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53. Higgins JW, Bedwell DW, Zamek-Gliszczynski MJ. Ablation of both organic cation transporter (OCT)1 and OCT2 alters metformin pharmacokinetics but has no effect on tissue drug exposure and pharmacodynamics. Drug Metab Dispos [Internet]. 2012 [cited 2014 Mar 17]; 40(6):1170-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22407892 54. Graham GG, Punt J, Arora M, Day RO, Doogue MP, Furlong TJ, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet [Internet]. 2011 [cited 2014 Mar 17]; 50(2):81-98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21241070 55. Khatua TN, Padiya R, Karnewar S, Kuncha M, Agawane SB, Kotamraju, et al. Garlic provides protection to mice heart against isoproterenol-induced oxidative damage: role of nitric oxide. Nitric Oxide [Internet]. 2012 [cited 2014 Feb 5]; 27(1):9-17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22484451 56. Gupta P, Kanwal A, Putcha UK, Bulani Y, Sojitra B, Khatua TN, et al. Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication. Jornal of Translational Medicine [Internet]. 2013 [cited 2014 Feb 8]; 11:80. Available from: http://www.translational-medicine.com/content/pdf/1479-5876-11-80.pdf 57. Murugesan M, Revathi R, Manju V. Cardioprotective effect of fenugreek on isoproterenol-induced myocardial infarction in rats. Indian J Pharmacol [Internet]. 2011 [cited 2014 Feb 8]; 43:516-9. Available from: http://www.ijponline.com/article.asp?issn=02537613;year=2011;volume=43;issue=5;spage=516;epage=519;aulast=Murugesan 58. AVMA Guidelines for the euthanasia of an animals: 2013 edition [Internet]. Schaumburg: American Veterinary Medical Association; 2013 [cited 2014 Feb 7]. Available from: https://www.avma.org/kb/policies/documents/euthanasia.pdf 59. Heart dissection [Internet]. Oxford (UK): European Mouse Phenotyping Resource of Standardised Screens (EMPReSS); 2004 [cited 2014 Feb 8]. Available from: http://www.mousebook.org/sops/020_001_heart_dissection_080407.pdf
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2014 Jul 14]; 37:300-13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14599305 70. Kaliste-Korhonen E, Eskola S. Fighting in NIH/S male mice: consequence for behaviour in resident-intruder tests and physiological parameters. Lab Anim [Internet]. 2000 [cited 2014 Jul 14]; 34:189-98. Available from: http://lan.sagepub.com/content/34/2/189.full.pdf
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LAMPIRAN
Lampiran 1. Ethical Clearance
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Lampiran 2. Izin Penelitian
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Lampiran 3. Sertifikat Hewan Coba
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Lampiran 4. Dokumentasi Penelitian
hewan coba
penyondean
pembedahan
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tempat pemeliharaan
pemberian makan dan minum ad libitum
pengukuran panjang tibia
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Lampiran 5. Luaran Analisis Program Statistik
N ISO 9 MET+ISO 11 MET 11 K 11 Total 42
Mean 236.18764 166.65958 156.25721 141.87973 172.34384
Descriptives Luas Penampang Kardiomiosit 95% Confidence Interval for Mean Std. Deviation Std. Error Lower Bound Upper Bound 63.449817 21.149939 187.41479 284.95849 39.299550 11.849260 140.25778 193.06137 44.672729 13.469335 126.24566 186.26876 23.092445 6.962634 126.36601 157.39344 54.779943 8.452729 155.27321 189.41448
Minimum 115.925 99.949 103.179 105.358 99.949
Tests of Normality Kolmogorov-Smirnova Shapiro-Wilk Group Statistic df Sig. Statistic df Sig. * Luas Penampang ISO .199 9 .200 .966 9 .859 * Kardiomiosit MET+ISO .145 11 .200 .981 11 .971 MET .197 11 .200* .915 11 .279 * K .171 11 .200 .957 11 .735 *. This is a lower bound of the true significance. a. Lilliefors Significance Correction
!
