Nutrigenomic effect of conjugated linoleic acid on growth and meat quality indices of growing rabbit
Autoři:
A. M. Abdelatty aff001; Shereen A. Mohamed aff002; Mahmoud M. A. Moustafa aff002; Asmaa K. Al-Mokaddem aff003; M. R. Baker aff004; Ahmed A. Elolimy aff005; Shawky A. Elmedany aff006; Shaymaa Hussein aff007; Omar A. A. Farid aff008; Osama G. Sakr aff009; Mohamed A. Elhady aff010; Massimo Bionaz aff011
Působiště autorů:
Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
aff001; Department of Genetics and Genetic Engineering, Faculty of Agriculture, Benha University, Qalyubia, Egypt
aff002; Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza,Egypt
aff003; Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
aff004; Department of Animal Sciences, University of Illinois, Urbana, IL, United States of America
aff005; Regional Center for Food and Feed, Agriculture Research Center; Giza, Egypt
aff006; Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
aff007; Department of Physiology, National Organization for Drug Control and Research, Giza, Egypt
aff008; Animal Production Department (Poultry Physiology), Faculty of Agriculture, Cairo University, Giza, Egypt
aff009; Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
aff010; Department of Animal and Rangeland sciences, Oregon State University, Oregon, United States of America
aff011
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0222404
Souhrn
Conjugated linoleic acid was detected in rabbit caecotrophs, due to the presence of microbial lipid activity in rabbit cecum. However, the effect of CLA as a functional food in growing rabbit is not well established. Therefore, this study was conducted to determine the effect of CLA on production, meat quality, and its nutrigenomic effect on edible parts of rabbit carcass including skeletal muscle, liver, and adipose tissue. Therefore, seventy five weaned V-Line male rabbits, 30 days old, were randomly allocated into three dietary treatments receiving either basal control diet, diet supplemented with 0.5% (CLAL), or 1% CLA (CLAH). Total experimental period (63 d) was segmented into 7 days adaptation and 56 days experimental period. Dietary supplementation of CLA did not alter growth performance, however, the fat percentage of longissimus lumborum muscle was decreased, with an increase in protein and polyunsaturated fatty acids (PUFA) percentage. Saturated fatty acids (SFA) and mono unsaturated fatty acids (MUFA) were not increased in CLA treated groups. There was tissue specific sensing of CLA, since subcutaneous adipose tissue gene expression of PPARA was downregulated, however, CPT1A tended to be upregulated in liver of CLAL group only (P = 0.09). In skeletal muscle, FASN and PPARG were upregulated in CLAH group only (P ≤0.01). Marked cytoplasmic vacuolation was noticed in liver of CLAH group without altering hepatocyte structure. Adipocyte size was decreased in CLA fed groups, in a dose dependent manner (P <0.01). Cell proliferation determined by PCNA was lower (P <0.01) in adipose tissue of CLA groups. Our data indicate that dietary supplementation of CLA (c9,t11-CLA and t10,c12- CLA) at a dose of 0.5% in growing rabbit diet produce rabbit meat rich in PUFA and lower fat % without altering growth performance and hepatocyte structure.
Klíčová slova:
Fatty acids – Diet – Meat – Fats – Skeletal muscles – Rabbits – Adipose tissue – Oleic acid
Zdroje
1. Carabaño R, Piquer J, Menoyo D, Badiola I. The digestive system of the rabbit. Nutrition of the Rabbit. 2010; 1–18.
2. Leiber F, Meier JS, Burger B, Wettstein HR, Kreuzer M, Hatt JM, et al. Significance of coprophagy for the fatty acid profile in body tissues of rabbits fed different diets. Lipids. 2008; 43(9):853–865.
3. Betancourt López CA, Bernal Santos MG, Vázquez Landaverde PA, Bauman DE, Harvatine KJ, Srigley CT, et al. Both Dietary Fatty Acids and Those Present in the Cecotrophs Contribute to the Distinctive Chemical Characteristics of New Zealand Rabbit Milk Fat. Lipids. 2018; 53(11–12):1085–1096. doi: 10.1002/lipd.12127 30739314
4. Gómez-Conde MS, Menoyo D, Chamorro S, Bote CL, Rebollar PG, De Blas JC. Conjugated linoleic acid content in cecotrophes, suprarenal and intramuscular fat in rabbit fed commercial diets. World Rabbit Science.2010; 14(2): 95–99.
