42

DAFTAR PUSTAKA

1. WHO. Methanol Poisoning Outbreaks [Internet]. 2011. Available from:

http://www.who.int/environmental_health_emergencies/poisoning/methano

l_information.pdf

2. Barceloux DG, Krenzelok EP, Olson K, Watson W. American Academy of

Clinical Toxicology Practice Guidelines on the Treatment of Ethylene

Glycol Poisoning. Ad Hoc Committee. J Toxicol Clin Toxicol.

1999;37(5):537–60.

3. Goldfrank L. Goldfrank’s Toxicologic Emergencies. 9th ed. 2011.

4. El-Bakary A a, El-Dakrory S a, Attalla SM, Hasanein N a, Malek H a.

Ranitidine as an alcohol dehydrogenase inhibitor in acute methanol toxicity

in rats. Hum Exp Toxicol [Internet]. 2010;29(2):93–101. Available from:

http://www.ncbi.nlm.nih.gov/pubmed/20026516

5. Li FX, Lu J, Xu YJ, Tong ZQ, Nie CL HR. Formaldehyde-mediated

chronic damage may be related to sporadic neurodegeneration. 2008;

6. Yang MF, Lu J, Miao JY, Rizak J, Yang JZ, Zhai RW, et al. Alzheimer’s

Disease and Methanol Toxicity (Part 1): Chronic Methanol Feeding Led to

Memory Impairments and Tau Hyperphosphorylation in Mice. 2014;

7. Rubinstein D, Escott E, Kelly JP. Methanol intoxication with putaminal

and white matter necrosis: MR and CT findings. AJNR Am J Neuroradiol

[Internet]. 1995;16(7):1492–4. Available from:

http://www.ncbi.nlm.nih.gov/pubmed/7484638

8. Susan Standring, PhD Ds. Gray’s Anatomy 40th edition [Internet].

Churchill Livingstone. 2009. Available from:

http://www.us.elsevierhealth.com/anatomy/gray-anatomy-expert-

consult/9780443066849/

9. Bartsch T. The Clinical Neurobiology of the Hippocampus: An Integrative

View, Volume 151 [Internet]. OUP Oxford; 2012 [cited 2016 Jan 14]. 310

p. Available from:

https://books.google.com/books?id=_J0PcQtq5m8C&pgis=1

10. Wright A. Section 4: Homeostasis and Higher Brain Function, Chapter 5.

42

Limbic System: Hippocampus. In: Neuroscience Online: an Electronic

Textbook for Neuroscience. 1997.

11. Catani M, Dell’Acqua F, Thiebaut de Schotten M. A revised limbic system

model for memory, emotion and behaviour. Neuroscience and

Biobehavioral Reviews. 2013. p. 1724–37.

12. Rolls ET. Limbic systems for emotion and for memory, but no single

limbic system. Cortex. 2015. p. 119–57.

13. Mega MS, Cummings JL, Salloway S, Malloy P. The limbic system: an

anatomic, phylogenetic, and clinical perspective. J Neuropsychiatry Clin

Neurosci. 1997;9(3):315–30.

14. Isaacson RL, Neil J Smelser, Paul B Baltes. Limbic System. Int Encycl Soc

Behav Sci [Internet]. 2001;2:8858–62. Available from:

http://www.sciencedirect.com/science/article/B7MRM-4MT09VJ-

4XS/2/9e7fa303f8769577cb0e460f32fb60c7

15. Barger N, Hanson KL, Teffer K, Schenker-Ahmed NM, Katerina

semendeferi. Evidence for evolutionary specialization in human limbic

structures. Front Hum Neurosci [Internet]. 2014;8(707):277. Available

from:

http://journal.frontiersin.org/article/10.3389/fnhum.2014.00277/abstract\np

apers3://publication/doi/10.3389/fnhum.2014.00277

16. Shorvon S. The Human Hippocampus. Functional Anatomy,

Vascularization and Serial Sections with MRI. J Anat. 2000;197:513–8.

17. Isaacson RL, Larry RS. Hippocampus. Encycl Neurosci [Internet].

2004;1119–27. Available from:

http://www.sciencedirect.com/science/article/pii/B978008045046902026X

18. Andersen P, Morris R, Amaral D, Bliss T, O’ Keefe J. The Hippocampus

Book. The Hippocampus Book. 2009. 1-852 p.

19. Papp E, Leergaard B, Calabrese E, Johnson G BJ. Waxholm space atlas of

the sprague dawley rat brain. National Institutes of Health Public Access.

2014.

20. Paulsen F WJ. Sobotta atlas of human anatomy Volume 1 Head, Neck,

Upper Limb. 14th Ed. 2006.

