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Abstrak :
Latar Belakang: Kehilangan massa tulang pada artritis reumatoid (AR) terjadi akibat ketidakseimbangan proses resorpsi dan formasi tulang. Tumor necrosis factor-α (TNF-a) adalah salah satu sitokin proinflamasi utama yang secara langsung dapat menyebabkan peningkatan resorpsi tulang, namun peranannya pada proses formasi tulang belum secara jelas diketahui. Aktivitas formasi tulang dapat dihambat oleh Dickkopf-1 (DKK-1) yang meningkat pada pasien AR. Penilaian turnover tulang dapat dilakukan dengan mengukur kadar C-terminal telopeptide (CTX) dan N-terminal propeptide (PINP) yang saat ini menjadi standar untuk penanda turnover tulang. Tujuan: Penelitian ini bertujuan untuk mendapatkan gambaran aktivitas turnover tulang pada pasien AR dengan melihat korelasi antara TNF-α dengan DKK-1 dan CTX untuk penilaian resorpsi tulang, dan korelasi antaran TNF-α dengan DKK-1 dan P1NP untuk penilaian formasi tulang. Metode: Penelitian ini merupakan studi potong lintang dengan 38 subjek artritis reumatoid perempuan premenopause. Pengambilan sampel dilakukan secara konsekutif di poliklinik reumatologi Rumah Sakit Cipto Mangunkusumo. Pemeriksaan TNF-α, DKK-1, CTX, dan P1NP dilakukan dengan metode ELISA. Hasil: Pada penelitian ini didapatkan median durasi menderita penyakit adalah 5 tahun. 60,5% pasien berada dalam kondisi remisi atau aktivitas penyakit rendah, 36,8% dalam kondisi aktivitas penyakit sedang, dan 2,6% pasien dalam kondisi aktivitas penyakit tinggi. Didapatkan median kadar TNF-a adalah 10.6 pg/mL, rerata kadar DKK-1 adalah 4027 pg/mL, rerata kadar CTX adalah 2,74 ng/mL, serta median nilai P1NP adalah 34 pg/mL. Kadar DKK-1 dan CTX dijumpai lebih tinggi sedangkan kadar P1NP lebih rendah jika dibandingkan dengan kadar pasien AR pada penelitian-penelitian sebelumnya. Penelitian ini menemukan korelasi positif lemah antara TNF-α dengan P1NP, sedangkan variabel lain tidak menunjukkan korelasi yang signifikan. Simpulan: Pada penelitian ini ditemukan korelasi positif lemah antara TNF-α dengan P1NP. Dijumpai kadar TNF-a yang rendah, DKK-1 yang tinggi, dan CTX yang tinggi dengan kadar P1NP yang rendah yang menunjukkan respon perbaikan tulang pada pasien AR tidak dapat mengimbangi tingginya aktivitas resorpsi tulang.

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Background: Bone mass loss in rheumatoid arthritis (RA) is due to the imbalance of bone resorption and formation process.Tumor necrosis factor-α (TNF-a) is one of the main proinflammatory cytokines that can directly increase bone resorption, but its effect on bone formation is still uncertain. Bone formation could be inhibited by Dickkopf-1 (DKK-1) that is increased in RA patients. Bone turnover could be determined by assessing the level of C-terminal telopeptide (CTX) and N-terminal propeptide (PINP), both are standard measurement for bone turnover markers. Objective: This study aims to examine bone turnover in RA patients by analysing correlation between TNF-α with DKK-1 and CTX for assesment of bone resorption, and correlation between TNF-α with DKK-1 and P1NP for assesment of bone formation. Methods: This is a cross-sectional study with 38 subjects of RA premenopausal women. The subjects were collected with consecutive sampling technique in rheumatology outpatient clinic in Rumah Sakit Cipto Mangunkusumo, Jakarta. Measurement of serum TNF-α, DKK-1, CTX, and P1NP levels were done using ELISA technique. Results: The median duration of RA in this study is 5 years. 60,5% of the patients were in remission or low activity disease, 36,8% were in moderate activity disease, and 2,6% were in high activity disease. The median value of TNF-a was 10.6 pg/mL, mean value of DKK-1 was 4027 pg/mL, mean value of CTX was 2,74 ng/mL, and mean value of P1NP was 34 pg/mL. DKK-1 and CTX levels were increased while P1NP level was lower compared to the RA patients in previous studies. This study found weak positive correlation between TNF-α and P1NP, while the other variables showed no significant correlation. Conclusions: This study demonstrated weak positive correlation between TNF-α and P1NP. We found low level of TNF-α, high level of DKK-1, and high level of CTX with low level of P1NP that indicate that the bone repair response could not keep up to the high bone resorption activity in RA patients.

