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Estimation of time of death by quantification of melatonin in corpses

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Abstract

A method for the estimation of time of death (TOD), was evaluated by measuring the melatonin (MT) content of pineal bodies (PBs), sera and urine samples from 85 cadavers. A total of 44 cadavers were investigated in Sapporo (geographical coordinates N 43° 4′, E 141° 21′) and 41 in Tokyo (N 35° 39′, E 139° 44′). MT contents were measured by radioimmunoassay (RIA) in 75 PBs, 27 sera and 14 urine samples. Exponential differences of pineal MT content were recognized between peaks in nighttime and nadirs in daytime, ranging from 0.099 to 63.2 ng/PB. Circadian rhythms were also observed for the concentrations of MT in serum (11–205 pg/ml), and in urine (7.5–137.5 pg/ml). Consequently, criteria for the TOD estimation are proposed as follows. 1) Pineal MT contents — (1) 0–0.2 ng/PB: TOD 1100–1700 hours, (2) 0.2–0.3 ng/PB: TOD 0700–2000 hours, (3) 0.3–1 ng/PB: inconclusive, (4) 1–4 ng/PB: TOD 1600–1000 hours, (5) 4–8 ng/PB: TOD 2000–0800 hours, (6) over 8 ng/PB: TOD 2000–0500 hours, 2) Serum MT concentration — (1) 0–100 pg/ml: inconclusive, (2) over 100 pg/ml: TOD 2200–0100 hours, and 3) Urinary MT concentration — (1) 0–35 pg/ml: inconclusive, (2) over 35 pg/ml: TOD 1800–0600 hours. The range of the estimation can be limited by a combination of these 3 criteria. The present method can be combined with other methods for estimating the TOD to decrease the range.

Zusammenfassung

Eine Methode zur Bestimmung der Todeszeit (TZ) wurde evaluiert, indem der Melatonin-Gehalt der Epiphysen, Serum und Urin-Proben von 85 Leichen gemessen wurde. Insgesamt wurden 44 Leichen in Sapporo (geographische Koordinaten N 43°, 4′, E 141° 21′) und 41 Leichen in Tokio (N 35° 39′, E 139° 44′) untersucht. Die Melatonin-Gehalte wurden mit Hilfe des Radioimmunoassays (RIA) in 85 Epiphysen, 27 Seren und 14 Urinproben untersucht. Exponentielle Differenzen des epiphysären Melatonin-Gehalts wurden zwischen den nächtlichen Spitzenwerten und den „Nadirs” während der Tageszeit beobachtet. Diese variierten zwischen 0,099 und 63,2 ng/Epiphyse. Zirkadian-Rhythmen wurden ebenfalls beobachtet für die Konzentrationen von Melatonin im Serum (11–205 pg/ml) und in Urin (7,5–137,5 pg/ml). Folglich werden die Kriterien für die Bestimmung der TZ wie folgt vorgeschlagen: 1) Epiphysäre Melatonin-Gehalte —(1) 0–0,2 ng/Epiphyse: TZ 1100–1700 Uhr, (2) 0,2–0,3 ng/Epiphyse: TZ 0700–2000 Uhr, (3) 0.3–1 ng/Epiphyse: unentschieden, (4) 1–4 ng/Epiphyse: TZ 1600–1000 Uhr, (5) 4–8 ng/Epiphyse: TZ 2000–0800 Uhr, (6) über 8 ng/Epiphyse: TZ 2000–0500 Uhr; 2) Serum-Melatonin-Gehalte — (1) 0–100 pg/ml: unentschieden, (2) über 100 pg/ml: TZ 2200–0100 Uhr und 3) Urin-Melatonin-Gehalte — (1) 0–35 pg/ml: unentschieden, (2) über 35 pg/ml: TZ 1800–0600 Uhr. Die Streubreite der Bestimmung kann durch eine Kombination dieser 3 Kriterien eingeengt werden. Die vorliegende Methode kann mit anderen Methoden zur Bestimmung der Todeszeit kombiniert werden, um deren Variationsbreite zu verringern.

