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"Latar belakang. Pada penyakit graves (GD), konsentrasi vitamin D berbanding terbalik dengan titer antibodi dan berbanding lurus dengan status remisi. Pembentukan autoantibodi diawali dari pajanan self antigen oleh sel dendritik (DC), sebagai antigen presenting cell (APC), ke sel T naif. Kemampuan DC sebagai APC ditentukan oleh tingkat kematangannya. Sel dendritik, APC utama pada GD, bersifat lebih aktif dalam respons imun dibandingkan dengan subjek sehat. Studi pada SLE, MS, dan penyakit crohn menunjukkan efek imunoregulator vitamin D terutama melalui hambatan pematangan DC sehingga fungsi imunogenitasnya berkurang.Tujuan. Mengetahui efek 1,25-D3 in vitro dan 1α-D3 in vivo terhadap pematangan DC pasien GDMetode. Pada periode Mei 2014 sampai dengan Maret 2015 dilakukan studi eksperimental dan klinis, masing-masing pada 12 dan 25 pasien GD fase hipertiroid. Pada studi eksperimental, dilakukan kultur monocyte derived dendritic cell (MDDC) pasien GD dengan atau tanpa intervensi 1,25-D3 in vitro pada tahap monosit dan maturasi distimulasi dengan lipopolysaccharide (LPS). Pada studi klinis, sebanyak 12 dan 13 pasien GD, masing-masing mendapatkan 1α-D3 dan plasebo selama 8 minggu, di samping mendapatkan terapi standar PTU 100 mg 3 kali sehari. Kultur MDDC dilakukan sebelum dan sesudah suplementasi dan dilakukan perbandingan pematangan DC sebelum dan sesudah suplementasi pada kedua kelompok. Pematangan DC dilihat dari ekspresi penanda DC (HLA-DR, CD80, CD40, CD83, CD14, dan CD206) dan rasio sitokin IL-12/IL-10 pada supernatan kultur.Hasil. Pada studi in vitro, pascastimulasi LPS, DC yang dikultur dengan 1,25-D3 menunjukkan ekspresi HLA-DR, CD80, CD40, dan CD83 lebih rendah serta ekspresi CD14 dan CD206 yang lebih tinggi dibandingkan dengan DC yang dikultur dengan LPS saja. Pada DC yang dikultur dengan 1,25-D3, didapatkan rasio IL-12/IL-10 lebih rendah daripada DC tanpa 1,25-D3. Pada studi klinis, apabila dibandingkan antara ekspresi penanda DC serta rasio IL-12/IL-10 sebelum dan sesudah suplementasi 1α-D3 selama 8 minggu, belum didapatkan perbedaan yang bermakna pada ekspresi penanda DC dan rasio sitokin IL-12/IL-10.Simpulan. Pemberian 1,25-D3 in vitro menghambat pematangan DC pasien GD, sedangkan efek pemberian 1α-D3 in vivo terhadap pematangan DC belum dapat ditunjukkan pada penelitian ini.

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Background. In graves? disease (GD), vitamin D levels is inversely proportional to antibody titer and proportionally associated with remission status. The development of autoantibody is initiated by self-antigen exposure by dendritic cells (DC) as the antigen presenting cells (APC) to the naïve T cells. The ability of DC as APC is determined by its maturity level. Dendritic cells, the major APC in GD, have more active immune responses than those in healthy subjects. Studies on systemic lupus erythematosus (SLE), multiple sclerosis (MS) and crohn?s disease have demonstrated immunoregulator effects of vitamin D, mainly through inhibition of DC maturation, which may lead to lower immunogenic function.

Aim. To identify the effect of 1,25-D3 in vitro and 1α-D3 in vivo on DC maturation in patients with GD.

Method. Our study consisted of an experimental and a clinical study started from May 2014 until March 2015, which was conducted in 12 and 25 GD patients with thyrotoxicosis, respectively. In the experimental study, cultures of monocyte derived dendritic cell (MDDC) of GD patients were performed, with or without intervention of 1,25-D3 in vitro at monocytic phase and the maturation was stimulated by lipopolysaccharide (LPS). In the clinical study, there were 12 GD patients who received 1α-D3 supplementation and 13 GD patients who received placebo for 8 weeks, in addition to the standard treatment of PTU 100 mg three times a day. MDDC cultures and comparison of DC maturation were performed before and after the supplementation for both groups. DC maturation was evaluated based on the expression of DC markers (HLA-DR, CD80, CD40, CD83, CD14 and CD206) and the ratio of cytokines IL-12/IL-10 levels in the culture supernatants.