5. Baumgard LH, Cor BA, Dwyer DA, Saebo A, Bauman DE. Identification of the conjugated linoleic acid isomer that inhibits milk fat synthesis. Am J Physiol Regul Integr Comp Physiol. 2000; 278: 179–184.
6. Andrade PVD, Schmidely P. Effect of duodenal infusion of trans10, cis12-CLA on milk performance and milk fatty acid profile in dairy goats fed high or low concentrate diet in combination with rolled canola seed. Reprod. Nutr. Dev. 2006; 46:31–48. doi: 10.1051/rnd:2005062
7. Sirri F, Tallarico N, Meluzzi A, Franchini A. Fatty acid composition and productive traits of broiler fed diets containing conjugated linoleic acid. Poult. Sct. 2003;82: 1356–1361.
8. Pastorelli G, Macchioni MVM, Fiego PLO, Santoro DP, Panseri P, Rossi S, et al. Influence of dietary conjugated linoleic acid on the fatty acid composition and volatile compounds profile of heavy pig loin muscle. J. Sci. Food Agric. 2005; 85: 2227–2234. doi: 10.1002/jsfa.5638
9. Koronowicz AA, Banks P, Szymczyk B, Master LA, Piasna E, Szczepański WD. et al. Dietary conjugated linoleic acid affects blood parameters, liver morphology and expression of selected hepatic genes in laying hens. British Poultry Science.2016; 57(5): 663–673 doi: 10.1080/00071668.2016.1192280 27267260
10. Bauman DE, Baumgard LH, Corl BA, Griinari DJ. Biosynthesis of conjugated linoleic acid in ruminants. In Proc. Am. Soc. Anim. Sci. 1999; 77: 1–14.
11. McGuire MA. McGuire MK. Conjugated linoleic acid (CLA): A ruminant fatty acid with beneficial effects on human health. Journal of Animal Science, 77(E-Suppl), 1–8. and fatty acid oxidation in adipocytes. Journal of lipid research.2000;52(5):873–884.
12. Bionaz M, Baumrucker CR, Shirk E, Heuvel JV, Block E, Varga GA. Characterization of Madin-Darby bovine kidney cell line for peroxisome proliferator-activated receptors: Temporal response and sensitivity to fatty acids. Journal of Dairy Science.2008; 91(7):2808–2813. doi: 10.3168/jds.2007-0789 18565938
13. Lehnen TE, da Silva MR, Camacho A, Marcadenti A, Lehnen AMA. review on effects of conjugated linoleic fatty acid (CLA) upon body composition and energetic metabolism. Journal of the International Society of Sports Nutrition.2015; 12(1):12–36.
14. Phua W, Wong M, Liao Z, Tan N. An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors. International journal of molecular sciences. 2018; 19(5): 1425. doi: 10.3390/ijms19051425 29747466
15. Corrales P, Izquierdo-Lahuerta A, Medina-Gómez G. Maintenance of kidney metabolic homeostasis by PPAR gamma. International journal of molecular sciences. 2018; 19(7):2063. https://doi.org/10.3390/ijms19072063
16. Corino C, Mourot J, Magni S, Pastorelli G, Rosi F. Influence of dietary conjugated linoleic acid on growth, meat quality, lipogenesis, plasma leptin and physiological variables of lipid metabolism in rabbits. Journal of Animal Science. 2002; 80(4):1020–1028.
17. Marounek M, Skrivanova V, Dokoupilova A, Czauderna M, Berladyn A. Meat quality and tissue fatty acid profiles in rabbits fed diets supplemented with conjugated linoleic acid. Veterinarni Medicina. 2007; 52(12):552–561.
18. AVMA Panel on Euthanasia. American Veterinary Medical Association. 2000 Report of the AVMA Panel on Euthanasia. J. Am. Vet. Med.Assoc. 2001;218:669–696.
