems in both parents. The prevalence of both types of risk factor was higher in the children whose parents had no educational problems. There were, however, 25 children (15%) whose parents had no history of educational problems and in whom medical risk factors were either absent or minimal. PMID:3178264

  8. Care Of The Mentally Retarded

    PubMed Central

    Jacobs, J.

    1979-01-01

    Mental retardation is a clinical syndrome, not an intellectual defect or brain disease per se. As such, physicians should not participate in the downgrading labelling of moron, idiot and imbecile. Such labelled people are difficult to relate to and this results in the concept of 'nil expectations' in which the whole of society participates. Maladaptation in this syndrome is more related to poor environmental input than to basic organic defect, and is a family problem. The family doctor is in an ideal situation to help the family handle the problems of anger, shame, guilt, rejection. If aware of his own feelings, he should also be the coordinator of the physical needs of the child and the alternatives available for maximal input. Imagesp1344-a PMID:21297810

  9. New scheme for finite-retardation limitations of linear retarders with fixed axes in polarization control

    NASA Astrophysics Data System (ADS)

    Chen, Hua; Li, Mo; Liang, Wen-Ye; Wang, Dong; He, De-Yong; Wang, Shuang; Yin, Zhen-Qiang; Chen, Wei; Guo, Guang-Can; Han, Zheng-Fu

    2016-01-01

    Finite retardation ranges of linear retarders with fixed axes limit their applications in polarization control. In this work, we present a simple and efficient constraint scheme for this finite-retardation limitation. Its theoretical basis is given geometrically and mathematically. The new polarization control algorithm combines the constraint scheme and a widely-used maximum-search algorithm. Both simulations and experiments confirm the effectiveness and practicality of the proposed scheme and control algorithm. In experiments, the control system uses four cascaded linear retarders with fast axes alternately oriented at 0° and 45°. Each retarder (fiber squeezer) has a finite retardation range of 4π. For a 15-min test, the mean (maximum) polarization error angle is 0.09 (0.28) rad while stabilizing a polarization fluctuation at an average speed of 26 rad/s. Furthermore, no events of hitting retardation limits occur.

  10. Β-alanine and l-histidine transport across the inner blood-retinal barrier: potential involvement in L-carnosine supply.

    PubMed

    Usui, Takuya; Kubo, Yoshiyuki; Akanuma, Shin-Ichi; Hosoya, Ken-Ichi

    2013-08-01

    The supply of L-carnosine, a bioactive dipeptide of β-alanine and l-histidine, to the retina across the blood-retinal barrier (BRB) was studied. The in vivo and in vitro studies revealed low uptake activities for [(3)H]Gly-Sar, a representative dipeptide, suggesting that l-carnosine transport plays only a minor role at the BRB. The in vivo study using rats showed approximately 18- and 23-fold greater retinal uptake indexes (RUI) for [(3)H]β-alanine and [(3)H]l-histidine compared with that of a paracellular marker, respectively. The RUI of [(3)H]β-alanine was taurine- and γ-aminobutyric acid-sensitive, and the in vitro uptake by TR-iBRB2 cells showed time- concentration- and temperature-dependent [(3)H]β-alanine uptake, suggesting that a carrier-mediated process was involved in β-alanine transport across the inner BRB. [(3)H]β-Alanine uptake was inhibited by taurine and β-guanidinopropionic acid, suggesting that taurine transporter (TAUT/SLC6A6) is responsible for the influx transport of β-alanine across the inner BRB. Regarding l-histidine, the l-leucine-sensitive RUI of [(3)H]l-histidine was identified, and the in vitro [(3)H]l-histidine uptake by TR-iBRB2 cells suggested that a carrier-mediated process was involved in l-histidine transport across the inner BRB. The inhibition profile suggested that L-type amino acid transporter (LAT1/SLC7A5) is responsible for the influx transport of l-histidine across the inner BRB. These results show that the influx transports of β-alanine and l-histidine across the inner BRB is carried out by TAUT and LAT1, respectively, suggesting that the retinal l-carnosine is supplied by enzymatic synthesis from two kinds of amino acids transported across the inner BRB.

  11. Zinc L-carnosine suppresses inflammatory responses in lipopolysaccharide-induced RAW 264.7 murine macrophages cell line via activation of Nrf2/HO-1 signaling pathway.

    PubMed

    Ooi, Theng Choon; Chan, Kok Meng; Sharif, Razinah

    2017-10-01

    Zinc L-carnosine (ZnC) is a chelate of Zn and L-carnosine and is used clinically in the treatment of peptic ulcer. In this study, we aim to investigate the involvement of heme oxygenase-1 (HO-1) in the anti-inflammatory effects of ZnC in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages. We used immunoblotting analysis to evaluate the involvement of HO-1 in the anti-inflammatory effects of ZnC and the signaling pathway involved was measured using Dual luciferase reporter assay. Results from immunoblotting analysis demonstrated that pretreatment of cells with ZnC enhanced the expression of HO-1 in RAW 264.7 cells. Pretreatment of cells with HO-1 inhibitor (tin protoporphyrin IX dichloride) significantly attenuated the inhibitory effects of ZnC on nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression and NF-κB activation in LPS-induced RAW 264.7 cells, suggesting that HO-1 play an important role in the suppression of inflammatory responses induced by ZnC. Furthermore, results from co-immunoprecipitation of Nrf2 and Keap1 and dual luciferase reporter assay showed that pretreatment of ZnC was able to activate the Nrf2 signaling pathway. Treatment of cells with p38 inhibitor (SB203580), c-Jun N-terminal kinase inhibitor (SP600125), and MEK 1/2 inhibitor (U0126) did not significantly suppress the induction of HO-1 by ZnC. Moreover, our present findings suggest that the effects of ZnC on NO production, HO-1 expression, and Nrf2 activation were attributed to its Zn subcomponent, but not l-carnosine. Pretreatment with ZnC was able to activate Nrf2/HO-1 signaling pathway, thus suppressing the expression of inflammatory mediators, such as NO and iNOS in LPS-induced RAW 264.7 cells.

  12. 45 CFR 1308.10 - Eligibility criteria: Mental retardation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... DISABILITIES Health Services Performance Standards § 1308.10 Eligibility criteria: Mental retardation. (a) A child is classified as mentally retarded who exhibits significantly sub-average intellectual...

  13. Public health implications of components of plastics manufacture. Flame retardants.

    PubMed Central

    Pearce, E M; Liepins, R

    1975-01-01

    The four processes involved in the flammability of materials are described and related to the various flame retardance mechanisms that may operate. Following this the four practical approaches used in improving flame retardance of materials are described. Each approach is illustrated with a number of typical examples of flame retardants or synthetic procedures used. This overview of flammability, flame retardance, and flame retardants used is followed by a more detailed examination of most of the plastics manufactured in the United States during 1973, their consumption patterns, and the primary types of flame retardants used in the flame retardance of the most used plastics. The main types of flame retardants are illustrated with a number of typical commercial examples. Statistical data on flame retardant market size, flame retardant growth in plastics, and price ranges of common flame retardants are presented. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. PMID:1175568

  14. [Correlations between vocal qualities and mental retardation].

    PubMed

    Biondi, S; Zappala, M; Amato, G; Consoli, F

    1990-01-01

    This research is intended to verify the existence of vocal spectrographic alterations, with particular reference to the values of Fundamental Frequency, in patients with different levels of Mental Retardation. The results show the existence of a direct correspondence between the values of the Fundamental Frequency and the level of Mental Retardation: the spectrographic characteristics appear to be more altered in subjects with severe Mental Retardation. The spectrographics patterns are characterized by the presence of bi-phonation particularly at the onset time and at the end, and by a noise signal on constant frequency. The shifts of Fundamental Frequency and voice breakage are rarely detected.

  15. A polymeric flame retardant additive for rubbers

    SciTech Connect

    Ghosh, S.N.; Maiti, S.

    1993-12-31

    Synthesis of a polyphosphonate by the interfacial polymerization of bisphenol-A (BPA) and dichloro-phenyl phosphine oxide (DCPO) using cetyltrimethyl ammonium chloride (TMAC) as phase transfer catalyst (PTC) was reported. The polyphosphonate was characterized by elemental analysis, IR, TGA, DSC and 1H-NMR spectroscopy. The flame retardancy of the polymer was done by OI study. The polymer was used as a fire retardant additive to rubbers such as natural rubber (NR), styrene-butadiene rubber(SBR), nitrile rubber (NBR) and chloroprene rubber (CR). The efficiency of the fire retardant property of this additive was determined by LOI measurements of the various rubber samples.