Abstrak :
Background: Diabetes Mellitus is a chronic disease characterised by elevated levels of blood glucose known as hyperglycaemia. Diabetes is due to impaired insulin action in the metabolism of glucose and can result in impaired wound healing. Excessive production of pro-inflammatory cytokines, an increased number of macrophages and neutrophils, and decreased levels of transforming growth factor ? beta 1 (TGF-β1) serum can be characteristic of impaired wound healing. This study aims to determine the effects of squid extract on certain wound parameters such as levels of tumour necrosis factor ? alpha (TNF-α), and TGF-β1 serum and the number of macrophages and neutrophils. Methods: This was a post-test only, randomized controlled group study that was conducted on male Wistar rats. Experimental animals were divided into 6 groups; (1) normal wound with standard diet, (2) diabetic wound with standard diet, (3) diabetic wound with chitosan supplement, (4) diabetic wound given squid extract orally once a day, (5) diabetic wound given squid extract orally twice a day, and (6) diabetic wound given squid extract orally once every two days. Levels of TNF-α and TGF-β1 serum were observed using Enzyme-Linked Immunosorbent Assay. Haematocylin and eosin staining was used to observed macrophage and neutrophil counts. All data was analysed statistically by one-way analysis of variance. Results: TNF-α serum levels showed a significant decrease (p < 0.05) in subjects that received squid extract orally once every two days. The mean levels of TGF-β1 showed no significant differences. The mean number of macrophage cells showed a significant decrease (p < 0.05) in all treatment groups. The mean number of neutrophil cells also showed significant decrease (p < 0.05) in all treatment groups. Conclusions: Squid extract is effective in lowering the TNF-α serum levels and the number of macrophages and neutrophils cells in Wistar rats. However, there were insignificant findings on increasing levels of TGF-β1 serum. This data suggests that squid extract is most effective during the inflammatory phase of wound healing which takes places about 2-4 days after wound creation.

Abstrak :
Diabetes Mellitus is a chronic disease characterised by elevated levels of blood glucose known as hyperglycaemia. Diabetes is due to impaired insulin action in the metabolism of glucose and can result in impaired wound healing. Excessive production of pro-inflammatory cytokines, an increased number of macrophages and neutrophils, and decreased levels of transforming growth factor ? beta 1 (TGF-β1) serum can be characteristic of impaired wound healing. This study aims to determine the effects of squid extract on certain wound parameters such as levels of tumour necrosis factor ? alpha (TNF-α), and TGF-β1 serum and the number of macrophages and neutrophils. Methods: This was a post-test only, randomized controlled group study that was conducted on male Wistar rats. Experimental animals were divided into 6 groups; (1) normal wound with standard diet, (2) diabetic wound with standard diet, (3) diabetic wound with chitosan supplement, (4) diabetic wound given squid extract orally once a day, (5) diabetic wound given squid extract orally twice a day, and (6) diabetic wound given squid extract orally once every two days. Levels of TNF-α and TGF-β1 serum were observed using Enzyme-Linked Immunosorbent Assay. Haematocylin and eosin staining was used to observed macrophage and neutrophil counts. All data was analysed statistically by one-way analysis of variance. Results: TNF-α serum levels showed a significant decrease (p < 0.05) in subjects that received squid extract orally once every two days. The mean levels of TGF-β1 showed no significant differences. The mean number of macrophage cells showed a significant decrease (p < 0.05) in all treatment groups. The mean number of neutrophil cells also showed significant decrease (p < 0.05) in all treatment groups. Conclusions: Squid extract is effective in lowering the TNF-α serum levels and the number of macrophages and neutrophils cells in Wistar rats. However, there were insignificant findings on increasing levels of TGF-β1 serum. This data suggests that squid extract is most effective during the inflammatory phase of wound healing which takes places about 2-4 days after wound creation. Keywords: diabetic wound, squid, TNF

