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Sample records for carnosine

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

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Supuran, Claudiu T; Scozzafava, Andrea

    2002-01-01

    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....

  2. Reaction of carnosine with aged proteins: another protective process?

    Science.gov (United States)

    Hipkiss, Alan R; Brownson, Carol; Bertani, Mariana F; Ruiz, Emilio; Ferro, Albert

    2002-04-01

    Cellular aging is often associated with an increase in protein carbonyl groups arising from oxidation- and glycation-related phenomena and suppressed proteasome activity. These "aged" polypeptides may either be degraded by 20S proteasomes or cross-link to form structures intractable to proteolysis and inhibitory to proteasome activity. Carnosine (beta-alanyl-l-histidine) is present at surprisingly high levels (up to 20 mM) in muscle and nervous tissues in many animals, especially long-lived species. Carnosine can delay senescence in cultured human fibroblasts and reverse the senescent phenotype, restoring a more juvenile appearance. As better antioxidants/free-radical scavengers than carnosine do not demonstrate these antisenescent effects, additional properties of carnosine must contribute to its antisenescent activity. Having shown that carnosine can react with protein carbonyls, thereby generating "carnosinylated" polypeptides using model systems, we propose that similar adducts are generated in senescent cells exposed to carnosine. Polypeptide-carnosine adducts have been recently detected in beef products that are relatively rich in carnosine, and carnosine's reaction with carbonyl functions generated during amino acid deamidation has also been described. Growth of cultured human fibroblasts with carnosine stimulated proteolysis of long-labeled proteins as the cells approached their "Hayflick limit," consistent with the idea that carnosine ameliorates the senescence-associated proteolytic decline. We also find that carnosine suppresses induction of heme-oxygenase-1 activity following exposure of human endothelial cells to a glycated protein. The antisenescent activity of the spin-trap agent alpha-phenyl-N-t-butylnitrone (PBN) towards cultured human fibroblasts resides in N-t-butyl-hydroxylamine, its hydrolysis product. As hydroxylamines are reactive towards aldehydes and ketones, the antisenescent activity of N-t-butyl-hydroxylamine and other hydroxylamines may

  3. Effectiveness of carnosine on disturbed electrolytes homeostasis ...

    African Journals Online (AJOL)

    We aimed to assess the effect of well known antioxidant carnosine on disturbed plasma and intraerythrocytes electrolytes and Na+-K+-ATPase activity by cisplatin. 24 male albino Wistar rats were selected and divided into 4 groups: Group I = untreated control; Group II = cisplatin control (received cisplatin at a dose of 3 mg/ ...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Barbora de Courten

    Full Text Available 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.

  6. Carnosine may reduce lung injury caused by radiation therapy.

    Science.gov (United States)

    Guney, Yildiz; Turkcu, Ummuhani Ozel; Hicsonmez, Ayse; Andrieu, Meltem Nalca; Guney, H Zafer; Bilgihan, Ayse; Kurtman, Cengiz

    2006-01-01

    Ionising radiation is known one of the most effective tools in the therapy of cancer but in many thoracic cancers, the total prescribed dose of radiation that can be safely administered to the target volume is limited by the risk of complications arising in the normal lung tissue. One of the major reasons for cellular injury after radiation is the formation of reactive oxygen species (ROS). Radiation pneumonitis is an acute phase side-effect which generally subsides after a few weeks and is followed by a chronic phase characterized by inflammation and fibrosis, that can develop months or years after irradiation. Carnosine is a dipeptide composed by the amino acids beta-histidine and l-alanine. The exact biological role of carnosine is not totally understood, but several studies have demonstrated that it possesses strong and specific antioxidant properties, protects against radiation damage,and promotes wound healing. The antioxidant mechanism of carnosine is attributed to its chelating effect against metal ions, superoxide dismutase (SOD)-like activity, ROS and free radicals scavenging ability . Either its antioxidant or anti-inflammatuar properties, we propose that carnosine ameliorates irradiation-induced lung injury. Thus, supplementing cancer patients to whom applied radiation therapy with carnosine, may provide an alleviation of the symptoms due to radiation-induced lung injury. This issue warrants further studies.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  9. Influence of Skeletal Muscle Carnosine Content on Fatigue during Repeated Resistance Exercise in Recreationally Active Women

    Science.gov (United States)

    Varanoske, Alyssa N.; Hoffman, Jay R.; Church, David D.; Baker, Kayla M.; Dodd, Sarah J.; Coker, Nicholas A.; Oliveira, Leonardo P.; Dawson, Virgil L.; Stout, Jeffrey R.

    2017-01-01

    Carnosine is a naturally occurring intramuscular dipeptide that is thought to attenuate fatigue during high-intensity exercise. Carnosine content is influenced by various factors, including gender and diet. Despite research reporting that carnosine content is lower in women compared to men and lower in vegetarians compared to omnivores, no investigations have examined carnosine content in women based on dietary protein intake and its effect on muscle fatigue. Twenty recreationally active women were assigned to either a high (HI; n = 5), moderate (MOD; n = 10), or low (LO; n = 5) group based upon intramuscular carnosine content of the vastus lateralis. Each participant underwent two unilateral maximal voluntary isometric contractions (MVIC) of the knee extensors separated by an isokinetic exercise protocol consisting of five sets of 50 repeated maximal unilateral contractions. Magnitude-based inferences were used to analyze group differences. Percent decline in rate of force development and peak torque (PT) during the MVICs and changes in PT and mean torque during the muscle-fatiguing protocol were lower in HI compared to both MOD and LO. Additionally, absolute and relative dietary protein intake were greater in HI compared to MOD or LO. Results indicated that greater intramuscular carnosine content was reflective of greater dietary protein intake and that individuals with higher carnosine content displayed a greater attenuation of fatigue compared to those with lower carnosine. PMID:28880219

  10. L-Carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts

    International Nuclear Information System (INIS)

    Shao Lan; Li Qinghuan; Tan Zheng

    2004-01-01

    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

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ketabi, Sepideh, E-mail: sepidehketabi@yahoo.com [Department of Chemistry, East Tehran Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Rahmani, Leila [Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Falavarjan (Iran, Islamic Republic of)

    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 NH{sub 3}{sup +} 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 NH{sub 3}{sup +} produced the most stable complex in aqueous solution. This tendency could be observed in gas and liquid phase similarly. - Highlights: • Carnosine dipeptide (an anti-ageing compound and neuron protection in relation to Alzheimer's dementia) can be stabilized against degradation by binding to Carbon nanotube as a transporter. • Functionalization with carnosine increases the solubility of carbon nanotube considerably and so such systems hold great potential in the field of nanomedicine. • Complexation free energies confirm the interaction of carnosine dipeptide with carbon nanotube in aqueous solution. • Carnosine zwitter ion via NH{sub 3}{sup +} have the most interaction energy with carbon nanotube.

  13. Antioxidative activity of carnosine in gamma irradiated ground beef and beef patties

    International Nuclear Information System (INIS)

    Badr, H.M.

    2005-01-01

    The activity of carnosine as a natural antioxidant in gamma irradiated ground beef and beef patties was studied. Samples of ground beef, in absence and presence of 0.5% or 1.0% carnosine, as well as raw and cooked beef patties prepared with 1.5% salt (NaCl), in absence and presence of 0.5% or 1.0% carnosine, were gamma irradiated at doses of 2 and 4 KGy. Then, the extent of oxidation in irradiated and non-irradiated samples of ground beef and raw beef patties was determined during refrigerated (4± 1 degree C) and frozen (-18 degree C) storage, while was determined for cooked beef patties during refrigerated storage only. Moreover, the determination of metmyoglobin (MetMb) accumulation and sensory evaluation for the visual colour were carried out for samples of ground beef and raw patties. The results indicated that salt or salt and cooking can accelerate the oxidative processes and significantly increased the peroxide value (PV) and thiobarbituric acid reactive substances (TBARS) in the prepared non-irradiated samples. However, salt slowed down the accumulation of MetMb in raw patties. Irradiation treatments and storage in absence of carnosine significantly increased with higher rates the PV and TBARS in salted or salted and cooked beef samples. Moreover, irradiation and storage significantly increased the formation of MetMb in ground beef and raw patties in absence of carnosine. Addition of carnosine significantly reduced the oxidative processes and MetMb formation (proportionally to the used concentration) in samples post irradiation and during storage. Furthermore, carnosine exerted significant efficacy in maintaining an acceptable visual red colour post irradiation and during storage of ground beef and raw patties. These results demonstrate that carnosine can be successfully used as a natural antioxidant to increase the oxidative stability in gamma irradiated raw and cooked meat products

  14. Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage

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    Jie Deng

    2018-04-01

    Full Text Available Oxidative DNA damage in bone marrow cells is the main side effect of chemotherapy drugs including cyclophosphamide (CTX. However, not all antioxidants are effective in inhibiting oxidative DNA damage. In this study, we report the beneficial effect of carnosine (β-alanyl-l-histidine, a special antioxidant with acrolein-sequestering ability, on CTX-induced bone marrow cell suppression. Our results show that carnosine treatment (100 and 200 mg/kg, i.p. significantly inhibited the generation of reactive oxygen species (ROS and 8-hydroxy-2′-deoxyguanosine (8-oxo-dG, and decreased chromosomal abnormalities in the bone marrow cells of mice treated with CTX (20 mg/kg, i.v., 24 h. Furthermore, carnosine evidently mitigated CTX-induced G2/M arrest in murine bone marrow cells, accompanied by reduced ratios of p-Chk1/Chk1 and p-p53/p53 as well as decreased p21 expression. In addition, cell apoptosis caused by CTX was also suppressed by carnosine treatment, as assessed by decreased TUNEL-positive cell counts, down-regulated expressions of Bax and Cyt c, and reduced ratios of cleaved Caspase-3/Caspase-3. These results together suggest that carnosine can protect murine bone marrow cells from CTX-induced DNA damage via its antioxidant activity. Keywords: Carnosine, Cyclophosphamide, Oxidative DNA damage, Sister chromatid exchange, Apoptosis, Cell cycle arrest

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

    Science.gov (United States)

    Renner, Christof; Zemitzsch, Nadine; Fuchs, Beate; Geiger, Kathrin D; Hermes, Matthias; Hengstler, Jan; Gebhardt, Rolf; Meixensberger, Jürgen; Gaunitz, Frank

    2010-01-06

    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. 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 microl 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. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pavlos, Dimitrios; Petropouleas, Panayiotis; Hatzipanayioti, Despina, E-mail: stambaki@chem.uoa.gr

    2015-11-05

    Highlights: • Study on models of neutral cations and anions of carnosine at the B3LYP/TZVP level. • The {sup 1}O{sub 2}-adducts of these models resulted in oxygenated carnosine. • Theoretical parameters correlated to experimental results for carn and carn-H{sub 2}O{sub 2}. • Theoretical models of Nickel-carn complexes have been investigated. • Isolation and characterization of the solid [Ni(carn){sub 2}(H{sub 2}O){sub 5}] have been performed. - Abstract: 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 {sup 1}O{sub 2}, may lead to oxygenated species. The theoretical spectroscopic parameters have been correlated to our experimental results. The effect of H{sub 2}O{sub 2} 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){sub 2}(H{sub 2}O){sub 5}], the COO−, N{sub π} and/or NH{sub 2} were bonded. When H{sub 2}O{sub 2} 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.

  17. Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress.

    Science.gov (United States)

    Ozel Turkcu, Ummuhani; Bilgihan, Ayşe; Biberoglu, Gursel; Mertoglu Caglar, Oznur

    2010-06-01

    Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.

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

    Directory of Open Access Journals (Sweden)

    Stephanie P Cartwright

    Full Text Available 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.

  19. Concentrations in beef and lamb of taurine, carnosine, coenzyme Q(10), and creatine.

    Science.gov (United States)

    Purchas, R W; Rutherfurd, S M; Pearce, P D; Vather, R; Wilkinson, B H P

    2004-03-01

    Levels of taurine, carnosine, coenzyme Q(10), and creatine were measured in beef liver and several muscles of beef and lamb and in cooked and uncooked meat. The amino acid taurine has numerous biological functions, the dipeptide carnosine is a buffer as well as an antioxidant, coenzyme Q(10) is also an antioxidant present within mitochondria, and creatine along with creatine phosphate is involved with energy metabolism in muscle. Large differences were shown for all compounds between beef cheek muscle (predominantly red fibres) and beef semitendinosus muscle (mainly white fibres), with cheek muscle containing 9.9 times as much taurine, and 3.2 times as much coenzyme Q(10), but only 65% as much creatine and 9% as much carnosine. Levels in lamb relative to beef semitendinosus muscles were higher for taurine but slightly lower for carnosine, coenzyme Q(10) and creatine. Values for all the compounds varied significantly between eight lamb muscles, possibly due in part to differences in the proportion of muscle fibre types. Slow cooking (90 min at 70 °C) of lamb longissimus and semimembranosus muscles led to significant reductions in the content of taurine, carnosine, and creatine (Plamb, but that these levels vary between muscles, between animals, and with cooking.

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

    International Nuclear Information System (INIS)

    Oezdemir, Mahir S; Reyngoudt, Harmen; Deene, Yves de; Sazak, Hakan S; Fieremans, Els; Delputte, Steven; D'Asseler, Yves; Derave, Wim; Lemahieu, Ignace; Achten, Eric

    2007-01-01

    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 pH i 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 ( 1 H 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 1 H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo

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

    Directory of Open Access Journals (Sweden)

    Meixensberger Jürgen

    2010-01-01

    Full Text Available Abstract 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 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.

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

    Directory of Open Access Journals (Sweden)

    Yao Shen

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  6. Unfolding the mechanism of cisplatin induced pathophysiology in spleen and its amelioration by carnosine.

    Science.gov (United States)

    Banerjee, Sharmistha; Sinha, Krishnendu; Chowdhury, Sayantani; Sil, Parames C

    2018-01-05

    cis-Diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic and is widely used for the treatment of various types of solid tumors. Bio-distribution of cisplatin to other organs due to poor targeting towards only cancer cells constitutes the backbone of cisplatin-induced toxicity. The adverse effect of this drug on spleen is not well characterized so far. Therefore, we have set our goal to explore the mechanism of the cisplatin-induced pathophysiology of the spleen and would also like to evaluate whether carnosine, an endogenous neurotransmitter and antioxidant, can ameliorate this pathophysiological response. We found a dose and time-dependent increase of the pro-inflammatory cytokine, TNF-α, in the spleen tissue of the experimental mice exposed to 10 and 20 mg/kg body weight of cisplatin. The increase in inflammatory cytokine can be attributed to the activation of the transcription factor, NF-ĸB. This also aids in the transcription of other pro-inflammatory cytokines and cellular adhesion molecules. Exposure of animals to cisplatin at both the doses resulted in ROS and NO production leading to oxidative stress. The MAP Kinase pathway, especially JNK activation, was also triggered by cisplatin. Eventually, the persistence of inflammatory response and oxidative stress lead to apoptosis through extrinsic pathway. Carnosine has been found to restore the expression of inflammatory molecules and catalase to normal levels through inhibition of pro-inflammatory cytokines, oxidative stress, NF-ĸB and JNK. Carnosine also protected the splenic cells from apoptosis. Our study elucidated the detailed mechanism of cisplatin-induced spleen toxicity and use of carnosine as a protective agent against this cytotoxic response. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Role of Carnosine and Melatonin in Ameliorating Cardiotoxicity of Titanium Dioxide Nanoparticles in the Rats

    Directory of Open Access Journals (Sweden)

    Nouf Al-Rasheed

    2015-08-01

    Full Text Available The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2 and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-α and Interleukin-6 (IL-6 was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

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

    NARCIS (Netherlands)

    Zhang, Shiqi; Ntasis, Emmanouil; Kabtni, Sarah; van den Born, Jaap; Navis, Gerjan; Bakker, Stephan J. L.; Kraemer, 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

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

    NARCIS (Netherlands)

    Albrecht, Thomas; Schilperoort, Maaike; Zhang, Shiqi; Braun, Jana D.; Qiu, Jiedong; Rodriguez, Angelica; Pastene, Diego O.; Kraemer, Bernhard K.; Koeppel, Hannes; Baelde, Hans; de Heer, Emile; Altomare, Alessandra Anna; 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  15. Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer.

    Directory of Open Access Journals (Sweden)

    Peter Arner

    Full Text Available 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.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.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.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.

  16. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Barbara Iovine

    Full Text Available 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

  17. The detox strategy in smoking comprising nutraceutical formulas of non-hydrolyzed carnosine or carcinine used to protect human health.

    Science.gov (United States)

    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

  18. Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial.

    Science.gov (United States)

    Blancquaert, Laura; Baguet, Audrey; Bex, Tine; Volkaert, Anneke; Everaert, Inge; Delanghe, Joris; Petrovic, Mirko; Vervaet, Chris; De Henauw, Stefaan; Constantin-Teodosiu, Dumitru; Greenhaff, Paul; Derave, Wim

    2018-04-01

    Balanced vegetarian diets are popular, although they are nearly absent in creatine and carnosine and contain considerably less carnitine than non-vegetarian diets. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist. We aimed to investigate the effect of transiently switching omnivores onto a vegetarian diet for 6 months on muscle and plasma creatine, carnitine and carnosine homeostasis. In a 6-month intervention, forty omnivorous women were ascribed to three groups: continued omnivorous diet (control, n 10), vegetarian diet without supplementation (Veg+Pla, n 15) and vegetarian diet combined with daily β-alanine (0·8-0·4 g/d) and creatine supplementation (1 g creatine monohydrate/d) (Veg+Suppl, n 15). Before (0 months; 0M), after 3 months (3M) and 6 months (6M), a fasted venous blood sample and 24-h urine was collected, and muscle carnosine content was determined by proton magnetic resonance spectroscopy (1H-MRS). Muscle biopsies were obtained at 0M and 3M. Plasma creatine and muscle total creatine content declined from 0M to 3M in Veg+Pla (P=0·013 and P=0·009, respectively), whereas plasma creatine increased from 0M in Veg+Suppl (P=0·004). None of the carnitine-related compounds in plasma or muscle showed a significant time×group interaction effect. 1H-MRS-determined muscle carnosine content was unchanged over 6M in control and Veg+Pla, but increased in Veg+Suppl in soleus (Pvegetarian diet in omnivorous women, which was ameliorated when accompanied by low-dose dietary creatine supplementation. Carnitine and carnosine homeostasis was unaffected by a 3- or 6-month vegetarian diet, respectively.