  16. Carnosine Reduces Oxidative Stress and Reverses Attenuation of Righting and Postural Reflexes in Rats with Thioacetamide-Induced Liver Failure.

    PubMed

    Milewski, Krzysztof; Hilgier, Wojciech; Fręśko, Inez; Polowy, Rafał; Podsiadłowska, Anna; Zołocińska, Ewa; Grymanowska, Aneta W; Filipkowski, Robert K; Albrecht, Jan; Zielińska, Magdalena

    2016-02-01

    Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of L-histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (β-alanyl-L-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the well documented anti-OS activity of His. Amino acids [His or Car (100 mg/kg)] were administrated 2 h before TAA (i.p., 300 mg/kg 3× in 24 h intervals) injection into Sprague-Dawley rats. The animals were thus tested for: (i) brain prefrontal cortex and blood contents of Car and His, (ii) amount of reactive oxygen species (ROS), total antioxidant capacity (TAC), GSSG/GSH ratio and thioredoxin reductase (TRx) activity, and (iii) behavioral changes (several models were used, i.e. tests for reflexes, open field, grip test, Rotarod). Brain level of Car was reduced in TAA rats, and His administration significantly elevated Car levels in control and TAA rats. Car partly attenuated TAA-induced ROS production and reduced GSH/GSSG ratio, whereas the increase of TRx activity in TAA brain was not significantly modulated by Car. Further, Car improved TAA-affected behavioral functions in rats, as was shown by the tests of righting and postural reflexes. Collectively, the results support the hypothesis that (i) Car may be added to the list of neuroprotective compounds of therapeutic potential on HE and that (ii) Car mediates at least a portion of the OS-attenuating activity of His in the setting of TAA-induced liver failure.

  17. Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1) gene with diabetic nephropathy in north Indians

    PubMed Central

    Yadav, Ashok K.; Sinha, Nisha; Kumar, Vinod; Bhansali, Anil; Dutta, Pinaki; Jha, Vivekanand

    2016-01-01

    Background & objectives: CNDP1 gene, present on chromosome 18q22.3-23, encodes carnosinase, the rate-limiting enzyme in hydrolysis of carnosine to β-alanine and L-histidine. Linkage of CTG trinucleotide (leucine) repeat polymorphism in CNDP1 gene with diabetic nephropathy has been observed in several populations. However, this association is conflicting and population-dependent. We investigated this association in type 2 diabetes mellitus (T2DM) patients with and without nephropathy in north India. Methods: A total of 564 individuals [199 T2DM without nephropathy (DM), 185 T2DM with nephropathy (DN) and 180 healthy individuals (HC)] were enrolled. CNDP1 CTG repeat analysis was done by direct sequencing of a 377 base pair fragment in exon 2. Results: The most frequent leucine (L) repeats were 5L-5L, 6L-5L and 6L-6L. 5L-5L genotype frequency was reduced in DN (24.3%) as compared to DM (34.7%, P=0.035) and HC (38.4%, P=0.005). Similarly, 5L allele frequency was lower in DN (46.8%) as compared to DM (57.3%, P=0.004) and HC (60.5%, P<0.001). The genotype and allelic frequencies were similar in DM and HC groups. No gender specific difference was observed in the genotype or allelic frequencies between groups. Interpretation & conclusions: Compared to healthy individuals and those with diabetes but no kidney disease, patients with diabetic nephropathy exhibited lower frequencies of 5L-5L genotype and 5L allele of CNDP1 gene, suggesting that this allele might confer protection against development of kidney disease in this population. PMID:27834323

  18. Genomic imbalances in mental retardation

    PubMed Central

    Kriek, M; White, S; Bouma, M; Dauwerse, H; Hansson, K; Nijhuis, J; Bakker, B; van Ommen, G-J B; den Dunnen, J T; Breuning, M

    2004-01-01

    Introduction: It has been estimated that cytogenetically visible rearrangements are present in ~1% of newborns. These chromosomal changes can cause a wide range of deleterious developmental effects, including mental retardation (MR). It is assumed that many other cases exist where the cause is a submicroscopic deletion or duplication. To facilitate the detection of such cases, different techniques have been developed, which have differing efficiency as to the number of loci and patients that can be tested. Methods: We implemented multiplex amplifiable probe hybridisation (MAPH) to test areas known to be rearranged in MR patients (for example, subtelomeric/pericentromeric regions and those affected in microdeletion syndromes) and to look for new regions that might be related to MR. Results: In this study, over 30 000 screens for duplications and deletions were carried out; 162 different loci tested in each of 188 developmentally delayed patients. The analysis resulted in the detection of 19 rearrangements, of which ~65% would not have been detected by conventional cytogenetic analysis. A significant fraction (46%) of the rearrangements found were interstitial, despite the fact that only a limited number of these loci have so far been tested. Discussion: Our results strengthen the arguments for whole genome screening within this population, as it can be assumed that many more interstitial rearrangements would be detected. The strengths of MAPH for this analysis are the simplicity, the high throughput potential, and the high resolution of analysis. This combination should help in the future identification of the specific genes that are responsible for MR. PMID:15060096

  19. [X-linked mental retardation].

    PubMed

    Billuart, Pierre; Chelly, Jamel; Gilgenkrantz, Simone

    2005-11-01

    X-linked mental retardation (XLMR) affects 1.8 per thousand male births and is usually categorized as "syndromic" (MRXS) or "non-specific" (MRX) forms according to the presence or absence of specific signs in addition to the MR. Up to 60 genes have been implicated in XLMR and certain mutations can alternatively lead to MRXS or MRX. Indeed the extreme phenotypic and allelic heterogeneity of XLMR makes the classification of most genes difficult. Therefore, following identification of new genes, accurate retrospective clinical evaluation of patients and their families is necessary to aid the molecular diagnosis and the classification of this heterogeneous group of disorders. Analyses of the protein products corresponding to XLMR genes show a great diversity of cellular pathways involved in MR. Common mechanisms are beginning to emerge : a first group of proteins belongs to the Rho and Rab GTPase signaling pathways involved in neuronal differentiation and synaptic plasticity and a second group is related to the regulation of gene expression. In this review, we illustrate the complexity of XLMR conditions and present recent data about the FMR1, ARX and Oligophrenin 1 genes.

  20. Engineering Flame Retardant Biodegradable Nanocomposites

    NASA Astrophysics Data System (ADS)

    He, Shan; Yang, Kai; Guo, Yichen; Zhang, Linxi; Pack, Seongchan; Davis, Rachel; Lewin, Menahem; Ade, Harald; Korach, Chad; Kashiwagi, Takashi; Rafailovich, Miriam

    2013-03-01

    Cellulose-based PLA/PBAT polymer blends can potentially be a promising class of biodegradable nanocomposites. Adding cellulose fiber reinforcement can improve mechanical properties of biodegradable plastics, but homogeneously dispersing hydrophilic cellulose in the hydrophobic polymer matrix poses a significant challenge. We here show that resorcinol diphenyl phosphates (RDP) can be used to modify the surface energy, not only reducing phase separation between two polymer kinds but also allowing the cellulose particles and the Halloysite clay to be easily dispersed within polymer matrices to achieve synergy effect using melt blending. Here in this study we describe the use of cellulose fiber and Halloysite clay, coated with RDP surfactant, in producing the flame retardant polymer blends of PBAT(Ecoflex) and PLA which can pass the stringent UL-94 V0 test. We also utilized FTIR, SEM and AFM nanoindentation to elucidate the role RDP plays in improving the compatibility of biodegradable polymers, and to determine structure property of chars that resulted in composites that could have optimized mechanical and thermal properties. Supported by Garcia Polymer Center and NSF Foundation.

  1. Comparison of colony-formation efficiency of bovine fetal fibroblast cell lines cultured with low oxygen, hydrocortisone, L-carnosine, bFGF, or different levels of FBS.

