Summary: A cholesterol derivative found in human feces, gallstones, eggs, and other biological matter.

Top Publications

  1. Hashimoto N, Ito Y, Han K, Shimada K, Sekikawa M, Topping D, et al. Potato pulps lowered the serum cholesterol and triglyceride levels in rats. J Nutr Sci Vitaminol (Tokyo). 2006;52:445-50 pubmed
    ..On the other hand, HK pulp inhibited the synthesis of fatty acids at the mRNA levels of FAS and SREBP-1c, which might lead to a reduction of the serum TG level. ..
  2. Stine K, Hercules R, Duff J, Walker B. Interaction of the glycoalkaloid tomatine with DMPC and sterol monolayers studied by surface pressure measurements and Brewster angle microscopy. J Phys Chem B. 2006;110:22220-9 pubmed
    ..Strong interactions are observed with cholestanol- and coprostanol-containing monolayers, and BAM reveals formation of spiked aggregates upon interaction with 7:..
  3. Szalat A, Gershkovich P, Ben Ari A, Shaish A, Liberman Y, Boutboul E, et al. Rifampicin-induced CYP3A4 activation in CTX patients cannot replace chenodeoxycholic acid treatment. Biochim Biophys Acta. 2007;1771:839-44 pubmed
    Cerebrotendinous xanthomatosis (CTX) is a rare neurodegenerative disorder with cholestanol accumulation resulting from mutations in the sterol 27-hydroxylase gene (CYP27A)...
  4. Bhattacharyya A, Lin D, Connor W. Cholestanol metabolism in patients with cerebrotendinous xanthomatosis: absorption, turnover, and tissue deposition. J Lipid Res. 2007;48:185-92 pubmed
    To study the metabolism of cholestanol in patients with cerebrotendinous xanthomatosis (CTX), we measured the cholestanol absorption, the cholesterol and cholestanol turnover, and the tissue content of sterols in two patients...
  5. Hallikainen M, Vidgren H, Agren J, Kiviniemi V, Miettinen T, Gylling H. Postprandial behavior of plasma squalene and non-cholesterol sterols in men with varying cholesterol absorption. Clin Chim Acta. 2006;374:63-8 pubmed
    ..marker) and postprandial cholesterol metabolism evaluated with plasma levels of cholesterol absorption (cholestanol and plant sterols) and synthesis markers (desmosterol and lathosterol)...
  6. Pilo de la Fuente B, Sobrido M, Giros M, Pozo L, Lustres M, Barrero F, et al. [Usefulness of cholestanol levels in the diagnosis and follow-up of patients with cerebrotendinous xanthomatosis]. Neurologia. 2011;26:397-404 pubmed publisher
    ..Such a deficiency results in a reduced production of chenodeoxycholic acid and in an increased formation of cholestanol. It is clinically characterized by cataracts, diarrhoea, xanthomas, premature arteriosclerosis and a number of ..
  7. Båvner A, Shafaati M, Hansson M, Olin M, Shpitzen S, Meiner V, et al. On the mechanism of accumulation of cholestanol in the brain of mice with a disruption of sterol 27-hydroxylase. J Lipid Res. 2010;51:2722-30 pubmed publisher
    ..xanthomatosis (CTX) is due to a lack of sterol 27-hydroxylase (CYP27A1) and is characterized by cholestanol-containing xanthomas in brain and tendons. Mice with the same defect do not develop xanthomas...
  8. Panzenboeck U, Andersson U, Hansson M, Sattler W, Meaney S, Bjorkhem I. On the mechanism of cerebral accumulation of cholestanol in patients with cerebrotendinous xanthomatosis. J Lipid Res. 2007;48:1167-74 pubmed
    ..of sterol 27-hydroxylase deficiency in humans [cerebrotendinous xanthomatosis (CTX)] is the development of cholestanol-containing brain xanthomas...
  9. von Bahr S, Movin T, Papadogiannakis N, Pikuleva I, Rönnow P, Diczfalusy U, et al. Mechanism of accumulation of cholesterol and cholestanol in tendons and the role of sterol 27-hydroxylase (CYP27A1). Arterioscler Thromb Vasc Biol. 2002;22:1129-35 pubmed
    ..the enzyme sterol 27-hydroxylase (CYP27A1), develop prominent xanthomas in tendons and brain containing both cholestanol and cholesterol, with a cholestanol:cholesterol ratio higher than that in the circulation...