19. NRC. 1977. Nutritional requirements of rabbits (2nd ed.). Washington, DC: National Academy Press.
20. EFSA. Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). Safety and efficacy of methylester of conjugated linoleic acid (t10,c12 isomer) for pigs for fattening, sows and cows. EFSA Journal 2016;14(1):4348, 65 pp. doi: 10.2903/j.efsa.2016.4348
21. Oliveira RC, Pralle RS, de Resende LC, Nova CHP, Caprarulo V, Jendza JA. et al. Prepartum supplementation of conjugated linoleic acids (CLA) increased milk energy output and decreased serum fatty acids and β-hydroxybutyrate in early lactation dairy cows. PloS one.2018; 13(5): e0197733. doi: 10.1371/journal.pone.0197733
22. Lambert EV, Goedecke JH, Bluett K, Heggie K, Claassen A, Rae DE, … et al. Conjugated linoleic acid versus high-oleic acid sunflower oil: effectson energy metabolism, glucose tolerance, blood lipids, appetiteand body composition in regularly exercising individuals. British Journal of Nutrition.2007;97:1001–1011. doi: 10.1079/S0007114507172822
23. AOAC. 2000 Official methods of analysis. 17th ed., Vols. 1 and 2. Gaithersburg, MD: Association of the Official Analytical Chemists.
24. Flecknell P, Lofgren JL, Dyson MC, Marini RR, Swindle MM, Wilson RP. Preanesthesia, anesthesia, analgesia, and euthanasia. In Laboratory Animal Medicine. 2015; 1135–1200. Academic Press. doi: 10.1016/B978-0-12-409527-4.00024–9
25. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry. 1972; 18(6): 499–502. 4337382
26. Norbert WT. Clinical guide to laboratory tests. 3 rd ed. Philadilphia.W. B. Saunders Company. 1995.
27. Allain CC, Poon LS, Chan CS, Richmond WFC, Fu PC. Enzymatic determination of total serum cholesterol. Clinical chemistry.1974; 20 (4): 470–475. 4818200
28. Burtis CA, Ashwood ER. Tietz Textbook of ClinicalChemistry, 3rd edn. W.B. Saunders Co., Philadelphia, PA. 1999.
29. Niven SJ, Beal JD, Brooks PH. The simultaneous determination of short chain fatty acid, monosaccharides and ethanol in fermented liquid pig diets. Animal feed science and technology. 2004; 117(3–4):339–345.
30. AOAC. Official methods of analysis. 18th ed., international, Gaithersburg, USA AOAC. 2012.
31. Bancroft JD, Gamble M. (Eds.). Theory and practice of histological techniques. 2008; Elsevier Health Sciences.
32. Yilmaz S, Ates E, Tokyol C., Pehlivan T, Erkasap S, Koken T. The protective effect of erythropoietin on ischaemia/reperfusion injury of liver. HPB. 2004; 6(3):169–173.
33. Corino C, Di Giancamillo A, Rossi R, Domeneghini C. Dietary conjugated linoleic acid affects morphofunctional and chemical aspects of subcutaneous adipose tissue in heavy pigs. The Journal of nutrition. 2005; 135(6):1444–1450. doi: 10.1093/jn/135.6.1444 15930450
34. Hall PA, Levison DA, Woods AL, Yu CCW, Kellock DB, Watkins JA, Barnes DM, et al. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: An index of cell proliferation with evidence of deregulated expression in some, neoplasms. J Pathol. 1990; 162(4):285–94.
35. Bologna‐Molina R, Damián‐Matsumura P, Molina‐Frechero N. An easy cell counting method for immunohistochemistry that does not use an image analysis program. Histopathology. 2011; 59(4): 801–803. doi: 10.1111/j.1365-2559.2011.03954.x 21939456
36. Bancroft JD, Stevens A. Theory and Practice of Histological Techniques, Edinburgh: Churchill Livingstone. 1982; 2: 20–41
37. Norollahi SA, Kokhaee P, Rashidy-Pour A, Hojati V, Norollahi SE, Larijani LV, et al. Comparison of Methods of RNA Extraction From Breast and Gastric Cancer Tissues. Crescent Journal of Medical and Biological Sciences. 2018; 5(1):25–28.