    PubMed

    Talbot, Neil C; Powell, Anne M; Caperna, Thomas J

    2004-01-01

    A comparison of colony-formation efficiency (CFE) was made between six independent bovine fetal fibroblast (BFF) cell lines used in somatic cell nuclear transfer. Variation in CFE was assessed under different culture conditions. The conditions examined were ambient atmosphere (approximately 20% oxygen) culture versus 5% oxygen culture, three levels of fetal bovine serum (FBS) in the medium (5%, 10% or 20%), and the amendment of 10% FBS medium with basic fibroblast growth factor (1 ng/mL), L-carnosine (20 mM), or hydrocortisone (1 microM). The six BFF cell lines showed significant differences from one another in CFE. No significant difference in CFE was found with reduced oxygen culture. L-Carnosine also had no significant effect on CFE. A FBS concentration of 10% was found to produce the best overall CFE. Hydrocortisone treatment reduced the size of colonies although the number of colonies formed was not affected. Basic FGF increased the size of colonies but the number of colonies formed was not affected. The results showed that different BFF cell lines varied significantly in their CFE. Also, some medium supplements or culture conditions that have shown positive CFE effects on the fibroblasts of other species failed to show significant positive CFE effects on the BFF cell lines tested.

  2. PCBs, PBBs and Brominated Flame Retardants

    EPA Science Inventory

    This chapter introduces selected organohalogen chemicals such as polychlorinated biphenyls (PCB5), polychiorinated biphenyls (PBBs), and brominated flame retardants (BFRs) with emphasis on the background, physicochemical properties, environmental levels, health effects and possib...

  3. Brominated Flame Retardants and Perfluorinated Chemicals

    EPA Science Inventory

    Brominated flame retardants (BFRs) and perfluorinated chemicals (PFCs) belong to a large class of chemicals known as organohalogens. It is believed that both BFRs and PFCs saved lives by reducing flammability of materials commonly used and bactericidal (biocidal) properties. Thes...

  4. Teaching mending skills to mentally retarded adolescents.

    PubMed Central

    Cronin, K A; Cuvo, A J

    1979-01-01

    This experiment presents a model for analyzing community living skills and teaching them to mentally retarded adolescents. A task analysis of three mending skills was developed and validated, aided by consultation with persons having expertise in home economics and mental retardation. The task analysis was modified to compensate for the constraints imposed by the trainees' disabilities. Five moderately retarded youths received training on sewing hems, buttons, and seams. Sewing skills were acquired rapidly and maintained. The behavior generalized from trained to untrained tasks on their common components for all subjects. A multiple baseline across participants combined with a multiple baseline across responses demonstrated the combined effectiveness of an objectively validated, detailed task analysis; graduated sequence of prompts; and response consequences in training and maintaining community living skills with mentally retarded adolescents. PMID:117004

  5. Teaching mending skills to mentally retarded adolescents.

    PubMed

    Cronin, K A; Cuvo, A J

    1979-01-01

    This experiment presents a model for analyzing community living skills and teaching them to mentally retarded adolescents. A task analysis of three mending skills was developed and validated, aided by consultation with persons having expertise in home economics and mental retardation. The task analysis was modified to compensate for the constraints imposed by the trainees' disabilities. Five moderately retarded youths received training on sewing hems, buttons, and seams. Sewing skills were acquired rapidly and maintained. The behavior generalized from trained to untrained tasks on their common components for all subjects. A multiple baseline across participants combined with a multiple baseline across responses demonstrated the combined effectiveness of an objectively validated, detailed task analysis; graduated sequence of prompts; and response consequences in training and maintaining community living skills with mentally retarded adolescents.

  6. Video Tape and the Mentally Retarded

    ERIC Educational Resources Information Center

    Weisbord, H. F.

    1972-01-01

    Three uses of video tape recordings with the mentally retarded; discussed briefly are staff training or teacher education, parental involvement in the child's education, and therapeutic uses by psychiatrists and psychologists. (CB)

  7. Retarded Children at Camp with Normal Children

    ERIC Educational Resources Information Center

    Flax, Norman; Peters, Edward N.

    1969-01-01

    Statistical analysis of data from written forms and scales (designed to measure children's behavior in groups), observations, and interviews indicated that many educalble mentally retarded children can participate successfully in camp activities with normal children. (DR)

  8. Sterilization of Persons with Mental Retardation.

    ERIC Educational Resources Information Center

    Elkins, Thomas E.; Andersen, H. Frank

    1992-01-01

    This article examines the historical, legal, and ethical concerns regarding sterilization for persons with mental retardation and offers guidelines to help counsel individuals with disabilities or their families regarding decision making about sterilization. (DB)

  9. Brominated Flame Retardants and Perfluorinated Chemicals

    EPA Science Inventory

    Brominated flame retardants (BFRs) and perfluorinated chemicals (PFCs) belong to a large class of chemicals known as organohalogens. It is believed that both BFRs and PFCs saved lives by reducing flammability of materials commonly used and bactericidal (biocidal) properties. Thes...

  10. Physical Education: Equipment for Teaching the Retarded

    ERIC Educational Resources Information Center

    Chaya, John

    1976-01-01

    Equipment designed to help mentally retarded students develop flexibility, eye-hand and eye-foot coordination, muscle coordination, body balance and control, and social involvement in their peer group. (Author/MLF)

  11. PCBs, PBBs and Brominated Flame Retardants

    EPA Science Inventory

    This chapter introduces selected organohalogen chemicals such as polychlorinated biphenyls (PCB5), polychiorinated biphenyls (PBBs), and brominated flame retardants (BFRs) with emphasis on the background, physicochemical properties, environmental levels, health effects and possib...

  12. Retardation analytical model to extend service life

    NASA Technical Reports Server (NTRS)

    Matejczyk, D.

    1984-01-01

    A fatigue crack growth model that incorporates crack growth retardation effects and is applicable to the materials characteristics and service environments of high performance LH2/LO2 engine systems was developed and tested.

  13. Retardation Measurements of Infrared PVA Wave plate

    NASA Astrophysics Data System (ADS)

    Sun, Y.; Z, H.; W, D.; D, Y.; Z, Z.; S, J.

    The wave plate made of Polyvinyl Alcohol PVA plastic film has several advantages such as its lower cost and insensitivity to temperature and incidence angle so it has been used in the Solar Multi-Channel Telescope SMCT in China But the important parameter retardations of PVA wave plates in the near infrared wavelength have never been provided In this paper a convenient and high precise instrument to get the retardations of discrete wavelengths or a continuous function of wavelength in near infrared is developed In this method the retardations of wave plates have been determined through calculating the maximum and minimum of light intensity The instrument error has been shown Additionally we can get the continuous direction of wavelength retardations in the ultraviolet visible or infrared spectral in another way

  14. Galactosaemia: A Preventable Form of Mental Retardation.

    ERIC Educational Resources Information Center

    Hayes, Alan; And Others

    1986-01-01

    Galectosaemia, a treatable and potentially preventable cause of brain damage and mental retardation is discussed with emphasis on neonatal screening tests, treatment with a galactose-free diet, and evidence of treatment effectiveness. (DB)

  15. Physical Education: Equipment for Teaching the Retarded

    ERIC Educational Resources Information Center

    Chaya, John

    1976-01-01

    Equipment designed to help mentally retarded students develop flexibility, eye-hand and eye-foot coordination, muscle coordination, body balance and control, and social involvement in their peer group. (Author/MLF)

  16. Job Enrichment and the Mentally Retarded Worker.

    ERIC Educational Resources Information Center

    Morris, Jerry L.; And Others

    1981-01-01

    The effect of job enrichment on the production rate of 14 mentally retarded adult workers was evaluated. Job enrichment led to increases in standard rates of production for high IQ Ss and lower rates for low IQ Ss. (Author)

  17. Epilepsy, Mental Retardation, and Anticonvulsant Therapy.

    ERIC Educational Resources Information Center

    Kaufman, Kenneth Roland; Katz-Garris, Lynda

    1979-01-01

    Inappropriate or inadequately documented medication for patients in mental retardation institutions is a major medical and economic problem. Within a 127-patient ward, 41 patients were treated with anticonvulsants. Of these patients, 24 had no documented indications for usage. (Author)

  18. Epilepsy, Mental Retardation, and Anticonvulsant Therapy.

    ERIC Educational Resources Information Center

    Kaufman, Kenneth Roland; Katz-Garris, Lynda

    1979-01-01

    Inappropriate or inadequately documented medication for patients in mental retardation institutions is a major medical and economic problem. Within a 127-patient ward, 41 patients were treated with anticonvulsants. Of these patients, 24 had no documented indications for usage. (Author)

  19. Musical aptitudes, musical interests and mental retardation.

    PubMed

    Miller, L K

    1991-08-01

    A modified version of the Bentley scales of musical aptitude was given to a sample of mild and moderately retarded adults chosen on the basis of alleged musical interest or experience. Several comparison groups were also given the assessment battery. The musical nominees generally performed more accurately than both matched retarded subjects with no particular musical interests and a group of normal children matched on (Wechsler) vocabulary scores. The musical nominees showed especially high performance on the subtest assessing voice analysis in chords.

