Physical, Chemical and Mineralogical Properties of Gallstones obtained from Antalya Province of Turkey

Abstract

Gallbladder stone disease is the most common disease with a high prevalence in many societies in the word. In the literature, the primary risk factors discussed for this disease have been evaluated as gaining and losing weight rapidly, obesity, age, gender, genetic factors, having given birth too many children, life style and medications. The aim of this investigation is to find out the chemical and physical properties of gallstones in patients living in the province of Antalya, Turkey. For this purpose, the chemical and mineralogical properties of 1243 gallstone samples from 69 patients were analyzed using X-ray diffractometer (XRD), scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) applications. In accordance with the outcome of SEM and FTIR analysis, cholesterol, calcium carbonate, calcium bilirubinate, calcium phosphate, carbonate apatite, and protein contents were observed. Cholesterol was detected in 95% of 69 patients; with 44 samples obtained from female patients. X-Ray Diffractometer (XRD) analysis showed newberyite, struvite, and aragonite minerals were found in the composition of gallstones. Newberyite was present in 59% of the samples. The physical, chemical and mineralogical characteristics of these gallstones are very important for the understanding of gallstone formation. The results of the study are consistent with the 5F Rule (Female, Forty, Fatty, Fair, Fertile). The relationship between bilirubinate and the presence of bacteria was determined. The presence of barium acetate and aluminum silicate in gallstones revealed the relationship with environmental pollutants.

Keywords

• gallstone properties
• newberyite
• struvite
• aragonite
• medical geology

Türkiye'nin Antalya İlinde Safra Kesesi Taşlarının Fiziksel, Kimyasal ve Mineralojik Özelliklerinin Analizi

Abstract

Safra taşı hastalığı, dünya çapında birçok toplumda yüksek prevalansa sahip en yaygın hastalıktır. Literatürde bu hastalık için tartışılan başlıca risk faktörleri hızlı kilo alımı, obezite, yaş, cinsiyet, genetik faktörler, çok çocuk doğurma, yaşam tarzı ve ilaçlardır. Bu çalışmanın amacı, Antalya'da yaşayan hastalarda safra kesesi taşlarının kimyasal ve fiziksel özelliklerini belirlemektir. Bu amaçla, 69 hastadan alınan 1243 safra taşı örneğinin kimyasal ve mineralojik özellikleri X-ışını difraktometresi (XRD), taramalı elektron mikroskobu (SEM) ve Fourier Dönüşümlü Kızılötesi Spektroskopisi (FTIR) uygulamaları kullanılarak analiz edilmiştir. SEM ve FTIR analiz sonuçlarına göre kolesterol, kalsiyum karbonat, kalsiyum bilirubinat, kalsiyum fosfat, karbonat apatit ve protein içerikleri gözlenmiştir. Kolesterol 69 hastanın %95'inde tespit edilmiştir; 44 örnek kadın hastalardan elde edilmiştir. X-Işını Difraktometre (XRD) analizi safra taşlarının bileşiminin nevberyit, struvit ve aragonit minerallerini içerdiğini göstermiştir. Nevberyit örneklerin %59'unda mevcuttur. Bu safra taşlarının fiziksel, kimyasal ve mineralojik özellikleri safra taşı oluşumunu anlamak için çok önemlidir. Çalışmanın sonuçları 5F Kuralı (Female, Forty, Fatty, Fair, Fertile) ile uyumludur. Bilirubinat ile bakteri varlığı arasındaki ilişki belirlenmiştir. Safra taşlarında baryum asetat ve alüminyum silikat varlığı çevresel kirleticilerle bir ilişki olduğunu ortaya koymuştur.

Keywords

• Aragonit
• nevberit
• safta taşı özellikleri
• struvit
• tıbbi jeoloji

References

1. Altinkaya, N., Koc, Z., Alkan, O., Demir, S. & Belli, S. (2011). Multidetector computed tomography diagnosis of ileal and anthropologic gallstone ileus. Turkish Journal of Trauma and Emergency Surgery, 17(5), 461-463. https://doi.org/10.5505/tjtes.2011.50103
2. Altura, B. M. (1991). Basic Biochemistry and Physiology of Magnesium; A Brief Review, Magnes Trace Element, 10, 167-71 .