Results. In the in vitro study and following the LPS stimulation, DC cells cultured with 1,25-D3 showed lower expression of HLA-DR, CD80, CD40 and CD83 and higher expression of CD14 and CD206 compared to DC cultured with LPS alone. DC, which were cultured with 1,25-D3 had lower ratio of IL-12/IL-10 levels than those cultured without 1,25-D3. In the clinical study, when the expression of DC marker as well as the ratio of IL-12/IL-10 levels between before and after the 8-week supplementation of 1α-D3 were compared, we found no significant difference on the expression of DC markers and the ratio of IL-12/IL10.

Conclusion. In vitro 1,25-D3 supplementation inhibits DC maturation in patients with GD; while the effects of in vivo 1α-D3 treatment on DC maturation have not been clearly demonstrated in the present study yet."

"Latar belakang: Penuaan merupakan proses yang kompleks, antara lain ditandai oleh deplesi sel punca dan inflamasi kronis. Oleh karena itu, pemberian sel punca mesenkimal (SPM) eksogen tampak menjanjikan untuk mencegah atau mengatasi proses penuaan. SPM diketahui mempunyai kemampuan imunomodulasi, memicu regenerasi, dan dapat berdiferensiasi. Penelitian ini bertujuan untuk mengetahui efek pemberian SPM Korda Umbilikalis Manusia (SPM-KUM) pada tikus tua. Metode: Penelitian ini dilakukan pada tahun 2016-2020 di Fakultas Kedokteran Universitas Indonesia dan Fakultas Kedokteran Hewan Institut Pertanian Bogor. Eksperimen dilakukan pada tikus Sprague-Dawley tua betina dan jantan berumur 22-24 bulan. Tikus tua dibagi menjadi dua kelompok, kontrol dan perlakuan. Kelompok perlakuan terdiri dari dua kelompok dosis SPM-KUM yaitu 106 /kg BB (A) dan 107 /kg BB (B). SPM-KUM diberikan secara intravena selama satu tahun dengan interval 3 bulan sedangkan kelompok kontrol diberikan NaCl 0.9%. Efek SPM-KUM pada penuaan dilihat dari kesintasan, berat badan, performa rotarod, parameter stress oksidatif (MDA dan DNA adduct), parameter inflamasi (IL-6 dan TNF-α), telomer, hormon reproduksi (estradiol dan testosteron), dan gambaran histopatologi organ hati dan ginjal. Ekspresi antibodi anti-human juga diperiksa untuk konfirmasi diferensiasi SPM-KUM di jaringan. Di akhir penelitian, tikus muda usia 3-4 bulan digunakan sebagai pembanding. Hasil: Setelah satu tahun, tikus tua mengalami kematian, pemendekan telomer, penurunan performa rotarod, peningkatan kadar MDA, DNA adduct, IL-6 dan TNF-α, peningkatan sel Kupffer di hati serta peningkatan ekspresi lipofuscin, infiltrat inflamasi, dan p53 di hati dan ginjal. Pemberian SPM-KUM pada tikus tua memperbaiki kesintasan terutama pada tikus betina yang diberikan dosis 107 /kg BB. Kelompok tersebut memiliki telomer lebih panjang, performa rotarod lebih baik, IL-6 menurun, dan TNF-α menurun. Pemberian SPM-KUM juga meningkatkan jumlah sel Kupffer di hati dan mengurangi ekspresi lipofuscin di ginjal tanpa mempengaruhi inflamasi dan ekspresi p53 di hati dan ginjal akibat penuaan. Tidak ditemukan ekspresi antibodi terhadap mitokondria manusia di jaringan hati dan ginjal tikus. Kesimpulan: Pemberian SPM-KUM dapat mencegah proses penuaan dengan mempertahankan panjang telomer, menurunkan sitokin pro inflamasi, memperbaiki performa fisik, mengurangi ekspresi lipofuscin terutama di ginjal sehingga memperbaiki kesintasan. Seluruh efek tersebut terutama karena efek parakrin SPM.