  20. Influence of Retardants to Burning Lignocellulosic Materials

    NASA Astrophysics Data System (ADS)

    Tureková, Ivana; Harangozó, Jozef; Martinka, Jozef

    2011-01-01

    The paper deals with monitoring retardant changes of lignocellulosic materials. Combustion of lignocellulosic materials and fire-technical characteristics are described. In assessing the retarding effect of salt NH4H2PO4, fire-technical characteristics as limiting oxygen index (LOI) were measured, and by using thermoanalytical TG and DSC methods. High-temperature process of cellulose degradation at various flame concentrations was studied.

  1. Insulin secretion in children with growth retardation.

    PubMed

    Boscherini, B; Finocchi, G; Lostia, O; Mancuso, G; Montani, P; Pasquino, A M; Rezza, E; Rocchio, J; Taggi, F; Zorretta, D

    1977-12-30

    The effect of tolbutamide administration on insulin secretion was studied in 69 children with growth retardation. Diminished insulin secretion was found in all the patients, compared to the control group. This insulin deficit was most evident in patients with isolated, total GH deficiency and least evident in children with idiopathic short stature. Intermediate values were found in dwarfism due to isolated, partial GH deficiency. These results favour the hypothesis that hypoinsulinism contributes to the somatotropin deficiency in causing growth retardation.

  2. Gitelman's syndrome: Rare presentation with growth retardation

    PubMed Central

    Gaur, A.; Ambey, R.; Gaur, B. K.

    2014-01-01

    Gitelman's syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis, hypokalemia, hypomagnesaemia, hypocalciuria, hyperreninemia and without hypertension. Gitelman's syndrome is caused by mutations of the SLC12A3 gene, which encodes the Na/Cl co-transporter (NCCT) in the distal convoluted tubule. Majority of cases manifest during adolescence or adulthood and growth retardation is not the common feature. We report a rare presentation of Gitelman's syndrome in a four-year-old boy with growth retardation. PMID:24574637

  3. Realidades Acerca de la Deficiencia Mental = Facts about Mental Retardation.

    ERIC Educational Resources Information Center

    Texas State Dept. of Mental Health and Mental Retardation, Austin.

    This document consists of two booklets, one in Spanish and one in English, both covering the same text: the characteristics of mentally retarded individuals, the prevalence of mentally retarded persons in Texas, causes of mental retardation, prevention possibilities, and services available to mentally retarded persons in Texas. A distinction is…

  4. Realidades Acerca de la Deficiencia Mental = Facts about Mental Retardation.

    ERIC Educational Resources Information Center

    Texas State Dept. of Mental Health and Mental Retardation, Austin.

    This document consists of two booklets, one in Spanish and one in English, both covering the same text: the characteristics of mentally retarded individuals, the prevalence of mentally retarded persons in Texas, causes of mental retardation, prevention possibilities, and services available to mentally retarded persons in Texas. A distinction is…

  5. Fast quantitative retardance imaging of biological samples using quandri-wave interferometry (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Aknoun, Sherazade; Savatier, Julien; Bon, Pierre; Wattellier, Benoit; Monneret, Serge

    2017-02-01

    We describe a technique based on the use of a high-resolution quadri-wave lateral shearing interferometer to perform quantitative linear birefringence measurements on biological samples [1] such as living cells and tissues. The system combines QPI with different excitation polarizations to create retardance images. This creates a new kind of image contrast based on the local retardance, reveals the structure of sample anisotropic components and adds specificity to label-free phase images. We implemented this technique allowing us to take retardance images in less than 1 second which allows us to make high speed acquisitions to reconstruct tissues virtual slides with different modalities (i.e intensity, phase and retardance). Comparisons between healthy and tumoral 10 µm thick skin tissues and collagen orientation studies in the latter will be presented. [1] S. Aknoun, P. Bon, J. Savatier, B. Wattellier, and S. Monneret, "Quantitative retardance imaging of biological samples using quadriwave lateral shearing interferometry," Opt. Express 23, 16383-16406 (2015).

  6. Dendritic spine abnormalities in mental retardation.

    PubMed

    von Bohlen Und Halbach, Oliver

    2010-12-01

    Abnormalities in dendritic spine morphologies are often associated with mental retardation. Since dendritic spines are thought to represent a morphological correlate of neuronal plasticity, altered spine morphologies may underlie or contribute to cognitive deficits seen in mental retardation. Signaling cascades that are important for cytoskeletal regulation may have an impact upon spine morphologies. The Rho GTPase signaling pathway has been shown to be involved in the regulation of the cytoskeleton and to play fundamental roles in the structural plasticity of dendritic spines. Moreover, alterations in the Rho GTPase signaling pathway have been shown to contribute to mental retardation. Recently, different mental retardation-associated genes have been identified that encode modulators of the Rho GTPases. Disturbances in these genes can lead to mental retardation and-on the morphological level-to alterations in dendritic spines. Thus, getting more insight into the Rho GTPase signaling pathways, and the molecules involved, would not only help in understanding the basic mechanisms by which the morphologies of dendritic spines are modulated but may also allow the development of therapeutic strategies to counteract some aspects of mental retardation.

  7. An "enigmatic" L-carnosine (β-alanyl-L-histidine)? Cell proliferative activity as a fundamental property of a natural dipeptide inherent to traditional antioxidant, anti-aging biological activities: balancing and a hormonally correct agent, novel patented oral therapy dosage formulation for mobility, skeletal muscle power and functional performance, hypothalamic-pituitary- brain relationship in health, aging and stress studies.

    PubMed

    Babizhayev, Mark A; Yegorov, Yegor E

    2015-01-01

    Hypothalamic releasing and inhibiting hormones are major neuroendocrine regulators of human body metabolism being driven directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. The alternative physiological or therapeutic interventions utilizing the pharmaco-nutritional boost of imidazole-containing dipeptides (non-hydrolized oral form of carnosine, carcinine, N-acetylcarnosine lubricant eye drops) can maintain health, enhance physical exercise performance and prevent ageing. Carnosine (β-alanyl-L-histidine) is synthesized in mammalian skeletal muscle. There is an evidence that the release of carnosine from the skeletal muscle sarcomeres moieties during physical exercise affects autonomic neurotransmission and physiological functions. Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function. Carnosine and its imidazole-containing dipeptide derivatives are renowned for their anti-aging, antioxidant, membrane protective, metal ion chelating, buffering, anti-glycation/ transglycating activities used to prevent and treat a spectrum of age-related and metabolic diseases, such as neurodegenerative disease, sight threatening eye diseases, Diabetes mellitus and its complications, cancers and other disorders due to their wide spectrum biological activities. The precursor of carnosine (and related imidazole containing compounds) synthesis in skeletal muscles beta-alanine is used as the

  8. Glyoxalase I retards renal senescence.

    PubMed

    Ikeda, Yoichiro; Inagi, Reiko; Miyata, Toshio; Nagai, Ryoji; Arai, Makoto; Miyashita, Mitsuhiro; Itokawa, Masanari; Fujita, Toshiro; Nangaku, Masaomi