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References

  1. Wurtman RJ (1986) Melatonin in humans. J Neural Transm Suppl 21:1–8

    Google Scholar 

  2. Takahashi K, Inoue S, Honma K, Murakami N (1991) Thinking of chronobiology. A symposium record. Clin Neurosci 9:546–558 (in Japanese)

    Google Scholar 

  3. Takatori T, Ji L, Terazawa K, Wu B, Mikami H (1989) Development of monoclonal antibody reactive with melatonin. Frontiers of Forensics, Proceedings 3rd Indo-Pacific Congress on Legal Medicine and Forensic Sciences: 319–321

  4. Terazawa K, Ji L, Mikami H, Togashi T, Takatori T (1991) Production and characterization of monoclonal antibodies reactive with melatonin. J Immunoassay 12:413–424

    Google Scholar 

  5. Mikami H, Terazawa K, Takatori T, Tomaru Y, Ji L, Kanamori M (1992) Radioimmunoassay for melatonin using an antiserum raised against a novel antigen. Jpn J Legal Med 46:111–116

    Google Scholar 

  6. Greiner AC, Chan SC (1977) Melatonin content of the human pineal gland. Science 6:83–84

    Google Scholar 

  7. Beck O, Borg S, Lundman A (1982) Concentration of 5-methoxyindoles in the human pineal gland. J Neural Transm 54:111–116

    Google Scholar 

  8. Lynch HJ (1971) Diurnal oscillations in pineal melatonin content. Life Sci 10:791–795

    Google Scholar 

  9. Stanley M, Brown GM (1988) Melatonin levels are reduced in the pineal glands of suicide victims. Psychopharmacol Bull 24:484–488

    Google Scholar 

  10. Reiter RJ (1987) The melatonin message: duration versus coincidence hypotheses. Life Sci 40:2119–2131

    Google Scholar 

  11. Pelham RW, Vaughan GM, Sandock KL, Vaughan MK (1973) Twenty-four-hour cycle of a melatonin-like substance in the plasma of human males. J Clin Endocrinol Metab 37:341–344

    Google Scholar 

  12. Arendt J (1978) Melatonin assay in body fluids. J Neural Transm Suppl 13:265–278

    Google Scholar 

  13. Arendt J, Hampton S, English J, Kwasowski P, Marks V (1982) 24-hour profiles of melatonin, cortisol, insulin, C-peptide and GIP following a meal and subsequent fasting. Clin Endocrinol 16:89–95

    Google Scholar 

  14. Iguchi H, Kato K, Ibayashi H (1982) Age-dependent reduction in serum melatonin concentrations in healthy human subjects. J Clin Endocrinol Metab 55:27–29

    Google Scholar 

  15. Iguchi H, Kato K, Ibayashi H (1982) Melatonin serum levels and metabolic clearance rate in patients with liver cirrhosis. J Clin Endocrinol Metab 54:1025–1027

    Google Scholar 

  16. Ehrenkranz JRL, Tamarkin L, Comite F, Johnsonbaugh RE, Bybee DE, Loriaux DL, Cutler Jr GB (1982) Daily rhythm of plasma melatonin in normal and precocious puberty. J Clin Endocrinol Metab 55:307–310

    Google Scholar 

  17. Tamarkin L (1982) Decreased nocturnal plasma melatonin peak in patients with estrogen receptor positive breast cancer. Science 216:1003–1005

    Google Scholar 

  18. Arendt J, Bojkowski C, Franey C, Wright J, Marks V (1985) Immunoassay of 6-hydroxymelatonin sulfate in human plasma and urine. Abolition of the urinary 24-hour rhythm with atenolol. J Clin Endocrinol Metab 60:1166–1173

    Google Scholar 

  19. Berga SL, Mortola JF, Yen SSC (1988) Amplification of nocturnal melatonin secretion in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 66:242–244

    Google Scholar 

  20. Sturner WQ, Lynch HJ, Deng MH, Gleason RE, Wurtman RJ (1990) Melatonin concentrations in the sudden infant death syndrome. Forensic Sci Int 45:171–180

    Google Scholar 

  21. Petterborg LJ, Kjellman BF, Thalén BE, Wetterberg L (1991) Effect of a 15 minute light pulse on nocturnal serum melatonin levels in human volunteers. J Pineal Res 10:9–13

    Google Scholar 

  22. Smith JA, Helliwell PS, Isdale A, Astbury C, Padwick DJ, Bird HA (1991) Human nocturnal blood melatonin and liver acetylation status. J Pineal Res 10:14–17

    Google Scholar 

  23. Karasek M, Pawlikowski M, Nowakowska-Jankiewicz B, Kolodziej-Maciejewska H, Zieleniewski J, Cieslak D, Liedenberger F (1990) Circadian variations in plasma melatonin, FSH, LH, and prolactin and testosterone levels in infertile men. J Pineal Res 9:149–157

    Google Scholar 

  24. Arendt J (1986) Assay of melatonin and its metabolites: results in normal and unusual environments. J Neural Transm Suppl 21:11–33