43

21. Hall JE. Textbook of Medical Physiology. 13th Ed. 2015.

22. Soebowo, Sarjadi, Wijaya I, Amarwati S, Miranti I PA. Pedoman Kuliah

Mahasiswa Patologi Anatomi 1. 2014.

23. Babu KM, Rosenbaum CD, Boyer EW. Head CT in patient with metabolic

acidosis. J Med Toxicol [Internet]. 2008;4(4):275–6. Available from:

http://www.ncbi.nlm.nih.gov/pubmed/19031380

24. Troncoso J, Rubio A, Fowler DR. Essential Forensic Neuropathology.

2010.

25. Auer RN. Effect of Age and Sex on N-Methyl-D-Aspartate Antagonist-

Induced Neuronal Necrosis in Rats. Stroke [Internet]. 1996;27(4):743–6.

Available from: http://stroke.ahajournals.org/content/27/4/743.full

26. Fuchs E, Flugge G, Czeh B. Remodeling of neuronal networks by stress.

Front Biosci. 2006;11(August 2015):2746–58.

27. Upton JW, Kaiser WJ, Mocarski ES. Virus inhibition of RIP3-dependent

necrosis. Cell Host Microbe. 2010;7(4):302–13.

28. Rohleder N, Kirschbaum C. Effects of nutrition on neuro-endocrine stress

responses. Curr Opin Clin Nutr Metab Care [Internet]. 2007;10(4):504–10.

Available from: http://www.ncbi.nlm.nih.gov/pubmed/17563471

29. Armstrong D, Halliday W, Hawkings C, Takashima S. Pediatric

Neuropathology: A Text-Atlas [Internet]. Springer Science & Business

Media; 2008 [cited 2016 Jan 25]. 443 p. Available from:

https://books.google.com/books?id=VJY20uS-BagC&pgis=1

30. Methanol Toxicological Overview [Internet]. [cited 2016 Jan 19].

Available from:

https://www.gov.uk/government/uploads/system/uploads/attachment_data/f

ile/456293/Methanol_TO_PHE_260815.pdf

31. ACUTE TOXICITY SUMMARY METHANOL [Internet]. [cited 2016 Jan

19]. Available from: http://oehha.ca.gov/air/acute_rels/pdf/67561a.pdf

32. McCoy HG, Cipolle RJ, Ehlers SM, Sawchuk RJ, Zaske DE. Severe

methanol poisoning. Application of a pharmacokinetic model for ethanol

therapy and hemodialysis. Am J Med. 1979;67(5):804–7.

33. Korabathina K. Methanol Toxicity [Internet]. 2015. Available from:

44

http://emedicine.medscape.com/article/1174890-overview

34. Dally AM. Fatal Methanol Intoxication – Two Exceptional Cases.

Toxichem Krimtech. 2015;

35. Kraut JA, Kurtz I. Toxic alcohol ingestions: Clinical features, Diagnosis,

and management. Clin J Am Soc Nephrol. 2008;3(1):208–25.

36. Acid-Base Physiology: 8.6 Metabolic Acidosis due to Drugs and Toxins

[Internet]. [cited 2016 Jan 19]. Available from:

http://www.anaesthesiamcq.com/AcidBaseBook/ab8_6a.php

37. Strum WB. Ranitidine. JAMA [Internet]. 1983;250(14):1894–6. Available

from: http://jama.jamanetwork.com/article.aspx?articleid=388242

38. van Hecken AM, Tjandramaga TB, Mullie A, Verbesselt R, de Schepper

PJ. Ranitidine: single dose pharmacokinetics and absolute bioavailability in

man. Br J Clin Pharmacol. 1982;14(2):195–200.

39. Ranitidine [Internet]. 2016. Available from:

http://www.drugs.com/pro/ranitidine.html

40. Ding J. Handbook of Metabolic Pathways of Xenobiotics. 2nd ed. John

Wiley & Sons; 2014.

41. Azeemuddin M, Naqi R. Case Series MRI findings in methanol

intoxication : a report of three cases. :1099–101.

42. Lwanga S.K., Lemeshow S. Sample size determination in health studies A

practicle manual. World Health Organization. 1991. p. 38.

43. WHO. Methanol poisoning outbreaks. 2014;

44. Nabila N. Pengaruh Pemberian Metanol Dan Etanolterhadap Tingkat

Kerusakan Sel Hepar Tikus Wistar. 2011;1–16.

45. Patnaik R, Mohanty S SH. Blockade of histamine H2 receptors attenuate

blood-brain barrier permeability, cerebral blood flow disturbances, edema

formation and cell reactions following hyperthermic brain injury in the rat.