38. Wakil SJ, Abu-Elheiga LA. Fatty acid metabolism: target for metabolic syndrome. Journal of lipid research. 2009. 50 138–143. doi: 10.1194/jlr.R800079-JLR200 19047759
39. Warfel JD, Vandanmagsar B, Dubuisson OS, Hodgeson SM, Elks CM, Ravussin E, et al. Examination of carnitine palmitoyltransferase 1 abundance in white adipose tissue: implications in obesity research. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2017; 312(5):R816–R820.
40. Lupu R, & Menendez J. Pharmacological Inhibitors of Fatty Acid Synthase (FASN)-Catalyzed Endogenous Fatty Acid Biogenesis: A New Family of Anti-Cancer Agents? Current Pharmaceutical Biotechnology, 2006; 7(6), 483–494. doi: 10.2174/138920106779116928 17168665
41. Perera RJ, Marcusson EG, Koo S, Kang X, Kim Y, White N, et al. Identification of novel PPARg target genes in primary human adipocytes.Gene. 2006; 369:90–99
42. Xu J, Xiao G, Trujillo C, Chang V, Blanco L, Joseph S. et al. Peroxisome proliferator-activated receptor α (PPARα) influences substrate utilization for hepatic glucose production. Journal of Biological Chemistry. 2002; 277(52): 50237–50244. doi: 10.1074/jbc.M201208200
43. Bionaz M, Chen S, Khan MJ, Loor JJ. Functional role of PPARs in ruminants: Potential targets for fine-tuning metabolism during growth and lactation. PPAR research.2013; ID 684159, 28 pages http://dx.doi.org/10.1155/2013/684159.
44. Ruijter JM, Ramakers C, Hoogaars WM, Karlen Y, Bakker O, van den Hoff MJ, et al. Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic acids research. 2009; 37(6): e45 doi: 10.1093/nar/gkp045 19237396
45. Andersen CL, Ledet-Jensen J, Ørntoft T. Normalization of real-time quantitative RT-PCR data: a model based variance estimation approach to identify genes suited for normalization—applied to bladder- and colon-cancer data-sets. Cancer Research. 2004; (64): 5245–5250.
46. Marounek M, Skrivanova V, Dokoupilova A, Czauderna M, Berladyn A. Meat quality and tissue fatty acid profiles in rabbits fed diets supplemented with conjugated linoleic acid. Veterinarni Medicina. 2007; 52(12):552–561.
47. Remely M, Aumueller E, Merold C, Dworzak S, Hippe B, Zanner J, et al. Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity. Gene. 2014; 537(1): 85–92.
48. Chaplin A, Parra P, Serra F, Palou A. Conjugated Linoleic Acid Supplementation under a High-Fat Diet Modulates Stomach Protein Expression and Intestinal Microbiota in Adult Mice. PLoS ONE. 2015; 10(4): e0125091. doi: 10.1371/journal.pone.0125091 25915857
49. Corino C, Fiego DL, Macchioni P, Pastorelli G, DiGiancamillo A, Domeneghini C, et al. Influence of dietary conjugated linoleic acids and vitamin E on meat quality, and adipose tissue in rabbits. Meat Science. 2007; 76(1): 19–28.
50. Du M, Ahn DU. Dietary CLA affects lipid metabolism in broiler chicks. Lipids. 2003; 38(5): 505–511.
51. Chai BK, Lau YS, Loong BJ, Rais MM, Ting KN, Dharmani DM, et al. Co-administration of conjugated linoleic acid and rosiglitazone increases atherogenic co-efficient and alters isoprenaline-induced vasodilatation in rats fed high fat diet. Physiological research. 2018; 67(5):729–740.
52. Kritchevsky D, Tepper SA, Wright S, Tso P, Czarnecki SK. Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits. Journal of American College Nutr. 2000; 19(4):4725–4775.