    2011-12-01

    Although kidney functions deteriorate with age, little is known about the general morphological alterations and mechanisms of renal senescence. We hypothesized that carbonyl stress causes senescence and investigated the possible role of glyoxalase I (GLO1), which detoxifies precursors of advanced glycation end products in the aging process of the kidney. We observed amelioration of senescence in GLO1-transgenic aged rats (assessed by expression levels of senescence markers such as p53, p21(WAF1/CIP1), and p16(INK4A)) and a positive rate of senescence-associated β-galactosidase (SABG) staining, associated with reduction of renal advanced glycation end product accumulation (estimated by the amount of carboxyethyl lysine). GLO1-transgenic rats showed amelioration of interstitial thickening (observed as an age-related presentation in human renal biopsy specimens) and were protected against age-dependent decline of renal functions. We used GLO1 overexpression or knockdown in primary renal proximal tubular epithelial cells to investigate the effect of GLO1 on cellular senescence. Senescence markers were significantly up-regulated in renal proximal tubular epithelial cells at late passage and in those treated with etoposide, a chemical inducer of senescence. GLO1 cellular overexpression ameliorated and knockdown enhanced the cellular senescence phenotypes. Furthermore, we confirmed the association of decreased GLO1 enzymatic activity and age-dependent deterioration of renal function in aged humans with GLO1 mutation. These findings indicate that GLO1 ameliorates carbonyl stress to retard renal senescence. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Multistage Pressure-Retarded Osmosis

    NASA Astrophysics Data System (ADS)

    Bharadwaj, Devesh; Fyles, Thomas M.; Struchtrup, Henning

    2016-10-01

    One promising sustainable energy source is the chemical potential difference between salt and freshwater. The membrane process of pressure-retarded osmosis (PRO) has been the most widely investigated means to harvest salinity gradient energy. In this report, we analyse the thermodynamic efficiency of multistage PRO systems to optimize energy recovery from a salinity gradient. We establish a unified description of the efficiencies of the component pumps (P), turbines (T), pressure exchangers (PX), and membrane modules (M) and exploit this model to determine the maximum available work with respect to the volume of the brine produced, the volume of the sea water consumed, or the volume of the freshwater that permeates the membrane. In an idealized series configuration of 1-20 modules (P-M-T), the three optimization conditions have significantly different intermediate operating pressures in the modules, but demonstrate that multistage systems can recover a significantly larger fraction of the available work compared to single-stage PRO. The biggest proportional advantage occurs for one to three modules in series. The available work depends upon the component efficiencies, but the proportional advantage of multistage PRO is retained. We also optimize one- and two-stage PX-M-T and P-M-T configurations with respect to the three volume parameters, and again significantly different optimal operating conditions are found. PX-M-T systems are more efficient than P-M-T systems, and two-stage systems have efficiency advantages that transcend assumed component efficiencies. The results indicate that overall system design with a clear focus on critical optimization parameters has the potential to significantly improve the near-term practical feasibility of PRO.

  10. Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis.

    PubMed

    Nokin, Marie-Julie; Durieux, Florence; Peixoto, Paul; Chiavarina, Barbara; Peulen, Olivier; Blomme, Arnaud; Turtoi, Andrei; Costanza, Brunella; Smargiasso, Nicolas; Baiwir, Dominique; Scheijen, Jean L; Schalkwijk, Casper G; Leenders, Justine; De Tullio, Pascal; Bianchi, Elettra; Thiry, Marc; Uchida, Koji; Spiegel, David A; Cochrane, James R; Hutton, Craig A; De Pauw, Edwin; Delvenne, Philippe; Belpomme, Dominique; Castronovo, Vincent; Bellahcène, Akeila

    2016-10-19

    Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer. Little is known regarding the impact of MG-mediated carbonyl stress on tumor progression. Breast tumors with MG stress presented with high nuclear YAP, a key transcriptional co-activator regulating tumor growth and invasion. Elevated MG levels resulted in sustained YAP nuclear localization/activity that could be reverted using Carnosine, a scavenger for MG. MG treatment affected Hsp90 chaperone activity and decreased its binding to LATS1, a key kinase of the Hippo pathway. Cancer cells with high MG stress showed enhanced growth and metastatic potential in vivo. These findings reinforce the cumulative evidence pointing to hyperglycemia as a risk factor for cancer incidence and bring renewed interest in MG scavengers for cancer treatment.

  11. Intrauterine radiation exposures and mental retardation

    SciTech Connect

    Miller, R.W.

    1988-08-01

    Small head size and mental retardation have been known as effects of intrauterine exposure to ionizing radiation since the 1920s. In the 1950s, studies of Japanese atomic-bomb survivors revealed that at 4-17 wk of gestation, the greater the dose, the smaller the brain (and head size), and that beginning at 0.5 Gy (50 rad) in Hiroshima, mental retardation increased in frequency with increasing dose. No other excess of birth defects was observed. Otake and Schull (1984) pointed out that the period of susceptibility to mental retardation coincided with that for proliferation and migration of neuronal elements from near the cerebral ventricles to the cortex. Mental retardation could be the result of interference with this process. Their analysis indicated that exposures at 8-15 wk to 0.01-0.02 Gy (1-2 rad) doubled the frequency of severe mental retardation. This estimate was based on small numbers of mentally retarded atomic-bomb survivors. Although nuclear accidents have occurred recently, new cases will hopefully be too rare to provide further information about the risk of mental retardation. It may be possible, however, to learn about lesser impairment. New psychometric tests may be helpful in detecting subtle deficits in intelligence or neurodevelopmental function. One such test is PEERAMID, which is being used in schools to identify learning disabilities due, for example, to deficits in attention, short- or long-term memory, or in sequencing information. This and other tests could be applied in evaluating survivors of intrauterine exposure to various doses of ionizing radiation. The results could change our understanding of the safety of low-dose exposures.

  12. Reactions to the Labels "Institutionalized" and "Mentally Retarded" by Retarded and Nonretarded Persons.

    ERIC Educational Resources Information Center

    Gibbons, Frederick X.; Gibbons, Barbara N.

    The effects of labels, "mentally retarded" and "institutionalized" on the evaluations and causal attributions of nonretarded persons, and on the social distance preferences of EMR persons, were assessed. In addition, each group was asked to predict the likelihood of a labeled (mentally retarded) or a nonlabeled target person achieving success at a…

  13. Cooperative and Competitive Behavior of Retarded and Non-Retarded Children at Two Ages.

    ERIC Educational Resources Information Center

    Madsen, Millard C.; Connor, Catherine

    Cooperative and competitive interaction (interpersonal relationship) between pairs of retarded and nonretarded children of ages 6 to 7 and 11 to 12 were assessed in a situation involving a marble pull apparatus in which competitive interaction was nonadaptive in terms of reward attainment. The retarded group was significantly more cooperative than…

  14. [Clinical features of strabismus in psychomotor retardation].

    PubMed

    Arias-Cabello, Belina; Arroyo-Yllanes, María Estela; Pérez-Pérez, José Fernando; Fonte-Vázquez, Anselmo

    2016-01-01

    In psychomotor retardation there is an abnormal development of mental, sensory and motor skills associated with ocular manifestations. There are biological and psychosocial risk factors that predispose an individual to neurological damage. From 50% to 80% of patients with strabismus retardation have special features that differentiate it from the rest of strabismus in healthy patients. To determine the most common type of strabismus in patients with psychomotor retardation and their clinical features. Patients with psychomotor retardation and strabismus were included. An ophthalmological examination was performed, as well as an evaluation of the characteristics of strabismus, including perinatal and post-natal history. Esotropia was the most frequent squint with 65.3%, followed by exotropia with 32.7%. The variability in the squint magnitude was 60% in both types, and 6 patients had dissociated vertical deviation. Most of the patients started to present strabismus since they were born. The most frequent perinatal risk factors were threatened miscarriage, pre-eclampsia, foetal distress, and hypoxia. Esotropia is the most common type of strabismus in psychomotor retardation. The variability of squint magnitude is a characteristic in these patients. The moderate variability is the most frequent in both esotropia and exotropia. The most common refractive error is hyperopic astigmatism in esotropia and the myopic kind in exotropia. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  15. X linked mental retardation: a clinical guide.