  19. HIIT Augments Muscle Carnosine in the Absence of Dietary Beta-Alanine Intake.

    Science.gov (United States)

    Salles Painelli, Vitor de; Nemezio, Kleiner Márcio; Jéssica, Ana; Franchi, Mariana; Andrade, Isabel; Riani, Luiz Augusto; Saunders, Bryan; Sale, Craig; Harris, Roger Charles; Gualano, Bruno; Artioli, Guilherme Giannini

    2018-06-21

    Cross-sectional studies suggest that training can increase muscle carnosine (MCarn), although longitudinal studies have failed to confirm this. A lack of control for dietary β-alanine intake or muscle fibre type shifting may have hampered their conclusions. The purpose of the present study was to investigate the effects of high-intensity interval training (HIIT) on MCarn. Twenty vegetarian men were randomly assigned to a control (CON; n=10) or HIIT (n=10) group. HIIT was carried out on a cycle ergometer for 12 weeks, with progressive volume (6-12 series) and intensity (140-170% lactate threshold [LT]). MCarn was quantified in whole-muscle and individual fibres; expression of selected genes (CARNS, CNDP2, ABAT, TauT and PAT1) and muscle buffering capacity in vitro (βmin vitro) were also determined. Exercise tests were performed to evaluate total work done (TWD), VO2max, ventilatory thresholds (VT) and LT. TWD, VT, LT, VO2max and βmin vitro were improved in the HIIT group (all P0.05). MCarn (in mmol·kg dry muscle) increased in the HIIT (15.8±5.7 to 20.6±5.3; p=0.012) but not the CON group (14.3±5.3 to 15.0±4.9; p=0.99). In type I fibres, MCarn increased in the HIIT (from 14.4±5.9 to 16.8±7.6; p=0.047) but not the CON group (from 14.0±5.5 to 14.9±5.4; p=0.99). In type IIa fibres, MCarn increased in the HIIT group (from 18.8±6.1 to 20.5±6.4; p=0.067) but not the CON group (from 19.7±4.5 to 18.8±4.4; p=0.37). No changes in gene expression were shown. In the absence of any dietary intake of β-alanine, HIIT increased MCarn content. The contribution of increased MCarn to the total increase in βmin vitro appears to be small.

  20. 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?

    Science.gov (United States)

    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

  1. l-Carnosine As an Adjunctive Therapy to Risperidone in Children with Autistic Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Hajizadeh-Zaker, Reihaneh; Ghajar, Alireza; Mesgarpour, Bita; Afarideh, Mohsen; Mohammadi, Mohammad-Reza; Akhondzadeh, Shahin

    2018-02-01

    This study aimed at investigating the efficacy and tolerability of l-carnosine as an add-on to risperidone in the management of children with autism. This was a 10-week, randomized, double-blind, placebo-controlled study. Seventy drug-free children aged 4-12 years old with a diagnosis of autism spectrum disorder (ASD), according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. (DSM-5) who had an Aberrant Behavior Checklist-Community (ABC-C) scale irritability subscale score of ≥12, entered the study. The patients were randomly assigned to l-carnosine (800 mg/day in 2 divided doses) or placebo in addition to risperidone titrated up to 2 mg/day (based on body weight) for 10 weeks. The children were assessed by using ABC-C at baseline and weeks 5 and 10 post-baseline. The primary outcome measure was the mean change in the ABC-C irritability subscale score, and other subscale scores were defined as secondary outcomes. Using the general linear model repeated measures, no significant effect was observed for time × treatment interaction on the irritability subscale scores. However, significant effect was detected on the hyperactivity/noncompliance subscale [F (1.62, 64.96) = 3.53, p-value = 0.044]. No significant improvements were obtained on the lethargy/social withdrawal, stereotypic behavior, and inappropriate speech subscale scores. Significantly greater score reduction in the hyperactivity/noncompliance subscale occurred in the l-carnosine group compared with the placebo group at the end of the trial. Extrapyramidal Symptom Rating Scale Scores and its changes did not differ between the two groups. The frequency of other side effects was not significantly different between the two groups. Although no significant difference was detected on the irritability subscale scores, l-carnosine add-on can improve hyperactivity/noncompliance subscales of the ABC-C rating scale in patients with ASD.

  2. 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.

    Science.gov (United States)

    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

  3. Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats.

    Science.gov (United States)

    Wang, Ai-Hong; Ma, Qian; Wang, Xin; Xu, Gui-Hua

    2018-02-01

    Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke.

  4. Effects of Dietary L-carnosine and Alpha-lipoic Acid on Growth Performance, Blood Thyroid Hormones and Lipid Profiles in Finishing Pigs

    Directory of Open Access Journals (Sweden)

    Yinghui Bao

    2015-10-01

    Full Text Available The present study was conducted to determine the effects of L-carnosine (LC and/or alpha-lipoic acid (ALA supplementation on growth performance, blood thyroid hormones and lipid profiles in finishing pigs. A total of 40 (Landrace×Yorkshire pigs with an initial body weight of 57.93±3.14 kg were randomly allocated to 4 experimental diets using a 2×2 factorial arrangement with 2 LC supplemental levels (0 or 0.1% and 2 ALA supplemental levels (0 or 0.03% in basal diets. The results showed that pigs fed LC-supplemented diets increased final live weight, average daily gain, and average daily feed intake compared to those of pigs fed without LC-supplemented diets (p0.05. Additionally, LC supplementation increased serum triiodothyronine, thyroxine levels, and ALA supplementation increased serum triiodothyronine levels (p<0.05. Serum total cholesterol and triglycerides levels were significantly decreased in LC and ALA supplemented groups, respectively (p<0.05. Moreover, serum low density lipoprotein cholesterol levels were lower in the ALA-supplemented groups than those of pigs fed without ALA-supplemented diets (p<0.05. However, no significant LC×ALA interaction effect on growth performance, blood thyroid hormones and lipid profiles was found. This study suggested that dietary supplementation of LC resulted in better growth performance compared to that of ALA supplementation. L-carnosine and/or ALA supplementation positively modified blood lipid profiles, which may have the potential to prevent cardiovascular diseases.

  5. Skin beautification with oral non-hydrolized versions of carnosine and carcinine: Effective therapeutic management and cosmetic skincare solutions against oxidative glycation and free-radical production as a causal mechanism of diabetic complications and skin aging.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoliy I; Savel'yeva, Ekaterina L; Lankin, Vadim Z; Yegorov, Yegor E

    2012-10-01

    Advanced glycation Maillard reaction end products (AGEs) are causing the complications of diabetes and skin aging, primarily via adventitious and cross-linking of proteins. Long-lived proteins such as structural collagen are particularly implicated as pathogenic targets of AGE processes. The formation of α-dicarbonyl compounds represents an important step for cross-linking proteins in the glycation or Maillard reaction. The purpose of this study was to investigate the contribution of glycation coupled to the glycation free-radical oxidation reactions as markers of protein damage in the aging of skin tissue proteins and diabetes. To elucidate the mechanism for the cross-linking reaction, we studied the reaction between a three-carbon α-dicarbonyl compound, methylglyoxal, and amino acids using EPR spectroscopy, a spectrophotometric kinetic assay of superoxide anion production at the site of glycation and a chemiluminescence technique. The transglycating activity, inhibition of transition metal ions peroxidative catalysts, resistance to hydrolysis of carnosine mimetic peptide-based compounds with carnosinase and the protective effects of carnosine, carcinine and related compounds against the oxidative damage of proteins and lipid membranes were assessed in a number of biochemical and model systems. A 4-month randomized, double-blind, controlled study was undertaken including 42 subjects where the oral supplement of non-hydrolized carnosine (Can-C Plus® formulation) was tested against placebo for 3 months followed by a 1-month supplement-free period for both groups to assess lasting effects. Assessment of the age-related skin parameters and oral treatment efficacy measurements included objective skin surface evaluation with Visioscan® VC 98 and visual assessment of skin appearance parameters. The results together confirm that a direct one-electron transfer between a Schiff base methylglyoxal dialkylimine (or its protonated form) and methylglyoxal is responsible for

  6. Do fatty acids help in overcoming reading difficulties? A double-blind, placebo-controlled study of the effects of eicosapentaenoic acid and carnosine supplementation on children with dyslexia.

    Science.gov (United States)

    Kairaluoma, L; Närhi, V; Ahonen, T; Westerholm, J; Aro, M

    2009-01-01

    There are claims that dietary supplementation of unsaturated fatty acids could help children with dyslexia to overcome their reading problems. However, these claims have not yet been empirically tested. This study was designed to test whether dietary supplementation was superior to placebo in treating reading, spelling or other reading-related skills of children with dyslexia. The experimental group (eicosapentaenoic acid, EPA, n = 30) ate dietary supplements and the control group (placebo, n = 31) placebos during the 90-day treatment period. The supplements contained omega-3 fatty acid (ethyl-EPA, 500 mg/day) and carnosine (400 mg/day). The groups were matched for reading skills, grade, gender, attention problems, intelligence and amount of special education. The literacy-related skills of the two groups were assessed before and after the treatment period. No group differences were observed between EPA and placebo in measures of reading accuracy or speed, spelling, decoding fluency, arithmetical skills, reading-related language skills, attention or behavioural problems. The present findings do not support the hypothesis that omega-3 fatty acid (ethyl-EPA) or carnosine has a role in the treatment of reading and spelling problems in children with dyslexia.

  7. Bioactivation antioxidant and transglycating properties of N-acetylcarnosine autoinduction prodrug of a dipeptide L-carnosine in mucoadhesive drug delivery eye-drop formulation: powerful eye health application technique and therapeutic platform.

    Science.gov (United States)

    Babizhayev, Mark A

    2012-06-01

    A considerable interest in N-acetylcarnosine ocular drug design for eye health is based on clinical strategies to improve ocular drug delivery through metabolic enzymatic activation. Human biology aspects of ocular N-acetylcarnosine deacetylation during its pass through the cornea to the aqueous humor and dipeptide hydrolyzing enzymes are characterized. Novel approaches to ocular drug delivery increasing intraocular bioavailability of N-acetylcarnosine biologically activated metabolite carnosine become an integral development ensuring prolonged retention of the medication in the mucoadhesive precorneal area and facilitating transcorneal penetration of the natural dipeptide with the corneal promoters. A comprehensive list of techniques for peptide drug design, synthesis, purification, and biological analyses was considered: liquid chromatography (LC), high performance liquid chromatography (HPLC), (1) H and (13) C nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectroscopy, and spectrophotometry. The antioxidant activity of therapeutics-targeted molecules was studied in aqueous solution and in a lipid membrane environment. A deglycation therapeutic system was developed involving removal, by transglycation of sugar or aldehyde moieties from Schiff bases by histidyl-hydrazide compounds or aldehyde scavenger L-carnosine. Clinical studies included ophthalmoscopy, visual acuity (VA), halometer disability glare tests, slit-image, and retro-illumination photography. N-acetylcarnosine 1% lubricant eye drops are considered as an auto-induction prodrug and natural ocular redox state balance therapies with implications in prevention and treatment of serious eye diseases that involve pathways of continuous oxidative damage to ocular tissues(cataracts, primary open-angle glaucoma, age-related macular degeneration) and sight-threatening glycosylation processes (diabetic retinopathy and consequent visual impairment) important for public health. The results of

  8. Evaluation of radioprotective effect of carnosine (beta- alanyl-1- histidine on the wound healing in rats Avaliação do efeito radioprotetor da carnosina (beta-alanil-1- histidina no processo de cicatrização em ratos

    Directory of Open Access Journals (Sweden)

    Rosana Aramaki Tanaka

    2005-09-01

    Full Text Available The purpose of this study was to evaluate the radioprotective effect of carnosine (beta- alanyl-1-histidine on the wound healing in rats. Therefore, 48 male rats were submitted to a surgical procedure to perform a rectangular wound in the anterior-dorsal region. The animals were divided into 4 experimental groups randomly chosen: control; irradiated; carnosine irradiated and carnosine group. The irradiated and carnosine irradiated group were exposed to a dose (6Gy of gamma irradiation, in the whole body, 72 hours after surgery. The carnosine and carnosine irradiated groups, in addition to the surgical procedure and the irradiation, received two doses of carnosine aqueous solution, the first one being injected 48 hours after surgery, and the second one 1 hour and 30 minutes before irradiation. The tissue repair of the 4 groups was evaluated at 4, 7, 14, and 21 days after inflicting the wound, by morphological, histochemical and histophysical methods. At all examined periods, it could be observed that the animals from the carnosine irradiated group presented a better developed granulation tissue than the irradiated group and closely similar to that of the control group. Thus, under the experimental conditions used, it was possible to conclude that carnosine is an effective radioprotective substance.O objetivo deste estudo foi avaliar o efeito radioprotetor da carnosina (beta-alanil-1-histidina no processo de cicatrização em ratos. Para isto, 48 ratos machos foram submetidos a um procedimento cirúrgico para realização de uma ferida retangular na região dorsal anterior. Os animais foram divididos aleatoriamente em 4 grupos experimentais: controle, irradiado, carnosina irradiado e carnosina. Os grupos carnosina e carnosina irradiado foram exposto a uma dose de corpo todo de 6 Gy de radiação gama, 72 horas após a cirurgia para confecção da ferida. O grupo carnosina e carnosina irradiado, adicionalmente, ao procedimento cirúrgico e a

  9. Carnosine-graphene oxide conjugates decorated with hydroxyapatite as promising nanocarrier for ICG loading with enhanced antibacterial effects in photodynamic therapy against Streptococcus mutans.

    Science.gov (United States)

    Gholibegloo, Elham; Karbasi, Ashkan; Pourhajibagher, Maryam; Chiniforush, Nasim; Ramazani, Ali; Akbari, Tayebeh; Bahador, Abbas; Khoobi, Mehdi

    2018-04-01

    Antimicrobial photodynamic therapy (aPDT) has been emerged as a noninvasive strategy to remove bacterial contaminants such as S. mutans from the tooth surface. Photosensitizer (PS), like indocyanine green (ICG), plays a key role in this technique which mainly suffers from the poor stability and concentration-dependent aggregation. An appropriate nanocarrier (NC) with enhanced antibacterial effects could overcome these limitations and improve the efficiency of ICG as a PS. In this study, various ICG-loaded NCs including graphene oxide (GO), GO-carnosine (Car) and GO-Car/Hydroxyapatite (HAp) were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Filed Emission Scanning Electron Microscopy (FE-SEM), Energy Dispersive Spectroscopy (EDS), Zeta Potential and Ultraviolet-Visible spectrometry (UV-Vis). The colony forming unit and crystal violet assays were performed to evaluate the antimicrobial and anti-biofilm properties of PSs against S. mutans. The quantitative real-time PCR approach was also applied to determine the expression ratio of the gtfB gene in S. mutans. The zeta potential analysis and UV-Vis spectrometry indicated successful loading of ICG onto/into NCs. GO-Car/HAp showed highest amount of ICG loading (57.52%) and also highest aqueous stability after one week (94%). UV-Vis spectrometry analyses disclosed a red shift from 780 to 800 nm for the characteristic peak of ICG-loaded NCs. In the lack of aPDT, GO-Car@ICG showed the highest decrease in bacterial survival (86.4%) which indicated that Car could significantly promote the antibacterial effect of GO. GO@ICG, GO-Car@ICG and GO-Car/HAp@ICG mediated aPDT, dramatically declined the count of S. mutans strains to 91.2%, 95.5% and 93.2%, respectively (P < 0.05). The GO@ICG, GO-Car@ICG, GO-Car/HAp@ICG significantly suppressed the S. mutans biofilm formation by 51.4%, 63.8%, and 56.8%, respectively (P < 0.05). The expression of gtfB gene was

  10. Non-hydrolyzed in digestive tract and blood natural L-carnosine peptide ("bioactivated Jewish penicillin") as a panacea of tomorrow for various flu ailments: signaling activity attenuating nitric oxide (NO) production, cytostasis, and NO-dependent inhibition of influenza virus replication in macrophages in the human body infected with the virulent swine influenza A (H1N1) virus.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoliy I; Yegorov, Yegor E

    2013-01-01

    in excessive amounts mediate the overreaction of the host's immune response against the organs or tissues in which viruses are replicating, and this may explain the mechanism of tissue injuries observed in influenza virus infection of various types. In this article, the types of protection of carnosine in its bioavailable non-hydrolyzed forms in formulations are considered against reactive oxygen radical species-dependent injury, peroxynitrite damage, and other types of viral injuries in which impaired immune responses to viral pathogens are usually involved. Carnosine (β-alanyl-L-histidine) shows the pharmacological intracellular correction of NO release, which might be one of the important factors of natural immunity in controlling the initial stages of influenza A virus infection (inhibition of virus replication) and virus-induced regulation of cytokine gene expression. The protective effects of orally applied non-hydrolyzed formulated species of carnosine include at least the direct interaction with NO, inhibition of cytotoxic NO-induced proinflammatory condition, and attenuation of the effects of cytokines and chemokines that can exert profound effects on inflammatory cells. These data are consistent with the hypothesis that natural products, such as chicken soup and chicken breast extracts rich in carnosine and its derivative anserine (β-alanyl-1-methyl-L-histidine), could contribute to the pathogenesis and prevention of influenza virus infections and cold but have a limitation due to the susceptibility to enzymatic hydrolysis of dipeptides with serum carnosinase and urine excretion after oral ingestion of a commercial chicken extract. The formulations of non-hydrolyzed in digestive tract and blood natural carnosine peptide and isopeptide (γ-glutamyl-carnosine) products, manufactured at the cGMP-certified facility and patented by the authors, have promise in the control and prevention of influenza A (H1N1) virus infection, cough, and cold.

  11. An urea, arginine and carnosine based cream (Ureadin Rx Db ISDIN shows greater efficacy in the treatment of severe xerosis of the feet in Type 2 diabetic patients in comparison with glycerol-based emollient cream. A randomized, assessor-blinded, controlled trial

    Directory of Open Access Journals (Sweden)

    Federici Adalberto

    2012-09-01

    Full Text Available Abstract Background Xerosis is a common skin disorder frequently observed in diabetic patients. An effective hydration of foot skin in diabetics is a relevant preventive strategy in order to maintain a healthy foot. Urea is considered an effective hydrating and emollient topical product. The aim of the present study was to evaluate the efficacy of topical urea 5% with arginine and carnosine (Ureadin Rx Db, ISDIN Spain (UC in comparison with glycerol-based emollient topical product (Dexeryl, Pierre Fabre (EC, in Type 2 diabetic patients. Methods We assessed the effect of UC on skin hydration in a randomized, evaluator-blinded comparative study in 40 type II diabetic patients, aged 40–75 years, treated with UC or the comparator for 28 days with a twice-daily application. The principal outcomes were the Dryness Area Severity Index (DASI Score and the Visual Analogue Score (VAS for skin dryness evaluated at baseline and at the end of study period by an investigator unaware of treatment allocation. Results UC induced significantly greater hydration than EC with an 89% reduction in DASI score (from 1.6 to 0.2; p  Conclusion Application of urea 5%, arginine and carnosine cream increases skin hydration and alleviates the condition of skin dryness in Type 2 diabetic patients in comparison with a control glycerol-based emollient product. (Dutch Trials Register trial number 3328.

  12. Diabetic nephropathy : pathology, genetics and carnosine metabolism

    NARCIS (Netherlands)

    Mooyaart, Antien Leonora

    2011-01-01

    My thesis concerns different aspects of diabetic nephropathy. A pathologic classification of diabetic nephropathy is developed, a meta-analyis of genes in diabetic nephropathy is developed and the other chapters are about the CNDP1 gene in relation to kidney disease, mainly diabetic nephropathy.

  13. Effectiveness of carnosine on disturbed electrolytes homeostasis ...

    African Journals Online (AJOL)

    Jane

    2011-07-20

    Jul 20, 2011 ... of the cells to cisplatin may result from the interaction of specific proteins with ..... respiration, which is similar to uncoupling of oxidative phosphorylation (Binet ... cellular ion homeostasis with decreased cellular K+ content, increased ... of sodium and hydrogen ions will take place passively. Also, magnesium ...