Abstrak :
Latar Belakang: Pada artritis reumatoid diketahui terjadi kehilangan massa tulang, baik secara lokal maupun sistemik. TNF-a adalah sitokin utama yang berperan pada proses resorpsi tulang, namun perannya pada formasi tulang belum diketahui. Penelitian ini akan menilai korelasi TNF-adengan proses formasi tulang yang dinilai dengan P1NP, terutama berhubungan dengan SFRP-1 yang merupakan inhibitor alami osteoblas. Sampai saat ini belum ada penelitian yang menilai hubungan sitokin proinflamasi TNF-a, SFRP1 terhadap kedua penanda turnover tulang(CTX dan P1NP) secara sistemik pada pasien artritis reumatoid. Tujuan: Penelitian ini bertujuan untuk mendapat gambaran aktivitas turnovertulang pada pasien AR dengan melihat korelasi antara TNF-adengan SFRP-1, CTX dan P1NP, dan korelasi SFRP1 dengan P1NP. Metode: Penelitian ini merupakan studi potong lintang dengan 38 subjek perempuan premenopause dengan AR. Pengambilan sampel dilakukan secara konsekutif di poliklinik reumatologi Rumah Sakit Cipto Mangunkusumo. Pemeriksaan TNF-a, SFRP-1, CTX, dan P1NP dilakukan dengan metode ELISA. Hasil: Pada penelitian ini didapatkan median durasi menderita AR 5 tahun. 60,6% pasien berada dalam kondisi remisi dan aktivitas rendah. Kadar TNF-amedian 10,6 pg/mL, rerata kadar SFRP-1 9,29 ng/mL, rerata kadar CTX 2,74 ng/mL, serta kadar P1NP 34 pg/mL. Kadar SFRP-1 dan CTX dijumpai meningkat sedangkan P1NP relatif lebih rendah bila dibandingkan dengan kadar populasi normal pada penelitian-penelitian terdahulu. Pada penelitian ini dijumpai adanya korelasi positif lemah antara TNF-a dengan P1NP (r=0,363, p=0,026), begitu juga SFRP-1 dengan P1NP (r=0,341; p=0,036), sedangkan variabel lain tidak menunjukkan korelasi yang bermakna. Simpulan: Pada penelitian ini didapatkan korelasi positif lemah antara TNF-adengan P1NP, dan korelasi positif lemah antara SFRP-1 dengan P1NP. Namun dijumpai kadar CTX yang tinggidan kadar P1NP yang rendah, menunjukkan respon resorpsi meningkat namun tidak diimbangi dengan formasi pada pasien AR perempuan premenopause. ......Background: Rheumatoid arthritis is known to have a loss of bone mass, both locally and systemically. TNF-a is the main inflammatory cytokine that can directly increase bone resorption. However, its role in bone formation is still unknown. This study will assess the correlation of TNF-a with the process of bone formation evaluated with P1NP, mainly related to the SFRP-1 pathway which is a natural inhibitor of osteoblasts. However, there are currently no studies that assess the correlation of inflammatory cytokines TNF-a, SFRP-1, with bone turnover marker (CTX and P1NP) in rheumatoid arthritis patients Objective: This study aims to examine bone turnover in RA patients by analyzing the correlation between TNF-a with SFRP-1 and CTX and P1NP, and correlation SFRP-1 with P1NP Methods: This is a cross-sectional study in 38 subjects of premenopausal women with RA. The Subjects were collected with consecutive sampling technique in rheumatology outpatient clinic in Rumah SakitCipto Mangunkusumo, Jakarta. Measurement of serum TNF-a, SFRP-1, CTX, and P1NP levels were done using ELISA technique. Results: In this study, the median duration of RA is 5 years. 60.6% of the patients were in remission and low activity disease. The median value of TNF-a was 10.6 pg/mL, the mean value of SFRP-1 was 9.29 ng/mL, the mean value of CTX was 2.74 ng/mL, and mean value of P1NP was 34 pg/mL. SFRP-1 and CTX levels were increased while P1NP level was relatively lower compared to the normal population value in previous studies. There was a weak positive correlation between TNF-a and P1NP(r=0.363, p=0.026), also SFRP-1 and P1NP(r=0.341; p=0.036),while the other variables showed no significant correlation. Conclusions: This study demonstrated weak positive correlation between TNF-a and P1NP, and weak positive correlation between SFRP-1 and P1NP. However high value of CTX and low value of P1NP showed that a high resorption response cannot be balanced with bone formation activity in patients with rheumatoid arthritis in premenopausal woman.