    PubMed

    Raymond, F L

    2006-03-01

    Mental retardation is more common in males than females in the population, assumed to be due to mutations on the X chromosome. The prevalence of the 24 genes identified to date is low and less common than expansions in FMR1, which cause Fragile X syndrome. Systematic screening of all other X linked genes in X linked families with mental retardation is currently not feasible in a clinical setting. The phenotypes of genes causing syndromic and non-syndromic mental retardation (NLGN3, NLGN4, RPS6KA3(RSK2), OPHN1, ATRX, SLC6A8, ARX, SYN1, AGTR2, MECP2, PQBP1, SMCX, and SLC16A2) are first discussed, as these may be the focus of more targeted mutation analysis. Secondly, the relative prevalence of genes causing only non-syndromic mental retardation (IL1RAPL1, TM4SF2, ZNF41, FTSJ1, DLG3, FACL4, PAK3, ARHGEF6, FMR2, and GDI) is summarised. Thirdly, the problem of recurrence risk where a molecular genetics diagnosis has not been made and what proportion of the male excess of mental retardation is due to monogenic disorders of the X chromosome are discussed.

  16. Reduced Cortical Thickness in Mental Retardation

    PubMed Central

    Wang, Chao; Wang, Jiaojian; Zhang, Yun; Yu, Chunshui; Jiang, Tianzi

    2011-01-01

    Mental retardation is a developmental disorder associated with impaired cognitive functioning and deficits in adaptive behaviors. Many studies have addressed white matter abnormalities in patients with mental retardation, while the changes of the cerebral cortex have been studied to a lesser extent. Quantitative analysis of cortical integrity using cortical thickness measurement may provide new insights into the gray matter pathology. In this study, cortical thickness was compared between 13 patients with mental retardation and 26 demographically matched healthy controls. We found that patients with mental retardation had significantly reduced cortical thickness in multiple brain regions compared with healthy controls. These regions include the bilateral lingual gyrus, the bilateral fusiform gyrus, the bilateral parahippocampal gyrus, the bilateral temporal pole, the left inferior temporal gyrus, the right lateral orbitofrontal cortex and the right precentral gyrus. The observed cortical thickness reductions might be the anatomical substrates for the impaired cognitive functioning and deficits in adaptive behaviors in patients with mental retardation. Cortical thickness measurement might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications. PMID:22216343

  17. Advances in X-linked mental retardation.

    PubMed

    Stevenson, Roger E

    2005-12-01

    Mutations in genes on the X chromosome rival chromosome aberrations as a cause of mental retardation. Progress in the clinical and molecular delineation of X-linked mental retardation has outpaced progress in understanding autosomal mental retardation. This is a result in large part of the identification of large families in which mental retardation has segregated in an X-linked pattern and the greater ease with which molecular technologies can be applied to hemizygosity in males. About one-third of the estimated 165 genes associated with syndromal mutations of genes on the X chromosome and one-fourth of the estimated 100 genes associated with nonsyndromal mutations of genes on the X chromosome have been identified. In a number of instances, the same gene is responsible for syndromal and nonsyndromal mutations of genes on the X chromosome. The molecular delineation of mutations of genes on the X chromosome has allowed certain conditions to be lumped together on the basis of allelism and has caused others that appear clinical similar to remain separate. The clinical and molecular advances have allowed X-linked mental retardation to be more clearly delineated, have provided the means of confirmatory laboratory testing, and have ushered in an era of carrier testing, prenatal diagnosis, and prevention strategies.

  18. Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers.

    PubMed

    Davison, Glen; Marchbank, Tania; March, Daniel S; Thatcher, Rhys; Playford, Raymond J

    2016-08-01

    Heavy exercise causes gut symptoms and, in extreme cases, heat stroke that is due to the increased intestinal permeability of luminal toxins. We examined whether zinc carnosine (ZnC), a health-food product taken alone or in combination with bovine colostrum (a natural source of growth factors), would moderate such effects. Eight volunteers completed a 4-arm, double-blind, placebo-controlled crossover protocol (14 d of placebo, ZnC, colostrum, or ZnC plus colostrum) before undertaking standardized exercise 2 and 14 d after the start of treatment. Changes in epithelial resistance, apoptosis signaling molecules, and tight junction (TJ) protein phosphorylation in response to a 2°C rise in body temperature were determined with the use of Caco-2 and HT29 intestinal cells. Body temperature increased 2°C, and gut permeability (5-h urinary lactulose:rhamnose ratios) increased 3-fold after exercise (from 0.32 ± 0.016 baseline to 1.0 ± 0.017 at 14 d; P < 0.01). ZnC or colostrum truncated the rise by 70% after 14 d of treatment. The combination treatment gave an additional benefit, and truncated exercise induced increase at 2 d (30% reduction; P < 0.01). A 2°C temperature rise in in vitro studies caused the doubling of apoptosis and reduced epithelial resistance 3-4-fold. ZnC or colostrum truncated these effects (35-50%) with the greatest response seen with the combination treatment (all P < 0.01). Mechanisms of action included increasing heat shock protein 70 and truncating temperature-induced changes in B cell leukemia/lymphoma-2 associated X protein α and B cell lymphoma 2. ZnC also increased total occludin and reduced phosphorylated tyrosine claudin, phosphorylated tyrosine occludin, and phosphorylated serine occludin, thereby enhancing the TJ formation and stabilization. ZnC, taken alone or with colostrum, increased epithelial resistance and the TJ structure and may have value for athletes and in the prevention of heat stroke in military personnel. This trial was

  19. [The inhibitory effect and the mechanism of ethanol absorption by L-carnosine zinc complex in mouse gastrointestinal tract].

    PubMed

    Natsuki, R; Nozaki, M; Fujimura, H

    1998-12-01

    The effect of L-carnosine-zinc complex(Car-Zn) on ethanol absorption was investigated after oral administration(adm) to mice. One hour after oral adm of Car-Zn, and 14C-ethanol was given orally or intraperitoneally(i.p.). After passage of time, the blood was drawn from the tail vein, and 14C-radioactivities determined. The Car-Zn showed a dose-dependent inhibition of the appearance of 14C-radioactivities in blood following oral 14C-ethanol loading, while Zn acetate did not induce any alteration as compared with control. Car-Zn pretreatment did not induce any change in the blood 14C-radioactivity when ethanol was given i.p. The 14C-radioactivity and zinc in gastrointestinal tract after oral adm of Car-Zn and 14C-ethanol showed significantly higher levels than those of control for 7 hr. Distribution of 14C-radioactivities in other organs of Car-Zn treated mice were lower than those of control 3 hr after adm, while it was similar or higher than those of control 7 hr after adm. The excretions of 14C-radioactivity through expiration in Car-Zn group was a lower than that of control. Also, the urinary and fecal excretions of 14C-radioactivity were low values at 5.0% and 0.5% of the administered dose 72 hr after adm, respectively. Also, the 14C-radioactivities remaining in the organs did not detect or were very low values. In vitro study, Car-Zn stimulated the metabolism of ethanol to acetaldehyde and acetic acid in 9,000 g supernatant of small intestine. The major route of excretions of 14C-radioactivity may be excreted into the expired air. The results suggest that Car-Zn shows a long-term adhesive and permeable action on gastrointestinal tract in the mouse; as a result, this may inhibited ethanol absorption.

  20. Pallister-Killian syndrome: case report with pineal tumor.

    PubMed

    Mauceri, L; Sorge, G; Incorpora, G; Pavone, L

    2000-11-06

    Pallister-Killian syndrome, an aneuploidy syndrome, comprises a characteristic facial appearance, mental retardation, and multiple other anomalies. It is caused by mosaicism with a supernumerary isochromosome 12p. This chromosomal abnormality has been reported also in human germ cell tumors. We report on a 15-year-old girl with Pallister-Killian syndrome and pineal tumor.

  1. Glycyl-histidyl-lysine (GHK) is a quencher of alpha,beta-4-hydroxy-trans-2-nonenal: a comparison with carnosine. insights into the mechanism of reaction by electrospray ionization mass spectrometry, 1H NMR, and computational techniques.