More Information


  1. Seyama Y. Cholestanol metabolism, molecular pathology, and nutritional implications. J Med Food. 2003;6:217-24 pubmed
    b>Cholestanol, not cholesterol, is a minor component in the human body and in foods, but an increase in cholestanol concentration in serum induces a pathological condition named cerebrotendinous xanthomatosis (CTX)...
  2. Dotti M, Lutjohann D, von Bergmann K, Federico A. Normalisation of serum cholestanol concentration in a patient with cerebrotendinous xanthomatosis by combined treatment with chenodeoxycholic acid, simvastatin and LDL apheresis. Neurol Sci. 2004;25:185-91 pubmed
    The concentrations of serum cholesterol, cholestanol and non-cholesterol sterols were measured in a patient with cerebrotendinous xanthomatosis under different therapeutic regimens...
  3. Miettinen T, Strandberg T, Gylling H. Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol. Arterioscler Thromb Vasc Biol. 2000;20:1340-6 pubmed
    Coronary patients with low baseline ratios of serum cholestanol and plant sterols to cholesterol (indicating low cholesterol absorption) but not those with high ratios (high absorption) experienced reduced recurrences of coronary events ..
  4. Verrips A, van Engelen B, Wevers R, van Geel B, Cruysberg J, van den Heuvel L, et al. Presence of diarrhea and absence of tendon xanthomas in patients with cerebrotendinous xanthomatosis. Arch Neurol. 2000;57:520-4 pubmed
    ..We recommend that the presence of 2 of the 4 clinical hallmarks of CTX prompt thorough metabolic screening, including determination of urine bile alcohol excretion and serum cholestanol level, because CTX is a treatable disease.
  5. Mondelli M, Sicurelli F, Scarpini C, Dotti M, Federico A. Cerebrotendinous xanthomatosis: 11-year treatment with chenodeoxycholic acid in five patients. An electrophysiological study. J Neurol Sci. 2001;190:29-33 pubmed
    ..Two sisters of patients who never took CDCA showed progressive worsening of clinical manifestations, upper limb SEPs and BAEPs. ..
  6. Wolff E, Vergnes M, Portugal H, Defoort C, Amiot Carlin M, Lairon D, et al. Cholesterol-absorber status modifies the LDL cholesterol-lowering effect of a Mediterranean-type diet in adults with moderate cardiovascular risk factors. J Nutr. 2011;141:1791-8 pubmed publisher
    ..b>Cholestanol and sitosterol, as well as desmosterol and lathosterol, surrogate markers of cholesterol absorption or ..
  7. Jiménez Jiménez C, Carrero Lerida J, Sealey Cardona M, Ruiz Perez L, Urbina J, Gonzalez Pacanowska D. Delta24(25)-sterol methenyltransferase: intracellular localization and azasterol sensitivity in Leishmania major promastigotes overexpressing the enzyme. Mol Biochem Parasitol. 2008;160:52-9 pubmed publisher
    ..We also found in this study that cells overproducing the enzyme do not have increased resistance to the sterol methenyltransferase inhibitor 22, 26 azasterol. ..
  8. Reddy S, Sanders T, Owen R, Thompson M. Faecal pH, bile acid and sterol concentrations in premenopausal Indian and white vegetarians compared with white omnivores. Br J Nutr. 1998;79:495-500 pubmed
  9. Isobe K, Tarao M, Zakaria M, Chiem N, Minh L, Takada H. Quantitative application of fecal sterols using gas chromatography-mass spectrometry to investigate fecal pollution in tropical waters: western Malaysia and Mekong Delta, Vietnam. Environ Sci Technol. 2002;36:4497-507 pubmed
    ..On the basis of these criteria, extensive monitoring of sediments suggests that poor sanitary conditions exist in most of the urbanized area of Malaysia and in several urban and rural sites in Vietnam. ..