3. Antalya Provincial Environmental Status Report. webdosya.csb.gov.tr/db/ced/icerikler/antalya_2017_cevre_durum_raporu 20180705142911.pdf (2017).
4. Ashok, M., Rautray, T., Nayak, P., Vijayan, V., Jayanthi, V. & Narayana, K. S. (2003). Energy-dispersive X-ray fluorescence analysis of gallstones. Journal of Radioanalytical and Nuclear Chemistry, 257(2), 333-335. https://doi.org/10.1023/A:1024735930031
5. Athanasiadou, D., Godelitsas, A., Sokaras, D., Karydas, A. G., Dotsika, E., Potamitis, C., ... & Becker, U., 2013. New insights into the chemical and isotopic composition of human-body biominerals. I: Cholesterol gallstones from England and Greece. Journal of Trace Elements in Medicine and Biology, 27(2), 79-84. https://doi.org/10.1016/j.jtemb.2012.08.004
6. Baysal, A., Kececioglu, S. & Arslan, P. (1991). Compositionof Foods, Turkish Dietetic Association Publication No 1.Yenicag, Basın-Yayın San, Ankara, Turkey.
7. Bazzano, L. A., Thompson, A. M., Tees, M. T., Nguyen, C. H. & Winham, D. M. (2011). Non-soy legume consumption lowers cholesterol levels: a meta-analysis of randomized controlled trials. Nutrition, Metabolism and Cardiovascular Diseases, 21(2), 94-103. https://doi.org/10.1016/j.numecd.2009.08.012
8. Bijvoet, Olav L. M. (1977). Kidney function in calcium and phosphate metabolism. In: Metabolic bone disease. Academic Press, p. 49-140. https://doi.org/10.1016/B978-0-12-068701-5.50008-7

9. Bistgani, M. M. & Imani, R. (2013). Bacteria isolated from patients with cholelithiasis and their antibacterial susceptibility pattern. Iranian Red Crescent Medical Journal, 15(8), 759 https://doi.org/10.5812/ircmj.3883
10. Butanovs, E., Zolotarjovs, A., Kuzmin, A. & Polyakov, B. (2021). Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. https://doi.org/10.1016/j.nima.2021.165736
11. Cen, L., Pan, J., Zhou, B., Yu, C., Li, Y., Chen, W. & Shen, Z. (2018). Helicobacter Pylori infection of the gallbladder and the risk of chronic cholecystitis and cholelithiasis: A systematic review and meta‐analysis. Helicobacter, 23(1), Article no: e12457. https://doi.org/10.1111/hel.12457
12. Chuang, S. C., Hsi, E. & Lee, K. T. (2012). Mucin genes in gallstone disease. Clinica Chimica Acta, 413(19-20), 1466-1471. https://doi.org/10.1016/j.cca.2012.06.015
13. Cohen, S. Z., Creeger, S. M., Carsel, R. F. & Enfield, C. G. (1984). Potential pesticide contamination of groundwater from agricultural uses. Treatment and Disposal of Pesticide Wastes, 259, 297. https://doi.org/10.1021/bk-1984-0259.ch018
14. Damalas, C. A., Telidis, G. K. & Thanos, S. D. (2008). Assessing farmers' practices on disposal of pesticide waste after use. Science of the total environment, 390(2-3), 341-345. https://doi.org/10.1016/j.scitotenv.2007.10.028
15. Dorvash, M. R., Khoshnood, M. J., Saber, H., Dehghanian, A., Mosaddeghi, P. & Firouzabadi, N. (2018). Metformin treatment prevents gallstone formation but mimics porcelain gallbladder in C57Bl/6 mice. European Journal of Pharmacology, 833, 165-172. https://doi.org/10.1016/j.ejphar.2018.06.002
16. Finkelman, R. B., Skinner H. C. W, Plumlee, G. S. & Bunnell, J. E. (2001). Medical Geology. Geotimes, 20-23
17. Flores, C., Maguilnik, I., Hadlich, E. & Goldani, L. Z. (2003). Microbiology of choledochal bile in patients with choledocholithiasis admitted to a tertiary hospital. J Gastroenterol Hepatol, 18(3):333-6. https://doi.org/10.1046/j.1440-1746.2003.02971.x
18. Gazali, Z., Thakur, S. N. & Rai, A. K. (2019). Compositional study of gallbladder stone using photoacoustic spectroscopy. Optics & Laser Technology, 111, 696-700. https://doi.org/10.1016/j.optlastec.2018.09.003
19. Glasdam, S. M., Glasdam, S. & Peters, G. H. (2016). The importance of magnesium in the human body: a systematic literature review. In Advances in Clinical Chemistry,73, 169-193. https://doi.org/10.1016/bs.acc.2015.10.002
20. Golovanova, 0. A., Pakhik, N. A., Berezina, N. Y., & Yudina, L. N. (2006). Comparative characteristics of the mineral and microelement composition of gallstones extracted from patients in the Novosibirsk and Omsk regions. Chemistry for Sustainable Development, 14, 125- 131.