    PubMed

    Beretta, Giangiacomo; Artali, Roberto; Regazzoni, Luca; Panigati, Monica; Facino, Roberto Maffei

    2007-09-01

    Histidine-containing oligopeptides are currently studied as detoxifying agents against cytotoxic alpha,beta-unsaturated aldehydes (prototype: 4-hydroxy-2-nonenal, HNE), electrophilic end products formed by decomposition of omega-6 polyunsaturated fatty acids, associated with severe pathologies such as diabetes, nephropathy, retinopathy, and neurodegenerative diseases. This study evaluated the quenching reaction against HNE of the endogenous tripeptide l-glycyl- l-histidyl- l-lysine (GHK), an oligopeptide discovered to be a growth-modulating factor and also a strong activator of wound healing. We first evaluated the HNE consumption (50 microM, HPLC-UVDAD method) in the presence of GHK (1 mM) in physiomimetic conditions (phosphate buffer, pH 7.4) and confirmed GHK/HNE adduct formation by mass spectrometric analysis (ESI-MS/MS) and (1)H NMR analyses. These results indicated that GHK was an effective quencher of HNE, although significantly less potent than the reference compound carnosine, and that HNE modulation by GHK can contribute to the satisfactory outcome of the wound-healing process. In the second part of the study, we investigated the quenching reaction between GHK and HNE, in parallel to carnosine, using (1)H NMR and computational analyses. At a mechanistic level, this explained the different reactivity of the two peptides: (i) The greater stability of the macrocyclic intermediate HNE/carnosine was compared to HNE/GHK. (ii) GHK in solution has a quasi-folded conformation due to the interaction of four intramolecular hydrogen bonds, three of which need to be broken for the transition state to form (energy barrier, approximately 20 kcal/mol). By contrast, carnosine, with an extended conformation and only one hydrogen bond, requires less energy to reach the transition state ( approximately 7 kcal/mol). (iii) The different stereoelectronic features of the transition state lead to the intramolecular Michael reaction, that is, the favorable superimposition of

  2. Flame-retardant carbon nanotube films

    NASA Astrophysics Data System (ADS)

    Janas, Dawid; Rdest, Monika; Koziol, Krzysztof K. K.

    2017-07-01

    We have demonstrated fire-retardancy properties of a polymer matrix-free CNT film for the first time. As compared with classical fire-retardant materials such as Kevlar, Twaron or Nomex, the CNT film showed a spectrum of advantages. The material is lightweight, flexible and well-adherent to even the most complicated shapes. The results have showed that by using CNTs for fire-retardancy we can extend the operational time almost two-fold, what makes CNTs a much better protection than the solutions employed nowadays. We believe that among other great properties of CNT, their macroscopic assemblies such as CNT films show significant potential for becoming a fire protective coating, which exhibits high performance in not sustaining fire.

  3. [Drug dependence, smoking and fetal growth retardation].

    PubMed

    Hanzal, E; Hoffmann, G; Kölbl, H

    1992-07-01

    Illicit drug abuse, as well as smoking, are known risk factors in the development of intrauterine growth retardation. In an attempt to clarify the influence of these two aetiological factors, a retrospective analysis was carried out. 35 drug- and nicotine-addicted pregnant women were compared to 104 smokers and 101 non-smoking controls with regard to foetal outcome. Relative risk estimates for intrauterine growth retardation of the drug and nicotine group were 3.14 (95% confidence limits 1.88-5.25; p = 0.0001) whereas the smoking group had 1.39 (95% confidence limits 0.96-2.02; p = 0.0482) compared to non-smoking controls. The foetal outcome was best in the latter group: children of drug-addicted mothers had a considerably higher morbidity and mortality rate. This study shows an almost threefold risk for intrauterine growth retardation in drug-addicts who smoke, compared to nicotine abuse alone.

  4. Biodegradation of brominated and organophosphorus flame retardants.

    PubMed

    Waaijers, Susanne L; Parsons, John R

    2016-04-01

    Brominated flame retardants account for about 21% of the total production of flame retardants and many of these have been identified as persistent, bioaccumulative and toxic. Nevertheless, debromination of these chemicals under anaerobic conditions is well established, although this can increase their toxicity. Consequently, the production and use of these chemicals has been restricted and alternative products have been developed. Many of these are brominated compounds and share some of the disadvantages of the chemicals they are meant to replace. Therefore, other, nonbrominated, flame retardants such as organophosphorus compounds are also being used in increasing quantities, despite the fact that knowledge of their biodegradation and environmental fate is often lacking. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Plasma impregnation of wood with fire retardants

    NASA Astrophysics Data System (ADS)

    Pabeliña, Karel G.; Lumban, Carmencita O.; Ramos, Henry J.

    2012-02-01

    The efficacy of chemical and plasma treatments with phosphate and boric compounds, and nitrogen as flame retardants on wood are compared in this study. The chemical treatment involved the conventional method of spraying the solution over the wood surface at atmospheric condition and chemical vapor deposition in a vacuum chamber. The plasma treatment utilized a dielectric barrier discharge ionizing and decomposing the flame retardants into innocuous simple compounds. Wood samples are immersed in either phosphoric acid, boric acid, hydrogen or nitrogen plasmas or a plasma admixture of two or three compounds at various concentrations and impregnated by the ionized chemical reactants. Chemical changes on the wood samples were analyzed by Fourier transform infrared spectroscopy (FTIR) while the thermal changes through thermo gravimetric analysis (TGA). Plasma-treated samples exhibit superior thermal stability and fire retardant properties in terms of highest onset temperature, temperature of maximum pyrolysis, highest residual char percentage and comparably low total percentage weight loss.

  6. "Idiopathic" mental retardation and new chromosomal abnormalities.

    PubMed

    Galasso, Cinzia; Lo-Castro, Adriana; El-Malhany, Nadia; Curatolo, Paolo

    2010-02-14

    Mental retardation is a heterogeneous condition, affecting 1-3% of general population. In the last few years, several emerging clinical entities have been described, due to the advent of newest genetic techniques, such as array Comparative Genomic Hybridization. The detection of cryptic microdeletion/microduplication abnormalities has allowed genotype-phenotype correlations, delineating recognizable syndromic conditions that are herein reviewed. With the aim to provide to Paediatricians a combined clinical and genetic approach to the child with cognitive impairment, a practical diagnostic algorithm is also illustrated. The use of microarray platforms has further reduced the percentage of "idiopathic" forms of mental retardation, previously accounted for about half of total cases. We discussed the putative pathways at the basis of remaining "pure idiopathic" forms of mental retardation, highlighting possible environmental and epigenetic mechanisms as causes of altered cognition.

  7. Mentally retarded workers' reactions to their jobs.

    PubMed

    Shapira, Z; Cnaan, R A; Cnaan, A

    1985-09-01

    Reactions of 34 mentally retarded employees to their jobs were examined in a field study conducted at a sheltered workshop. Three experienced social workers observed a group of retarded employees whose job was assembling toys. The workers were then interviewed on their perceptions of and reactions to their job characteristics and supervision, and these were related to performance data that included performance time, productivity, and effort ratings. Results showed that performance measures were related to perceived job characteristics and that growth-need strength (people's needs for personal development and achievement) affected these relationships. On the basis of these results, we discussed the feasibility of using motivation models for retarded workers that were designed for nonretarded workers.

  8. [Considerations of psychopathology in mental retardation].

    PubMed

    Masi, G

    1994-06-01

    There is a high incidence of psychiatric disorders in mentally retarded subjects: one third to two thirds of mentally retarded subjects exhibit psychiatric disorders, a proportion which is much higher than that found in subjects with normal intelligence. The issue is to clarify the nature of the relationship between cognitive and psychiatric disorders (generally analyzed in a dichotomous approach). A way to analyze the phenomenon is to consider a psychopathological approach, which can define the underlying mechanisms responsible for this incidence. The aim of this paper is to analyze the explicatory value of deficient cognitive development, as the main factor determining a specific personality organization. Direct and indirect effects of cognitive impairment on the development of personality disorders are described: the first, in terms of how cognitive deficit (i.e. severity, homogeneity in several cognitive domains, pattern of development) disorganizes personality; the second, in terms of impact that cognitive deficit could have on the child's relationship with the external world, especially with the mother. In order to illustrate these viewpoint, the paper discusses the role of cognitive functions in the development of personality. Specifically, the way the normal child processes his perceptual and motor experiences is analyzed, that is pursuit of new causal links in his knowledge seeking activity of mastering the world. The child's primitive relationship with the world is then aimed at learning, exploring and searching for new causal links. In the light of these considerations, what the child with Mental Retardation experiences is discussed. A series of psychopathological mechanisms in Mental Retardation are postulated. The organization of the Mentally Retarded child's internal world is described, as reflected in Rorschach protocols, which outline a chaotic and primitive internal world, but with a specificity of its own. Finally, the paper discusses the

  9. High resolution magic angle spinning NMR spectroscopy reveals that pectoralis muscle dystrophy in chicken is associated with reduced muscle content of anserine and carnosine.