  10. Kobayashi M, Hamada T, Goto H, Imaizumi K, Ikeda I. Comparison of effects of dietary unesterified and esterified plant sterols on cholesterol absorption in rats. J Nutr Sci Vitaminol (Tokyo). 2008;54:210-4 pubmed
  11. Ostrowska M, Banaszkiewicz K, Kiławiec A, Róg T, Lutjohann D, Szczudlik A. Cerebrotendinous xanthomatosis: a rare cause of spinocerebellar syndrome. Neurol Neurochir Pol. 2011;45:600-603 pubmed publisher
    ..During the next two years of the follow-up, serum cholestanol and 7?-hydroxycholesterol levels decreased in response to the therapy, but this was not reflected in the ..
  12. Jusakul A, Loilome W, Namwat N, Haigh W, Kuver R, Dechakhamphu S, et al. Liver fluke-induced hepatic oxysterols stimulate DNA damage and apoptosis in cultured human cholangiocytes. Mutat Res. 2012;731:48-57 pubmed publisher
    ..These oxysterols induce apoptosis and DNA damage in cholangiocytes. Insufficient and impaired DNA repair of such mutated cells may enhance clonal expansion and further drive the change in cellular phenotype from normal to malignant. ..
  13. von der Lühe B, Dawson L, Mayes R, Forbes S, Fiedler S. Investigation of sterols as potential biomarkers for the detection of pig (S. s. domesticus) decomposition fluid in soils. Forensic Sci Int. 2013;230:68-73 pubmed publisher
    ..Further research is suggested for additional soil sampling before and after three months to investigate the abundance of these and other sterols. ..
  14. Quilliot D, Boman F, Creton C, Pelletier X, Floquet J, Debry G. Phytosterols have an unfavourable effect on bacterial activity and no evident protective effect on colon carcinogenesis. Eur J Cancer Prev. 2001;10:237-43 pubmed
    ..These data confirm the capacity of phytosterols to decrease cholesterol absorption, but indicate that a large excess of phytosterol must be avoided until further research on its effects on carcinogenesis has been done. ..
  15. Sugama S, Kimura A, Chen W, Kubota S, Seyama Y, Taira N, et al. Frontal lobe dementia with abnormal cholesterol metabolism and heterozygous mutation in sterol 27-hydroxylase gene (CYP27). J Inherit Metab Dis. 2001;24:379-92 pubmed
    ..Examination revealed increased serum levels of cholestanol with abnormal cholesterol metabolism and a heterozygous mutation of the sterol 27-hydroxylase gene (CYP27)...
  16. Palmié Peixoto I, Rocha M, Urbina J, de Souza W, Einicker Lamas M, Motta M. Effects of sterol biosynthesis inhibitors on endosymbiont-bearing trypanosomatids. FEMS Microbiol Lett. 2006;255:33-42 pubmed
  17. Midtvedt A, Carlstedt Duke B, Norin K, Saxerholt H, Midtvedt T. Development of five metabolic activities associated with the intestinal microflora of healthy infants. J Pediatr Gastroenterol Nutr. 1988;7:559-67 pubmed
    ..Environmental factors, such as the diet, seem to be of importance. In general, the functions seem to develop slower in those children receiving breast milk exclusively than in those receiving formula supplements. ..
  18. Petucci C, Guler L, KENTTAMAA H. Differentiation of stereoisomeric steroids by reactions with phosphenium ions. J Am Soc Mass Spectrom. 2002;13:362-70 pubmed
    ..The different reactivities of the three pairs of steroid isomers and of each diastereomeric compound pair are rationalized by reaction enthalpies and steric effects based on straightforward and predictable reaction mechanisms. ..
  19. Lamon Fava S, Schaefer E, Garuti R, Salen G, Calandra S. Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous xanthomatosis. Clin Genet. 2002;61:185-91 pubmed
    ..Because of the disruption of the 27-hydroxylase activity, CTX patients have elevated plasma levels of cholestanol, a by-product of abnormal bile acid synthesis. The present authors describe a female patient with CTX...
  20. Inoue T, Taguchi I, Abe S, Toyoda S, Sakuma M, Node K. Inhibition of intestinal cholesterol absorption might explain cholesterol-lowering effect of telmisartan. J Clin Pharm Ther. 2011;36:103-10 pubmed publisher
    ..This study was designed to investigate the mechanism of cholesterol reduction. We measured serum levels of cholestanol, a cholesterol absorption marker, and lathosterol, a cholesterol synthesis marker, in 20 patients with both ..