    Google Scholar 

  25. Wetterberg L (1978) Melatonin in humans: physiological and clinical studies. J Neural Transm Suppl 13:289–310

    Google Scholar 

  26. Reiter RJ (1991) That ubiquitously acting pineal hormone. News in Physiological Sciences 6:223–227

    Google Scholar 

  27. Taborsky RG, Delvigs P, Page IH (1965) 6-Hydroxyindoles and the metabolism of melatonin. J Med Chem 8:855–858

    Google Scholar 

  28. Kopin JI, Pare CMB, Axelrod J, Weissbach H (1961) The fate of melatonin. J Biol Chem 236:3072–3075

    Google Scholar 

  29. Kopin JI, Pare CMB, Axelrod J, Weissbach H (1960) 6-Hydroxylation, the major metabolic pathway for melatonin. Biochim Biophys Acta 40:377–378

    Google Scholar 

  30. Hirata F, Hayashi O (1974) In vitro and in vivo formation of two new metabolites of melatonin. J Biol Chem 249:1311–1313

    Google Scholar 

  31. Lerner AB, Nordlund JJ (1978) Melatonin. J Neural Transm Suppl 13:289–310

    Google Scholar 

  32. Leone RM, Silman RE (1984) Melatonin can be metabolized in the rat to produceN-acetylserotonin in addition to 6-hydroxymelatonin. Endocrinology 114:1825–1832

    Google Scholar 

  33. Vakkuri O, Tervo J, Luttinen R, Ruotsalainen H, Rahkammaa E, Leppäluoto J (1987) A cyclic isomer of 2-hydroxymelatonin: a novel metabolite of melatonin. Endocrinology 120:2453–2459

    Google Scholar 

  34. Young IM, Leone RM, Francis P, Stovell P, Silman RE (1985) Melatonin is metabolized to N-acetyl serotonin and 6-hydroxymelatonin in man. J Clin Endocrinol Metab 60:114–119

    Google Scholar 

  35. Bojkowski CJ, Arendt J, Shih MC, Markey SP (1987) Melatonin secretion in humans assessed by measuring its metabolite, 6-sulfatoxymelatonin. Clin Chem 33:1343–1348

    Google Scholar 

  36. Bojkowski CJ, Arendt J (1990) Factors influencing urinary 6-sulphatoxymelatonin, a major melatonin metabolite, in normal human subjects. Clin Endocrinol 33:435–444

    Google Scholar 

  37. Tetsuo M, Poth M, Markey SP (1982) Melatonin metabolite excretion during childhood and puberty. J Clin Endocrinol Metab 55:311–313

    Google Scholar 

  38. Kawata F (1990) Studies on monoamine metabolism in the rat brain with overdosage of manganese. Jpn J Legal Med 44: 137–146 (in Japanese)

    Google Scholar 

  39. Carlsson A, Svennerholm L, Winblad B (1980) Seasonal and circadian monoamine variations in human brains examined post mortem. Acta Psychiatr Scand Suppl 61:75–85

    Google Scholar 

  40. Nair NPV, Hariharasubramanian N, Pilapil C, Issac I, Thavundayil JX (1986) Plasma melatonin. An index of brain aging in humans? Biol Phsychiatry 21:141–150

    Google Scholar 

  41. Reiter RJ, Richardson BA, Johnson LY, Ferguson BN, Dinh DT (1980) Pineal melatonin rhythm: reduction in aging Syrian hamsters. Science 210:1372–1373

    Google Scholar 

  42. Arendt J, Wirz-Justice A, Bradtke J (1977) Annual rhythm of serum melatonin in man. Neurosci Lett 7:327–330

    Google Scholar 

  43. Rosental NE, Sach DA, Jacobsen FM, James SP, Parry BL, Arendt J, Tamarkin L, Wehr TA (1986) Melatonin in seasonal affective disorder and phototherapy. J Neural Transm Suppl 21:257–267

    Google Scholar 

  44. Adler JS, Kripke DF, Loving RT, Berga SL (1992) Peripheral vision suppression of melatonin. J Pineal Res 12:49–52

    Google Scholar 

  45. National Astronomical Observatory (1992) Rika nenpyo (Chronological Scientific Tables), Maruzen, Tokyo

    Google Scholar 

  46. Oxenkrug GF, Anderson GF, Dragovic L, Blaivas M, Riederer P (1990) Circadian rhythms of human pineal melatonin, related indoles, and beta adrenoreceptors: post-mortem evaluation. J Pineal Res 9:1–11

    Google Scholar 

  47. Laakso ML, Hatonen T, Stenberg D, Alila A, Smith S (1993) One-hour exposure to moderate illuminance (500 lux) shifts the human melatonin rhythm. J Pineal Res 15:21–26

    Google Scholar 

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Mikami, H., Terazawa, K., Takatori, T. et al. Estimation of time of death by quantification of melatonin in corpses. Int J Leg Med 107, 42–51 (1994). https://doi.org/10.1007/BF01247274

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  • DOI: https://doi.org/10.1007/BF01247274

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