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Introduction: Ageing is a complex process, which is marked by stem cell depletion and chronic inflammation as the main findings. Therefore, exogenous mesenchymal stem cells (MSC) administration appears to be a promising therapy for preventing or overcoming the ageing process. Furthermore, MSC is known for its immunomodulatory activity, regenerative ability, and differentiation. The present study is aimed to evaluate the effect of human umbilical cord MSC (hUCMSC) on aged rats.

Methods: The study was conducted during 2016-2020 at Faculty of Medicine Universitas Indonesia and Faculty of Veterinary Medicine Bogor Agricultural University. The experiment was conducted on female and male Sprague-Dawley rats of 22-24 months old. Aged rats were divided into control and hUCMSC-treated groups. The hUCMSC-treated groups were divided into two subgroups that received two doses of hUCMSC intravenously, i.e., 106 /kg BW (A) and 107 /kg BW (B), four times a year within three months interval. The control group received normal saline injection. The hUCMSC effect on ageing was evaluated by means of survival, body weight, rotarod performance, oxidative stress parameters (MDA and DNA adduct), pro-inflammatory parameters (IL-6 and TNF-α), telomeres, reproductive hormones (estradiol and testosterone), and histopathological features of liver and kidneys. Anti-human antibodies were also detected to confirm the differentiation of hUCMSC in tissues. At the end of the study, young rats of 3-4 months old were sacrificed as a comparison.

Results: The administration of hUCMSC 107 /kg BB in aged rats could improve survival, especially in female aged rats. This female group had the longest mean telomere length, improved rotarod performance, decreased IL-6 and TNF-α. hUCMSC increased Kupffer cells in liver and reduced lipofuscin expression in kidney without further effect on tissue inflammation and p53 expression. In addition, there was no anti-human mitochondria antibody expression in tissue.

Conclusion: hUCMSC could inhibit the ageing process through telomere length maintenance, pro-inflammatory cytokine suppression, physical performance improvement, followed by increased survival. Those effects were mainly through the paracrine effect of the MSC. "

"Latar belakang: Penuaan merupakan proses yang kompleks, antara lain ditandai oleh deplesi sel punca dan inflamasi kronis. Oleh karena itu, pemberian sel punca mesenkimal (SPM) eksogen tampak menjanjikan untuk mencegah atau mengatasi proses penuaan. SPM diketahui mempunyai kemampuan imunomodulasi, memicu regenerasi, dan dapat berdiferensiasi. Penelitian ini bertujuan untuk mengetahui efek pemberian SPM Korda Umbilikalis Manusia (SPM-KUM) pada tikus tua. Metode: Penelitian ini dilakukan pada tahun 2016-2020 di Fakultas Kedokteran Universitas Indonesia dan Fakultas Kedokteran Hewan Institut Pertanian Bogor. Eksperimen dilakukan pada tikus Sprague-Dawley tua betina dan jantan berumur 22-24 bulan. Tikus tua dibagi menjadi dua kelompok, kontrol dan perlakuan. Kelompok perlakuan terdiri dari dua kelompok dosis SPM-KUM yaitu 106 /kg BB (A) dan 107 /kg BB (B). SPM-KUM diberikan secara intravena selama satu tahun dengan interval 3 bulan sedangkan kelompok kontrol diberikan NaCl 0.9%. Efek SPM-KUM pada penuaan dilihat dari kesintasan, berat badan, performa rotarod, parameter stress oksidatif (MDA dan DNA adduct), parameter inflamasi (IL-6 dan TNF-α), telomer, hormon reproduksi (estradiol dan testosteron), dan gambaran histopatologi organ hati dan ginjal. Ekspresi antibodi anti-human juga diperiksa untuk konfirmasi diferensiasi SPM-KUM di jaringan. Di akhir penelitian, tikus muda usia 3-4 bulan digunakan sebagai pembanding. Hasil: Setelah satu tahun, tikus tua mengalami kematian, pemendekan telomer, penurunan performa rotarod, peningkatan kadar MDA, DNA adduct, IL-6 dan TNF-α, peningkatan sel Kupffer di hati serta peningkatan ekspresi lipofuscin, infiltrat inflamasi, dan p53 di hati dan ginjal. Pemberian SPM-KUM pada tikus tua memperbaiki kesintasan terutama pada tikus betina yang diberikan dosis 107 /kg BB. Kelompok tersebut memiliki telomer lebih panjang, performa rotarod lebih baik, IL-6 menurun, dan TNF-α menurun. Pemberian SPM-KUM juga meningkatkan jumlah sel Kupffer di hati dan mengurangi ekspresi lipofuscin di ginjal tanpa mempengaruhi inflamasi dan ekspresi p53 di hati dan ginjal akibat penuaan. Tidak ditemukan ekspresi antibodi terhadap mitokondria manusia di jaringan hati dan ginjal tikus. Kesimpulan: Pemberian SPM-KUM dapat mencegah proses penuaan dengan mempertahankan panjang telomer, menurunkan sitokin pro inflamasi, memperbaiki performa fisik, mengurangi ekspresi lipofuscin terutama di ginjal sehingga memperbaiki kesintasan. Seluruh efek tersebut terutama karena efek parakrin SPM. Kata kunci: Penuaan, SPM-KUM, Telomer, Sel Kupffer, IL-6, TNF-α, Lipofuscin