  21. Said J, Trybala E, Andersson E, Johnstone K, Liu L, Wimmer N, et al. Lipophile-conjugated sulfated oligosaccharides as novel microbicides against HIV-1. Antiviral Res. 2010;86:286-95 pubmed publisher
    ..Two of these compounds comprising a sulfated tetrasaccharide linked to a cholestanol group by a glycosidic bond, showed low toxicity and high selectivity indices...
  22. van Heijst A, Verrips A, Wevers R, Cruysberg J, Renier W, Tolboom J. Treatment and follow-up of children with cerebrotendinous xanthomatosis. Eur J Pediatr. 1998;157:313-6 pubmed
    ..CTX was diagnosed and effects of therapy were evaluated by determination of the serum cholestanol/cholesterol ratio (CCR) and the urinary excretion of bile alcohols...
  23. Brown A, Hang J, Dussault P, Carr T. Plant sterol and stanol substrate specificity of pancreatic cholesterol esterase. J Nutr Biochem. 2010;21:736-40 pubmed publisher
    ..Thus, PCE may play an important but discriminatory role in vivo in the liberation of free phytosterols to compete with cholesterol for micellar solubilization and absorption. ..
  24. Sittiwet C, Gylling H, Hallikainen M, Pihlajamaki J, Moilanen L, Laaksonen D, et al. Cholesterol metabolism and non-cholesterol sterol distribution in lipoproteins of type 1 diabetes: the effect of improved glycemic control. Atherosclerosis. 2007;194:465-72 pubmed
    In type 1 diabetes, the ratios to cholesterol of serum absorption markers, e.g., cholestanol, are elevated and those of synthesis markers, e.g., lathosterol, are reduced suggesting perturbed cholesterol metabolism...
  25. Lupattelli G, De Vuono S, Mannarino E. Patterns of cholesterol metabolism: pathophysiological and therapeutic implications for dyslipidemias and the metabolic syndrome. Nutr Metab Cardiovasc Dis. 2011;21:620-7 pubmed publisher
    ..Cholesterol metabolism is studied by measuring plasma levels of campesterol, sitosterol and cholestanol, that is, plant sterols which are recognised as surrogate cholesterol-absorption markers and lathosterol or ..
  26. Shah V, Dunstan H, Taylor W. An efficient diethyl ether-based soxhlet protocol to quantify faecal sterols from catchment waters. J Chromatogr A. 2006;1108:111-5 pubmed
    ..Moreover, it was revealed that the diethyl ether-based soxhlet extraction method used less solvent and was logistically easier. ..
  27. Gagne F, Blaise C, Lachance B, Sunahara G, Sabik H. Evidence of coprostanol estrogenicity to the freshwater mussel Elliptio complanata. Environ Pollut. 2001;115:97-106 pubmed
    ..One of these compounds appears to be the C17 oxidation product of coprostanol, whose polarity is similar to that of estradiol. The results present evidence that coprostanol is estrogenic to freshwater mussels. ..
  28. Uchida K, Satoh T, Narushima S, Itoh K, Takase H, Kuruma K, et al. Transformation of bile acids and sterols by clostridia (fusiform bacteria) in Wistar rats. Lipids. 1999;34:269-73 pubmed
    ..Escherichia coli transformed neither bile acids nor sterols. These data suggest that clostridia play an important role in the formation of secondary bile acids and coprostanol in rats. ..
  29. Adachi J, Ueno Y, Miwa A, Asano M, Nishimura A, Tatsuno Y. Epicoprostanol found in adipocere from five human autopsies. Lipids. 1997;32:1155-60 pubmed
    ..In addition, we showed the time-course of epicoprostanol accumulation. The relationship between the time of adipocere formation and the characteristic lipid composition is discussed. ..
  30. Suh S, Kim H, Park H, Ki C, Kim M, Jin S, et al. Three siblings with Cerebrotendinous Xanthomatosis: a novel mutation in the CYP27A1 gene. Eur J Med Genet. 2012;55:71-4 pubmed publisher
    ..These siblings presented with elevated cholestanol levels and typical manifestations such as tendon xanthomas, cataracts, osteopenia, mental retardation, ..