21. Göbel, T., Kubitz, R., Blondin, D., & Häussinger, D. (2011). Intrahepatic type II gall bladder perforation by a gall stone in a CAPD patient. European journal of medical research, 16(5), 213-216. https://doi.org/10.1186/2047-783X-16-5-213
22. Griffith, D. P. (1978). Struvite stones. Kidney International, Vol. 13, 372 - 382. https://doi.org/10.1038/ki.1978.55
23. Grigor'eva, I. N. (2020). Gallstone disease, obesity and the Firmicutes/Bacteroidetes ratio as a possible biomarker of gut dysbiosis. Journal of Personalized Medicine, 11(1), 13. https://doi.org/10.3390/jpm11010013
24. Grubbs, R. D. & Maguire, M. E. (1987). Magnesium as a regulatory cation: Criteria and Evajuation. Magnesium, 6, 113-27.
25. Güdücüoğlu, H., Bozkurt, H., Bayram, Y., Yaman, G., Berktas, M. (2004). Microorganisms isolated from bile samples of the patients who had cholecystectomy and their antibiotics susceptibilities. Genel Tıp Dergisi (Journal of General Medicine), 14(1), 13-7.
26. Hanafi, N. I., Mohamed, A. S., Kadir, S. A., Hamimah, S. & Othman, M. H. D. (2018). Overview of bile acids signaling and perspective on the signal of ursodeoxycholic acid, the most hydrophilic bile acid, in the heart. Biomolecules, 8(4), 159. https://doi.org/10.3390/biom8040159
27. Hu, H., Shao, W., Liu, Q., Liu, N., Wang, Q., Xu, J., ... & Gu, A. (2022). Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion. Nature Communications, 13(1), 252. https://doi.org/10.1038/s41467-021-27758-8
28. Hundal, R., & Shaffer, E. A. (2014). Gallbladder cancer: epidemiology and outcome. Clinical Epidemiology, 99-109. https://doi.org/10.2147/CLEP.S37357
29. Huner, U., Gulec, H. A. & Damar Huner, I. (2017). Effect of gas type and application distance on atmospheric pressure plasma jet-treated flax composites. Journal of Reinforced Plastics and Composites, 36(17), 1197-1210. https://doi.org/10.1177/0731684417703490
30. Iordanidis, A., Garcia-Guinea, J., Giousef, C., Angelopoulos, A., Doulgerakis, M. & Papadopoulou, L. (2013). Characterization of gallbladder stones from cholelithiasis patients of Northern Greece, using complementary techniques. Spectroscopy Letters, 46(4), 301-306. https://doi.org/10.1080/00387010.2012.728552
31. Ismail, A.A. & Ismail, N.A. (2016). Magnesium: A mineral essential for health yet generally underestimated or even ignored. J. Nutr. Food Sci, 6(2). https://doi.org/10.4172/2155-9600.1000523
32. Kabakci D., Yalcin M. G. & Elpek G. O. (2016). The Determination of the Mineralogical and Chemical Composition of Gallstones (Antalya) and Assessment in Terms of Medical Geology. 69th Geological Congress of Turkey, 11-15 April 2016, 46-47. ISBN: 978-605-01-0869-9
33. Kleiner, O., Ramesh, J., Huleihel, M., Cohen, B., Kantarovich, K., Levi, C. & Mordechai, S. (2002). A comparative study of gallstones from children and adults using FTIR spectroscopy and fluorescence microscopy. BMC Gastroenterology, 2(1), 3. https://doi.org/10.1186/1471-230x-2-3
34. Kose, S. H., Grice, K., Orsi, W. D., Ballal, M. & Coolen, M. J. L. (2018). Metagenomics of pigmented and cholesterol gallstones: the putative role of bacteria. Scientific Reports, 8, Article 11218. https://doi.org/10.1038/s41598-018-29571-8