2000;

46. Ding D, Moskowitz SI, Li R, Lee SB, Esteban M, Tomaselli K, et al.

Acidosis induces necrosis and apoptosis of cultured hippocampal neurons.

Exp Neurol [Internet]. 2000;162(1):1–12. Available from:

http://www.ncbi.nlm.nih.gov/pubmed/10716884

45

47. Singh M, Bhatia R. Emergencies in Neurology. Byword Books Private

Limited; 2011. 384 p

46

Lampiran

Lampiran 1. Hasil Analisis SPSS

Homogenitas Berat Badan

Test of Homogeneity of Variances

bb_tikus

Levene Statistic df1 df2 Sig.

1.365 2 12 .292

Case Processing Summary

Cases

Valid Missing Total

N Percent N Percent N Percent

bb_tikus 15 100.0% 0 0.0% 15 100.0%

Descriptives

Statistic Std. Error

bb_tikus Mean 188.47 3.049

95% Confidence Interval for

Mean

Lower Bound 181.93

Upper Bound 195.01

5% Trimmed Mean 188.02

Median 187.00

Variance 139.410

Std. Deviation 11.807

Minimum 172

Maximum 213

Range 41

Interquartile Range 19

Skewness .431 .580

Kurtosis -.463 1.121

Tests of Normality

47

Kolmogorov-Smirnova Shapiro-Wilk

Statistic df Sig. Statistic df Sig.

bb_tikus .124 15 .200* .956 15 .629

*. This is a lower bound of the true significance.

a. Lilliefors Significance Correction

Crosstabs

Case Processing Summary

Cases

Valid Missing Total

N Percent N Percent N Percent

nekrosis_a * nekrosis_p 15 100.0% 0 0.0% 15 100.0%

nekrosis_a * nekrosis_p Crosstabulation

Count

nekrosis_p

Total rendah sedang tinggi sangat tinggi

nekrosis_a rendah 7 1 0 0 8

sedang 0 2 0 0 2

tinggi 0 0 4 0 4

sangat tinggi 0 0 0 1 1

Total 7 3 4 1 15

Symmetric Measures

Value

Asymptotic

Standardized

Errora Approximate T

b

Approximate

Significance

Measure of Agreement Kappa .897 .099 5.343 .000

N of Valid Cases 15

a. Not assuming the null hypothesis.

b. Using the asymptotic standard error assuming the null hypothesis.

Means

Case Processing Summary

Cases

48

Included Excluded Total

N Percent N Percent N Percent

nekrosis_p * perlakuan 15 100.0% 0 0.0% 15 100.0%

Report

nekrosis_p

perlakuan Mean Std. Deviation Median Minimum Maximum

kontrol negatif 1.20 .447 1.00 rendah sedang

kontrol positif 3.20 .447 3.00 tinggi sangat tinggi

perlakuan 1.40 .548 1.00 rendah sedang

Total 1.93 1.033 2.00 rendah sangat tinggi

Explore perlakuan

Case Processing Summary

perlakuan

Cases

Valid Missing Total

N Percent N Percent N Percent

nekrosis_p kontrol negatif 5 100.0% 0 0.0% 5 100.0%

kontrol positif 5 100.0% 0 0.0% 5 100.0%

perlakuan 5 100.0% 0 0.0% 5 100.0%

Descriptives

perlakuan Statistic Std. Error

nekrosis_p kontrol negatif Mean 1.20 .200

95% Confidence Interval for

Mean

Lower Bound .64

Upper Bound 1.76

5% Trimmed Mean 1.17

Median 1.00

Variance .200

Std. Deviation .447

Minimum 1

Maximum 2

Range 1

Interquartile Range 1

Skewness 2.236 .913

49

Kurtosis 5.000 2.000

kontrol positif Mean 3.20 .200

95% Confidence Interval for

Mean

Lower Bound 2.64

Upper Bound 3.76

5% Trimmed Mean 3.17

Median 3.00

Variance .200

Std. Deviation .447

Minimum 3

Maximum 4

Range 1

Interquartile Range 1

Skewness 2.236 .913

Kurtosis 5.000 2.000

perlakuan Mean 1.40 .245

95% Confidence Interval for

Mean

Lower Bound .72

Upper Bound 2.08

5% Trimmed Mean 1.39

Median 1.00

Variance .300

Std. Deviation .548

Minimum 1

Maximum 2

Range 1

Interquartile Range 1

Skewness .609 .913

Kurtosis -3.333 2.000

Tests of Normality

perlakuan

Kolmogorov-Smirnova Shapiro-Wilk

Statistic df Sig. Statistic df Sig.