  31. Benesch M, Mannock D, McElhaney R. Sterol chemical configuration and conformation influence the thermotropic phase behaviour of dipalmitoylphosphatidylcholine mixtures containing 5?-cholestan-3?- and -3?-ol. Chem Phys Lipids. 2011;164:70-7 pubmed publisher
  32. Lin D, Connor W. Fecal steroids of the coprolite of a Greenland Eskimo mummy, AD 1475: a clue to dietary sterol intake. Am J Clin Nutr. 2001;74:44-9 pubmed
    ..The sterol nucleus is stable when frozen. The analysis of coprolite showed that the young Eskimo woman had consumed a diet very low in plant sterols and moderate to low in cholesterol content. ..
  33. Clark D, Soory M. Steroid 5alpha-reductase activity of Treponema denticola. Oral Microbiol Immunol. 2007;22:326-32 pubmed
    ..These results suggest that the 3-oxo-5alpha-steroid 4-dehydrogenase family protein gene of T. denticola codes for a functional protein that resembles mammalian 5alpha-R isoenzyme 2 with regard to co-factor requirement and pH optimum. ..
  34. Panda S, Chattoraj S, Broitman S. Correlation of neomycin, faecal neutral and acid sterols with colon carcinogenesis in rats. Br J Cancer. 1999;80:1132-6 pubmed
    ..Therefore coprostanol might possibly be associated with colon carcinogenesis in DMH-fed rats and cholesterol metabolism in gut appears to be related to the development of tumours. ..
  35. Bjorkhem I, Hansson M. Cerebrotendinous xanthomatosis: an inborn error in bile acid synthesis with defined mutations but still a challenge. Biochem Biophys Res Commun. 2010;396:46-9 pubmed publisher
    Cerebrotendinous xanthomatosis [CTX] is a rare disease characterized by the accumulation of cholesterol and cholestanol in brain and tendons caused by a mutation in the sterol 27-hydroxylase gene [CYP27A1] involved in bile acid synthesis...
  36. Vilela C, Batista D, Baptista Neto J, Ghiselli R. Benthic foraminifera distribution in a tourist lagoon in Rio de Janeiro, Brazil: a response to anthropogenic impacts. Mar Pollut Bull. 2011;62:2055-74 pubmed publisher
    ..PAHs and coprostanol high indexes, and the absence or low presence of microfauna in samples around the lagoon margin confirm illegal flows from gas stations and domestic sewage. ..
  37. Lahti M, Oikari A. Vertical distribution of pharmaceuticals in lake sediments-citalopram as potential chemomarker. Environ Toxicol Chem. 2012;31:1738-44 pubmed publisher
    ..When considering the consumption and the observed concentration profiles of pharmaceuticals, a clear increasing trend of citalopram toward the surface was evident at site A. ..
  38. Hakala K, Vuoristo M, Miettinen T. Serum cholesterol, cholesterol precursors and plant sterols in different inflammatory bowel diseases. Digestion. 1996;57:83-9 pubmed
    ..cholesterol precursors (delta 8-cholestenol, desmosterol and lathosterol), markers of cholesterol synthesis, cholestanol and plant sterols (campesterol and sitosterol), markers of cholesterol absorption and biliary secretion...
  39. Heinrich M, Levental I, Gelman H, Janmey P, Baumgart T. Critical exponents for line tension and dipole density difference from lipid monolayer domain boundary fluctuations. J Phys Chem B. 2008;112:8063-8 pubmed publisher
    ..Additionally, photobleaching effects and domain size influence were quantified and found to be small in our system. We suggest that the method of flicker spectroscopy can be helpful in identifying line-active compounds. ..
  40. Burnett J, Moses E, Croft K, Brown A, Grainger K, Vasikaran S, et al. Clinical and biochemical features, molecular diagnosis and long-term management of a case of cerebrotendinous xanthomatosis. Clin Chim Acta. 2001;306:63-9 pubmed
    ..Serum cholestanol concentrations were decreased with the HMG-CoA reductase inhibitor simvastatin alone and greater reductions ..
  41. Addona G, Sandermann H, Kloczewiak M, Miller K. Low chemical specificity of the nicotinic acetylcholine receptor sterol activation site. Biochim Biophys Acta. 2003;1609:177-82 pubmed
    ..The importance of cholesterol's planar ring structure was tested by comparing planar cholestanol (5alpha-cholestan-3beta-ol) with nonplanar coprostanol (5beta-cholestan-3beta-ol). Both supported activation...
