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Abstrak :
[ABSTRAK
Latar Belakang : Continous ambulatory peritoneal dialysis (CAPD) telah menjadi alternatif selain hemodialisis untuk pengobatan penyakit ginjal tahap akhir. Fibrosis peritoneum merupakan penyebab utama terjadinya kerusakan membran peritoneum. Mekanisme fibrosis peritoneum belum diketahui secara pasti, namun ditengarai transforming growth factor ? β (TGF ?β) berhubungan erat terhadap terjadinya fibrosis peritoneum. Tujuan : Tujuan penelitian ini adalah untuk mengetahui pengaruh kombinasi ACE inhibitor (ACEI) dan calcium channel Blocker (CCB) terhadap penurunan ekspresi TGF ? β dan fibrosis peritoneum tikus jantan yang telah dilakukan CAPD. Metode Penelitian : Penelitian eksperimental, post test only control group design. Tiga puluh tikus Dawley spraque dibagi menjadi lima kelompok yaitu kelompok kontrol (kelompok 1) dan kelompok perlakuan dengan pemberian masing-masing cairan CAPD 4,25% (kelompok2) lisinopril 1,44 mg oral dan CAPD (kelompok 3) diltiazem CD 6,48 mg oral dan CAPD (kelompok 4) lisinopril 1,44 mg dan diltiazem CD 6,48 mg oral dan CAPD (kelompok 5). Setelah 4 minggu tikus dikorbankan dengan cara dislokasi cervical kemudian diperiksa ekspresi TGF ? β dan terjadinya fibrosis pada peritoneum tikus, selanjutnya dibuat sediaan histopatologi dan diwarnai dengan hematoksilin eosin serta imunohistokimia menggunakan antihuman TGF-ß. Hasil : Dua puluh peritoneum tikus berhasil diperiksa. Rerata skor TGF-β kelompok kontrol 1,8, kelompok CAPD 2, kelompok lisinopril dan CAPD 1,8, kelompok diltiazem CD dan CAPD 1,8, kelompok lisinopril dan diltiazem CD dan CAPD 1,7 (p=0,959). Rerata skor fibrosis peritoneum kelompok kontrol 1,1, kelompok CAPD 2,6, kelompok lisinopril dan CAPD 1,2, kelompok diltiazem CD dan CAPD 1,3, kelompok lisinopril dan diltiazem CD dan CAPD1,5 (p=0,268) Simpulan : Kombinasi lisinopril dan diltiazem mempunyai kecenderungan menurunkan ekspresi TGF ? β lebih baik dibandingkan lisinopril maupun diltiazem yang diberikan secara terpisah tetapi tidak bermakna secara statistik. Kombinasi lisinopril dan diltiazem mempunyai kecenderungan mengurangi fibrosis peritoneum tetapi tidak bermakna secara statistik dan tidak lebih baik dibandingkan lisinopril maupun diltiazem bila diberikan secara terpisah.

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ABSTRACT
Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor ? β(TGF ? β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF ? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn?t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor ? β(TGF ? β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF ? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn?t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor ? β(TGF ? β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF ? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn?t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor ? β(TGF ? β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF ? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn?t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor ? β(TGF ? β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF ? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn?t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis., Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor – β(TGF – β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF – β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF – β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF – β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn’t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.]

Abstrak :
Coronary Artery Disease CAD merupakan kondisi ketidakseimbangan suplai dan kebutuhan oksigen miokardial yang disebabkan oleh berbagai faktor sehingga terapi yang diberikan berupa kombinasi obat. Penggunaan kombinasi obat meningkatkan terjadinya interaksi obat. Penelitian ini bertujuan untuk menganalisis potensi interaksi obat kombinasi golongan nitrat dan calcium channel blocker CCB dengan obat lain pada pasien CAD rawat jalan di RSUD Pasar Minggu tahun 2017. Desain penelitian ini adalah cross-sectional dengan pengambilan data retrospektif. Sampel yang memenuhi kriteria inklusi sebanyak 167 resep. Kejadian interaksi obat diperiksa menggunakan Micromedex. Hasil menunjukkan bahwa terdapat 142 resep yang memiliki potensi interaksi. Potensi interaksi terbanyak terjadi dengan tingkat keparahan mayor 62,2, diikuti keparahan moderat 33,8. Obat yang paling banyak menimbulkan interaksi adalah kombinasi amlodipin dengan simvastatin. Kesimpulan dari penelitian ini adalah penggunaan kombinasi nitrat dan CCB dengan obat lain pada pasien CAD berpotensi menyebabkan interaksi, sehingga perlu disarankan melakukan pemeriksaan laboratorium secara berkala atau penyesuaian rejimen dosis untuk meminimalisasi terjadinya interaksi. ...... Coronary Artery Disease CAD is imbalances of supply and demand of myocardial oxygens which is caused by multiple factors, thus requires drug combinations as therapy. The use of such drug combinations may increase the incidence of drug interactions. This study aim is analyze the potentials of drug combinations between nitrate and CCB category with other drugs on outpatients with CAD at Pasar Minggu General Hospital in 2017. Design of this study is cross sectional with retrospective data collection. Samples which corresponds to inclusion criteria are 167 prescriptions. The occurrence of drug interactions are checked using Micromedex . Result showed that there were 142 prescriptions with potentials of interactions. The largest potential in drug interactions occur in major severity 62,23 followed by moderate severity 33,77. The drug that causes drug interactions the most is combination of amlodipin and simvastatin. This study concluded that the use of nitrate and CCB drug combinations with other drugs has the potential to cause interactions, therefore periodic laboratory checkups needs or adjustment of dosage regimen to be recommended to minimize the incidence of drug interactions.