35. Kurtul, Y. H., Sahin, G., Ekin, E. E., Erok, B. & Adas G. T. (2017). Diagnostic Contribution of Magnetic Resonance Cholangiopancreatography in Biliary Obstruction: Additional Findings and Misdiagnosis. JAREM, 7, 135-9. https://doi.org/10.5152/jarem.2017.1371
36. Lammert, F., Gurusamy, K., Ko, C. W., Miquel, J. F., Mendez-Sanchez, N., Portincasa, P. & Wang, D. Q. H. (2016). Gallstones. Nature reviews Disease primers, 2(1), 1-17. https://10.1038/nrdp.2016.24
37. Liu, G., Xing, D., Wang, H. & Wu, J. (2002). Vibrational spectroscopic study of human pigment gallstones and their insoluble materials. Journal of Molecular Structure, 616(1-3), 187-191. https://doi.org/10.1016/S0022-2860(02)00330-7
38. Mandarano, G. & Sim, J. (2008). The diagnostic MRCP examination: overcoming technical challenges to ensure clinical success. Biomedical Imaging and Intervention Journal, 4, Article e28. https://doi.org/10.2349/biij.4.4.e28
39. McBride, M.B. (1995). Toxic metal accumulation from agricultural use of sludge: are USEPA regulations protective?. Journal of Environmental Quality, 24(1), 5-18. https://doi.org/10.2134/jeq1995.00472425002400010002x
40. Mir, M. A., Malik, U. Y., Wani, H. & Bali, B. S. (2013). Prevalence, pattern, sensitivity and resistance to antibiotics of different bacteria isolated from port site infection in low risk patients after elective laparoscopic cholecystectomy for symptomatic cholelithiasis at tertiary care hospital of Kashmir. International Wound Journal, 10(1), 110-113. https://doi.org/10.1111/j.1742-481X.2012.00963.x
41. Moctezuma-Velázquez, C., Gómez-Sámano, M. Á., Cajas-Sánchez, M. B., Reyes-Molina, D. L., Galindo-Guzmán, M., Meza-Arana, C. E., Cuevas-Ramos, D., Gómez-Pérez, F. J. & Gulias-Herrero, A., (2017). High dietary magnesium intake is significantly and independently associated with higher insulin sensitivity in a Mexican-mestizo population: a brief cross-sectional report. Revista de Investigación Clínica, 69(1), 40-46. https://doi.org/10.24875/ric.17002086
42. Moe, S.M. (2008). Disorders involving calcium, phosphorus, and magnesium. Primary Care: Clinics in Office Practice, 35(2), 215-237. https://doi.org/10.1016/j.pop.2008.01.007
43. Molinero, N., Ruiz, L., Milani, C., Gutiérrez-Díaz, I., Sánchez, B., Mangifesta, M., Segura, J., Cambero, I., Campelo, A.B., García-Bernardo, C.M., Cabrera, A., Rodríguez, J.I., González, S.I., Rodríguez, J.M., Ventura, M., Delgado, S. & Margolles, A. (2019). The human gallbladder microbiome is related to the physiological state and the biliary metabolic profile. Microbiome, 7(1), 100. https://doi.org/10.1186/s40168-019-0712-8
44. Nan, X., Prabha, R. D., Rashid, M. & Patel, B. (2023). Journey of a stone-thirty years on. Journal of Surgical Case Reports, 2, rjad069. https://doi.org/10.1093/jscr/rjad069
45. Omer, L. S. (2011). Quantitative analysis in (33) traces metals in human gallstones by ICP-AES. International Journal of Chemistry, 3(2), 105. https://doi.org/10.5539/ijc.v3n2p105
46. Ortega, R. M., Fernández-Azuela, M., Encinas-Sotillos, A., Andres, P. & Lopez-Sobaler, A. M. (1997). Differences in diet and food habits between patients with gallstones and controls. Journal of the American College of Nutrition, 16(1), 88-95. https://doi.org/10.1080/07315724.1997.10718655
47. Önür, N. D. & Beyler, A. R. (2001). Safra Asitleri Metabolizmasi. Ankara Universitesi Tıp Fakültesi Mecmuası, 54(1). (in Turkish).