  42. Wiegand V, Chang T, Strauss J, Fahrenholz F, Gimpl G. Transport of plasma membrane-derived cholesterol and the function of Niemann-Pick C1 Protein. FASEB J. 2003;17:782-4 pubmed
    ..under physiological and pathophysiological conditions, a novel fluorescent cholesterol analog, 6-dansyl cholestanol (DChol), has been synthesized. We present several lines of evidence that DChol mimics cholesterol...
  43. Rugonyi S, Smith E, Hall S. Kinetics for the collapse of trilayer liquid-crystalline disks from a monolayer at an air-water interface. Langmuir. 2005;21:7303-7 pubmed
  44. Moghadasian M. Cerebrotendinous xanthomatosis: clinical course, genotypes and metabolic backgrounds. Clin Invest Med. 2004;27:42-50 pubmed
    ..A search of MEDLINE, using the keywords cerebrotendinous xanthomatosis, brain xanthoma, tendon xanthoma, cholestanol, cholesterol and bile alcohol for articles covering clinical manifestations, laboratory findings, pathology, ..
  45. Bjorkhem I. Cerebrotendinous xanthomatosis. Curr Opin Lipidol. 2013;24:283-7 pubmed publisher
    ..xanthomatosis (CTX) is a rare neurological disease characterized by accumulation of cholesterol and cholestanol in brain and tendons caused by a mutation in the sterol 27-hydroxylase gene (CYP27A1)...
  46. Derrien M, Jardé E, Gruau G, Pourcher A, Gourmelon M, Jadas Hecart A, et al. Origin of fecal contamination in waters from contrasted areas: stanols as Microbial Source Tracking markers. Water Res. 2012;46:4009-16 pubmed publisher
    ..The data presented in this study show that this addition would improve the determination of fecal contamination sources when the contamination levels are low to moderate. ..
  47. Daughton C. Real-time estimation of small-area populations with human biomarkers in sewage. Sci Total Environ. 2012;414:6-21 pubmed publisher
  48. Nimmo M, Cross N. Structural features of sterols required to inhibit human sperm capacitation. Biol Reprod. 2003;68:1308-17 pubmed
    ..The present results support the hypothesis that sperm sterols block capacitation by increasing order of phospholipids. ..
  49. Hansson M, Olin M, Floren C, von Bahr S, van t Hooft F, Meaney S, et al. Unique patient with cerebrotendinous xanthomatosis. Evidence for presence of a defect in a gene that is not identical to sterol 27-hydroxylase. J Intern Med. 2007;261:504-10 pubmed
    ..e. high levels of bile alcohols and cholestanol and extremely low levels of 27-hydroxycholesterol in plasma)...
  50. Liu X, Ogawa H, Kishida T, Ebihara K. Hypolipidaemic effect of maize starch with different amylose content in ovariectomized rats depends on intake amount of resistant starch. Br J Nutr. 2009;101:328-39 pubmed publisher
    ..These results show that starch rich in RS is more effective in preventing ovarian hormone deficiency-induced hyperlipidaemia. ..
  51. Miettinen T, Gylling H, Lindbohm N, Miettinen T, Rajaratnam R, Relas H. Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins. J Lab Clin Med. 2003;141:131-7 pubmed
    We studied changes in serum cholestanol and plant sterols (indexes of cholesterol absorption) and cholesterol precursors (indexes of cholesterol synthesis) in response to cholesterol reduction by way of 1 year's treatment with ..
  52. Montone R, Martins C, Bícego M, Taniguchi S, da Silva D, Campos L, et al. Distribution of sewage input in marine sediments around a maritime Antarctic research station indicated by molecular geochemical indicators. Sci Total Environ. 2010;408:4665-71 pubmed publisher
    ..A low correlation was found between total LABs and fecal steroids, which could be attributed to the contribution of the natural sources of steroids. ..
  53. Burghaus L, Liu W, Haupt W. [Cerebrotendinous xanthomatosis]. Dtsch Med Wochenschr. 2007;132:1463-6 pubmed
    ..A bilateral cataract operation had been performed during adolescence. An elevated concentration of cholestanol and a normal cholesterol level were found in the blood samples...