Maximum 330.790 234.393 233.819 183.130 330.790
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Test of Homogeneity of Variances Luas Penampang Kardiomiosit Levene Statistic 2.026
df1 3
df2 38
Sig. .127
ANOVA Luas Penampang Kardiomiosit Sum of Squares Between Groups 50093.808 Within Groups 72940.719 Total 123034.526
N ISO 11 MET+ISO 11 MET 11 K 11 Total 44
Mean 27.18 27.91 28.82 27.36 27.82
Std. Deviation 1.537 2.982 2.359 1.859 2.265
df
Mean Square 3 16697.936 38 1919.493 41
F 8.699
BERAT BADAN HARI KE-1 Descriptives Berat Badan (pre) 95% Confidence Interval for Mean Std. Error Lower Bound Upper Bound Minimum Maximum .464 26.15 28.21 25 30 .899 25.91 29.91 23 32 .711 27.23 30.40 25 34 .560 26.11 28.61 25 31 .341 27.13 28.51 23 34
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Sig. .000
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Tests of Normality Kolmogorov-Smirnova Group ISO
Berat Badan (pre)
Statistic
df
.234
Shapiro-Wilk
Sig.
11
MET+ISO .123 11 MET .197 11 K .184 11 *. This is a lower bound of the true significance. a. Lilliefors Significance Correction
Statistic
df
.096
.924 11
.351
*
.953 11 .947 11 .900 11
.679 .602 .187
.200 .200* .200*
Test of Homogeneity of Variances Berat Badan (pre) Levene Statistic
df1
df2
Sig.
1.861
3
40
.152
ANOVA Berat Badan (pre) Between Groups Within Groups Total
Sum of Squares 17.818 202.727 220.545
df
Mean Square F 3 5.939 1.172 40 5.068 43
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!
Sig.
Sig. .332
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Multiple Comparisons Dependent Variable: Luas Penampang Kardiomiosit LSD 95% Confidence Interval Mean (I) Group (J) Group Difference (I-J) Std. Error Sig. Lower Bound Upper Bound * ISO MET+ISO 69.527065 19.692036 .001 29.66262 109.39151 * MET 79.929429 19.692036 .000 40.06499 119.79387 * K 94.306914 19.692036 .000 54.44247 134.17136 * MET+ISO ISO -69.527065 19.692036 .001 -109.39151 -29.66262 MET 10.402363 18.681506 .581 -27.41637 48.22109 K 24.779848 18.681506 .193 -13.03888 62.59858 * MET ISO -79.929429 19.692036 .000 -119.79387 -40.06499 MET+ISO -10.402363 18.681506 .581 -48.22109 27.41637 K 14.377485 18.681506 .446 -23.44125 52.19622 * K ISO -94.306914 19.692036 .000 -134.17136 -54.44247 MET+ISO -24.779848 18.681506 .193 -62.59858 13.03888 MET -14.377485 18.681506 .446 -52.19622 23.44125 *. The mean difference is significant at the 0.05 level.
!
68 !
Case Processing Summary: Survival Group K ISO MET MET+ISO Overall
Total N 11 11 11 11 44
N of Events 0 2 0 0 2
Censored N Percent 11 100.0% 9 81.8% 11 100.0% 11 100.0% 42 95.5%
Overall Comparisons Chi-Square Log Rank (Mantel-Cox)
df
6.292 3 Breslow (Generalized Wilcoxon) 6.286 3 Tarone-Ware 6.289 3 Test of equality of survival distributions for the different levels of Group.
!
Sig. .098 .099 .098
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BERAT BADAN HARI KE-28 Descriptives Group Berat Badan (post)
ISO
Statistic Mean 95% Confidence Interval for Mean
Lower Bound
24.79
Upper Bound
28.32
5% Trimmed Mean
26.51
Median
27.00
Variance
5.278
Std. Deviation
2.297
Minimum
23
Maximum
31
Range
3
Skewness
.386
.717
Kurtosis
1.172
1.400
28.27
.935
Mean 95% Confidence Interval for Mean
Lower Bound
26.19
Upper Bound
30.36
5% Trimmed Mean
28.03
Median
27.00
Variance
9.618
Std. Deviation
3.101
Minimum
25
Maximum
36
Range
11
Interquartile Range
MET
4
Skewness
1.729
.661
Kurtosis
3.375
1.279
26.18
1.016
Mean 95% Confidence Interval for Mean
Lower Bound
23.92
Upper Bound
28.45
5% Trimmed Mean
26.15
Median
26.00
Variance
11.364
Std. Deviation
3.371
Minimum
22
Maximum
31
Range
9
Interquartile Range
K
7
Skewness
-.096
.661
Kurtosis
-1.706
1.279
26.09
.780
Mean 95% Confidence Interval for Mean
Lower Bound
24.35
Upper Bound
27.83
5% Trimmed Mean
26.10
Median
26.00
Variance
6.691
Std. Deviation
2.587
Minimum
22
Maximum
30
Range Interquartile Range
!