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Introduction: Ageing is a complex process, which is marked by stem cell depletion and chronic inflammation as the main findings. Therefore, exogenous mesenchymal stem cells (MSC) administration appears to be a promising therapy for preventing or overcoming the ageing process. Furthermore, MSC is known for its immunomodulatory activity, regenerative ability, and differentiation. The present study is aimed to evaluate the effect of human umbilical cord MSC (hUCMSC) on aged rats. Methods: The study was conducted during 2016-2020 at Faculty of Medicine Universitas Indonesia and Faculty of Veterinary Medicine Bogor Agricultural University. The experiment was conducted on female and male Sprague-Dawley rats of 22-24 months old. Aged rats were divided into control and hUCMSC-treated groups. The hUCMSCtreated groups were divided into two subgroups that received two doses of hUCMSC intravenously, i.e., 106 /kg BW (A) and 107 /kg BW (B), four times a year within three months interval. The control group received normal saline injection. The hUCMSC effect on ageing was evaluated by means of survival, body weight, rotarod performance, oxidative stress parameters (MDA and DNA adduct), pro-inflammatory parameters (IL6 and TNF-α), telomeres, reproductive hormones (estradiol and testosterone), and histopathological features of liver and kidneys. Anti-human antibodies were also detected to confirm the differentiation of hUCMSC in tissues. At the end of the study, young rats of 3-4 months old were sacrificed as a comparison. Results: The administration of hUCMSC 107 /kg BB in aged rats could improve survival, especially in female aged rats. This female group had the longest mean telomere length, improved rotarod performance, decreased IL-6 and TNF-α. hUCMSC increased Kupffer cells in liver and reduced lipofuscin expression in kidney without further effect on tissue inflammation and p53 expression. In addition, there was no anti-human mitochondria antibody expression in tissue. Conclusion: hUCMSC could inhibit the ageing process through telomere length maintenance, pro-inflammatory cytokine suppression, physical performance improvement, followed by increased survival. Those effects were mainly through the paracrine effect of the MSC. Keywords: Ageing, hUCMSC, IL-6, Kupffer cell, Lipofuscin, Telomere, TNF-α"