  14. Advanced drug delivery of N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine), carcinine (beta-alanylhistamine) and L-carnosine (beta-alanyl-L-histidine) in targeting peptide compounds as pharmacological chaperones for use in tissue engineering, human disease management and therapy: from in vitro to the clinic.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2010-11-01

    A pharmacological chaperone is a relatively new concept in the treatment of certain chronic disabling diseases. Cells maintain a complete set of functionally competent proteins normally and in the face of injury or environmental stress with the use of various mechanisms, including systems of proteins called molecular chaperones. Proteins that are denatured by any form of proteotoxic stress are cooperatively recognized by heat shock proteins (HSP) and directed for refolding or degradation. Under non-denaturing conditions HSP have important functions in cell physiology such as in transmembrane protein transport and in enabling assembly and folding of newly synthesized polypeptides. Besides cellular molecular chaperones, which are stress-induced proteins, there have been recently reported chemical, or so-called pharmacological chaperones with demonstrated ability to be effective in preventing misfolding of different disease causing proteins, specifically in the therapeutic management of sight-threatening eye diseases, essentially reducing the severity of several neurodegenerative disorders (such as age-related macular degeneration), cataract and many other protein-misfolding diseases. This work reviews the biological and therapeutic activities protected with the patents of the family of imidazole-containing peptidomimetics Carcinine (β-alanylhistamine), N-acetylcarnosine (N-acetyl-β-alanylhistidine) and Carnosine (β-alanyl-L-histidine) which are essential constituents possessing diverse biological and pharmacological chaperone properties in human tissues.

  15. Telomere Attrition in Human Lens Epithelial Cells Associated with Oxidative Stress Provide a New Therapeutic Target for the Treatment, Dissolving and Prevention of Cataract with N-Acetylcarnosine Lubricant Eye Drops. Kinetic, Pharmacological and Activity-Dependent Separation of Therapeutic Targeting: Transcorneal Penetration and Delivery of L-Carnosine in the Aqueous Humor and Hormone-Like Hypothalamic Antiaging Effects of the Instilled Ophthalmic Drug Through a Safe Eye Medication Technique.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2016-01-01

    the lens response to oxidative damages, aging and health, cataract versus neuroendocrine regulation and disease. The cumulative results demonstrate that carnosine, released ophthalmically from the patented 1% Nacetylcarnosine prodrug lubricant eye drops, at physiological concentration might remarkably reduce the rate of telomere shortening in the lens cells subjected to oxidative stress in the lack of efficient antioxidant lens protection. Carnosine promotes the protection of normal cells from acquiring phenotypic characteristics of cellular senescence. The data of visual functions (visual acuity, glare sensitivity) in older adult subjects and older subjects with cataract treated with 1% N-acetylcarnosine lubricant eye drops showed significant improvement as compared, by contrast with the control group which showed generally no improvement in visual functions, with no difference from baseline in visual acuity and glare sensitivity readings. N-acetylcarnosine derived from the lubricant eye drops may be transported into the hypothalamic tuberomammillary nucleus (TMN) histamine neurons and gradually hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and hormone-like antiaging and anti-cataract physiological function. The research utilizing the N-acetylcarnosine lubricant eye drops powerful therapeutic platform provides the findings related to the intraocular uptake exposure sources as well as a timing dosage and duration systemic absorption of said preparation from the conjunctional sac reaching the hypothalamus with activities transfer into the hypothalamic-neuroendocrine pathways affecting across the hypothalamus metabolic pathway the telomere biology and cataract disease occurrence, reversal and prevention and the average expected lifespan of an individual. Such findings can be translated into clinical practice and may provide a basis for personalized cataract

  16. Evaluation of the effect of carnosine, its novel derivative trolox-carnosine and trolox in a pre-clinical study focussing on the regulation of immunity

    Directory of Open Access Journals (Sweden)

    Slovák L.

    2016-09-01

    Full Text Available The neuroprotective or neurotoxic effects of the products of the kynurenine pathway of tryptophan metabolism highly depend on the action of kynurenine-3-monooxygenase (KMO. The present results show increased concentrations of the KMO in the plasma of rats repeatedly exposed to an immune challenge. Increased concentrations of this key enzyme are likely to cause a shift of kynurenine pathway towards enhanced production of neurotoxic metabolites.

  17. Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1 gene with diabetic nephropathy in north Indians

    Directory of Open Access Journals (Sweden)

    Ashok K Yadav

    2016-01-01

    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.

  18. Carnosine as a protective factor in diabetic nephropathy - Association with a leucine repeat of the carnosinase gene CNDP1

    NARCIS (Netherlands)

    Janssen, B; Hohenadel, D.; Brinkkoetter, P.; Peters, V.; Rind, N.; Fischer, C.; Rychlik, I.; Cerna, M.; Romzova, M.; de Heer, E.; Baelde, H.; Bakker, Stephan; Zirie, M.; Rondeau, E.; Mathieson, P.; Saleem, M.A.; Meyer, J.; Koppel, H.; Sauerhoefer, S.; Bartram, C.R.; Nawroth, P.; Hammes, H.P.; Yard, B.A.; Zschocke, J.; van der Woude, F.J.

    The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development

  19. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 187 ... ... 4a/b polymorphism in ulcerative colitis-associated colorectal cancer, Abstract .... Effects of Carnosine on Peroxisome Proliferator-Activated Receptor ... value of urinary CK-20 RNA and VEGF in bladder cancer, Abstract.

  20. Existence of carcinine, a histamine-related compound, in mammalian tissues

    International Nuclear Information System (INIS)

    Flancbaum, L.; Brotman, D.N.; Fitzpatrick, J.C.; Van Es, Theodorus; Kasziba, E.; Fisher, H.

    1990-01-01

    Carcinine (β-alanylhistamine) was synthesized in vitro from histamine and β-alanine. It was detected quantitatively using an HPLC method previously described for the quantification of the related compounds histamine, histidine, carnosine and 3-methylhistamine. Carcinine was identified in several tissues of the rat, guinea pig, mouse and human, and was then shown to be metabolically related in vivo to histamine, histidine, carnosine and 3-methylhistamine through radioisotopic labeling. The results demonstrate that carcinine may be concurrently quantitated using the same HPLC method as that used to measure histamine, histidine, carnosine and 3-methylhistamine. These findings suggest a role for carcinine in the carnosine-histidine-histamine metabolic pathway and the mammalian physiologic response to stress

  1. Central administration of dipeptides, beta-alanyl-BCAAs, induces hyperactivity in chicks

    Directory of Open Access Journals (Sweden)

    Denbow D Michael

    2007-05-01

    Full Text Available Abstract Background Carnosine (β-alanyl-L-histidine is a putative neurotransmitter and has a possible role in neuron-glia cell interactions. Previously, we reported that carnosine induced hyperactivity in chicks when intracerebroventricularly (i.c.v. administered. In the present study, we focused on other β-alanyl dipeptides to determine if they have novel functions. Results In Experiment 1, i.c.v. injection of β-alanyl-L-leucine, but not β-alanyl-glycine, induced hyperactivity behavior as observed with carnosine. Both carnosine and β-alanyl-L-leucine stimulated corticosterone release. Thus, dipeptides of β-alanyl-branched chain amino acids were compared in Experiment 2. The i.c.v. injection of β-alanyl-L-isoleucine caused a similar response as β-alanyl-L-leucine, but β-alanyl-L-valine was somewhat less effective than the other two dipeptides. β-Alanyl-L-leucine strongly stimulated, and the other two dipeptides tended to stimulate, corticosterone release. Conclusion These results suggest that central β-alanyl-branched chain amino acid stimulates activity in chicks through the hypothalamus-pituitary-adrenal axis. We named β-alanyl-L-leucine, β-alanyl-L-isoleucine and β-alanyl-L-valine as Excitin-1, Excitin-2 and Excitin-3, respectively.

  2. A new method for non-invasive estimation of human muscle fiber type composition.

    Directory of Open Access Journals (Sweden)

    Audrey Baguet

    Full Text Available BACKGROUND: It has been established that excellence in sports with short and long exercise duration requires a high proportion of fast-twitch (FT or type-II fibers and slow-twitch (ST or type-I fibers, respectively. Until today, the muscle biopsy method is still accepted as gold standard to measure muscle fiber type composition. Because of its invasive nature and high sampling variance, it would be useful to develop a non-invasive alternative. METHODOLOGY: Eighty-three control subjects, 15 talented young track-and-field athletes, 51 elite athletes and 14 ex-athletes volunteered to participate in the current study. The carnosine content of all 163 subjects was measured in the gastrocnemius muscle by proton magnetic resonance spectroscopy ((1H-MRS. Muscle biopsies for fiber typing were taken from 12 untrained males. PRINCIPAL FINDINGS: A significant positive correlation was found between muscle carnosine, measured by (1H-MRS, and percentage area occupied by type II fibers. Explosive athletes had ∼30% higher carnosine levels compared to a reference population, whereas it was ∼20% lower than normal in typical endurance athletes. Similar results were found in young talents and ex-athletes. When active elite runners were ranked according to their best running distance, a negative sigmoidal curve was found between logarithm of running distance and muscle carnosine. CONCLUSIONS: Muscle carnosine content shows a good reflection of the disciplines of elite track-and-field athletes and is able to distinguish between individual track running distances. The differences between endurance and sprint muscle types is also observed in young talents and former athletes, suggesting this characteristic is genetically determined and can be applied in early talent identification. This quick method provides a valid alternative for the muscle biopsy method. In addition, this technique may also contribute to the diagnosis and monitoring of many conditions and

  3. Biopolymeric receptor for peptide recognition by molecular imprinting approach—Synthesis, characterization and application

    International Nuclear Information System (INIS)

    Singh, Lav Kumar; Singh, Monika; Singh, Meenakshi

    2014-01-01

    The present work is focused on the development of a biocompatible zwitterionic hydrogel for various applications in analytical chemistry. Biopolymer chitosan was derivatized to obtain a series of zwitterionic hydrogel samples. Free amino groups hanging on the biopolymeric chain were reacted with γ-butyrolactone to quaternize the N-centers of polymeric chain. N,N-methylene-bis-acrylamide acts as a crosslinker via Michael-type addition in the subsequent step and facilitated gelation of betainized chitosan. These biopolymeric hydrogel samples were fully characterized by FTIR, 1 H NMR, 13 C NMR spectra, SEM and XRD. Hydrogels were further characterized for their swelling behavior at varying parameters. The extent of swelling was perceived to be dictated by solvent composition such as pH, ionic strength and temperature. This valuable polymeric format is herein chosen to design an artificial receptor for dipeptide ‘carnosine’, which has adequate societal significance to be analytically determined, by molecular imprinting. Electrostatic interactions along with complementary H-bonding and other hydrophobic interactions inducing additional synergetic effect between the template (carnosine) and the imprinted polymer led to the formation of imprinted sites. The MIP was able to selectively and specifically take up carnosine from aqueous solution quantitatively. Thus prepared MIPs were characterized by FTIR spectroscopy, SEM providing evidence for the quality and quantity of imprinted gels. The binding studies showed that the MIP illustrated good recognition for carnosine as compared to non-imprinted polymers (NIPs). Detection limit was estimated as 3.3 μg mL −1 . Meanwhile, selectivity experiments demonstrated that imprinted gel had a high affinity to carnosine in the presence of close structural analogues (interferrants). - Highlights: • Development of a biocompatible zwitterionic hydrogel • A series of chitosan-derived zwitterionic hydrogel samples • Polymeric

  4. Muscle interstitial potassium kinetics during intense exhaustive exercise

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai; Mohr, Magni; Pedersen, Lasse Dannemann

    2003-01-01

    Interstitial K+ ([K+]i) was measured in human skeletal muscle by microdialysis during exhaustive leg exercise, with (AL) and without (L) previous intense arm exercise. In addition, the reproducibility of the [K+]i determinations was examined. Possible microdialysis-induced rupture of the sarcolemma...... was assessed by measurement of carnosine in the dialysate, because carnosine is only expected to be found intracellularly. Changes in [K+]i could be reproduced, when exhaustive leg exercise was performed on two different days, with a between-day difference of approximately 0.5 mM at rest and 1.5 m......M at exhaustion. The time to exhaustion was shorter in AL than in L (2.7 +/- 0.3 vs. 4.0 +/- 0.3 min; P exercise period in AL compared with L (9.2 +/- 0.7 vs. 6.4 +/- 0.9 mM; P

  5. Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications

    Science.gov (United States)

    Xie, Zhengzhi; Baba, Shahid P.; Sweeney, Brooke R.; Barski, Oleg A.

    2015-01-01

    Aldehydes are generated by oxidized lipids and carbohydrates at increased levels under conditions of metabolic imbalance and oxidative stress during atherosclerosis, myocardial and cerebral ischemia, diabetes, neurodegenerative diseases and trauma. In most tissues, aldehydes are detoxified by oxidoreductases that catalyze the oxidation or the reduction of aldehydes or enzymatic and nonenzymatic conjugation with low molecular weight thiols and amines, such as glutathione and histidine dipeptides. Histidine dipeptides are present in micromolar to millimolar range in the tissues of vertebrates, where they are involved in a variety of physiological functions such as pH buffering, metal chelation, oxidant and aldehyde scavenging. Histidine dipeptides such as carnosine form Michael adducts with lipid-derived unsaturated aldehydes, and react with carbohydrate-derived oxo- and hydroxy- aldehydes forming products of unknown structure. Although these peptides react with electrophilic molecules at lower rate than glutathione, they can protect glutathione from modification by oxidant and they may be important for aldehyde quenching in glutathione-depleted cells or extracellular space where glutathione is scarce. Consistent with in vitro findings, treatment with carnosine has been shown to diminish ischemic injury, improve glucose control, ameliorate the development of complications in animal models of diabetes and obesity, promote wound healing and decrease atherosclerosis. The protective effects of carnosine have been linked to its anti-oxidant properties, it ability to promote glycolysis, detoxify reactive aldehydes and enhance histamine levels. Thus, treatment with carnosine and related histidine dipeptides may be a promising strategy for the prevention and treatment of diseases associated with high carbonyl load. PMID:23313711

  6. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

    Directory of Open Access Journals (Sweden)

    Laila Ziko

    2015-01-01

    Full Text Available Cisplatin (CisPt is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2 cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death. Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death.

  7. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

    Science.gov (United States)

    Riad, Sandra; Bougherara, Habiba

    2015-01-01

    Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death). PMID:25685789

  8. Free amino acid profile of Bubalus bubalis L. meat from the Campania region

    Directory of Open Access Journals (Sweden)

    Nicola Landi

    Full Text Available ABSTRACT In this study, we determined the amount of carnosine and anserine in water buffalo meat without hanging treatment and the free amino acid profile by using amino acid analyser with post-column ninhydrin derivatization procedure. The main free amino acids present in samples were glutamic acid (>60 mg/100 g, followed by alanine, glycine, and arginine. Other protein amino acids were detected in minor amounts (less than 2 mg/100 g. Among the non-protein amine-containing compounds, taurine and urea were the most abundant. The analysis showed that 50% of the total free amino acids was represented by dipeptides carnosine (average ~130.3 mg/100 g and anserine (average ~17.9 mg/100 g. Thus, this study for the first time reports the free amino acids profile of water buffalo meat and the content of carnosine and anserine, potentially involved in the darkening meat process and their ratio, that could be used to estimate the water buffalo meat portion in mixed meat products.

  9. Changes in urinary amino acids excretion in relationship with muscle activity markers over a professional cycling stage race: in search of fatigue markers.

    Science.gov (United States)

    Corsetti, Roberto; Barassi, Alessandra; Perego, Silvia; Sansoni, Veronica; Rossi, Alessandra; Damele, Clara Anna Linda; Melzi D'Eril, Gianlodovico; Banfi, Giuseppe; Lombardi, Giovanni

    2016-01-01

    The aim of this study was to identify the relationship between metabolic effort, muscular damage/activity indices, and urinary amino acids profile over the course of a strenuous prolonged endurance activity, as a cycling stage race is, in order to identify possible fatigue markers. Nine professional cyclists belonging to a single team, competing in the Giro d'Italia cycling stage race, were anthropometrically characterized and sampled for blood and urine the day before the race started, and on days 12 and 23 of the race. Diet was kept the same over the race, and power output and energy expenditure were recorded. Sera were assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase activities, and blood urea nitrogen), and creatinine, all corrected for plasma volume changes. Urines were profiled for amino acid concentrations, normalized on creatinine excretion. Renal function, in terms of glomerular filtration rate, was monitored by MDRD equation corrected on body surface area. Creatine kinase activity and blood urea were increased during the race as did serum creatinine while kidney function remained stable. Among the amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine, and 3-methyl histidine showed a net decreased, while homocysteine was increased. Taurine and the dipeptide carnosine (β-alanyl-L-histidine) were significantly correlated with the muscle activity markers and the indices of effort. In conclusion, the metabolic profile is modified strikingly due to the effort. Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and possibly the fatigue status on a long-term basis.

  10. Biomarkers of oxidative stress and cataract. Novel drug delivery therapeutic strategies targeting telomere reduction and the expression of telomerase activity in the lens epithelial cells with N-acetylcarnosine lubricant eye drops: anti-cataract which helps to prevent and treat cataracts in the eyes of dogs and other animals.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2014-01-01

    Cataracts in small animals are shown to be at least partially caused by oxidative damage to lens epithelial cells (LECs) and the internal lens; biomarkers of oxidative stress in the lens are considered as general biomarkers for life expectancy in the canine and other animals. Telomeres lengths and expressed telomerase activity in canine LECs may serve as important monitors of oxidative damage in normal LECs with documented higher levels of telomerase activity in cataractous LECs during cells' lifespan. Loss of functional telomere length below a critical threshold in LECs of canines during the effect of UV and chronic oxidative stress or metabolic failure, can activate programs leading to LEC senescence or death. Telomerase is induced in LECs of canines at critical stages of cataractogenesis initiation and exposure to oxidative stress through the involvement of catalytically active prooxidant transition metal (iron) ions. This work documents that transition metal ions (such as, ferrous ions- catalytic oxidants) might induce premature senescence in LECs of canines, telomere shortening with increased telomerase activity as adaptive response to UV light, oxidative and metabolic stresses. The therapeutic treatment with 1% N-acetylcarnosine (NAC) prodrug delivery is beneficial for prevention and dissolution of ripe cataracts in canines. This biological activity is based on the findings of ferroxidase activity pertinent to the dipeptide carnosine released ophthalmically from NAC prodrug of L-carnosine, stabilizing properties of carnosine on biological membranes based on the ability of the imidazole-containing dipeptides to interact with lipid peroxidation products and reactive oxygen species (ROS), to prevent membrane damage and delute the associated with membrane fragements protein aggregates. The advent of therapeutic treatment of cataracts in canines with N-acetylcarnosine lubricant eye drops through targeting the prevention of loss of functional telomere length below

  11. Metabolomic study of plasma from female mink (Neovison vison) with low and high residual feed intake during restrictive and ad libitum feeding

    DEFF Research Database (Denmark)

    Hedemann, Mette Skou; Damgaard, Birthe Marie

    2012-01-01

    was high during restrictive feeding, e.g. betaine, carnitine, and creatine. During ad libitum feeding the plasma level of metabolites that can be characterized as biomarkers of meat intake (creatinine, carnosine, 1- and 3 methylhistidine) was high. The plasma level of lysophosphatidylcholine species......Metabolite profiling may elucidate changes in metabolic pathways under various physiological or nutritional conditions. In the present study two groups of female mink characterized as having a high (16 mink) or low (14 mink) residual feed intake were investigated during restrictive and ad libitum...