.766
8
Interquartile Range
MET+ISO
Std. Error
26.56
8 5
Skewness
.387
.661
Kurtosis
-.646
1.279
70 !
Tests of Normality Kolmogorov-Smirnova Group Berat Badan (post) ISO MET+ISO MET K
Statistic .201 .262 .253 .241
df 9 11 11 11
Shapiro-Wilk
Sig. .200* .033 .048 .073
Statistic .940 .830 .869 .912
df 9 11 11 11
Sig. .581 .023 .076 .259
Tests of Normality Kolmogorov-Smirnova Group Transformasi data ISO BB (post) dengan MET+ISO fungsi LG10 MET
Statistic
.196 .245 .255 K .224 *. This is a lower bound of the true significance. a. Lilliefors Significance Correction
!
df
Shapiro-Wilk
Sig. 9 11 11 11
Statistic *
.200 .063 .045 .131
.946 .865 .864 .924
df
Sig. 9 11 11 11
.643 .067 .065 .349
71 !
Test of Homogeneity of Variances BB (post) yang ditransformasi Levene Statistic 1.394
df1 3
df2 38
Sig. .259
ANOVA BB (post) yang ditransformasi Sum of Squares Between Groups .009 Within Groups .081 Total .090
df
Mean Square 3 .003 38 .002 41
F 1.375
71 !
!
Sig. .265
72 !
N ISO 9 MET+ISO 11 MET 11 K 11 Total 42
Mean 136.67 129.09 118.18 130.00 128.10
Std. Deviation 20.616 23.856 18.878 24.495 22.332
Descriptives Berat Jantung (BJ) 95% Confidence Interval for Mean Std. Error Lower Bound Upper Bound Minimum Maximum 6.872 120.82 152.51 110 170 7.193 113.06 145.12 100 170 5.692 105.50 130.86 80 150 7.385 113.54 146.46 100 190 3.446 121.14 135.05 80 190
Tests of Normality Kolmogorov-Smirnova Group Statistic df Sig. Berat Jantung (BJ) ISO .186 9 .200* MET+ISO .212 11 .180 MET .189 11 .200* K .251 11 .052 *. This is a lower bound of the true significance. a. Lilliefors Significance Correction
!
Shapiro-Wilk Statistic Df .927 9 .894 11 .958 11 .858 11
Sig. .453 .155 .741 .054
73 !
Test of Homogeneity of Variances Berat Jantung (BJ) Levene Statistic
df1
df2
Sig.
.187
3
38
.905
ANOVA Berat Jantung (BJ) Sum of Squares df Mean Square Between Groups 1793.074 3 597.691 Within Groups 18654.545 38 490.909 Total 20447.619 41
N ISO 9 MET+ISO 11 MET 11 K 11 Total 42
Mean 6.3489 5.8136 5.2864 5.9555 5.8274
Std. Deviation 1.00026 1.08955 .73816 1.10354 1.02829
F 1.218
Descriptives BJ/PT 95% Confidence Interval for Mean Std. Error Lower Bound Upper Bound Minimum Maximum .33342 5.5800 7.1178 4.94 7.87 .32851 5.0817 6.5456 4.45 7.72 .22256 4.7905 5.7823 3.80 6.43 .33273 5.2141 6.6968 4.73 8.67 .15867 5.5069 6.1478 3.80 8.67
73 !
Sig. .317
!
74 !
Tests of Normality Kolmogorov-Smirnova Group Statistic df Sig. BJ/PT ISO .171 9 .200* MET+ISO .200 11 .200* MET .119 11 .200* K .179 11 .200* *. This is a lower bound of the true significance. a. Lilliefors Significance Correction Test of Homogeneity of Variances BJ/PT Levene Statistic df1 df2 Sig. .453 3 38 .717
74 !
!
Shapiro-Wilk Statistic df .947 9 .895 11 .974 11 .870 11
Sig. .660 .160 .928 .078
75 !
Between Groups Within Groups Total
ANOVA BJ/PT Sum of Squares df Mean Square 5.850 3 1.950 37.502 38 .987 43.352 41
F 1.976
Sig. .134
Descriptives BJ/BB
ISO MET+ISO MET K Total
!