nekrosis_p kontrol negatif .473 5 .001 .552 5 .000

kontrol positif .473 5 .001 .552 5 .000

perlakuan .367 5 .026 .684 5 .006

a. Lilliefors Significance Correction

NPar Tests

50

Kruskal-Wallis Test

Ranks

perlakuan N Mean Rank

nekrosis_p kontrol negatif 5 5.00

kontrol positif 5 13.00

perlakuan 5 6.00

Total 15

Test Statisticsa,b

nekrosis_p

Chi-Square 10.857

df 2

Asymp. Sig. .004

a. Kruskal Wallis Test

b. Grouping Variable:

perlakuan

NPar Tests Mann-Whitney Test

Ranks

perlakuan N Mean Rank Sum of Ranks

nekrosis_p kontrol negatif 5 3.00 15.00

kontrol positif 5 8.00 40.00

Total 10

Test Statisticsa

nekrosis_p

Mann-Whitney U .000

Wilcoxon W 15.000

Z -2.785

Asymp. Sig. (2-tailed) .005

Exact Sig. [2*(1-tailed Sig.)] .008b

a. Grouping Variable: perlakuan

b. Not corrected for ties.

NPar Tests

51

Mann-Whitney Test

Ranks

perlakuan N Mean Rank Sum of Ranks

nekrosis_p kontrol negatif 5 5.00 25.00

perlakuan 5 6.00 30.00

Total 10

Test Statisticsa

nekrosis_p

Mann-Whitney U 10.000

Wilcoxon W 25.000

Z -.655

Asymp. Sig. (2-tailed) .513

Exact Sig. [2*(1-tailed Sig.)] .690b

a. Grouping Variable: perlakuan

b. Not corrected for ties.

NPar Tests Mann-Whitney Test

Ranks

perlakuan N Mean Rank Sum of Ranks

nekrosis_p kontrol positif 5 8.00 40.00

perlakuan 5 3.00 15.00

Total 10

Test Statisticsa

nekrosis_p

Mann-Whitney U .000

Wilcoxon W 15.000

Z -2.739

Asymp. Sig. (2-tailed) .006

Exact Sig. [2*(1-tailed Sig.)] .008b

a. Grouping Variable: perlakuan

b. Not corrected for ties.

52

Lampiran 2. Cara kerja sediaan histopatologi

1) Menyiapkan wadah yang di isi dengan larutan formalin 10% buffer dengan

minimal lima kali volume jaringan

2) Testis yang telah diambil, segera dimasukkan ke dalam wadah tersebut

3) Memberi identitas pada semua wadah dengan identitas masing-masing

kelompok perlakuan

4) Dikirim ke Sentra Diagnostik Patologi Anatomi disertai dengan formulir

pengantar

5) Preparat kemudian dipotong dengan ketebalan maksimal 3-4 cm

6) Setelah dipotong diletakkan di dalam kaset jaringan, dan dimasukkan ke

wadah yang berisi formalin 10% buffer

7) Dilakukan proses pembuatan blok parafin, kemudian didinginkan di dalam

lemari es

8) Blok parafin dipotong menjadi lebih tipis menggunakan mikrotom sesuai

kebutuhan

9) Pita parafin dilebarkan dengan ditempelkan langsung pada kaca benda yang

telah dibasahi dengan air

10) Dimulai dengan proses pengecatan Hematoksilin dan Eosin (HE)

11) Perparat diberi cat Hematoksilin

12) Kemudian didiferensiasi dengan menggunakan air kran

13) Diberi cat Eosin

14) Kemudian di dehidrasi menggunakan alkohol 70%

15) Pada proses “clearing” menggunakan larutan xylol

16) Mouting adalah tahap terakhir yang kemudian dapat diamati di mikroskop

53

Lampiran 3. Ethical Clearance

54

Lampiran 4. Surat Keterangan Penelitian

55

Lampiran 5. Hasil Pengamatan Nekrosis Sel Hipokampus

Subjek Jumlah Nekrosis (persen) Kategori

Kontrol Negatif 1 6 1

Kontrol Negatif 2 17 1

Kontrol Negatif 3 11 1

Kontrol Negatif 4 26 2

Kontrol Negatif 5 9 1

Kontrol Positif 1 51 3

Kontrol Positif 2 52 3

Kontrol Positif 3 83 4

Kontrol Positif 4 59 3

Kontrol Positif 5 64 3

Perlakuan 1 32 2

Perlakuan 2 39 2

Perlakuan 3 12 1

Perlakuan 4 23 1

Perlakuan 5 21 1

56

Lampiran 6. Dokumentasi Penelitian

57