48. Palchik, N. A. & Moroz, T. N., (2005). Polymorph modifications of calcium carbonate in gallstones. Journal of Crystal Growth, 283(3-4), 450-456. https://doi.org/I10.1016/j.jcrysgro.2005.05.035
49. Parviainen, A., Marchesi, C., Suarez-Grau, J. M., Garrido, C. J., Perez-Lopez, R., Nieto, J. M. & Cobo-Cardenas, G. (2018). Unraveling the impact of chronic exposure to metal pollution through human gallstones. Science of the Total Environment, 624, 1031-1040. https://doi.org/10.1016/j.scitotenv.2017.12.224
50. Parviainen, A., Suarez-Grau, J. M., Perez-Lopez, R., Nieto, J. M., Garrido, C. J. & Cobo-Cardenas, G. (2016). Combined microstructural and mineralogical phase characterization of gallstones in a patient-based study in SW Spain-Implications for environmental contamination in their formation. Science of the Total Environment, 573, 433-443. https://doi.org/10.1016/j.scitotenv.2016.08.110
51. Petakovic, G., Korica, M, Gavrilovic, S., 2002. Bacteriologic examination of gallbladder contents, Med Pregl, 55(5-6):225-8. https://doi.org/10.2298/mpns0206225p
52. Pichugina, A. A., Tsyro, L.V. & Unger, F. G., (2018). IR Spectroscopy and X-Ray Phase Analysis of the Chemical Composition of Gallstones. Journal of Applied Spectroscopy, 84(6), 1024-1029. https://doi.org/10.1007/s10812-018-0581-0
53. Portincasa P., Moschetta A., Petruzzelli M., Palasciano G., Di Ciaula A. & Pezzolla A., (2006). Gallstone disease: symptoms and diagnosis of gallbladder stones. Best Practice & Research Clinical Gastroenterology, 20, 1017–29. https://doi.org/10.1016/j.bpg.2006.05.005
54. Qiao, T., Ma, R. H., Luo, X. B., Yang, L. Q., Luo, Z. L. & Zheng, P. M. (2013). The systematic classification of gallbladder stones. PLOS One, 8(10), Article e74887. https://doi.org/10.1371/journal.pone.0074887
55. Ramya, J. R., Arul, K. T., Epple, M., Giebel, U., Guendel-Graber, J., Jayanthi, V., Sharma, M., Rela, M. N. & Kalkura, S. N. (2017). Chemical and structural analysis of gallstones from the Indian subcontinent. Materials Science and Engineering, C, 78, 878-885. https://doi.org/10.1016/j.msec.2017.04.004
56. Rautray, T. R., Vijayan, V. & Panigrahi, S. (2007). Analysis of Indian pigment gallstones. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 255(2), 409-415 https://doi.org/10.1016/j.nimb.2006.12.147
57. Robins, S. J., Fasulo, J. M. & Patton, G. M., (1982). Lipids of pigment gallstones. Biochimica et Biophysica Acta, 712, 21–25. https://doi.org/10.1016/0005-2760(82)90079-0
58. Selinus, 0., Alloway, B., Centeno, J. A., Finkelman, R. B, Fuge, R., Lindh, U. & Smedley, P. (2005). Esential Medical Geology. 115-594. https://doi.org/10.1007/978-94-007-4375-5
59. Sharma, R., Soy, S., Kumar, C., Sachan, S. G. & Sharma, S.R. (2015). Analysis of gallstone composition and structure in Jharkhand region. Indian Journal of Gastroenterology, 34(1), 29-37. https://doi.org/10.1007/s12664-014-0523-6
60. Skar, V., Skar, A. G. & Bratlie, J. (1989). Beta-glucuronidase Activity in the Bile of Gallstone Patients Both with and without Duodenal Diverticula. Scandinavian Journal of Gastroenterology, 24, 205. https://doi.org/10.3109/00365528909093038