"Inkontinensia urin tekanan (IUT) merupakan kondisi bocornya urin saat tekananintrabdominal meningkat. Tatalaksana konservatif seperti latihan kegel (LK) yangmerupakan pilihan pertama dalam penanganan kasus IUT. Namun, terdapathambatan seperti kepatuhan yang buruk serta ketidakmampuan pasienmengontraksikan otot panggul, ketika menjalani program LK sehingga mengalamikegagalan dan berlanjut pada tindakan operasi. Penelitian ini bertujuan menyusunbuku panduan LK untuk membantu kepatuhan pasien dalam melakukan LK danmenganalisis luaran subjektif, klinis, kepatuhan, serta kekuatan kontraksi otot dasarpanggul pada pasien yang berlatih LK selama 12 minggu. Penelitian ini memilikidesain eksplorasi sequential mixed-method research yang terdiri atas penelitiankualitatif dan penelitian kuantitatif. Penelitian kualitatif bertujuan menyusun bukupanduan LK baku menggunakan tahapan analyze, design, development,implementation, and evaluation (ADDIE) dan penelitian kuantitatifmengujicobakan buku panduan LK tersebut dalam praktik klinis dan dievaluasiefektivitasnya dalam menangani IUT. Penelitian berlangsung sejak Agustus 2020sampai September 2022, di berbagai rumah sakit seperti RS dr.CiptoMangunkusumo, RS Fatmawati, RSCM Kintani, RS Buah Hati Ciputat danPamulang, RS Prikasih, dan RS YPK Mandiri. Luaran yang dievaluasi padapenelitian kuantitatif adalah gejala subjektif yang diukur berdasarkan kuesionerIIQ-7 dan UDI-6, gejala klinis yang diukur berdasarkan 1-hour pad test, kekuatanotot dasar panggul dengan perineometer, dan kepatuhan pasien. Buku panduan LKberhasil disusun menggunakan metode ADDIE dan diujicobakan pada tahappenelitian kuantitatif. Subjek penelitian adalah 178 pasien IUT dari berbagai rumahsakit dan 148 berhasil mengikuti penelitian hingga selesai. Setelah 12 minggu LKterdapat perbaikan gejala subjektif, gejala klinis, dan kekuatan otot panggul yangbermakna. Tidak ada perbedaan gejala subjektif yang bermakna antara kelompokintervensi dan kontrol. Terdapat perbedaan gejala klinis, kekuatan otot dasarpanggul, dan kepatuhan yang bermakna pada kelompok intervensi dan kontrol.Buku panduan LK yang berhasil disusun menggunakan metode ADDIE berhasilmeningkatkan gejala subjektif, klinis, kekuatan otot panggul, dan kepatuhan pasienIUT dalam melakukan LK. Jika dibandingkan kontrol, pasien yang menggunakanbuku panduan LK memiliki perbaikan gejala klinis, peningkatan kekuatan ototpanggul, dan peningkatan kepatuhan yang bermakna.

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Stress Urinary Incontinence (SUI) is a condition in which urine leaks when intraabdominal pressure increases. Worldwide, many women have suffered from SUI. Conservative management, one of which is Pelvic Floor Muscle Training (PFMT), is the first choice in handling IUT cases. However, various obstacles, such as poor compliance and the inability of women to contract the pelvic muscles, are often encountered by women undergoing the PFMT program. They would be likely to fail and undergo surgery. This study aimed to create a PFMT Guidebook and evaluate the effectiveness in improving subjective, clinical, compliance, and pelvic floor muscle contraction of SUI women after twelve weeks. This study was an exploratory sequential mixed-method research design consisting of qualitative and quantitative research. This qualitative study aims to compile a standardized PFMT guidebook using the ADDIE stage and quantitative research to test the PFMT guidebook in clinical practice and evaluate its effectiveness in dealing with SUI. This process took place from August 2020 untill September 2022 in various hospital centers such as CiptoMangunkusumo Hospital, Fatmawati Hospital, Kintani RSCM, Buah Hati Pamulang and Ciputat Hospitals, Prikasih Hospital, and YPK Mandiri Hospital. The outcomes evaluated in this quantitative study were subjective symptoms measured by the IIQ-7 and UDI-6 questionnaires, clinical symptoms measured by the 1-hour pad test, pelvic floor muscle strength using a perineometer, and patient compliance. ADDIE method helped us to create a PFMT guidebook. There were 178 SUI women from various hospitals recruited. 148 of them successfully followed this study to completion. After 12 weeks of PFMT, compared to the control group, there was no difference in clinical symptoms. There were significant differences in clinical symptoms, pelvic floor muscle strength, and adherence between the intervention and study groups. The PFMT guidebook created using the ADDIE method improved subjective, clinical symptoms, pelvic muscle strength, and SUI patient compliance in performing PFMT. Compared with controls, patients who used the PFMT manual significantly improved clinical symptoms, increased pelvic muscle strength, and increased compliance."