  12. Metabolomic elucidation of pork from different crossbreds

    DEFF Research Database (Denmark)

    Bertram, Hanne Christine S.; Straadt, Ida Krestine; Clausen, Morten Rahr

    , and correlations between individual metabolites and sensory attributes were elucidated. A high content of carnosine in the meat was associated with a low value of many sensory attributes related to meat flavor/taste. Surprsingly, IMP and inosine were in general not correlated with sensory attributes related...... to meat flavor/taste. Water-holding capacity and oxygen radical absorbance capacity (ORAC) of the meat were determined to elucidate the correlations between individual metabolites and these two parameters that are of importance for the technological meat quality. In conclusion, the present study reveals...

  13. How much chicken is food? Questioning the definition of food by analyzing amino acid composition of modern convenience products.

    Science.gov (United States)

    Hermanussen, M; Gonder, U; Stegemann, D; Wesolowski, M; Ulewicz-Magulska, B; Wartensleben, H; Hoffmann, G F

    2012-01-01

    Substantial differences exist between traditionally cooked and chemically designed ready-to-serve products and raise questions about the general principles and requirements of current food law. Differences in amino acid patterns were analyzed in four examples of chicken preparations (boiled chicken meat, traditionally prepared broth from whole chicken, and two commercial chicken broths), and four examples of vegetable broth (traditionally prepared, two commercial products one of which was claimed a BIO-product, and the classic German bouillon cube). Chicken meat contained 284 mg of free amino acids in 100 ml of the boiled meat homogenate, with physiological peaks of glutamate (14.5 mg/100 ml), glutamine (8.5 mg/100 ml), anserine (88 mg/100 ml) and carnosine (55 mg/100 ml). The patterns significantly differ in industrially designed chicken soups with elevated peaks of glutamate, and missing anserine or carnosine. Similar results were obtained in vegetable broths. In the classic German bouillon cube, glutamate accounts for 96% of all free amino acids. The amino acid composition of modern ready-to-serve chicken soups and vegetable broths are far from being similar to any natural composition. We need to question current legal definitions of food, and consider its impact on eating habits, appetite regulation and obesity.

  14. Analysis of human muscle extracts by proton NMR

    International Nuclear Information System (INIS)

    Venkatasubramanian, P.N.; Barany, M.; Arus, C.

    1986-01-01

    Perchloric acid extracts were prepared from pooled human muscle biopsies from patients diagnosed with scoliosis (SCOL) and cerebral palsy (CP). After neutralization with KOH and removal of perchlorate, the extracts were concentrated by freeze drying and dissolved in 2 H 2 O to contain 120 O.D. units at 280 nm per 0.5 ml. 1 H NMR spectroscopy was performed with the 5 mm probe of a Varian XL300 instrument. Creatine, lactate, carnosine, and choline were the major resonances in the one-dimensional spectra of both extracts. With creatine as reference, 2.5-fold more lactate was found in SCOL than in CP, and a much smaller difference was also found in their carnosine content. Two-dimensional COSY comparison revealed several differences between the two extracts. Taurine, N-acetyl glutamate, glycerophosphoryl choline (or phosphoryl choline) and an unidentified spot were present only in the extract from SCOL but not in that from CP. On the other hand, aspartate, hydroxy-proline, carnitine and glycerophosphoryl ethanolamine were only present in CP but absent in SCOL. Alanine, cysteine, lysine and arginine appeared in both extracts without an apparent intensity difference

  15. Antioxidant and antiglycation activities of the synthesised dipeptide, Asn-Trp, derived from computer-aided simulation of yam dioscorin hydrolysis and its analogue, Gln-Trp.

    Science.gov (United States)

    Han, Chuan-Hsiao; Lin, Yin-Shiou; Lin, Shyr-Yi; Hou, Wen-Chi

    2014-03-15

    Previous studies have shown that the Trp residue contributes to a high oxygen radical absorbance capacity (ORAC). Therefore, in this study, a Trp-containing dipeptide derived from a computer-aided simulation of pepsin hydrolysis of the yam tuber, dioscorin-namely, Asn-Trp (NW), and its analogue, Gln-Trp (QW)-were synthesised to compare their antioxidant and antiglycation activities with carnosine, homocarnosine, or glutathione (GSH). The antioxidant assays included hydroxyl radical-scavenging activity, anti-AAPH-induced hemolysis, and ORAC activity. NW had a significantly higher antioxidant activity than had QW and performed much better than carnosine, homocarnosine, or GSH. Using bovine serum albumin (BSA)/galactose or BSA/glucose as experimental models, NW had better antiglycation effects than had QW, as detected by an anti-N(ε)-(carboxymethyl)lysine (anti-CML) antibody. Moreover, NW and QW (50-200 μM) showed protection against methylglyoxal-induced cell deaths in human umbilical vein endothelial cells. These results suggest that NW, derived from computer-aided simulation of dioscorin hydrolysis, exhibits antioxidant and antiglycation activities, which thus shows the benefits of the yam tuber as an antioxidant-rich food. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Changes in endogenous bioactive compounds of Korean native chicken meat at different ages and during cooking.

    Science.gov (United States)

    Jayasena, Dinesh D; Jung, Samooel; Bae, Young Sik; Kim, Sun Hyo; Lee, Soo Kee; Lee, Jun Heon; Jo, Cheorun

    2014-07-01

    This study aimed to examine the effect of bird age on the contents of endogenous bioactive compounds, including carnosine, anserine, creatine, betaine, and carnitine, in meat from a certified meat-type commercial Korean native chicken strain (KNC; Woorimatdag). Additionally, the effects of the meat type (breast or leg meat) and the state of the meat (raw or cooked) were examined. Cocks of KNC were raised under similar standard commercial conditions at a commercial chicken farm. At various ages (10, 11, 12, 13, and 14 wk), breast and leg meats from a total of 10 birds from each age group were obtained. Raw and cooked meat samples were then prepared separately and analyzed for bioactive compounds. The age of the KNC had a significant effect only on the betaine content. The breast meat of KNC had higher amounts of carnosine and anserine but had lower amounts of betaine and carnitine than the leg meat (P cooking (P cooking, whereas breast meat showed almost complete retention of betaine and carnitine. The results of this study provide useful and rare information regarding the presence, amounts, and determinants of endogenous bioactive compounds in KNC meat, which can be useful for selection and breeding programs, and also for popularizing indigenous chicken meat. © 2014 Poultry Science Association Inc.

  17. Nutrients Composition in Fit Snacks Made from Ostrich, Beef and Chicken Dried Meat.

    Science.gov (United States)

    Zdanowska-Sąsiadek, Żaneta; Marchewka, Joanna; Horbańczuk, Jarosław Olav; Wierzbicka, Agnieszka; Lipińska, Paulina; Jóźwik, Artur; Atanasov, Atanas G; Huminiecki, Łukasz; Sieroń, Aleksander; Sieroń, Karolina; Strzałkowska, Nina; Stelmasiak, Adrian; De Smet, Stefaan; Van Hecke, Thomas; Hoffman, Louwrens C

    2018-05-25

    The aim of the study was to compare three types of meat snacks made from ostrich, beef, and chicken meat in relation to their nutrients content including fat, fatty acids, heme iron, and peptides, like anserine and carnosine, from which human health may potentially benefit. Dry meat samples were produced, from one type of muscle, obtained from ostrich ( m. ambiens ), beef ( m. semimembranosus ), and broiler chicken meat ( m. pectoralis major ). The composition of dried ostrich, beef, and chicken meat, with and without spices was compared. We show that meat snacks made from ostrich, beef, and chicken meat were characterized by high concentration of nutrients including proteins, minerals (heme iron especially in ostrich, than in beef), biologically active peptides (carnosine-in beef, anserine-in ostrich then in chicken meat). The, beneficial to human health, n -3 fatty acids levels differed significantly between species. Moreover, ostrich jerky contained four times less fat as compared to beef and half of that in chicken. In conclusion we can say that dried ostrich, beef, and chicken meat could be a good source of nutritional components.

  18. [Cycloferon biological activity characteristics].

    Science.gov (United States)

    Utkina, T M; Potekhina, L P; Kartashova, O L; Vasilchenko, A S

    2014-01-01

    Study the effect of cycloferon in experimental and clinical conditions on persistence properties of aurococci as well as features of their morpho-functional reaction by atomic force microscopy. The study was carried out in 12 Staphylococcus aureus clones isolated from mucous membrane of nose anterior part of a resident carrier. The effect of cycloferon in vivo was evaluated in 26 resident staphylococci carriers under the control of anti-carnosine activity of staphylococci. Anti-carnosine activity was determined by O.V. Bukharin et al. (1999), biofilm formation -by G.A. O'Toole et al. (2000). Staphylococci treated with cycloferon were studied by atomic force microscopy in contact mode using scanning probe SMM-2000 microscope. The decrease of persistence properties of staphylococci under the effect of cycloferon in vitro and in vivo may be examined as one of the mechanisms of biological activity of the preparation. A significant increase of S. aureus surface roughness and changes in their morphology under the effect of cycloferon allow stating the disorder of barrier functions in the aurococci cell wall. The data obtained expand the understanding of cycloferon biological activity mechanisms.

  19. Potentiation of intraocular absorption and drug metabolism of N-acetylcarnosine lubricant eye drops: drug interaction with sight threatening lipid peroxides in the treatment for age-related eye diseases.

    Science.gov (United States)

    Babizhayev, Mark A

    2009-01-01

    lenses obtained from patients with senile and complicated cataracts as compared to normal donors. Utilizing the pharmacokinetic studies and the specific purity N-acetylcarnosine (NAC) ingredient as a source of pharmacological principal L-carnosine, we have created an ophthalmic time-release prodrug form combined with a muco-adhesive lubricant compound carboxymethylcellulose and other essential corneal absorption promoter excipients tailoring the increased intraocular absorption of L-carnosine in the aqueous humor and optimizing its specific effect in producing the basic antioxidant activity in vivo and reducing toxic effects of lipid peroxides to the crystalline lens. L-Carnosine that finds its way into the aqueous humor can accumulate in the lens tissue for a reasonable period of time. However, administration of pure L-carnosine (1% solution) to the rabbit eye (instillation, subconjunctival injection) does not lead to accumulation of this natural compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eyes, and its effective concentration is exhausted more rapidly. The NAC prodrug eye drops optimize the clinical effects for the treatment of ophthalmic disorders (such as prevention and reversal of cataracts in human and animal [canine] eyes). The data provided predict a particular NAC ophthalmic prodrug's clinical effect; the suitable magnitude and duration of this effect suggest dose-related bioavailability of L-camosine released from NAC in the aqueous humor of the anterior eye segment. The ophthalmic NAC drug shows promise in the treatment of a range of ophthalmic disorders which have a component of oxidative stress in their genesis (including cataract and after-cataract, glaucoma, dry eye, vitreous floaters, inflammatory disorders, corneal, retinal and systemic diseases [such as diabetes mellitus and its ophthalmic complications]). The clinical efficacy of N-acetylcarnosine lubricant eye drops in ripe cataracts and

  20. Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products.

    Science.gov (United States)

    Burcham, Philip C; Kaminskas, Lisa M; Fontaine, Frank R; Petersen, Dennis R; Pyke, Simon M

    2002-12-27

    Elevated levels of reactive alpha,beta-unsaturated aldehydes (e.g. malondialdehyde, 4-hydroxynonenal and acrolein) in the affected tissues of various degenerative conditions suggest these substances are active propagators of the disease process. One experimental approach to attenuating damage by these intermediates employs 'aldehyde-sequestering drugs' as sacrificial nucleophiles, thereby sparing cell macromolecules and perhaps slowing disease progression. Drugs with demonstrated trapping activity toward lipid-derived aldehydes include various amine compounds such as aminoguanidine, carnosine and pyridoxamine. We have focused on identifying scavengers of acrolein, perhaps the most toxic aldehyde formed during lipid peroxidation cascades. Various phthalazine compounds (hydralazine and dihydralazine) were found to trap acrolein readily, forming hydrazone derivatives in a rapid Schiff-type reaction. These compounds strongly protect against acrolein-mediated toxicity in isolated hepatocytes.

  1. Improving meat quality through cattle feed enriched with mate extract

    DEFF Research Database (Denmark)

    Zawadzki, Andressa

    The use of plant extracts in animal feeding trials has been considered as a potential alternative to improve the redox stability of meat. Bioactive compounds from plant extracts can provide the antioxidative mechanisms required to improve animal health and welfare and, to protect meat against...... oxidation. Pharmacological properties and antioxidant effects have been associated to the extract of hops and to the extracts of yerba mate. However, the effects of hops and yerba mate as dietary supplement for animal feeding on the metabolic profile and the redox stability of meat have not been reported...... yet. Addition of extract of mate to a standard maize/soy feed at a level of 0.5, 1.0 or 1.5% to the diet of feedlot for cattle resulted in an increased level of inosine monophosphate, creatine, carnosine and of conjugated linoleic acid in the fresh meat. The tendency to radical formation in meat...

  2. Effect of ethanol consumption during gestation on maternal-fetal amino acid metabolism in the rat

    International Nuclear Information System (INIS)

    Lin, G.W.

    1981-01-01

    The distribution of 14 C-alpha-aminoisobutyric acid (AIB), administered intravenously, in maternal, fetal and placental tissues was examined in the rat on gestation-day 21. Ethanol consumption during gestation (day 6 through 21) significantly reduced the uptake of AIB by the placenta and fetus while exerting no influence on maternal tissue AIB uptake. The concentration of fetal plasma free histidine was decreased 50% as a result of maternal ethanol ingestion, but the free histidine level of maternal plasma was not altered. Since no effect on protein content of fetal tissue could be detected, it is speculated that reduced histidine to the fetus might significantly alter the amounts of histamine and carnosine formed via their precursor. The significance of these findings in relation to the Fetal Alcohol Syndrome is discussed

  3. Meat and meat products as a source of bioactive peptides

    Directory of Open Access Journals (Sweden)

    Alfonso Totosaus

    2016-12-01

    Full Text Available Meat is a high protein content food, with great nutritional and biological value. Meat protein hydrolysis begins with the muscle to meat conversion, during meat ageing. After slaughter, endogen enzymes are responsible of meat softening since myofibrillar anchorage proteins are degraded. Protein hydrolysis continues during food preparation. When meat reaches the stomach, pepsin is the first enzyme to interact. As the food travel trough out gastrointestinal tract, pancreatic enzymes degraded the remained protein and the peptidases made the final proteolysis process. The small proteins or peptides are the absorbed to the circulatory system and distributed to the rest of the body. Bioactive peptides activity of meat and meat products is anti-hypertensive mainly, where histidine, carnosine and anserine are the main peptides identified. Another peptide with anti-oxidant activity is glutathione. The content depends on animal species.

  4. Mate extract as feed additive for improvement of beef quality

    DEFF Research Database (Denmark)

    de Zawadzki, Andressa; Arrivetti, Leandro de O.R.; Vidal, Marília P.

    2017-01-01

    Mate (Ilex paraguariensis A.St.-Hil.) is generally recognized as safe (GRAS status) and has a high content of alkaloids, saponins, and phenolic acids. Addition of mate extract to broilers feed has been shown to increase the oxidative stability of chicken meat, however, its effect on beef quality...... from animals supplemented with mate extract has not been investigated so far. Addition of extract of mate to a standard maize/soy feed at a level of 0.5, 1.0 or 1.5% w/w to the diet of feedlot for cattle resulted in increased levels of inosine monophosphate, creatine and carnosine in the fresh meat....... The content of total conjugated linoleic acid increased in the meat as mate extract concentration was increased in the feed. The tendency to radical formation in meat slurries as quantified by EPR spin-trapping decreased as increasing mate extract addition to feed, especially after storage of the meat...

  5. The Effect of Chicken Extract on Mood, Cognition and Heart Rate Variability

    Directory of Open Access Journals (Sweden)

    Hayley Young

    2015-01-01

    Full Text Available Chicken extract, which is rich in anserine and carnosine, has been widely taken in Asian countries as a traditional remedy with various aims, including attenuation of psychological fatigue. The effects of consuming BRAND’S Essence of Chicken (EOC or a placebo on 46 young adults’ responses to a standard psychological “stressor” were considered. Heart rate variability (HRV, cortisol responses, mood and cognition were measured at baseline and after ten days supplementation. EOC resulted in feeling less anxious, depressed and confused and more agreeable and clearheaded. A decrease in HRV was observed after EOC but only in females. Cognition and cortisol levels were not influenced by EOC. Findings suggest that EOC may be a promising supplement to improve mood in a healthy population.

  6. Topical Peptide Treatments with Effective Anti-Aging Results

    Directory of Open Access Journals (Sweden)

    Silke Karin Schagen

    2017-05-01

    Full Text Available In the last two decades, many new peptides have been developed, and new knowledge on how peptides improve the skin has been uncovered. The spectrum of peptides in the field of cosmetics is continuously growing. This review summarizes some of the effective data on cosmeceutical peptides that work against intrinsic and extrinsic aging. Some peptides have been proven in their efficacy through clinical skin trials. Well-known and documented peptides like copper tripeptide are still under research to obtain more details on their effectiveness, and for the development of new treatments. Palmitoyl pentapeptide-4 and Carnosine are other well-researched cosmeceuticals. Additionally, there are many more peptides that are used in cosmetics. However, study results for some are sparse, or have not been published in scientific journals. This article summarizes topical peptides with proven efficacy in controlled in vivo studies.