    PubMed

    Sundekilde, Ulrik K; Rasmussen, Martin K; Young, Jette F; Bertram, Hanne Christine

    2017-02-15

    Increased incidences of pectoralis muscle dystrophy are observed in commercial chicken products, but the muscle physiological causes for the condition remain to be identified. In the present study a high-resolution magic angle spinning (HR-MAS) proton ((1)H) NMR spectroscopic examination of intact pectoralis muscle samples (n=77) were conducted to explore metabolite perturbations associated with the muscle dystrophy condition for the very first time. Both in chicken with an age of 21 and 31days, respectively, pectoralis muscle dystrophy was associated with a significantly lower content of anserine (p=0.034), carnosine (p=0.019) and creatine (p=0.049). These findings must be considered intriguing as they corroborate that characteristic muscle di-peptides composed of β-alanine and histidine derivatives such as anserine are extremely important in homeostasis of contractile muscles as a results of their role as buffering, anti-oxidative, and anti-glycation capacities.

  10. Hypothyroidism Enhances Tumor Invasiveness and Metastasis Development

    PubMed Central

    Martínez-Iglesias, Olaia; García-Silva, Susana; Regadera, Javier; Aranda, Ana

    2009-01-01

    Background Whereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development, the relationship between thyroid hormone levels and human cancer is a controversial issue. It has been reported that hypothyroidism might be a possible risk factor for liver and breast cancer in humans, but a lower incidence of breast carcinoma has been also reported in hypothyroid patients Methodology/Principal Findings In this work we have analyzed the influence of hypothyroidism on tumor progression and metastasis development using xenografts of parental and TRβ1–expressing human hepatocarcinoma (SK-hep1) and breast cancer cells (MDA-MB-468). In agreement with our previous observations tumor invasiveness and metastasis formation was strongly repressed when TRβ–expressing cells were injected into euthyroid nude mice. Whereas tumor growth was retarded when cells were inoculated into hypothyroid hosts, tumors had a more mesenchymal phenotype, were more invasive and metastatic growth was enhanced. Increased aggressiveness and tumor growth retardation was also observed with parental cells that do not express TRs. Conclusions/Significance These results show that changes in the stromal cells secondary to host hypothyroidism can modulate tumor progression and metastatic growth independently of the presence of TRs on the tumor cells. On the other hand, the finding that hypothyroidism can affect differentially tumor growth and invasiveness can contribute to the explanation of the confounding reports on the influence of thyroidal status in human cancer. PMID:19641612

  11. Oral Administration of Forskolin, Homotaurine, Carnosine, and Folic Acid in Patients with Primary Open Angle Glaucoma: Changes in Intraocular Pressure, Pattern Electroretinogram Amplitude, and Foveal Sensitivity.

    PubMed

    Mutolo, Maria Giulia; Albanese, Giuseppe; Rusciano, Dario; Pescosolido, Nicola

    2016-04-01

    To evaluate the effects of a food supplement containing forskolin, homotaurine, carnosine, folic acid, vitamins B1, B2, B6, and magnesium in patients with primary open angle glaucoma (POAG) already in treatment and compensated by intraocular pressure (IOP)-lowering drugs, during a period of 12 months. Twenty-two patients (44 eyes) with POAG, with their IOP compensated by topical drugs, were enrolled and randomly assigned to the food supplement or control treatment group. The additional food supplement treatment consisted of 2 tablets per day (1 in the morning, 1 in the evening) given for 1 year of a balanced association of homotaurine, Coleus forskohlii root extract, L-carnosine, folic acid, vitamins B1, B2, B6, and magnesium. Pattern Electroretinogram (PERG) amplitude, foveal sensitivity obtained with the visual field analyzer frequency doubling technology, and IOP were detected at enrollment (T0), 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4). We observed in treated patients a significant further decrease of IOP and an improvement of PERG amplitude at 6, 9, and 12 months, and foveal sensitivity at 12 months. All values remained substantially stable in control patients. The results of the present pilot study indicate that the components of the food supplement reach the eye in a detectable manner, as evidenced by the effects on the IOP. Moreover, they suggest a short-term neuroactive effect, as indicated by the improvement of PERG amplitude and foveal sensitivity in treated, but not in control patients.

  12. Aerobic Fitness for the Moderately Retarded.

    ERIC Educational Resources Information Center

    Bauer, Dan

    1981-01-01

    Intended for physical education teachers, the booklet offers ideas for incorporating aerobic conditioning into programs for moderately mentally retarded students. An explanation of aerobic fitness and its benefits is followed by information on initiating a fitness program with evaluation of height, weight, body fat, resting heart rate, and…

  13. PARENT ATTITUDES IN REARING MENTALLY RETARDED CHILDREN.

    ERIC Educational Resources Information Center

    LEICHMAN, NATHAN S.; WILLENBERG, ERNEST P.

    POSITIVE AND NEGATIVE ASPECTS OF REARING MENTAL RETARDATES WERE IDENTIFIED AND MEASURED DURING THIS STUDY BY EXAMINATIONS OF PARENTAL ATTITUDES AND HOW THESE ATTITUDES OFTEN AFFECT THE DAILY BEHAVIOR AND LEARNING READINESS OF CHILDREN WHILE IN SCHOOL. BEHAVIORAL FACTORS OF THE INDIVIDUAL CHILD WERE ANALYZED AND COMPARED WITH STATISTICS COVERING…

  14. Automatic Memory Processes in Mentally Retarded Persons.

    ERIC Educational Resources Information Center

    Stein, Debra Kosteski; And Others

    Automatic memory processes were investigated in 10 mild and moderately retarded persons (21 years old) and in 10 chronological age-matched college level and 10 mental age-matched elementary grade control subjects through use of a frequency estimation task. This task required the subjects to view a series of slides, then estimate how many times…

  15. BROMINATED FLAME RETARDANTS: WHY DO WE CARE?

    EPA Science Inventory

    Brominated flame retardants (BFRs) save lives and property by preventing the spread of fires or delaying the time of flashover, enhancing the time people have to escape. The worldwide production of BFRs exceeded 200,000 metric tons in 2003 placing them in the high production vol...

  16. Teaching Mending Skills to Mentally Retarded Adolescents.

    ERIC Educational Resources Information Center

    Cronin, Kathleen A.; Cuvo, Anthony J.

    1979-01-01

    A task analysis model for analyzing and teaching community living skills to the mentally handicapped was developed and validated with five moderately retarded youths (ages 17 to 20 years) who were taught mending skills (sewing hems, buttons, and seams). (Author/DLS)

  17. The Deaf Mentally Retarded: Understanding Their World.

    ERIC Educational Resources Information Center

    Sonies, Barbara C.

    Described photographically and textually in the brochure are the educational, vocational, and social needs of deaf mentally retarded (DMR) children and adults. The DMR person is discussed in relation to the double handicap which precludes educational benefits from a traditional program, secondary problems such as visual handicaps, and incidence…

  18. Puberty in the Girl Who is Retarded.

    ERIC Educational Resources Information Center

    Pattullo, Ann

    Designed to help mothers of mentally retarded girls deal with the problems and concerns of puberty, the booklet provides information on physical and emotional changes, menstruation, masturbation, heterosexual behavior, contraception, protection against sexual aggression, the possibilities of marriage, and additional sources of information.…

  19. Implementing Programs for Trainable Mentally Retarded Children.

    ERIC Educational Resources Information Center

    Indiana State Dept. of Public Instruction, Indianapolis.

    Guidelines for the development of programs for trainable mentally retarded children are presented. Major task areas identified are the family group, communication skills, physical development, socialization, recreational interests and skills, and preparation for work oriented activity. Six papers are presented: precision teaching and behavior…

  20. HEALTH EFFECTS OF BROMINATED FLAME RETARDANTS (BFRS)

    EPA Science Inventory

    Abstract Brominated flame retardant use has increased dramatically in order to provide fire safety to consumers. However, there is growing concern about widespread environmental contamination and potential health risks from some of these products. The most used products...