N
Mean
Std. Deviation
9 11 11 11 42
5.2000 4.5645 4.5518 5.0018 4.8119
.97848 .68238 .79004 .93065 .86091
95% Confidence Interval for Mean Std. Error
Lower Bound
Upper Bound
Minimum
Maximum
.32616 .20575 .23820 .28060 .13284
4.4479 4.1061 4.0211 4.3766 4.5436
5.9521 5.0230 5.0826 5.6270 5.0802
3.55 3.70 3.64 4.00 3.55
6.52 6.07 5.91 7.31 7.31
76 !
Tests of Normality Kolmogorov-Smirnova Group Statistic df Sig. BJ/BB ISO .197 9 .200* MET+ISO .178 11 .200* MET .204 11 .200* K .185 11 .200* *. This is a lower bound of the true significance. a. Lilliefors Significance Correction
Shapiro-Wilk Statistic df .939 9 .934 11 .896 11 .860 11
Test of Homogeneity of Variances BJ/BB Levene Statistic
df1
df2
Sig.
.348
3
38
.791
ANOVA BJ/BB Sum of Squares df Mean Square Between Groups 3.169 3 1.056 Within Groups 27.219 38 .716 Total 30.388 41
!
F 1.475
Sig. .237
Sig. .566 .448 .164 .058
77 !
Lampiran 6. Biodata Mahasiswa Identitas Nama
: Ihsan Fadilah
NIM
: 22010110120066
TTL
: Kotabumi, 18 Oktober 1992
Jenis Kelamin : Laki-laki Alamat
: Jalan Citra H30 Graha Estetika, Banyumanik, Semarang
Nomor Telp. : (024) 7463577 Nomor Ponsel : +6285279343000 E-mail
:
[email protected]
Riwayat Pendidikan Formal 1. TK
: TK Tunas Harapan, Lampung Utara
Lulus tahun : 1998
2. SD
: SDN 4 Tanjungaman, Lampung Utara
Lulus tahun : 2004
3. SMP
: SMPN 7 Kotabumi, Lampung Utara
Lulus tahun : 2007
4. SMA
: SMAN 2 Bandarlampung
Lulus tahun : 2010
5. FK Undip, masuk tahun : 2010 Keanggotaan Organisasi 1. Kelompok Studi Mahasiswa FK Undip
Tahun 2010 s.d 2014
2. Asisten Mahasiswa Bagian Anatomi FK Undip
Tahun 2012 s.d 2014
3. Pengabdian Masyarakat BEM FK Undip
Tahun 2011 s.d 2013
4. Asisten Mahasiswa Bagian Kimia FK Undip
Tahun 2011 s.d 2012
5. Rohis SMAN 2 Bandarlampung
Tahun 2007 s.d 2010
6. Karya Ilmiah Remaja SMAN 2 Bandarlampung
Tahun 2007 s.d 2009
7. Kesenian OSIS SMPN Kotabumi
Tahun 2005 s.d 2006
Pengalaman Penelitian 1. Yoghurt Kacang Tanah (Arachis hypogaea) sebagai Inovasi Pangan Sehat Anti-osteoporosis: Sebuah Studi Eksperimental pada Tikus Wistar Model Osteoporosis, 2014.
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78 !
2. Prevalensi Infeksi Cacing Cambuk (Trichuris trichiura) dan Cacing Tambang (Necator americanus dan Ancylostoma duodenale) pada Ibu Hamil di Kota Semarang, 2013-2014. 3. Analisis Genotype-Phenotype pada Penderita dan Karier Penderita Leber Hereditary Optic Neuropathy di Indonesia, 2012. 4. Efek Pemberian Yoghurt Kacang Tanah (Phaseolus vulgaris) terhadap Profil Lipid Serum dan Jumlah Coliform serta Lactobacilli Feses pada Tikus Dislipidemia, 2011. Pengalaman Presentasi dan Mengikuti Lomba Karya Ilmiah 1. Yoghurt Kacang Tanah (Arachis hypogaea) sebagai Inovasi Pangan Sehat Anti-osteoporosis: Sebuah Studi Eksperimental pada Tikus Wistar Model Osteoporosis. Direktorat Penelitian dan Pengabdian kepada Masyarakat Ditjen Pendidikan Tinggi Kementerian Pendidikan Nasional. [Penelitian Didanai] 2. Potensi Gen Antibodi PreS2 dalam Vektor Adenovirus melalui Microneedle Patch sebagai Vaccinotherapy Hepatitis B dan Karsinoma Hepatoseluler. FKK Universitas Muhammadiyah Jakarta. [Juara 1 Poster Ilmiah - Nasional] 3. Efek Pemberian Metformin terhadap Hipertrofi Miosit dan FIbrosis Interstisial Jantung pada Mencit Pasca-Infark Miokardium yang Diinduksi dengan Isoproterenol. Bidang Riset Himpunan Mahasiswa Kedokteran Umum Undip. [Juara 3 Proposal Penelitian - Program Studi] 4. Mycospray Berbasis Aspergillus niger Entomopatogenik: Sebuah Inovasi Pengontrolan Resistensi dan Populasi Aedes aegypti dalam Upaya Pengendalian Dengue. Departemen Riset BEM FK KM Undip. [Juara 1 Proposal Penelitian - Fakultas] 5. Yoghurt Kacang Tanah (Arachis hypogaea) sebagai Inovasi Pangan Sehat Anti-osteoporosis: Sebuah Studi Eksperimental pada Tikus Wistar Model Osteoporosis. Departemen Riset BEM FK KM Undip. [Juara 2 Proposal Penelitian - Fakultas]
78 !