  7. The effects of polaprezinc on radiation-induced taste alterations

    International Nuclear Information System (INIS)

    Nakamura, Katsumasa; Togao, Osamu; Shikama, Naoto

    2001-01-01

    The effects of polaprezinc (an insoluble zinc complex of L-carnosine) on taste abnormalities were investigated in 22 patients receiving radiation therapy to head and neck malignancies. The total doses to the tongue were 25.5-46.0 Gy (mean, 37.9 Gy). All patients received 75 mg of polaprezinc two times a day with an interval of 0-1,561 days (mean, 305.3 days) after the completion of radiation therapy. The duration of the drug administration was 25-353 days (mean, 96.9 days). Twenty patients (90.9%) were aware of an improvement of a partial or complete loss of taste. Polaprezinc is effective in improving loss of taste after radiation therapy. (author)

  8. The effects of polaprezinc on radiation-induced taste alterations

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Katsumasa; Togao, Osamu [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences; Shikama, Naoto (and others)

    2001-06-01

    The effects of polaprezinc (an insoluble zinc complex of L-carnosine) on taste abnormalities were investigated in 22 patients receiving radiation therapy to head and neck malignancies. The total doses to the tongue were 25.5-46.0 Gy (mean, 37.9 Gy). All patients received 75 mg of polaprezinc two times a day with an interval of 0-1,561 days (mean, 305.3 days) after the completion of radiation therapy. The duration of the drug administration was 25-353 days (mean, 96.9 days). Twenty patients (90.9%) were aware of an improvement of a partial or complete loss of taste. Polaprezinc is effective in improving loss of taste after radiation therapy. (author)

  9. Evidence for the role of histaminergic pathways in neuroprotective mechanism of ischemic postconditioning in mice.

    Science.gov (United States)

    Kaur, Indresh; Kumar, Amit; Jaggi, Amteshwar S; Singh, Nirmal

    2017-08-01

    The present study has been designed to investigate the possible role of histaminergic pathway in neuroprotective mechanism of ischemic postconditioning (iPoCo). Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was employed to produce I/R-induced cerebral injury in National Institutes of Health mice mice. iPoCo involving three episodes of carotid artery occlusion and reperfusion of 10 sec each was instituted immediately after BCAO just before prolonged reperfusion. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using Morris water maze test. Rotarod test, inclined beam-walking test, and neurological severity score (NSS) were performed to assess motor incoordination and sensorimotor abilities. Brain acetylcholine esterase (AChE) activity, brain myeloperoxidase (MPO) activity, brain thiobarbituric acid-reactive species (TBARS), and glutathione level (GSH) were also estimated. BCAO produced a significant rise in cerebral infarct size and NSS along with impairment of memory and motor coordination and biochemical alteration (↑AChE, ↑MPO ↓GSH, and ↑TBARS). iPoCo attenuated the deleterious effect of BCAO on infarct size, memory, NSS, motor coordination, and biochemical markers. Pretreatment of carnosine (a histamine [HA] precursor) potentiated the neuroprotective effects of iPoCo, whereas pretreatment of ketotifen (HA H1 receptor blocker and mast cell stabilizer) abolished the protective effects of iPoCo as well as that of carnosine on iPoCo. It may be concluded that neuroprotective effect of iPoCo probably involves activation of histaminergic pathways. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  10. Physiological and performance responses to a preseason altitude-training camp in elite team-sport athletes.

    Science.gov (United States)

    McLean, Blake D; Buttifant, David; Gore, Christopher J; White, Kevin; Liess, Carsten; Kemp, Justin

    2013-07-01

    Little research has been done on the physiological and performance effects of altitude training on team-sport athletes. Therefore, this study examined changes in 2000-m time-trial running performance (TT), hemoglobin mass (Hbmass), and intramuscular carnosine content of elite Australian Football (AF) players after a preseason altitude camp. Thirty elite AF players completed 19 days of living and training at either moderate altitude (~2130 m; ALT, n = 21) or sea level (CON, n = 9). TT performance and Hbmass were assessed preintervention (PRE) and postintervention (POST1) in both groups and at 4 wk after returning to sea level (POST2) in ALT only. Improvement in TT performance after altitude was likely 1.5% (± 4.8-90%CL) greater in ALT than in CON, with an individual responsiveness of 0.8%. Improvements in TT were maintained at POST2 in ALT. Hbmass after altitude was very likely increased in ALT compared with CON (2.8% ± 3.5%), with an individual responsiveness of 1.3%. Hbmass returned to baseline at POST2. Intramuscular carnosine did not change in either gastrocnemius or soleus from PRE to POST1. A preseason altitude camp improved TT performance and Hbmass in elite AF players to a magnitude similar to that demonstrated by elite endurance athletes undertaking altitude training. The individual responsiveness of both TT and Hbmass was approximately half the group mean effect, indicating that most players gained benefit. The maintenance of running performance for 4 wk, despite Hbmass returning to baseline, suggests that altitude training is a valuable preparation for AF players leading into the competitive season.

  11. High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation

    Science.gov (United States)

    Azzam, Edouard I.; Ferraris, Ronaldo P.; Howell, Roger W.

    2015-01-01

    We examined nutrient transport in the intestines of mice exposed to chronic low-LET 137Cs gamma rays. The mice were whole-body irradiated for 3 days at dose rates of 0, 0.13 and 0.20 Gy/h, for total dose delivery of 0, 9.6 or 14.4 Gy, respectively. The mice were fed either a control diet or a diet supplemented with high levels of vitamins A, C and E. Our results showed that nutrient transport was perturbed by the chronic irradiation conditions. However, no apparent alteration of the macroscopic intestinal structures of the small intestine were observed up to day 10 after initiating irradiation. Jejunal fructose uptake measured in vitro was strongly affected by the chronic irradiation, whereas uptake of proline, carnosine and the bile acid taurocholate in the ileum was less affected. D-glucose transport did not appear to be inhibited significantly by either 9.6 or 14.4 Gy exposure. In the 14.4 Gy irradiated groups, the diet supplemented with high levels of vitamins A, C and E increased intestinal transport of fructose compared to the control diet (day 10; t test, P = 0.032), which correlated with elevated levels of vitamins A, C and E in the plasma and jejunal enterocytes. Our earlier studies with mice exposed acutely to 137Cs gamma rays demonstrated significant protection for transport of fructose, glucose, proline and carnosine. Taken together, these results suggest that high levels of vitamins A, C and E dietary supplements help preserve intestinal nutrient transport when intestines are irradiated chronically or acutely with low-LET gamma rays. PMID:26484399

  12. Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice.

    Science.gov (United States)

    Chao de la Barca, Juan Manuel; Simard, Gilles; Sarzi, Emmanuelle; Chaumette, Tanguy; Rousseau, Guillaume; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Ferré, Marc; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Gueguen, Naïg; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Amati-Bonneau, Patrizia; Procaccio, Vincent; Hamel, Christian; Lenaers, Guy; Reynier, Pascal; Prunier-Mirebeau, Delphine

    2017-02-01

    Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1delTTAG/+ mice. Significant metabolic signatures were found only in the optic nerve and plasma of female mice. The optic nerve signature was characterized by altered concentrations of phospholipids, amino acids, acylcarnitines, and carnosine, whereas the plasma signature showed decreased concentrations of amino acids and sarcosine associated with increased concentrations of several phospholipids. In contrast, the investigation of 3-month-old presymptomatic Opa1delTTAG/+ mice showed no specific plasma signature but revealed a significant optic nerve signature in both sexes, although with a sex effect. The Opa1delTTAG/+ versus wild-type optic nerve signature was characterized by the decreased concentrations of 10 sphingomyelins and 10 lysophosphatidylcholines, suggestive of myelin sheath alteration, and by alteration in the concentrations of metabolites involved in neuroprotection, such as dimethylarginine, carnitine, spermine, spermidine, carnosine, and glutamate, suggesting a concomitant axonal metabolic dysfunction. Our comprehensive metabolomic investigations revealed in symptomatic as well as in presymptomatic Opa1delTTAG/+ mice, a specific sensitiveness of the optic nerve to Opa1 insufficiency, opening new routes for protective therapeutic strategies.

  13. A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients.

    Science.gov (United States)

    Derosa, Giuseppe; D'Angelo, Angela; Romano, Davide; Maffioli, Pamela

    2016-10-28

    The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L -carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG), post-prandial-glucose (PPG), glycated hemoglobin (HbA 1c ), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), lipid profile, high sensitivity C-reactive protein (Hs-CRP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA). There was a reduction of FPG, PPG, and HbA 1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L -carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers.

  14. A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Giuseppe Derosa

    2016-10-01

    Full Text Available The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L-carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG, post-prandial-glucose (PPG, glycated hemoglobin (HbA1c, fasting plasma insulin (FPI, HOMA-index (HOMA-IR, lipid profile, high sensitivity C-reactive protein (Hs-CRP, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, malondialdehyde (MDA. There was a reduction of FPG, PPG, and HbA1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L-carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers.

  15. N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population.

    Science.gov (United States)

    Babizhayev, Mark A; Burke, Leslie; Micans, Philip; Richer, Stuart P

    2009-01-01

    Innovative Vision Products, Inc. (IVP)'s scientists developed the lubricant eye drops (Can-C) designed as 1% N-acetylcarnosine (NAC) prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural L-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C eye drops. In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance), and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years. Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients' glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9 months of treatment with N-acetylcarnosine lubricant eye drops as those with the worth pretreatment vision. The authors made a reference to electronic records of the product sales to patients who have been made the repurchase of the Can-C eye drops since December 2001. Based on this analysis of recorded adjustments to inventory, various parameters were analyzed during the continued repurchase behavior program, including testimonials from buyers. With these figures, researchers judged on the

  16. N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: Glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population

    Directory of Open Access Journals (Sweden)

    Mark A Babizhayev

    2008-10-01

    Full Text Available Mark A Babizhayev1, Leslie Burke2, Philip Micans3, Stuart P Richer4,51Innovative Vision Products, Inc., County of New Castle, Delaware, USA; 2Wise Choice Products LLC, London, England, United Kingdom; 3IAS Group, Sark, United Kingdom; 4Eye Clinic DVA Medical Center, North Chicago, Illinois, USA; 5Department of Family and Preventive Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USABackground: Innovative Vision Products, Inc. (IVP’s scientists developed the lubricant eye drops (Can-C™ designed as 1% N-acetylcarnosine (NAC prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural L-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C™ eye drops.Objective and study design: In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance, and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years.Setting: Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients’ glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9

  17. Redefining face contour with a novel anti-aging cosmetic product: an open-label, prospective clinical study

    Directory of Open Access Journals (Sweden)

    Garre A

    2017-11-01

    Full Text Available Aurora Garre,1 Gemma Martinez-Masana,1 Jaime Piquero-Casals,2 Corinne Granger1 1Innovation and Development, ISDIN S.A., Barcelona, Spain; 2Dermik Clinic, Barcelona, Spain Background: Skin aging is accelerated by multiple extrinsic factors: ultraviolet radiation, smoking and pollution increase oxidative activity, damaging cellular and extracellular components such as DNA, proteins, and lipids. With age, collagen and hyaluronic acid levels decline, resulting in loss of elasticity and moisture of the skin. Over time this damage leads to characteristic signs that make the skin look older: altered facial contour, sagging skin, wrinkles, and an uneven complexion. This study evaluated the anti-aging effects of a new facial cream formulated with carnosine, Alteromonas ferment extract, crosspolymer hyaluronic acid, and a tripeptide. Methods: An open-label intra-individual study to assess the anti-aging efficacy of the investigational product in 33 women aged 45 to 65 years. The product was applied twice daily for 56 days. Facial contour and skin deformation, elasticity, hydration, and complexion were measured with specialized equipment at baseline and days 28 and 56. Additionally, subjects completed questionnaires at days 28 and 56 on the perceived efficacy and cosmetic characteristics of the product. Results: After 56 days of use of the investigational product, a redefining effect was observed, with a significant decrease in sagging jawline (7%. Skin was significantly more hydrated (12%, firmer (29%, and more elastic (20% (P<0.001 for all. On complexion assessment, skin texture (a measure of skin smoothness and spots (brown and red skin lesions also improved significantly (12% and 6% decrease, respectively. In the subjective self-evaluation, the majority of subjects reported that the skin was visibly tightened and more elastic, flexible, and moisturized (91%, 88%, 91%, and 90%, respectively. The product was well tolerated with no adverse events reported

  18. Reactive Oxygen Species and the Aging Eye: Specific Role of Metabolically Active Mitochondria in Maintaining Lens Function and in the Initiation of the Oxidation-Induced Maturity Onset Cataract--A Novel Platform of Mitochondria-Targeted Antioxidants With Broad Therapeutic Potential for Redox Regulation and Detoxification of Oxidants in Eye Diseases.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2016-01-01

    The aging eye appears to be at considerable risk from oxidative stress. A great deal of research indicates that dysfunctional mitochondria are the primary site of reactive oxygen species (ROS). More than 95% of O2 produced during normal metabolism is generated by the electron transport chain in the inner mitochondrial membrane. Mitochondria are also the major target of ROS. Cataract formation, the opacification of the eye lens, is one of the leading causes of human blindness worldwide, accounting for 47.8% of all causes of blindness. Cataracts result from the deposition of aggregated proteins in the eye lens and lens fiber cell plasma membrane damage, which causes clouding of the lens, light scattering, and obstruction of vision. ROS-induced damage in the lens cell may consist of oxidation of proteins, DNA damage, and/or lipid peroxidation, all of which have been implicated in cataractogenesis. This article is an attempt to integrate how mitochondrial ROS are altered in the aging eye along with those protective and repair therapeutic systems believed to regulate ROS levels in ocular tissues and how damage to these systems contributes to age-onset eye disease and cataract formation. Mitochondria-targeted antioxidants might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo. As a result of the combination of weak metal chelating, 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 biologic membranes and aqueous environments and act as the antiapoptotic natural drug compounds The authors developed and patented the new ophthalmic compositions, including N-acetylcarnosine, acting as a prodrug of naturally targeted to mitochondria L-carnosine endowed with pluripotent antioxidant activities combined with mitochondria

  19. Crystallization and preliminary crystallographic study of carnosinase CN2 from mice

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Tetsuo; Unno, Hideaki; Ujita, Sayuri; Otani, Hiroto; Okumura, Nobuaki; Hashida-Okumura, Akiko; Nagai, Katsuya; Kusunoki, Masami, E-mail: kusunoki@protein.osaka-u.ac.jp [Institute for Protein Research, Osaka University, 3-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2006-10-01

    Mouse carnosinase was crystallized in complex with Zn{sup 2+} or Mn{sup 2+} and the complexes are undergoing structure determination by the MAD method. Mammalian tissues contain several histidine-containing dipeptides, of which l-carnosine is the best characterized and is found in various tissues including the brain and skeletal muscles. However, the mechanism for its biosynthesis and degradation have not yet been fully elucidated. Crystallographic study of carnosinase CN2 from mouse has been undertaken in order to understand its enzymatic mechanism from a structural viewpoint. CN2 was crystallized by the hanging-drop vapour-diffusion technique using PEG 3350 as a precipitant. Crystals were obtained in complex with either Mn{sup 2+} or Zn{sup 2+}. Both crystals of CN2 belong to the monoclinic space group P2{sub 1} and have almost identical unit-cell parameters (a = 54.41, b = 199.77, c = 55.49 Å, β = 118.52° for the Zn{sup 2+} complex crystals). Diffraction data were collected to 1.7 and 2.3 Å for Zn{sup 2+} and Mn{sup 2+} complex crystals, respectively, using synchrotron radiation. Structure determination is ongoing using the multiple-wavelength anomalous diffraction (MAD) method.

  20. Crystallization and preliminary crystallographic study of carnosinase CN2 from mice

    International Nuclear Information System (INIS)

    Yamashita, Tetsuo; Unno, Hideaki; Ujita, Sayuri; Otani, Hiroto; Okumura, Nobuaki; Hashida-Okumura, Akiko; Nagai, Katsuya; Kusunoki, Masami

    2006-01-01

    Mouse carnosinase was crystallized in complex with Zn 2+ or Mn 2+ and the complexes are undergoing structure determination by the MAD method. Mammalian tissues contain several histidine-containing dipeptides, of which l-carnosine is the best characterized and is found in various tissues including the brain and skeletal muscles. However, the mechanism for its biosynthesis and degradation have not yet been fully elucidated. Crystallographic study of carnosinase CN2 from mouse has been undertaken in order to understand its enzymatic mechanism from a structural viewpoint. CN2 was crystallized by the hanging-drop vapour-diffusion technique using PEG 3350 as a precipitant. Crystals were obtained in complex with either Mn 2+ or Zn 2+ . Both crystals of CN2 belong to the monoclinic space group P2 1 and have almost identical unit-cell parameters (a = 54.41, b = 199.77, c = 55.49 Å, β = 118.52° for the Zn 2+ complex crystals). Diffraction data were collected to 1.7 and 2.3 Å for Zn 2+ and Mn 2+ complex crystals, respectively, using synchrotron radiation. Structure determination is ongoing using the multiple-wavelength anomalous diffraction (MAD) method

  1. Impact of red meat consumption on the metabolome of rats.

    Science.gov (United States)

    Jakobsen, Louise M A; Yde, Christian C; Van Hecke, Thomas; Jessen, Randi; Young, Jette F; De Smet, Stefaan; Bertram, Hanne Christine

    2017-03-01

    The scope of the present study was to investigate the effects of red versus white meat intake on the metabolome of rats. Twenty-four male Sprague-Dawley rats were randomly assigned to 15 days of ad libitum feeding of one of four experimental diets: (i) lean chicken, (ii) chicken with lard, (iii) lean beef, and (iv) beef with lard. Urine, feces, plasma, and colon tissue samples were analyzed using 1 H NMR-based metabolomics and real-time PCR was performed on colon tissue to examine the expression of specific genes. Urinary excretion of acetate and anserine was higher after chicken intake, while carnosine, fumarate, and trimethylamine N-oxide excretion were higher after beef intake. In colon tissue, higher choline levels and lower lipid levels were found after intake of chicken compared to beef. Expression of the apc gene was higher in response to the lean chicken and beef with lard diets. Correlation analysis revealed that intestinal apc gene expression was correlated with fecal lactate content (R 2 = 0.65). This study is the first to identify specific differences in the metabolome related to the intake of red and white meat. These differences may reflect perturbations in endogenous metabolism that can be linked to the proposed harmful effects associated with intake of red meat. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Proton MRS in neurological disorders

    Energy Technology Data Exchange (ETDEWEB)

    Bonavita, S.; Di Salle, F.; Tedeschi, G

    1999-05-01

    Proton magnetic resonance spectroscopy ({sup 1}H MRS) permits the acquisition of the signal arising from several brain metabolites. At long echo-time (TE) {sup 1}H MRS can detect N-acetyl-aspartate containing compounds, choline containing compounds, creatine+phosphocreatine and lactate. At short TE, lipids, tryglicerides, alanine, glutamate, glutamine, GABA, scyllo-inositol, glucose, myo-inositol, carnosine and histydine are visible. {sup 1}H MRS can be performed with single-voxel, multivoxel, single slice and multislice techniques. With single voxel {sup 1}H MRS it is possible to measure metabolites relaxation time, which allows the measurement of metabolite concentrations. This technique can be useful in the study of focal lesions in the central nervous system (CNS) such as epilepsy (pre-surgical identification of epileptic focus), brain tumors (evaluation of recurrence and radiation necrosis), stroke, multiple sclerosis, etc. Single slice and multislice {sup 1}H MRS imaging ({sup 1}H MRSI) can be performed only at long TE and permits the mapping of the brain metabolites distribution which makes them particularly useful in studying diffuse diseases and heterogeneous lesions of the CNS. {sup 1}H MRS can also be useful in the evaluation of 'ischemic penumbra' of stroke; developmental (myelin and neuronal dysgenesis); head trauma (evaluation of cerebral damage not visible with MRI); degenerative disorders (identification of microscopic pathology not visible with MRI); and metabolic diseases (metabolic disturbances with specific metabolic patterns)

  3. Water-Soluble Vitamin E-Tocopheryl Phosphate.

    Science.gov (United States)

    Zingg, Jean-Marc

    The hydrophobicity of vitamin E poses transport and metabolic challenges to regulate its bioavailability and to prevent its accumulation in lipid-rich tissues such as adipose tissue, brain, and liver. Water-soluble precursors of vitamin E (α-tocopherol, αT), such as its esters with acetate (αTA), succinate (αTS), or phosphate (αTP), have increased solubility in water and stability against reaction with free radicals, but they are rapidly converted during their uptake into the lipid-soluble vitamin E. Therefore, the bioavailability of these precursors as intact molecules is low; nevertheless, at least for αTS and αTP, the recent research has revealed unique regulatory effects on signal transduction and gene expression and the modulation of cellular events ranging from proliferation, survival/apoptosis, lipid uptake and metabolism, phagocytosis, long term potentiation, cell migration, telomere maintenance, and angiogenesis. Moreover, water-soluble derivatives of vitamin E including some based on αTP are increasingly used as components of nanocarriers for enhanced and targeted delivery of drugs and other molecules (vitamins, including αT and αTP itself, vitamin D3, carnosine, caffeine, docosahexaenoic acid (DHA), insulin) and cofactors such as coenzyme Q10. In this review, the chemical characteristics, transport, metabolic pathways, and molecular mechanisms of action of αTP in cells and tissues are summarized and put into perspective with its possible role in the prevention of a number of diseases. © 2018 Elsevier Inc. All rights reserved.