53. AbuGhazaleh AA, Holmes LD. Diet supplementation with fish oil and sunflower oil to increase conjugated linoleic acid levels in milk fat of partially grazing dairy cows. Journal of Dairy Science. 2007; 90(6): 2897–2904. doi: 10.3168/jds.2006-684 17517729
54. Maslak E, Buczek E, Szumny A, Szczepnski W, Franczyk-Zarow M, Kopec A, et al. Individual CLA isomers, c9t11 and t10c12, prevent excess liver glycogen storage and inhibit lipogenic genes expression induced by high-fructose diet in rats. BioMed research international. 2015. ID 535982, http://dx.doi.org/10.1155/2015/535982
55. Kanter J, Goodspeed L, Wang S, Kramer F, Wietecha T, Gomes-Kjerulf D, et al. 10, 12 Conjugated Linoleic Acid-Driven Weight Loss Is Protective against Atherosclerosis in Mice and Is Associated with Alternative Macrophage Enrichment in Perivascular Adipose Tissue. Nutrients. 2018; 10(10):1416. https://doi.org/10.3390/nu10101416.
56. Bandeali S, Farmer J. High-density lipoprotein and atherosclerosis: the role of antioxidant activity. Current atherosclerosis reports. 2012; 14(2):101–107.
57. Lee KN, Kritchevsky D, Pariza MW. Conjugated linoleic acid and ather6osclerosis in rabbits. Atherosclerosis. 1994;108(1): 19–25.
58. Talayero BG, Sacks FM. The role of triglycerides in atherosclerosis. Current cardiology reports. 2011; 13(6):544–552. doi: 10.1007/s11886-011-0220-3 21968696
59. Fielding CJ, Fielding PE. Molecular physiology of reverse cholesterol transport. Journal of lipid research. 1995; 36(2):211–228.
60. Vyas D, Kadegowda AK, Erdman RA. Dietary conjugated linoleic acid and hepatic steatosis: species-specific effects on liver and adipose lipid metabolism and gene expression. J. Nutr. Metab.2012.ID 932928, 13 pages doi: 10.1155/2012/932928 21869929
61. Brunt EM. Pathology of fatty liver disease. Modern Pathology. 2007; 20:S40–48. doi: 10.1038/modpathol.3800680 17486051
62. Liu X, Joseph SV, Wakefield AP, Aukema HM, Jones PJH. High Dose trans-10, cis-12 CLA Increases Lean Body Mass in Hamsters, but levates Levels of Plasma Lipids and Liver Enzyme Biomarkers. Lipids. 2012; 47:39–46. doi: 10.1007/s11745-011-3616-3 22038709
63. Kun P, Liqiang H. Effect of Conjugated Linoleic Acid on Metabolism and Lipogenic Gene Expression of Liver in Lactating Mice. In 2016 8th International Conference on Information Technology in Medicine and Education (ITME) 2016; 137–139.
64. Montagner A, Polizzi A, Fouché E, Ducheix S, Lippi Y, Lasserre F, et al. Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. Gut, 2016; 65(7): 1202–1214. doi: 10.1136/gutjnl-2015-310798 26838599
65. Guzmán M, Verme JL, Fu J, Oveisi F, Blázquez C, Piomelli D. Oleoylethanolamide stimulates lipolysis by activating the nuclear receptor peroxisome proliferator-activated receptor α (PPAR-α). Journal of biological chemistry. 2004; 279(27): 27849–27854. doi: 10.1074/jbc.M404087200 15123613
66. Goto T, Lee JY, Teraminami A, Kim YI, Hirai S, Uemura T, et al. Activation of peroxisome proliferator-activated receptor-alpha stimulates both differentiation and fatty acid oxidation in adipocytes. Journal of lipid research. 2011; 52(5):873–884.
67. Student AK, Hsu RY, Lane MD. Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes. Journal of Biological Chemistry. 1980; 255(10): 4745–4750.
68. Vu D, Ong JM, Clemens TL, Kern PA. 1, 25-Dihydroxyvitamin D induces lipoprotein lipase expression in 3T3-L1 cells in association with adipocyte differentiation. Endocrinology. 1996; 137(5):1540–1544.