!
79 !
6. Evidence-Based Medicine: Tribendimidine sebagai Obat Alternatif Terbaru untuk Terapi Ascariasis. Badan Analisis dan Pengembangan Ilmiah Nasional (BAPIN)-Ikatan Senat Mahasiswa Kedokteran Indonesia (ISMKI) beserta FK Universitas Padjajaran. [Finalis 6 Besar Gagasan Tertulis - Nasional] 7. Mycospray Berbasis Aspergillus niger Entomopatogenik: Sebuah Inovasi Pengontrolan Resistensi dan Populasi Aedes aegypti dalam Upaya Pengendalian Dengue. Himpunan Mahasiswa Kedokteran Umum Undip. [Juara 1 Gagasan Tertulis - Nasional] 8. Potensi Gen Antibodi PreS2 dalam Vektor Adenovirus melalui Microneedle Patch sebagai Vaccinotherapy Hepatitis B dan Karsinoma Hepatoseluler. Himpunan Mahasiswa Kedokteran Umum Undip. [Juara 3 Gagasan TertulisNasional] 9. Curcumin
in
Curcuma
longa
as
Inflammoregulator
to
Prevent
Carcinogenesis of Colitis-associated Colorectal Cancer Promoted by Commensal pks+ Escherichia coli. FK Universitas Indonesia. [Juara ke-5 Literature Review - Internasional] 10. Efek Pemberian Yoghurt Kacang Merah (Phaseolus vulgaris) terhadap Profil Lipid Serum dan Jumlah Coliform serta Lactobacilli Feses pada Tikus Dislipidemia. FK Udayana. [Juara 3 Penelitian - Nasional] 11. Potensi Antibodi PreS2 dalam Vektor Adenovirus melalui Microneedle Patch sebagai Vaccinotherapy Hepatitis B dan Karsinoma Hepatoseluler. FK Udayana. [Finalis 10 Besar Poster Ilmiah - Nasional] 12. Efek Pemberian Yoghurt Kacang Tanah (Arachis hypogaea) terhadap Kadar C-Telopeptida Serum, Kadar Alkali Fosfatase Serum dan Gambaran Histopatologi Tulang pada Tikus Ovariektomi Model Osteoporosis. Bidang Riset Himpunan Mahasiswa Kedokteran Umum Undip. [Juara 1 Proposal Penelitian - Program Studi] 13. Potensi Idebenone untuk Optimalisasi Fungsi Mitokondria pada Penderita Leber Hereditary Optic Neuropathy (LHON). FK Universitas Sriwijaya. [Finalis 10 Besar Gagasan Tertulis - Nasional]
79 !
!
80 !
14. Analisis Genotype-Phenotype pada Penderita dan Karier Leber Hereditary Optic Neuropathy di Indonesia. FK Undip. [Penelitian didanai] 15. Efek Pemberian Yoghurt Kacang Merah (Phaseolus vulgaris) terhadap Profil Lipid Serum dan Jumlah Coliform serta Lactobacilli Feses pada Tikus Dislipidemia. Direktorat Penelitian dan Pengabdian kepada Masyarakat Ditjen Pendidikan Tinggi Kementerian Pendidikan Nasional. [Penelitian Didanai] 16. Efek Pemberian Yoghurt Kacang Merah (Phaseolus vulgaris) terhadap Profil Lipid Serum dan Jumlah Coliform serta Lactobacilli Feses pada Tikus Dislipidemia. Fakultas Teknik Undip. [Juara 1 Proposal Penelitian Universitas]
80 !
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