Abstrak :
Pendahuluan: Salah satu faktor risiko penyakit osteoporosis pada wanita menopause adalah faktor genetik polimorfsme Tumor Necrosis Factor Alpha TNF-α. Tujuan: Penelitian ini bertujuan untuk melihat ada atau tidaknya polimorfisme dan perbedaan polimorfisme gen TNF-α-308G/A pada wanita pascamenopause dengan osteoporosis. Metode: 100 bahan biologis tersimpan 50 sampel wanita pascamenopause dengan osteoporosis dan 50 sampel individu sehat dianalisa menggunakan teknik PCR-RFLP dengan enzim retriksi NcoI, selanjutnya data diuji secara statistik menggunakan uji Chi-square. Hasil: Ditemukan banyak genotip AG baik pada kelompok osteoporosis dan kontrol. Pada kelompok osteoporosis tidak ditemukan genotip GG dan terdapat 76 genotip AG serta 24 genotip AA. Pada kelompok kontrol, terdapat 8 genotip GG, 82 genotip AG, dan 5 genotip AA. Kesimpulan: Terdapat polimorfisme genetik TNF-α-308G/A pada wanita menopause dengan osteoporosis, namun tidak terdapat perbedaan bermakna pada polimorfisme antara wanita pascamenopause dengan osteoporosis dan individu sehat p = 0.117 di populasi Indonesia. ......Introduction: One of the risk factor for osteoporosis in postmenopausal woman is genetic polymorphism factor which is Tumor Necrosis Factor Alpha TNF. Objectives: This research aims to look for genetic polymorphism and differentiate the distribution TNF 308G A gene polymorphism in postmenopausal woman with osteoporosis. Methods: 100 stored biological samples 50 samples of postmenopausal woman with osteoporosis and 50 healthy control samples were analyzed with PCR RFLP technique using NcoI restriction enzyme, and subsequently assessed with statistical analysis using Chi square test. Result: AG genotype was found with the highest amount in both samples. The postmenopausal group has 76 of AG genotype, 24 of AA genotype, and no GG genotype was found. The healthy control group has 8 of GG genotype, 82 of AG genotype, and 5 of AA genotype. Based on Fisher Extract test, there is no significant association between TNF 308G A and postmenopausal osteoporosis p value 0.117. Conclusion: The genetic polymorphism of TNF 308G A in postmenopausal woman was found, but the polymorphism didn rsquo t have any association with osteoporosis in Indonesia populations.

Abstrak :
Latar belakang: Proses pembedahan seperti kraniotomi mengakibatkan inflamasi, dimulai sejak awal insisi dan berdampak pada kejadian nyeri pascabedah yang memengaruhi lama rawat pasien. Lidokain intravena intraoperatif memiliki efek analgesik dan antiinflamasi yang terbukti efektif sebagai terapi ajuvan dalam manajemen nyeri pasca pembedahan abdominal. Penelitian ini bertujuan untuk mengevaluasi efek pemberian lidokain intravena kontinyu intraoperatif pada kraniotomi, terhadap nyeri pascabedah, kadar TNF-alfa, dan lama rawat. Metode: Randomized controlled trial ini menggunakan pengambilan sampel secara consecutive sampling. Sebanyak 50 subjek penelitian dengan tumor otak yang menjalani kraniotomi. Kelompok intervensi diberikan bolus intravena lidokain 2% dosis 1,5 mg/kgBB saat induksi, dilanjutkan rumatan 2 mg/kgBB/jam. Kelompok kontrol dengan pemberian NaCl 0,9% dengan volume sama. Luaran penelitian adalah skala nyeri pascabedah berdasarkan nilai NPS, kadar TNF-alfa dan lama rawat. Hasil: Skor nyeri sesuai nilai NPS pada 1 jam pascabedah, 6 jam pascabedah, dan 24 jam pascabedah antara kelompok intervensi dengan kontrol (p < 0,001). Terdapat perbedaan bermakna antar dua kelompok mengenai selisih kadar TNF-alfa prainduksi dengan 1 jam pascabedah (p = 0,001). Sedangkan selisih kadar TNF-alfa prainduksi dengan 24 jam antar dua kelompok tidak menunjukkan perbedaan signifikan (p = 0,334). Luaran lama rawat tidak berbeda bermakna. Simpulan: Pemberian lidokain intravena kontinyu intraoperatif dibandingkan plasebo pada kraniotomi berpengaruh terhadap nyeri pascabedah dan kadar TNF-alfa, namun tidak berpengaruh pada lama rawat. ......Background: Surgery such as craniotomy causes inflammation which affects the incidence of postoperative pain and then affect hospitalization duration. Lidocaine has analgesic and anti-inflammatory effects which effective as an adjuvant in the management of postoperative pain in abdominal surgery. This study aims are to investigate the effects of the intraoperative continuous intravenous lidocaine during craniotomy on postoperative pain, TNF-α levels, and hospitalization duration. Methods: This randomized controlled trial uses consecutive sampling method. A total of 50 subjects with brain tumors underwent craniotomy. The therapy group was given lidocaine 2% intravenous bolus 1.5 mg/kg at induction followed by maintenance at 2 mg/kg/hour, the control group was given NaCl 0.9% with the same volume. The outcomes assessed were postoperative pain, TNF-α levels, and hospitalization duration. Results: There was a significant difference in NPS 1-hour postoperative, 6-hour postoperative NPS, and 24-hour postoperative NPS scores between the treatment group and the control group (p < 0.001). There was a significant difference between pre-induction TNF-α levels and 1 hour postoperatively (p = 0.001) however pre-induction TNF-α levels with 24 hours was not significantly different (p = 0.334). There was no significant difference in hospitalization duration between those groups. Conclusions: Intraoperative continuous intravenous lidocaine administration compared to placebo at craniotomy had an effect on postoperative pain and TNF-α levels but had no effect on hospitalization duration.