69. Kennedy SR, Campbell PJ, Porter A, Tocher DR. Influence of dietaryconjugatedlinoleicacid (CLA) on lipid and fatty acid composition in liver and muscle of Atlantic salmon (Salmo salar).Comp. Biochem. Phys. B. 2005; 141:168–178.
70. Carta G, Murru E, Manca C, Abolghasemi A, Serra A, Mele M, et al. Natural conjugated linoleic acid enriched lamb meat fat modifies tissue fatty acid profile and increases n-3 HUFA score in obese Zucker rats. Proceedings of the Nutrition Society. 2018; 77 (OCE2), E29. Spring Conference 2018, Nutrient-nutrient interaction. doi: 10.1017/S002966511800023X
71. Tous N, Theil PK, Lauridsen C, Lizardo R, Vila B, Esteve-Garcia E. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs. Journal of animal science. 2012; 90(4):340–342.
72. Meadus WJ, MacInnis R, Dugan ME. Prolonged dietary treatment with conjugated linoleic acid stimulates porcine muscle peroxisome proliferator activated receptor gamma and glutamine-fructose aminotransferase gene expression in vivo. Journal of molecular endocrinology. 2002; 28(2): 79–86.
73. Cho K, Song Y, Kwon D. Conjugated linoleic acid supplementation enhances insulin sensitivity and peroxisome proliferator-activated receptor gamma and glucose transporter type 4 protein expression in the skeletal muscles of rats during endurance exercise. Iranian journal of basic medical sciences. 2016; 19(1): 20–27. 27096060
74. Moyes KM, Graugnard DE, Khan MJ. Mukesh Loor MJJ. Postpartal immunometabolic gene network expression and function in blood neutrophils are altered in response to prepartal energy intake and postpartal intramammary inflammatory challenge. J. Dairy Sci. 2014; 97:2165–2177.
75. Mohankumar SK, Taylor CG, Siemens L, Zahradka P. Activation of phosphatidylinositol-3 kinase, AMP-activated kinase and Akt substrate-160 kDa by trans-10, cis-12 conjugated linoleic acid mediates skeletal muscle glucose uptake. The Journal of nutritional biochemistry. 2013; 24(2): 445–456. doi: 10.1016/j.jnutbio.2012.01.006 22704782
76. Kim JH, Kim J, Park Y. Trans-10, cis-12 conjugated linoleic acid enhances endurance capacity by increasing fatty acid oxidation and reducing glycogen utilization in mice. Lipids. 2012; 47(9): 855–863.
77. Qin H, Liu Y, Lu N, Li Y, Sun CH. Cis-9, trans-11-Conjugated linoleic acid activates AMP-activated protein kinase in attenuation of insulin resistance in C2C12 myotubes. Journal of agricultural and food chemistry. 2009; 57(10):4452–4458. doi: 10.1021/jf900534w 19364109
78. Kim Y, Park Y. Conjugated linoleic acid (CLA) stimulates mitochondrial biogenesis signaling by the upregulation of PPARγ coactivator 1α (PGC-1α) in C2C12 cells. Lipids. 2015; 50(4):329–338.
79. Jeffrey MP, Yeonhwa P, Frank JG, Michael WP. Infuence of conjugated linoleic acid on body composition and target gene expression in peroxisome proliferator-activated receptor K-null mice. Biochimica et Biophysica Acta. 2001; (1533): 233–242
Článok vyšiel v časopise
PLOS One
2019 Číslo 10
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Těžké menstruační krvácení může značit poruchu krevní srážlivosti. Jaký management vyšetření a léčby je v takovém případě vhodný?
- Fixní kombinace paracetamol/kodein nabízí synergické analgetické účinky
Najčítanejšie v tomto čísle
- Correction: Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study
- Combining CDK4/6 inhibitors ribociclib and palbociclib with cytotoxic agents does not enhance cytotoxicity
- Experimentally validated simulation of coronary stents considering different dogboning ratios and asymmetric stent positioning
- Risk factors associated with IgA vasculitis with nephritis (Henoch–Schönlein purpura nephritis) progressing to unfavorable outcomes: A meta-analysis