61. Sleisenger & Fordtran. (1998). Gastrointestinal and Liver Disease, 6th ed., p. 631-644.
62. Soodan, R. K., Pakade, Y. B., Nagpal, A. & Katnoria, J. K. (2014). Analytical techniques for estimation of heavy metals in soil ecosystem. A tabulated review. Talanta, 125, 405-410. https://doi.org/10.1016/j.talanta.2014.02.033
63. Soto, J. A., Barish, M. A., Yucel, E. K., Siegenberg, D., Ferrucci, J. T. & Chuttani, R. (1996). Magnetic resonance cholangiography: comparison with endoscopic retrograde cholangio pancreatography. Gastroenterology 110(2), 589-97. https://doi.org/10.1053/gast.1996.v110.pm8566608
64. Srinivasan, K. (2016). BiologicaJ activities of red pepper (Capsicum annuum) and its pungent principle capsaicin: a review. Critical Reviews in Food Science and Nutrition, 56(9), 1488-1500 https://doi.org/10.1080/10408398.2013.772090
65. Stinton, L. M. & Shaffer, E. A. (2012). Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut and liver, 6(2), 172. https://doi.org/10.5009/gnl.2012.6.2.172
66. Suhara, M., Matsuda, K. & Sera, K., (1998). Elemental concentrations of four types of human gallstones by PIXE analysis. International Journal of PIXE, 8(01), 73-88. https://doi.org/10.1142/S0129083598000091
67. Suzuki, N., (1966). On bilirubin-metal complex compounds in relation to black pigments of gallstones. The Tohoku Journal of Experimental Medicine, 90, 195-205. https://doi.org/10.1620/tjem.90.195
68. Suzuki, N., Nakamura, Y., Kobayashi, N. & Sato, T. (1975). On metal elements in pure pigment gallstones. The Tohoku Journal of Experimental Medicine, 116(3), 233-240. https://doi.org/10.1620/tjem.116.233
69. Tazuma, S. (2017). Bile Acids and Gallstones: Epidemiology, Pathogenesis, Diagnosis, and Management. In Bile Acids in Gastroenterology (pp. 93-107). Springer, Tokyo. https://doi.org/10.1007/978-4-431-56062-3_6
70. Trotman, B.W., Ostrow, J.D., Soloway, R.D., Cheong, E.B. & Longyear, R.B. (1974). Pigment vs cholesterol cholelithiasis: comparison of stone and bile composition. The American Journal of Digestive Diseases, 19, 585–90. https://doi.org/10.1007/BF01073011
71. Unisa, S., Jagannath, P., Dhir, V., Khandelwal, C., Sarangi, L. & Roy, T.K. (2011). Population‐based study to estimate prevalence and determine risk factors of gallbladder diseases in the rural Gangetic basin of North India. HPB, 13(2), 117-125. https://doi.org/10.1111/j.1477-2574.2010.00255.x
72. Usai, D., Maritan, L., Dal Sasso, G., Artioli, G., Salvatori, S., Jakob, T. & Salviato, T. (2017). Late Pleistocene/Early Holocene Evidence of Prostatic Stones at Al Khiday Cemetery, Central Sudan. PLOS One, 12(1), e0169524. https://doi.org/10.1371/journal.pone.0169524
73. van Dam, R. M., Hu, F. B. & Willett, W. C. (2020). Coffee, caffeine, and health. New England Journal of Medicine, 383(4), 369-378.