  4. [The significance of free radicals and antioxidants due to the load induced by sport activity].

    Science.gov (United States)

    Holecek, V; Liska, J; Racek, J; Rokyta, R

    2004-01-01

    Sport performance is followed by a high production of free radicals. The main reasons are reperfusion after the previous imbalance between the increased need of the organism and the ability of blood supply by oxygen, increased production of ATP, decomposition of the cells particularly white blood cells, oxidation of the purin basis from DNA, stress, output of epinephrine release of free iron, increased temperature in the muscle and its inflammation, and the reception of free radicals from external environment. Peroxidation of lipids, proteins, DNA and other compounds follows the previous biochemical steps. Antioxidants are consumed by free radicals, antioxidative enzymes are released into blood plasma, intracellular calcium is increased, the production of nitric oxide rises, the levels of hydrogen peroxide and hypochlorous acid increase. These penetrate through the membranes and oxidatively damage the tissues. Training improves the ability of the organism to balance the increased load of free radicals. The damage can be lowered by the application of a mixture of antioxidants, the most important are vitamin C, A, E, glutathione, selenium, carnosine, eventually bioflavonoids and ginkgo biloba. The lack of antioxidants can significantly diminish the sport performance and therefore the supplementation with antioxidants is for top sportsmen but also for aged people advisable.

  5. Lipid stability in meat and meat products.

    Science.gov (United States)

    Morrissey, P A; Sheehy, P J; Galvin, K; Kerry, J P; Buckley, D J

    1998-01-01

    Lipid oxidation is one of the main factors limiting the quality and acceptability of meats and meat products. Oxidative damage to lipids occurs in the living animal because of an imbalance between the production of reactive oxygen species and the animal's defence mechanisms. This may be brought about by a high intake of oxidized lipids or poly-unsaturated fatty acids, or a low intake of nutrients involved in the antioxidant defence system. Damage to lipids may be accentuated in the immediate post-slaughter period and, in particular, during handling, processing, storage and cooking. In recent years, pressure to reduce artificial additive use in foods has led to attempts to increase meat stability by dietary strategies. These include supplementation of animal diets with vitamin E, ascorbic acid, or carotenoids, or withdrawal of trace mineral supplements. Dietary vitamin E supplementation reduces lipid and myoglobin oxidation, and, in certain situations, drip losses in meats. However, vitamin C supplementation appears to have little, if any, beneficial effects on meat stability. The effect of feeding higher levels of carotenoids on meat stability requires further study. Some studies have demonstrated that reducing the iron and copper content of feeds improves meat stability. Post-slaughter carnosine addition may be an effective means of improving lipid stability in processed meats, perhaps in combination with dietary vitamin E supplementation.

  6. Controlled drug release from cross-linked κ-carrageenan/hyaluronic acid membranes.

    Science.gov (United States)

    El-Aassar, M R; El Fawal, G F; Kamoun, Elbadawy A; Fouda, Moustafa M G

    2015-01-01

    In this work, hydrogel membrane composed of; kappa carrageenan (κC) and hyaluronic acid (HA) crosslinked with epichlorohydrine is produced. The optimum condition has been established based on their water absorption properties. Tensile strength (TS) and elongation (E%) for the formed films are evaluated. The obtained films were characterized by FTIR, scanning electron microscopy (SEM) and thermal analysis. All membranes were loaded with l-carnosine as a drug model. The swelling properties and kinetics of the release of the model drug from the crosslinked hydrogel membrane were monitored in buffer medium at 37°C. The equilibrium swelling of films showed fair dependency on the high presence of HA in the hydrogel. Moreover, the cumulative release profile increased significantly and ranged from 28% to 93%, as HA increases. SEM explored that, the porosity increased by increasing HA content; consequently, drug release into the pores and channels of the membranes is facilitated. In addition, water uptake % increased as well. A slight change in TS occurred by increasing the HA% to κC, while the highest value of strain for κC membrane was 498.38% by using 3% HA. The thermal stability of the κC/HA was higher than that of HA. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Patterns of free amino acids in German convenience food products: marked mismatch between label information and composition.

    Science.gov (United States)

    Hermanussen, M; Gonder, U; Jakobs, C; Stegemann, D; Hoffmann, G

    2010-01-01

    Free amino acids affect food palatability. As information on amino acids in frequently purchased pre-packaged food is virtually absent, we analyzed free amino acid patterns of 17 frequently purchased ready-to-serve convenience food products, and compared them with the information obtained from the respective food labels. Quantitative amino acid analysis was performed using ion-exchange chromatography. gamma-Aminobutyric acid (GABA) concentrations were verified using a stable isotope dilution gas chromatography/mass spectrometry (GC-MS) method. The patterns of free amino acids were compared with information obtained from food labels. An obvious mismatch between free amino acid patterns and food label information was detected. Even on considering that tomatoes and cereal proteins are naturally rich in glutamate, the concentrations of free glutamate outranged the natural concentration of this amino acid in several products, and strongly suggested artificial enrichment. Free glutamate was found to be elevated even in dishes that explicitly state 'no glutamate added'. Arginine was markedly elevated in lentils. Free cysteine was generally low, possibly reflecting thermal destruction of this amino acid during food processing. The meat and brain-specific dipeptide carnosine (CARN) was present in most meat-containing products. Some products did not contain detectable amounts of CARN in spite of meat content being claimed on the food labels. We detected GABA at concentrations that contribute significantly to the taste sensation. This investigation highlights a marked mismatch between food label information and food composition.

  8. Antioxidant activities of the synthesized thiol-contained peptides derived from computer-aided pepsin hydrolysis of yam tuber storage protein, dioscorin.

    Science.gov (United States)

    Han, Chuan-Hsiao; Liu, Ju-Chi; Fang, Sheng-Uei; Hou, Wen-Chi

    2013-06-01

    Our previous report showed that yam dioscorin and its peptic hydrolysates exhibit radical scavenging activities; however, the functions of these peptic hydrolases are still under investigation. In this study, the thiol-containing peptides derived from computer-aided simulation of pepsin hydrolysis of dioscorin, namely, KTCGNGME (diotide1), PPCSE (diotide2), CDDRVIRTPLT (diotide3), KTCGY (diotide4), and PPCTE (diotide5) were synthesized to compare their antioxidant activities with GSH and/or carnosine by examining hydroxyl radical scavenging activity by electron spin resonance spectrometry, anti-low-density lipoprotein peroxidation, anti-AAPH-induced hemolysis, and oxygen radical absorbance capacity activity. We found that while all the synthesized diotides showed antioxidant activity, diotide4 exhibited the highest levels. Moreover, all diotides (100 μM) showed protective effects against methylglyoxal-induced human umbilical vein endothelial cell death. These results suggest that thiol-containing diotides derived from dioscorin hydrolysis exhibit antioxidant activities and reveal the benefits of yam tuber as an antioxidant-rich food. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Strategies for designing novel functional meat products.

    Science.gov (United States)

    Arihara, Keizo

    2006-09-01

    In recent years, much attention has been paid to physiological functions of foods due to increasing concerns for health. Although there has been limited information of physiological functions of meat until recently, several attractive meat-based bioactive compounds, such as carnosine, anserine, l-carnitine, conjugated linoleic acid, have been studied. Emphasizing these activities is one possible approach for improving the health image of meat and developing functional meat products. This article provides potential benefits of representative meat-based bioactive compounds on human health and an overview of meat-based functional products. Strategies for designing novel functional meat products utilizing bioactive peptides and/or probiotic bacteria, is also discussed. This article focuses particularly on the possibility of meat protein-derived bioactive peptides, such as antihypertensive peptides. There are still some hurdles in developing and marketing novel functional meat products since such products are unconventional and consumers in many countries recognize meat and meat products to be bad for health. Along with accumulation of scientific data, there is an urgent need to inform consumers of the exact functional value of meat and meat products including novel functional foods.

  10. Metabolic Signature of Remote Ischemic Preconditioning Involving a Cocktail of Amino Acids and Biogenic Amines.

    Science.gov (United States)

    Chao de la Barca, Juan Manuel; Bakhta, Oussama; Kalakech, Hussein; Simard, Gilles; Tamareille, Sophie; Catros, Véronique; Callebert, Jacques; Gadras, Cédric; Tessier, Lydie; Reynier, Pascal; Prunier, Fabrice; Mirebeau-Prunier, Delphine

    2016-09-24

    Remote ischemic preconditioning (RIPC) is an attractive therapeutic procedure for protecting the heart against ischemia/reperfusion injury. Despite evidence of humoral mediators transported through the circulation playing a critical role, their actual identities so far remain unknown. We sought to identify plasmatic RIPC-induced metabolites that may play a role. Rat plasma samples from RIPC and control groups were analyzed using a targeted metabolomic approach aimed at measuring 188 metabolites. Principal component analysis and orthogonal partial least-squares discriminant analysis were used to identify the metabolites that discriminated between groups. Plasma samples from 50 patients subjected to RIPC were secondarily explored to confirm the results obtained in rats. Finally, a combination of the metabolites that were significantly increased in both rat and human plasma was injected prior to myocardial ischemia/reperfusion in rats. In the rat samples, 124 molecules were accurately quantified. Six metabolites (ornithine, glycine, kynurenine, spermine, carnosine, and serotonin) were the most significant variables for marked differentiation between the RIPC and control groups. In human plasma, analysis confirmed ornithine decrease and kynurenine and glycine increase following RIPC. Injection of the glycine and kynurenine alone or in combination replicated the protective effects of RIPC seen in rats. We have hereby reported significant variations in a cocktail of amino acids and biogenic amines after remote ischemic preconditioning in both rat and human plasma. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01390129. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  11. Hyperfine structure analysis in magnetic resonance spectroscopy: from astrophysical measurements towards endogenous biosensors in human tissue; Hyperfeinstruktur-Analyse in der Magnetresonanzspektroskopie: von astrophysikalischen Messungen zu endogenen Biosensoren in menschlichem Gewebe

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, L. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Medizinische Physik in der Radiologie; California Univ., Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab., Berkeley, CA (United States). Dept. of Chemistry

    2007-07-01

    The hyperfine interaction of two spins is a well studied effect in atomic systems. Magnetic resonance experiments demonstrate that the detectable dipole transitions are determined by the magnetic moments of the constituents and the external magnetic field. Transferring the corresponding quantum mechanics to molecular bound nuclear spins allows for precise prediction of NMR spectra obtained from metabolites in human tissue. This molecular hyperfine structure has been neglected so far in in vivo NMR spectroscopy but contains useful information, especially when studying molecular dynamics. This contribution represents a review of the concept of applying the Breit-Rabi formalism to coupled nuclear spins and discusses the immobilization of different metabolites in anisotropic tissue revealed by 1H NMR spectra of carnosine, phosphocreatine and taurine. Comparison of atomic and molecular spin systems allows for statements on the biological constraints for direct spin-spin interactions. Moreover, the relevance of hyperfine effects on the line shapes of multiplets of indirectly-coupled spin systems with more than two constituents can be predicted by analyzing quantum mechanical parameters. As an example, the superposition of eigenstates of the AMX system of adenosine 5'-triphosphate and its application for better quantification of 31P-NMR spectra will be discussed. (orig.)

  12. Hyperfine structure analysis in magnetic resonance spectroscopy: from astrophysical measurements towards endogenous biosensors in human tissue

    International Nuclear Information System (INIS)

    Schroeder, L.; California Univ., Berkeley, CA; Lawrence Berkeley National Lab., Berkeley, CA

    2007-01-01

    The hyperfine interaction of two spins is a well studied effect in atomic systems. Magnetic resonance experiments demonstrate that the detectable dipole transitions are determined by the magnetic moments of the constituents and the external magnetic field. Transferring the corresponding quantum mechanics to molecular bound nuclear spins allows for precise prediction of NMR spectra obtained from metabolites in human tissue. This molecular hyperfine structure has been neglected so far in in vivo NMR spectroscopy but contains useful information, especially when studying molecular dynamics. This contribution represents a review of the concept of applying the Breit-Rabi formalism to coupled nuclear spins and discusses the immobilization of different metabolites in anisotropic tissue revealed by 1H NMR spectra of carnosine, phosphocreatine and taurine. Comparison of atomic and molecular spin systems allows for statements on the biological constraints for direct spin-spin interactions. Moreover, the relevance of hyperfine effects on the line shapes of multiplets of indirectly-coupled spin systems with more than two constituents can be predicted by analyzing quantum mechanical parameters. As an example, the superposition of eigenstates of the AMX system of adenosine 5'-triphosphate and its application for better quantification of 31P-NMR spectra will be discussed. (orig.)

  13. [Hyperfine structure analysis in magnetic resonance spectroscopy: from astrophysical measurements towards endogenous biosensors in human tissue].

    Science.gov (United States)

    Schröder, Leif

    2007-01-01

    The hyperfine interaction of two spins is a well studied effect in atomic systems. Magnetic resonance experiments demonstrate that the detectable dipole transitions are determined by the magnetic moments of the constituents and the external magnetic field. Transferring the corresponding quantum mechanics to molecular bound nuclear spins allows for precise prediction of NMR spectra obtained from metabolites in human tissue. This molecular hyperfine structure has been neglected so far in in vivo NMR spectroscopy but contains useful information, especially when studying molecular dynamics. This contribution represents a review of the concept of applying the Breit-Rabi formalism to coupled nuclear spins and discusses the immobilization of different metabolites in anisotropic tissue revealed by 1H NMR spectra of carnosine, phosphocreatine and taurine. Comparison of atomic and molecular spin systems allows for statements on the biological constraints for direct spin-spin interactions. Moreover, the relevance of hyperfine effects on the line shapes of multiplets of indirectly-coupled spin systems with more than two constituents can be predicted by analyzing quantum mechanical parameters. As an example, the superposition of eigenstates of the A MX system of adenosine 5'-triphosphate and its application for better quantification of 31P-NMR spectra will be discussed.

  14. Ergothioneine, histidine, and two naturally occurring histidine dipeptides as radioprotectors against gamma-irradiation inactivation of bacteriophages T4 and P22

    International Nuclear Information System (INIS)

    Hartman, P.E.; Hartman, Z.; Citardi, M.J.

    1988-01-01

    Bacteriophages P22, T4+, and T4os (osmotic shock-resistant mutant with altered capsids) were diluted in 0.85% NaCl and exposed to gamma irradiation (2.79 Gy/min) at room temperature (24 degrees C). T4+ was more sensitive to inactivation than was P22, and the T4os mutant was even more sensitive than T4+. Catalase exhibited a strong protective effect and superoxide dismutase a weaker protection, indicating that H 2 O 2 or some product derived therefrom was predominant in causing inactivation of plaque formation. Low but significant (0.1-0.3 mM) reduced glutathione (GSH) enhanced phage inactivation, but a higher (1 mM) GSH concentration protected. A similar effect was found for the polyamine, spermidine. In contrast, 0.1 mM L-ergothioneine (2-thiol-L-histidine betaine) exhibited strong protection and 1 mM afforded essentially complete protection. L-Ergothioneine is present in millimolar concentrations in some fungi and is conserved up to millimolar concentrations in critical tissues when consumed by man. L-Histidine and two histidine-containing dipeptides, carnosine and anserine, protected at a concentration of 1 mM, a level at which they are present in striated muscles of various animals

  15. Variability in the contents of pork meat nutrients and how it may affect food composition databases.

    Science.gov (United States)

    Reig, Milagro; Aristoy, M-Concepción; Toldrá, Fidel

    2013-10-01

    Pork meat is generally recognised as a food with relevant nutritional properties because of its content in high biological value proteins, group B vitamins, minerals especially heme iron, trace elements and other bioactive compounds. But pork meat also contributes to the intake of fat, saturated fatty acids, cholesterol, and other substances that, in inappropriate amounts, may result in negative physiologically effects. However, there are relevant factors affecting the content of many of these substances and somehow such variability should be taken into consideration. So, genetics, age and even type of muscle have a relevant influence on the amount of fat and the contents in heme iron. Also the composition in fatty acids of triacylglycerols is very sensitive to the contents of cereals in the feed; for instance, polyunsaturated fatty acids may range from 10% to 22% in pork meat. The content of other nutrients, like vitamins E and A, are also depending on the type of feed. Some bioactive substances like coenzyme Q10, taurine, glutamine, creatine, creatinine, carnosine and anserine show a large dependence on the type of muscle. This manuscript describes the main factors affecting the composition of pork meat nutrients and how these changes may affect the general food composition databases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Radiation-induced changes in the patterns of free ninhydrin-reactive substances of meat

    International Nuclear Information System (INIS)

    Partmann, W.; Keskin, S.

    1979-01-01

    Samples of minced lean beef and pork, breast muscle of chicken, and white meat of carp packed in polyethylene/Hostaphan bags were irradiated in the presence of air at about 25 0 C with 10-MeV electrons. The doses applied were for beef 0.5-20 Mrad, and for other meat samples 10 Mrad. In the dose range of 0-5 Mrad, no statistically significant changes in the composition of the free amino acids and similar compounds usually present in beef were found. In the dose range between 10 and 20 Mrad a tendency towards small losses in such components became obvious. In beef samples irradiated at doses >= 0.5 Mrad a new substance (Y) appeared distinctly in the zone of the basic amino-acids. This compound was detected by two independent methods, column chromatography and high-voltage electrophoresis. The yellow colour of the band appearing above carnosine in the pherogram was striking. Substance Y was also found after irradiation of pork and chicken meat. At a dose of 10 Mrad the concentration of Y in white chicken meat was nearly three times higher than in beef and pork. After irradiation of white carp muscle no Y, but another new basic compound (X) was observed. In the pherograms it appeared as a brwonish-red band above β-alanine. (orig./AJ) [de

  17. Effects of Rice Bran, Flax Seed, and Sunflower Seed on Growth Performance, Carcass Characteristics, Fatty Acid Composition, Free Amino Acid and Peptide Contents, and Sensory Evaluations of Native Korean Cattle (Hanwoo

    Directory of Open Access Journals (Sweden)

    Chang Bon Choi

    2016-02-01

    Full Text Available This study was conducted to evaluate the effect of dietary supplementation with rice bran, flax seed, or sunflower seed to finishing native Korean cattle (Hanwoo on growth performances, carcass characteristics, fatty acid composition, free amino acid and peptide contents, and sensory evaluations of Longissimus muscle (LM. A total of 39 Hanwoo steers (average age of 22.2 mo and average body weight (BW of 552.2 kg were randomly divided into Control, rice bran (RB, flax seed (FS, or Sunflower seed (SS groups. The steers were group fed for 273 d until they reached an average age of 31.2 mo. Final BW was 768.2, 785.8, 786.2, and 789.0 kg, and average daily gain was 0.79, 0.85, 0.82, and 0.84 kg for the Control, RS, FS, and SS groups, respectively (p>0.05. Fat thickness of the FS group (19.8 mm was greater (p0.05 scores for flavor, umami, and overall palatability in sensory evaluations. In conclusion, supplementation of flax seed to diets of finishing Hanwoo steers improved sensory evaluations which might have been caused by increases in flavor related amino acids such as methionine, glutamic acid and α-AAA and peptides, anserine and carnosine, and their complex reactions.