Abstrak :
Diabetes melitus (DM) tipe 2 adalah penyakit yang berhubungan dengan kondisi inflamasi ringan kronis. Selain terjadi peningkatan kadar sitokin proinflamasi, diduga terjadi gangguan pada mediator antiinflamasi, yaitu enzim indoleamine 2,3-dioxygenase (IDO). Tujuan dari penelitian ini adalah menganalisis produksi IDO dari kultur peripheral blood mononuclear cells (PBMC) pada penderita DM tipe 2 dan meneliti hubungan IDO dengan kadar sitokin proinflamasi seperti TNF-α, IL-6, dan IFN-γ; serta sitokin antiinflamasi, IL-10. Sampel PBMC diambil dari 21 pasien DM tipe 2 dan 17 subjek kontrol sehat kemudian dilakukan kultur dengan stimulasi phytohemagglutinin (PHA). Setelah kultur selama 3 hari, produksi TNF-α, IL-6, IFN-γ, dan IL-10 diukur menggunakan multiplex immunoassay, sedangkan kadar IDO diukur menggunakan ELISA. Kadar IDO dari kultur PBMC tanpa stimulasi dan dengan stimulasi PHA secara signifikan lebih tinggi pada pasien DM tipe 2 dengan p<0,001 dan p=0,012. Sebanyak 52,8% pasien DM tipe 2 mengalami penurunan produksi IDO setelah distimulasi PHA dan hal tersebut berhubungan dengan kadar IFN-γ yang rendah dengan p=0,005. Di lain pihak, 42,8% pasien DM tipe 2 mengalami peningkatan produksi IDO setelah stimulasi PHA dan hal ini berhubungan dengan rasio TNF-α/IL-10 (r=0,513 p=0,079), IL-6/IL-10 (r=0,446 p=0,114) dan IFN-γ/IL-10 (r=0,422 p=0,129). Pada DM tipe 2, terjadi perubahan produksi IDO. IFN-γ yang rendah berkontribusi pada penurunan produksi IDO. Sementara itu, respon proinflamasi berhubungan dengan peningkatan produksi IDO. ......Type 2 diabetes mellitus (T2DM) is associated with chronic low-grade inflammatory condition. Besides the increased of proinflammatory cytokines level, it was found that anti-inflammatory mediators were disturbed. So, we would analyse the production of indoleamine 2,3-dioxygenase (IDO) in PHA-stimulated PBMC from type 2 DM patients and investigate its association to pro and anti-inflammatory cytokines. PBMC samples were collected from 21 patients with T2DM and 17 healthy subjects, then followed by 3-day PHA stimulation. In vitro production of TNF-α, IL-6, IFN-γ and IL-10 were measured using multiplex immunoassay; meanwhile, IDO level was assessed using ELISA. IDO concentration from unstimulated and PHA-stimulated PBMC were significantly higher in T2DM patients with p<0,001 and p=0.012 respectively. Reduced IDO production occurred in 52,8% of T2DM and it was associated with low interferon γ with p=0.005; whereas 42,8% of T2DM had higher IDO production and had moderate positive correlations with ratio of TNF-α/IL-10 (r=0,513 p=0,079), IL-6/IL-10 (r=0,446 p=0,114) and IFN-γ/IL-10 (r=0,422 p=0,129). We could conclude that there is an alteration of IDO production after PHA stimulation in T2DM. Low interferon γ level seems to contribute in reducing IDO production. In T2DM with higher IDO production, proinflammatory responses are more influential in increasing IDO production.