74. Varol, S., Davraz, A. & Varol, E. (2008). Yeraltı suyu kimyası ve safra etkisinin Tıbbi Jeoloji açısından degerlendirilmesi. TAF Preventive Medicine Bulletin, 714, 351-356. (in Turkish)
75. Vitetta, L., Sali, A., Moritz, V., Shaw, A., Carson, P., Little, P. & Elzarka, A. (1989). Bacteria and gallstone nucleation. Australian and New Zealand Journal of Surgery, 59(7), 571-577. https://doi.org/10.1111/j.1445-2197.1989.tb01633.x
76. Wang, D.Q., Cohen, D.E. & Carey, M.C. (2009). Biliary lipids and cholesterol gallstone disease. Journal of Lipid Research, 50 (Supplement), S406-S411. https://doi.org/10.1194/jlr.R800075-JLR200
77. Wang, J., Ma, X. Y., Feng, Y. F., Ma, Z. S., Ma, T. C., Zhang, Y., Li, X., Wang, L. & Lei, W. (2017). Magnesium ions promote the biological behaviour of rat calvarial osteoblasts by activating the PI3K/Aktsignalling pathway. Biological Trace Element Research, 179(2), 284-293. https://doi.org/10.1007/s12011-017-0948-8
78. Weerakoon, H., Navaratne, A., Ranasinghe, S., Sivakanesan, R., Galketiya, K.B. & Rosairo, S. (2015). Chemical characterization of gallstones: an approach to explore the aetiopathogenesis of gallstone disease in Sri Lanka. PLOS One, 10(4), Article e0121537. https://doi.org/10.1371/journal.pone.0121537
79. Yalcin, M. G. (2013). Examining the gallstones in Nigde Province. 2nd Medical Geology Workshop, 283-284. https://doi.org/10.13140/RG.2.1.3911.9121
80. Yalcin, M. G., Yuksel, S., Akcadag, T., Copuroglu, I. & Aslan, E. (2011). The Observation of Gall Bladder Stone with Petrography and FTIR Method, 64th Geological Congress of Turkey, 53-55.
81. Ye, F., Shen, H., Li, Z., Meng, F., Li, L., Yang, J., Chen, Y., Bo, X, Zhang, X. & Ni, M. (2016). Influence of the biliary system on biliary bacteria revealed by bacterial communities of the human biliary and upper digestive tracts. PloS one, 11(3), Article e0150519. https://doi.org/10.1371/journal.pone.0150519
82. Yu, J. K., Pan, H., Huang, S. M., Huang, N. L., Yao, C. C., Hsiao, K. M. & Wu, C. W. (2013). Calcium content of different compositions of gallstones and pathogenesis of calcium carbonate gallstones. Asian Journal of Surgery, 36(1), 26-35. https://doi.org/10.1016/j.asjsur.2012.06.001
83. Yuan, S., Gill, D., Giovannucci, E. L., & Larsson, S. C. (2022). Obesity, type 2 diabetes, lifestyle factors, and risk of gallstone disease: a Mendelian randomization investigation. Clinical Gastroenterology and Hepatology, 20(3), Article e529-e537. https://doi.org/10.1016/j.cgh.2020.12.034
84. Zhou, J. S., Chen, H. J., Ji, H., Shi, X. C., Li, X. X., Chen, L. Q., Du, Z. Y. & Yu, H. B. (2018). Effect of dietary bile acids on growth, body composition, lipid metabolism and microbiota in grass carp (Ctenopharyngodonidella). Aquaculture nutrition, 24(2), 802-813. https://doi.org/10.1111/anu.12609
85. Zuo, M., Rashid, A., Wang, Y., Jain, A., Li, D., Behari, A., Kapoor, V.K., Koay, E.J., Chang, P., Vauthey, J.N., Li, Y., Espinoza, J.A., Roa, J.C., Javle, M. (2016). RNA sequencing-based analysis of gallbladder cancer reveals the importance of the liver X receptor and lipid metabolism in gallbladder cancer. Oncotarget, 7(23), 35302. https://10.18632/oncotarget.9181