  18. Marked heterogeneity in growth characteristics of myoblast clonal cultures and myoblast mixed cultures obtained from the same individual.

    Science.gov (United States)

    Maier, Andrea B; Cohen, Ron; Blom, Joke; van Heemst, Diana; Westendorp, Rudi G J

    2012-01-01

    Sarcopenia is defined as an age-related decrease in skeletal muscle mass and function while adjacent satellite cells are unable to compensate for this loss. However, myoblast cultures can be established even in the presence of sarcopenia. It is yet unknown whether satellite cells from failing muscle in older age are equally affected, as human satellite cells have been assessed using myoblast mixed cultures and not by using myoblast clonal cultures. We questioned to what extent myoblast mixed cultures reflect the in vivo characteristics of single satellite cells from adult skeletal muscle. We established a myoblast mixed culture and three myoblast clonal cultures out of the same muscle biopsy and cultured these cells for 100 days. Replicative capacity and oxidative stress resistance were compared. We found marked heterogeneity between the myoblast clonal cultures that all had a significantly lower replicative capacity when compared to the mixed culture. Replicative capacity of the clonal cultures was inversely related to the β-galactosidase activity after exposure to oxidative stress. Addition of L-carnosine enhanced the remaining replicative capacity in all cultures with a concomitant marginal decrease in β-galactosidase activity. It is concluded that myoblast mixed cultures in vitro do not reflect the marked heterogeneity between single isolated satellite cells. The consequences of the heterogeneity on muscle performance remain to be established. Copyright © 2011 S. Karger AG, Basel.

  19. Effects of multibuffer supplementation on acid-base balance and 2,3-diphosphoglycerate following repetitive anaerobic exercise.

    Science.gov (United States)

    Kraemer, W J; Gordon, S E; Lynch, J M; Pop, M E; Clark, K L

    1995-12-01

    The purpose of this investigation was to determine the effects of a 3.5-day dietary multibuffer supplement (containing predominantly inorganic phosphate, or Pi, along with bicarbonate and carnosine, i.e., PhosFuel) on repetitive (four trials separated by 2 min rest) Wingate test (WT) performances and whole blood 2,3-diphosphoglycerate (2,3-DPG) concentrations in 10 recreationally trained road cyclists (T) and 10 normally active but untrained (UT) men. A 2-week washout period was utilized between experimental sessions. Venous blood samples were obtained via cannula once before exercise (baseline), immediately post each WT, and 3 min after the final WT (recovery). The data indicate that this supplement does not affect acid-base status with following intense anaerobic exercise and does not improve repetitive WT performance. However, the supplement does enhance post-exercise levels of 2,3-DPG and the 2,3-DPG/Hb ratio in recreationally trained cyclists while improving acute recovery of peak power in these men.

  20. Nutrients Composition in Fit Snacks Made from Ostrich, Beef and Chicken Dried Meat

    Directory of Open Access Journals (Sweden)

    Żaneta Zdanowska-Sąsiadek

    2018-05-01

    Full Text Available The aim of the study was to compare three types of meat snacks made from ostrich, beef, and chicken meat in relation to their nutrients content including fat, fatty acids, heme iron, and peptides, like anserine and carnosine, from which human health may potentially benefit. Dry meat samples were produced, from one type of muscle, obtained from ostrich (m. ambiens, beef (m. semimembranosus, and broiler chicken meat (m. pectoralis major. The composition of dried ostrich, beef, and chicken meat, with and without spices was compared. We show that meat snacks made from ostrich, beef, and chicken meat were characterized by high concentration of nutrients including proteins, minerals (heme iron especially in ostrich, than in beef, biologically active peptides (carnosine—in beef, anserine—in ostrich then in chicken meat. The, beneficial to human health, n-3 fatty acids levels differed significantly between species. Moreover, ostrich jerky contained four times less fat as compared to beef and half of that in chicken. In conclusion we can say that dried ostrich, beef, and chicken meat could be a good source of nutritional components.

  1. Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo

    Science.gov (United States)

    Abdullah, Muhammad; Kornegay, Joe N.; Honcoop, Aubree; Parry, Traci L.; Balog-Alvarez, Cynthia J.; Muehlbauer, Michael J.; Newgard, Christopher B.; Patterson, Cam

    2017-01-01

    Background: Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. Methods: We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Results: Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF) identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10−3), carnosine (0.40-fold of controls, p = 1.88 × 10−2), fumaric acid (0.40-fold of controls, p = 7.40 × 10−4), lactamide (0.33-fold of controls, p = 4.84 × 10−2), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10−2), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10−2), glutamic acid (2.48-fold of controls, p = 2.63 × 10−2), and proline (1.73-fold of controls, p = 3.01 × 10−2). Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10−4, FDR 4.7 × 10−2), where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid), suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle

  2. Nutraceuticals and Dietary Supplements to Improve Quality of Life and Outcomes in Heart Failure Patients.

    Science.gov (United States)

    Cicero, Arrigo F G; Colletti, Alessandro

    2017-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill or eject blood. It represents a major public health issue, with a prevalence of over 23 million worldwide. The lifetime risk of developing HF is one in five and the most important risk factors identified are ischemic heart disease, hypertension, smoking, obesity and diabetes. Preventive approaches are based on improvements of lifestyle, associated with pharmacological therapy. Several nutraceuticals have shown interesting clinical results in prevention of HF as well as in the treatment of the early stages of the disease, alone or in association with pharmacological therapy. The aim of this review is to resume the available clinical evidence on phytochemicals effect on HF prevention and/or treatment. A systematic search strategy was developed to identify trials in PubMed (January 1980 to April 2016). The terms 'nutraceuticals', 'dietary supplements', 'herbal drug' and 'heart failure' were incorporated into an electronic search strategy. Clinical trials reported that the intake of some nutraceuticals (hawthorn, coenzyme Q10, L-carnitine, Dribose, Carnosine, Vitamin D, Some probiotics, Omega-3 PUFAs, Beet nitrates) is associated with improvements in functional parameters such as ejection fraction, stroke volume and cardiac output in HF patients, with minimal side effects. These findings were sometimes reinforced by subsequent meta-analyses, which further concluded that benefits tended to be greater in earlier stage HF. The main mechanisms involved are antioxidant, antinflammatory, anti-ischemic and antiaggregant effects. Evidence suggests that the supplementation with nutraceuticals may be a useful option for effective management of HF, with the advantage of excellent clinical tolerance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. The influence of a single nucleotide polymorphism within CNDP1 on susceptibility to diabetic nephropathy in Japanese women with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Mahiro Kurashige

    Full Text Available BACKGROUND: Several linkage analyses have mapped a susceptibility locus for diabetic nephropathy to chromosome 18q22-23, and polymorphisms within the carnosine dipeptidase 1 gene (CNDP1, located on 18q22.3, have been shown to be associated with diabetic nephropathy in European subjects with type 2 diabetes. However, the association of this locus with diabetic nephropathy has not been evaluated in the Japanese population. In this study, we examined the association of polymorphisms within the CNDP1/CNDP 2 locus with diabetic nephropathy in Japanese subjects with type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped a leucine repeat polymorphism (D18S880 that is within CNDP1 along with 29 single nucleotide polymorphisms (SNPs in the CNDP1/CNDP2 locus for 2,740 Japanese subjects with type 2 diabetes (1,205 nephropathy cases with overt nephropathy or with end-stage renal disease [ESRD], and 1,535 controls with normoalbuminuria. The association of each polymorphism with diabetic nephropathy was analysed by performing logistic regression analysis. We did not observe any association between D18S880 and diabetic nephropathy in Japanese subjects with type 2 diabetes. None of the 29 SNPs within the CNDP1/CNDP2 locus were associated with diabetic nephropathy, but a subsequent sex-stratified analysis revealed that 1 SNP in CNDP1 was nominally associated with diabetic nephropathy in women (rs12604675-A; p = 0.005, odds ratio [OR] = 1.76, 95% confidence interval [CI], 1.19-2.61. Rs12604675 was associated with overt proteinuria (p = 0.002, OR = 2.18, 95% CI, 1.32-3.60, but not with ESRD in Japanese women with type 2 diabetes. CONCLUSIONS/SIGNIFICANCE: Rs12604675-A in CNDP1 may confer susceptibility to overt proteinuria in Japanese women with type 2 diabetes.

  4. Water-structuring technology with the molecular chaperone proteins: indicated application of the α-crystallin domains and imidazole-containing peptidomimetics in cosmetic skin care systems or dermatological therapeutic drug carrier formulations.

    Science.gov (United States)

    Babizhayev, Mark A; Nikolayev, Gennady M; Nikolayeva, Juliana G; Yegorov, Yegor E

    2011-01-01

    Changes in structural proteins and hydration during aging are responsible for altered skin morphologic and mechanical properties manifested as wrinkling, sagging, loss of elasticity, and apparent dryness. Impairment in protein hydration may add to the ultrastructural, mechanical, and biochemical changes in structural proteins in the aged skin. At Innovative Vision Products, Inc., we have pioneered a molecular chaperone protein-activated therapeutic or cosmetic platform to enable simultaneous analysis of water-binding and structuring characteristics for biology-related or skin aging and skin disease-related pathways. This cutting-edge technology has changed the hydration of proteins in photoaged skin which so that they are more compact and interact with water to limited degree. The mechanisms of skin diseases, aging, and cellular and signaling pathways mediated by targeting with molecular chaperone protein(s) are considered. Skin lesions that are growing, spreading, or pigmented, and those that occur on exposed areas of skin are likely to be treated by these emerging pharmacological chaperones that could have cosmetic or dermatological benefits. Examples of such chaperones are anti-/trans-glycation-imidazole-containing peptidomimetic(s) (natural L-carnosine derivatives and mimetics) combined with the molecular chaperone protein α-crystallin derived from a natural source, brine shrimp (Artemia franciscana) cysts, or with recombinant human αA-crystallin. This patented biotechnology represents an efficient tool with which to mitigate the consequences of free radical-induced skin damage. The article is organized to provide in one place all of the relevant technical information, such as high-performance nuclear magnetic resonance and electron spin resonance application tools, and to describe the entire process from sample preparation to data analysis, which is moving from biological studies to biotechnology batches of the product. The proposed biotechnology results in

  5. Vegan diets: practical advice for athletes and exercisers.

    Science.gov (United States)

    Rogerson, David

    2017-01-01

    With the growth of social media as a platform to share information, veganism is becoming more visible, and could be becoming more accepted in sports and in the health and fitness industry. However, to date, there appears to be a lack of literature that discusses how to manage vegan diets for athletic purposes. This article attempted to review literature in order to provide recommendations for how to construct a vegan diet for athletes and exercisers. While little data could be found in the sports nutrition literature specifically, it was revealed elsewhere that veganism creates challenges that need to be accounted for when designing a nutritious diet. This included the sufficiency of energy and protein; the adequacy of vitamin B12, iron, zinc, calcium, iodine and vitamin D; and the lack of the long-chain n -3 fatty acids EPA and DHA in most plant-based sources. However, via the strategic management of food and appropriate supplementation, it is the contention of this article that a nutritive vegan diet can be designed to achieve the dietary needs of most athletes satisfactorily. Further, it was suggested here that creatine and β-alanine supplementation might be of particular use to vegan athletes, owing to vegetarian diets promoting lower muscle creatine and lower muscle carnosine levels in consumers. Empirical research is needed to examine the effects of vegan diets in athletic populations however, especially if this movement grows in popularity, to ensure that the health and performance of athletic vegans is optimised in accordance with developments in sports nutrition knowledge.

  6. Redefining face contour with a novel anti-aging cosmetic product: an open-label, prospective clinical study.

    Science.gov (United States)

    Garre, Aurora; Martinez-Masana, Gemma; Piquero-Casals, Jaime; Granger, Corinne

    2017-01-01

    Skin aging is accelerated by multiple extrinsic factors: ultraviolet radiation, smoking and pollution increase oxidative activity, damaging cellular and extracellular components such as DNA, proteins, and lipids. With age, collagen and hyaluronic acid levels decline, resulting in loss of elasticity and moisture of the skin. Over time this damage leads to characteristic signs that make the skin look older: altered facial contour, sagging skin, wrinkles, and an uneven complexion. This study evaluated the anti-aging effects of a new facial cream formulated with carnosine, Alteromonas ferment extract, crosspolymer hyaluronic acid, and a tripeptide. An open-label intra-individual study to assess the anti-aging efficacy of the investigational product in 33 women aged 45 to 65 years. The product was applied twice daily for 56 days. Facial contour and skin deformation, elasticity, hydration, and complexion were measured with specialized equipment at baseline and days 28 and 56. Additionally, subjects completed questionnaires at days 28 and 56 on the perceived efficacy and cosmetic characteristics of the product. After 56 days of use of the investigational product, a redefining effect was observed, with a significant decrease in sagging jawline (7%). Skin was significantly more hydrated (12%), firmer (29%), and more elastic (20%) ( P <0.001 for all). On complexion assessment, skin texture (a measure of skin smoothness) and spots (brown and red skin lesions) also improved significantly (12% and 6% decrease, respectively). In the subjective self-evaluation, the majority of subjects reported that the skin was visibly tightened and more elastic, flexible, and moisturized (91%, 88%, 91%, and 90%, respectively). The product was well tolerated with no adverse events reported during the study. This new cosmetic product demonstrated anti-aging effects after 56 days of use, most notably a redefined facial contour and improved complexion. It is a safe and effective anti-aging product.

  7. Anti-Oxidative and Anti-Inflammation Activities of Pork Extracts.

    Science.gov (United States)

    Gil, Juae; Kim, Dongwook; Yoon, Seok-Ki; Ham, Jun-Sang; Jang, Aera

    2016-01-01

    This study was conducted to evaluate the antioxidative and anti-inflammatory effects of boiled pork powder (BPP) and hot water extract powder (HWEP) from 4 cuts of meat from Landrace × Yorkshire × Duroc (LYD). The highest DPPH radical scavenging activities determined were from BPP of Boston butt (13.65 M TE) and HWEP of loin (19.40 M TE) and ham (21.45 M TE). The 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities of BPP from shoulder ham (39.28 M TE) and ham (39.43 M TE) were higher than those of other meat cuts, while HWEP of ham exhibited the highest ABTS radical scavenging activity. A higher oxygen radical absorbance capacity was determined for BPP from ham (198.35 M TE) and in HWEP from loin (204.07 M TE), Boston butt (192.85 M TE), and ham (201.36 M TE). Carnosine content of BPP and HWEP from loin and were determined to be 106.68 and 117.77 mg/g on a dry basis, respectively. The anserine content of BPP (5.26 mg/g, dry basis) and HWEP (6.79 mg/g, dry basis) of shoulder ham exhibited the highest value as compared to the extracts from the other meat cuts. The viability of RAW 264.7 cells was increased with increasing HWEP from loin and ham treatment. In addition, the expression of IL-6 and TNF-α was significantly reduced by HWEP from loin and ham, in a dose dependent manner. These results suggested that boiled pork and hot water extract of pork have antioxidative and cytokine inhibitory effects.

  8. Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: Effect of sex and arsenic exposure

    Science.gov (United States)

    Huang, Madelyn C.; Douillet, Christelle; Su, Mingming; Zhou, Kejun; Wu, Tao; Chen, Wenlian; Galanko, Joseph A.; Drobná, Zuzana; Saunders, R. Jesse; Martin, Elizabeth; Fry, Rebecca C.; Jia, Wei; Stýblo, Miroslav

    2016-01-01

    Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex-specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation. PMID:26883664

  9. Cloning and nucleotide sequence analysis of pepV, a carnosinase gene from Lactobacillus delbrueckii subsp. lactis DSM 7290, and partial characterization of the enzyme.

    Science.gov (United States)

    Vongerichten, K F; Klein, J R; Matern, H; Plapp, R

    1994-10-01

    Cell extracts of Lactobacillus delbrueckii subsp. lactis DSM 7290 were found to exhibit unique peptolytic ability against unusual beta-alanyl-dipeptides. In order to clone the gene encoding this activity, designated pepV, a gene library of strain DSM 7290 genomic DNA, prepared in the low-copy-number plasmid pLG339, was screened for heterologous expression in Escherichia coli. Recombinant clones harbouring pepV were identified by their ability to allow the utilization of carnosine (beta-alanyl-histidine) as a source of histidine by the E. coli mutant strain UK197 (pepD, hisG). Complementation was observed in a colony harbouring a recombinant plasmid (pKV101), carrying pepV. A 2.4 kb fragment containing pepV was subcloned and its nucleotide sequence revealed an open reading frame (ORF) of 1413 nucleotides, corresponding to a protein with predicted molecular mass of 51998 Da. A single transcription initiation site 71 bp upstream of the ATG translational start codon was identified by primer extension. No significant homology was detected between pepV or its deduced amino acid sequence with any entry in the databases. The only similarity was found in a region conserved in the ArgE/DapE/CPG2/YscS family of proteins. This observation, and protease inhibitor studies, indicated that pepV is of the metalloprotease type. A second ORF present in the sequenced fragment showed extensive homology to a variety of amino acid permeases from E. coli and Saccharomyces cerevisiae.

  10. Radiation-induced changes in the patterns of free ninhydrin-reactive substances of meat

    International Nuclear Information System (INIS)

    Partmann, W.; Keskin, S.