Abstrak :
Golongan calcium channel blocker (CCB) turunan 1,4-dihidropiridin (DHP) merupakan terapi farmakologis lini pertama dalam hipertensi, dengan bukti efikasi dan profil keamanan yang baik. Obat-obat ini secara selektif menargetkan kanal kalsium tipe L. Namun, terdapat efek samping pada CCB DHP generasi ketiga yang paling sering diresepkan, yaitu amlodipine, berupa aktivasi mekanisme kompensasi homeostasis tubuh dalam meregulasi tekanan darah kembali ke tingkat patologis, serta seringnya terjadi edema perifer. Hal ini dapat menyebabkan penurunan efikasi terapi jangka panjang serta kepatuhan pasien. Pengembangan DHP generasi keempat seperti cilnidipine difokuskan untuk mengurangi kejadian efek samping ini dengan adanya tambahan aksi pada kanal kalsium tipe N. Oleh sebab itu, dapat dirancang analog-analog senyawa baru berdasarkan cilnidipine. Penelitian ini bertujuan untuk merancang dan menguji analog senyawa-senyawa ini dengan metode penambatan molekuler, serta melakukan sintesis dan karakterisasi terhadap salah satu senyawa yang dirancang, yaitu senyawa baru dibenzil 4-(2-klorofenil)-2,6-dimetil-1,4-dihidropiridin-3,5-dikarboksilat. Penambatan molekuler dilakukan dengan Autodock 4 terhadap makromolekul 6JP5 (tipe L) dan 7VFW (tipe N). Senyawa yang disintesis memiliki nilai ΔG –9,82 kkal/mol dan Ki sebesar 63,49 nM terhadap makromolekul 6JP5, serta memiliki ΔG sebesar –9,82 kkal/mol dan Ki sebesar 63,09 nM terhadap makromolekul 7VFW. Senyawa target disintesis dengan reaksi Hantzsch dengan bantuan microwaveselama 30 menit pada daya 400 W dalam etanol, lalu dipurifikasi dengan kromatografi lapis tipis preparatif, menghasilkan yield sebesar 0,598%. Elusidasi dan karakterisasi terhadap senyawa hasil sintesis dengan 1H dan 13C-NMR, densitometri, LC–MS/MS, dan spektroskopi inframerah telah mengonfirmasi bahwa senyawa hasil sintesis adalah benar merupakan senyawa target. ......The 1,4-dihydropyridine (DHP) derivatives of calcium channel blocker (CCB) are the first-line pharmacological therapy of hypertension, with the evidence of acceptable efficacy and safety profile. These drugs selectively target the L-type calcium channels. However, there are some side effects from the commonly prescribed DHP CCB, namely amlodipine, in the activation of homeostatic compensation mechanism to regulate blood pressure back to the pathological state, as well as the common incidence of peripheral edema. These can cause the reduction of long term efficacy and patients’ compliance. The development of fourth generation DHP such as cilnidipine is focused towards reducing the incidence of these side effects, by having an additional action against N-type calcium channels. Thus, analogs of new compounds based on cilnidipine can be designed. This study was aimed to design and test these compounds by molecular docking, and to synthesize and characterize one of the compound, which was dibenzyl 4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate. Molecular docking was done with AutoDock 4 against macromolecules 6JP5 (L-type) and 7VFW (N-type). The synthesized compound respectively yielded a ΔG and Ki value of –9,82 kcal/mol and 63,49 nM against 6JP5, and –9,82 kcal/mol and 63,09 nM against 7VFW. Synthesis was done with the Hantzsch reaction in microwave for 30 minutes at 400 W power in ethanol, followed by purification with preparative thin-layer chromatography, which gave a yield of 0,598%. Elucidation and characterization of the synthesized compound with 1H and 13C-NMR, densitometry, LC–MS/MS, and infrared spectroscopy had confirmed the identity of the target compound.