    1979-01-01

    Samples of minced lean beef and pork, breast muscle of chicken, and white meat of carp packed in polyethylene/Hostaphan bags were irradiated in the presence of air at about 25 0 C with 10-MeV electrons. The doses applied were for beef 0.5-20 Mrad, and for other meat samples 10 Mrad. In the dose range of 0-5 Mrad, no statistically significant changes in the composition of the free amino acids and similar compounds usually present in beef were found. In the dose range between 10 and 20 Mrad a tendency towards small losses in such components became obvious. In beef samples irradiated at doses >= 0.5 Mrad a new substance (Y) appeared distinctly in the zone of the basic amino-acids. This compound was detected by two independent methods, column chromatography and high-voltage electrophoresis. The yellow colour of the band appearing above carnosine in the pherogram was striking. Substance Y was also found after irradiation of pork and chicken meat. At a dose of 10 Mrad the concentration of Y in white chicken meat was nearly three times higher than in beef and pork. After irradiation of white carp muscle no Y, but another new basic compound (X) was observed. In the pherograms it appeared as a brownish-red band above β-alanine. The irradiation products X and Y may be used to find out whether meat of animals as used in this investigation had been exposed to radiation, if doses of 0.5 Mrad or higher were applied. (orig.) [de

  11. β-alanine supplementation improves isometric endurance of the knee extensor muscles

    Directory of Open Access Journals (Sweden)

    Sale Craig

    2012-06-01

    Full Text Available Abstract Background We examined the effect of four weeks of β-alanine supplementation on isometric endurance of the knee extensors at 45% maximal voluntary isometric contraction (MVIC. Methods Thirteen males (age 23 ± 6 y; height 1.80 ± 0.05 m; body mass 81.0 ± 10.5 kg, matched for pre-supplementation isometric endurance, were allocated to either a placebo (n = 6 or β-alanine (n = 7; 6.4 g·d-1 over 4 weeks supplementation group. Participants completed an isometric knee extension test (IKET to fatigue, at an intensity of 45% MVIC, before and after supplementation. In addition, two habituation tests were completed in the week prior to the pre-supplementation test and a further practice test was completed in the week prior to the post-supplementation test. MVIC force, IKET hold-time, and impulse generated were recorded. Results IKET hold-time increased by 9.7 ± 9.4 s (13.2% and impulse by 3.7 ± 1.3 kN·s-1 (13.9% following β-alanine supplementation. These changes were significantly greater than those in the placebo group (IKET: t(11 = 2.9, p ≤0.05; impulse: t(11 = 3.1, p ≤ 0.05. There were no significant changes in MVIC force in either group. Conclusion Four weeks of β-alanine supplementation at 6.4 g·d-1 improved endurance capacity of the knee extensors at 45% MVIC, which most likely results from improved pH regulation within the muscle cell as a result of elevated muscle carnosine levels.

  12. Crystal structure and mutational analysis of aminoacylhistidine dipeptidase from Vibrio alginolyticus reveal a new architecture of M20 metallopeptidases.

    Science.gov (United States)

    Chang, Chin-Yuan; Hsieh, Yin-Cheng; Wang, Ting-Yi; Chen, Yi-Chin; Wang, Yu-Kuo; Chiang, Ting-Wei; Chen, Yi-Ju; Chang, Cheng-Hsiang; Chen, Chun-Jung; Wu, Tung-Kung

    2010-12-10

    Aminoacylhistidine dipeptidases (PepD, EC 3.4.13.3) belong to the family of M20 metallopeptidases from the metallopeptidase H clan that catalyze a broad range of dipeptide and tripeptide substrates, including L-carnosine and L-homocarnosine. Homocarnosine has been suggested as a precursor for the neurotransmitter γ-aminobutyric acid (GABA) and may mediate the antiseizure effects of GABAergic therapies. Here, we report the crystal structure of PepD from Vibrio alginolyticus and the results of mutational analysis of substrate-binding residues in the C-terminal as well as substrate specificity of the PepD catalytic domain-alone truncated protein PepD(CAT). The structure of PepD was found to exist as a homodimer, in which each monomer comprises a catalytic domain containing two zinc ions at the active site center for its hydrolytic function and a lid domain utilizing hydrogen bonds between helices to form the dimer interface. Although the PepD is structurally similar to PepV, which exists as a monomer, putative substrate-binding residues reside in different topological regions of the polypeptide chain. In addition, the lid domain of the PepD contains an "extra" domain not observed in related M20 family metallopeptidases with a dimeric structure. Mutational assays confirmed both the putative di-zinc allocations and the architecture of substrate recognition. In addition, the catalytic domain-alone truncated PepD(CAT) exhibited substrate specificity to l-homocarnosine compared with that of the wild-type PepD, indicating a potential value in applications of PepD(CAT) for GABAergic therapies or neuroprotection.

  13. Novel and emerging treatments for autism spectrum disorders: a systematic review.

    Science.gov (United States)

    Rossignol, Daniel A

    2009-01-01

    Currently, only one medication (risperidone) is FDA-approved for the treatment of autism spectrum disorders (ASD). Perhaps for this reason, the use of novel, unconventional, and off-label treatments for ASD is common, with up to 74% of children with ASD using these treatments; however, treating physicians are often unaware of this usage. A systematic literature search of electronic scientific databases was performed to identify studies of novel and emerging treatments for ASD, including nutritional supplements, diets, medications, and nonbiological treatments. A grade of recommendation ("Grade") was then assigned to each treatment using a validated evidence-based guideline as outlined in this review: A: Supported by at least 2 prospective randomized controlled trials (RCTs) or 1 systematic review. B: Supported by at least 1 prospective RCT or 2 nonrandomized controlled trials. C: Supported by at least 1 nonrandomized controlled trial or 2 case series. D: Troublingly inconsistent or inconclusive studies or studies reporting no improvements. Potential adverse effects for each treatment were also reviewed. Grade A treatments for ASD include melatonin, acetylcholinesterase inhibitors, naltrexone, and music therapy. Grade B treatments include carnitine, tetrahydrobiopterin, vitamin C, alpha-2 adrenergic agonists, hyperbaric oxygen treatment, immunomodulation and anti-inflammatory treatments, oxytocin, and vision therapy. Grade C treatments for ASD include carnosine, multivitamin/mineral complex, piracetam, polyunsaturated fatty acids, vitamin B6/magnesium, elimination diets, chelation, cyproheptadine, famotidine, glutamate antagonists, acupuncture, auditory integration training, massage, and neurofeedback. The reviewed treatments for ASD are commonly used, and some are supported by prospective RCTs. Promising treatments include melatonin, antioxidants, acetylcholinesterase inhibitors, naltrexone, and music therapy. All of the reviewed treatments are currently considered

  14. A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel.

    Science.gov (United States)

    Frye, Richard E; Rossignol, Daniel; Casanova, Manuel F; Brown, Gregory L; Martin, Victoria; Edelson, Stephen; Coben, Robert; Lewine, Jeffrey; Slattery, John C; Lau, Chrystal; Hardy, Paul; Fatemi, S Hossein; Folsom, Timothy D; Macfabe, Derrick; Adams, James B

    2013-09-13

    Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports l-carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and l-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals

  15. A review of traditional and novel treatments for seizures in autism spectrum disorder: Findings from a systematic review and expert panel.

    Directory of Open Access Journals (Sweden)

    Richard Eugene Frye

    2013-09-01

    Full Text Available Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD, the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections and immunomodulation and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports L-carnitine, multivitamins and N-acetyl-L-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet and transcranial magnetic simulation. Zinc and L-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD

  16. Coupled Ca2+/H+ transport by cytoplasmic buffers regulates local Ca2+ and H+ ion signaling.

    Science.gov (United States)

    Swietach, Pawel; Youm, Jae-Boum; Saegusa, Noriko; Leem, Chae-Hun; Spitzer, Kenneth W; Vaughan-Jones, Richard D

    2013-05-28

    Ca(2+) signaling regulates cell function. This is subject to modulation by H(+) ions that are universal end-products of metabolism. Due to slow diffusion and common buffers, changes in cytoplasmic [Ca(2+)] ([Ca(2+)]i) or [H(+)] ([H(+)]i) can become compartmentalized, leading potentially to complex spatial Ca(2+)/H(+) coupling. This was studied by fluorescence imaging of cardiac myocytes. An increase in [H(+)]i, produced by superfusion of acetate (salt of membrane-permeant weak acid), evoked a [Ca(2+)]i rise, independent of sarcolemmal Ca(2+) influx or release from mitochondria, sarcoplasmic reticulum, or acidic stores. Photolytic H(+) uncaging from 2-nitrobenzaldehyde also raised [Ca(2+)]i, and the yield was reduced following inhibition of glycolysis or mitochondrial respiration. H(+) uncaging into buffer mixtures in vitro demonstrated that Ca(2+) unloading from proteins, histidyl dipeptides (HDPs; e.g., carnosine), and ATP can underlie the H(+)-evoked [Ca(2+)]i rise. Raising [H(+)]i tonically at one end of a myocyte evoked a local [Ca(2+)]i rise in the acidic microdomain, which did not dissipate. The result is consistent with uphill Ca(2+) transport into the acidic zone via Ca(2+)/H(+) exchange on diffusible HDPs and ATP molecules, energized by the [H(+)]i gradient. Ca(2+) recruitment to a localized acid microdomain was greatly reduced during intracellular Mg(2+) overload or by ATP depletion, maneuvers that reduce the Ca(2+)-carrying capacity of HDPs. Cytoplasmic HDPs and ATP underlie spatial Ca(2+)/H(+) coupling in the cardiac myocyte by providing ion exchange and transport on common buffer sites. Given the abundance of cellular HDPs and ATP, spatial Ca(2+)/H(+) coupling is likely to be of general importance in cell signaling.

  17. Metabolomic Profiling in Individuals with a Failing Kidney Allograft.

    Directory of Open Access Journals (Sweden)

    Roberto Bassi

    Full Text Available Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease.To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3. Ten healthy non-allograft individuals were chosen as controls.LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA and short-chain acylcarnitines (C4 and C12, (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively. The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively. In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05 in individuals with lower GFR levels.We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function.

  18. Antisera to gamma-aminobutyric acid. I. Production and characterization using a new model system.

    Science.gov (United States)

    Hodgson, A J; Penke, B; Erdei, A; Chubb, I W; Somogyi, P

    1985-03-01

    Antisera to the amino acid gamma-aminobutyric acid (GABA) have been developed with the aim of immunohistochemical visualization of neurons that use it as a neurotransmitter. GABA bound to bovine serum albumin was the immunogen. The reactivities of the sera to GABA and a variety of structurally related compounds were tested by coupling these compounds to nitrocellulose paper activated with polylysine and glutaraldehyde and incubating the paper with the unlabeled antibody enzyme method, thus simulating immunohistochemistry of tissue sections. The antisera did not react with L-glutamate, L-aspartate, D-aspartate, glycine, taurine, L-glutamine, L-lysine, L-threonine, L-alanine, alpha-aminobutyrate, beta-aminobutyrate, putrescine, or delta-aminolevulinate. There was cross-reaction with gamma-amino-beta-hydroxybutyrate, 1-10%, and the homologues of GABA: beta-alanine, 1-10%, delta-aminovalerate, approximately 10%, and epsilon-amino-caproate, approximately 10%. The antisera reacted slightly with the dipeptide gamma-aminobutyrylleucine, but not carnosine or homocarnosine. Immunostaining of GABA was completely abolished by adsorption of the sera to GABA coupled to polyacrylamide beads by glutaraldehyde. The immunohistochemical model is simple, amino acids and peptides are bound in the same way as in aldehyde-fixed tissue and, in contrast to radioimmunoassay, it uses an immunohistochemical detection system. This method has enabled us to define the high specificity of anti-GABA sera and to use them in some novel ways. The model should prove useful in assessing the specificity of other antisera.

  19. Smoking and health: association between telomere length and factors impacting on human disease, quality of life and life span in a large population-based cohort under the effect of smoking duration.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2011-08-01

    Reactive oxygen species (ROS) are of primary importance as they cause damage to lipids, proteins, and DNA either endogenously by cellular mechanism, or through exogenous exposure to environmental injury factors, including oxidation insult factors, such as tobacco smoke. Currently 46.3 million adults (25.7 percent of the population) are smokers. This includes 24 million men (28.1 percent of the total) and more than 22 million women (23.5 percent). The prevalence is highest among persons 25-44 years of age. Cigarette smokers have a higher risk of developing several chronic disorders. These include fatty buildups in arteries, several types of cancer and chronic obstructive pulmonary disease (lung problems). As peripheral leukocytes have been the main target of human telomere research, most of what is known about human telomere dynamics in vivo is based on these cells. Leukocyte telomere length (TL) is a complex trait that is shaped by genetic, epigenetic, and environmental determinants. In this article, we consider that smoking modifies leukocyte TL in humans and contributes to its variability among individuals, although the smoking effect on TL and its relation with other metabolic indices may accelerate biological aging and development of smoking-induced chronic diseases in a large human population-based cohorts with smoking behavior. Recent studies confirmed that individuals with shorter telomeres present a higher prevalence of arterial lesions and higher risk of cardiovascular disease mortality. This study originally suggests that efficient therapeutic protection of TL and structure in response to stresses that are known to reduce TL, such as oxidative damage or inflammation associated with tobacco smoking, would lead to better telomere maintenance. Recently, we have discovered the potential use of telomere-restorative imidazole-containing dipeptide (non-hydrolized carnosine, carcinine) based therapy for better survival of smokers. We conclude that a better

  20. CURRENT STATE OF POULTRY BREEDING AND ITS FUTURE TRENDS

    Directory of Open Access Journals (Sweden)

    Gordana Kralik

    2013-06-01

    Full Text Available Poultry production in eastern Croatia is developed by individual producers mainly in semi intensive way, and within the organized poultry systems where the process is organized in a modern, intensive way. There is a tradition of breeding hens and geese in this area. Poultry products - meat and eggs are important in supplying the population with animal protein, minerals and vitamins. Modern hybrid hens are used for egg production and for meat production in the intensive production. Today geese breeding in these areas are completely neglected. Croatia as a member of European Union, has possibility of the placement of autochthonous breeds of poultry such as Hrvatica hen, Zagorje turkey and Podravian goose. Financial supports at the national level are allocated for the first two autochthonous breeds of poultry because these breeds can, with good production traits, represent genetic resources and strategic reserves in the future development of domestic poultry genotypes. Poultry production is especial emphasis in accordance with the criteria of welfare and health of poultry. This paper discusses further development of poultry in terms of production of poultry meat and eggs as a functional food. The composition and content of nutricines in meat and eggs can be affected by feed composition. Desired nutricines are installed in muscular tissue of poultry by using feed and adding some components. Consumption of eggs and poultry meat enriched by selenium, lutein and omega-3 fatty acids affects the improvement of the quality of the human diet. The recent researches show that chicken can effectively be enriched in carnosine - ingredients that are now taught as “anti-aging” factor. Enrichment of poultry products with nutricines gives greater importance to these foods in the diet of the population than the former one, mainly based on the nutritional aspect. Greater selection of quality poultry products can be a significant factor in the development of

  1. Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia

    Science.gov (United States)

    Yang, Quan‐Jun; Zhao, Jiang‐Rong; Hao, Juan; Li, Bin; Huo, Yan; Han, Yong‐Long; Wan, Li‐Li; Li, Jie; Huang, Jinlu; Lu, Jin

    2017-01-01

    Abstract Background Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance‐based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model. Methods Eighty‐four cancer cachexia patients, 33 pre‐cachectic patients, 105 weight‐stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model. Results Forty‐six cancer cachexia patients, 22 pre‐cachectic patients, 68 weight‐stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre‐cachectic patients, 37 weight‐stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age‐matched and sex‐matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = −400.53 – 481.88 × log(Carnosine

  2. Use of Awamori-pressed Lees and Tofu Lees as Feed Ingredients for Growing Male Goats

    Directory of Open Access Journals (Sweden)

    Itsuki Nagamine

    2013-09-01

    microorganisms. As in the CFG, the total essential and non-essential amino acids in the loin of the AMFG and TMFG were well balanced. Compared to the CFG, the AMFG and TMFG were high in taurine and carnosine. The results indicate dried Awamori-pressed lees and Tofu lees can be used as a feed ingredient for raising male goats.

  3. Radioprotectors in Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nair, C.K.K. [Bhabha Atomic Research Centre, Mumbai (India); Parida, D.K.; Nomura, Taisei

    2001-03-01

    , orientin, and vicinin), DNA-binding ligands (Hoechst 33342), and other compounds (melatonin, carnosin, tempace, and tempol). The article also briefly explains the mechanisms of radiation protection (e.g., suppression of the formation of reactive species, detoxification of radiation-induced species, target stabilization, and enhancement of the repair and recovery processes) and of DNA repair and cell recovery processes. Although a large number of radioprotective compounds have been identified over the last 50 years, most of them have failed to make the transition from laboratory to clinic. Acute toxicity and inability to differentiate between tumor and normal cells are the main reasons for their failure to be applied clinically. The authors conclude the article by describing some approaches to overcoming problems associated with the toxicity of radioprotective agents. Future searches for effective radioprotectors may be directed at compounds that protect normoxic cells but afford no protection in a hypoxic environment, which is a common feature of all solid tumors. Other eandidates are compounds that are enzymatically converted to toxic derivatives in hypoxic tumor cells while remaining unchanged and protecting normal cells. (K.H.). 120 refs.

  4. From tryptophan to hydroxytryptophan: reflections on a busy life.

    Science.gov (United States)

    Fisher, Hans

    2009-01-01

    Given the very difficult odyssey of my early years, who could have imagined the incredible and successful journey that constituted my life path after age 13? I was born into a Jewish family in Breslau, Germany, right before the rise of Nazism and Hitler's election. After Kristallnacht, when my father was taken to Buchenwald Concentration Camp, we had to leave Germany as soon as possible. The first opportunity came in May of 1939, when we boarded the SS St. Louis bound for Havana, Cuba. Almost all passengers were denied entrance into Cuba, and the ship had to go back to Europe, where I ended up in France. In December of 1939, during World War II, I was fortunate to be able to leave France. This time I made it to Cuba, where my father was already in residence. A year later, my entire family was allowed into the United States. I took advantage of all the educational resources in this land of opportunity. I graduated valedictorian of my high school class and earned a four-year scholarship to Rutgers University, where I obtained a Bachelor of Science degree. I went on to earn a Master's degree from the University of Connecticut and finally a PhD from the University of Illinois. Within two months after graduating from Illinois, I was hired as an assistant professor of nutritional biochemistry at Rutgers, where I enjoyed a most productive research and teaching career. My PhD research involved tryptophan and niacin metabolism in the chick, and upon arrival at Rutgers I continued amino acid studies with the goal of assessing the essential amino acid requirements for egg production. This research was crowned with success and was followed with amino acid requirement studies for maintenance and for growth in rabbits, and ultimately with a reevaluation of requirements in adult humans. An outgrowth of the maintenance requirements led to a series of investigations into the metabolism of histidine, histamine, and carnosine (a histidine-containing dipeptide). Histamine, we found

  5. Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.

    Science.gov (United States)

    Tan, May Loong; Ho, Jacqueline J; Teh, Keng Hwang

    2016-09-28

    involving 116 children, mainly boys between 10 and 18 years of age, met the inclusion criteria. One study was conducted in a school setting, the other at a specialised clinic. Both studies used three months of a combination of omega-3 and omega-6 supplements as the intervention compared with placebo. Although both studies had generally low risk of bias, we judged the risk of reporting bias as unclear in one study, and as high in the other study. In addition, one of the studies was funded by industry and reported active company involvement in the study.None of the studies reported data on the primary outcomes of reading, writing, spelling and mathematics scores, as assessed by standardised tests.Evidence of low quality indicates that supplementation of PUFAs did not increase the risk of gastrointestinal disturbances (risk ratio 1.43, 95% confidence interval 0.25 to 8.15; two studies, 116 children). Investigators reported no other adverse effects.Both studies reported attention deficit hyperactivity disorder (ADHD)-related behaviour outcomes. We were unable to combine the results in a meta-analysis because one study reported findings as a continuous outcome, and the other as a dichotomous outcome. No other secondary outcomes were reported.We excluded one study because it used a cointervention (carnosine), and five other studies because they did not provide a robust diagnosis of a specific learning disorder. We identified one ongoing study and found three studies awaiting classification. Evidence is insufficient to permit any conclusions about the effect of PUFAs on the learning abilities of children with specific learning disorders. Well-designed RCTs with clearly defined populations of children with specific learning disorders who have been diagnosed by standardised diagnostic criteria are needed.