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"Artritis reumatoid ialah penyakit poliartritis kronik progresif yang menimbulkan deformasi, meliputi multisistem dan disertai morbiditas yang nyata. Obat-obatan imunosupresif telah digunakan untuk mengurangi/menghambat progresi penyakit. Penelitian ini diadakan untuk membandingkan keberhasilan azatioprin dan siklosporin pada penderita artritis reumatoid. Penelitian meliputi 100 penderita artritis reumatoid (sesuai kriteria American Rheumatism Association, 1987) yang dibagi atas dua kelompok: kelompok I mendapat azatioprin 1 mg/kg/h dan kelompok II mendapat siklosporin 2,5-3,0 mg/kg/h selama 16 minggu. Penilaian keberhasilan berdasarkan parameter klinis, biokimiawi dan radiologis. Semua penderita menunjukkan perbaikan nyata (nilai p < 0.001) pada semua parameter klinis, yaitu hilangnya nyeri, berkurangnya kekakuan pagi hari, sendi yang nyeri/membengkak dan waktu yang diperlukan untuk berjalan sejauh 50 kaki serta menguatnya kekuatan genggaman. Semua penderita menunjukkan penurunan LED (p < .001) tanpa perubahan apapun pada titer faktor reumatoid. Kedua obat menunjukkan keberhasilan yang sama (nilai p tidak bermakna) dalam hal perbaikan parameter klinis dan biokimiawi. Tetapi dengan siklosporin erosi tulang dan osteoporosis yukstaartikular lebih banyak berkurang. Sepuluh penderita menunjukkan nefrotoksisitas dengan siklosporin. Siklosporin lebih baik dari azatioprin dalam hal mengurangi derajat progresi kelainan sendi pada artritis reumatoid, tetapi insidens efek samping lebih tinggi, yang pada umumnya dapat diatasi. (Med J Indones 2002; 11: 153-7)

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Rheumatoid Arthritis (RA) is a chronic progressive deforming polyarthritic disease involving multisystems and associated with considerable morbidity. Immunosuppressive drugs have been used to reduce/arrest the progression of the disease. The present study was undertaken to compare the efficacy of Azathioprine and cyclosporin in Rheumatoid Arthritis patients. Study consisted of 100 patients of Rheumatoid Arthritis (as per criteria of American Rheumatism Association, 1987) divided into two groups : group I received Azathioprine 1 mg/kg/d and group II received cyclosporin 2.5-3.0 mg/kg/d for 16 weeks. Assessment of efficacy was based on clinical, biochemical and radiological parameters. All patients showed marked improvemen (p value < 0.001) in all clinical parameters i.e. relief in pain, reduction in morning stiffness, painful/swollen joint along with walking time for 50 feet and increase in grip strength. All patients showed reduction (p < 0.001) in ESR without any change in rheumatoid factor titres. Both drugs showed equal efficacy (p value = NS) in improvement of clinical and biochemical parameters. But cyclosporin showed more reduction in bony erosions and juxtaarticular osteoporosis. Ten patients showed nephrotoxicity with cyclosporin. Cyclosporin has an edge over azathioprine in reducing the rate of progression of joint change in Rheumatoid Arthritis but is associated with increased incidence of side effects that are generally manageable. (Med J Indones 2002; 11: 153-7)"

"ASBTRACTPurpose: The late postoperative complications of choledochal cyst (CC) surgery are serious and include intrahepatic stones and biliary carcinoma; therefore, long-term follow-up is crucial.Methods: The subjects of this retrospective study were patients who underwent surgery for CC at Kagoshima University Hospital between April, 1984 and December, 2016. We analyzed the operative results, early and late postoperative complications, and postoperative follow-up rate.Results: The study population comprised 110 CC patients (male/female: 33/77) ith a median age at surgery of 4 years, 3 months (range 12 days-17 years). The patients underwent hepaticoduodenostomy (n = 1; 0.9%) or hepaticojejunostomy (n = 109; 99.1%). Late complications included intrahepatic bile duct (IHBD) dilatation (n = 1; 0.9%), IHBD stones (n = 3; 2.7%), and adhesive ileus (n = 4; 3.6%). There was no incidence of biliary carcinoma in this series. The rates of follow-up at our institute within 10 years of surgery and more than 20 years after surgery were 69.2% (18 of 26) and 14.5% (8 of 55), respectively.Conclusions: The follow-up rate after definitive surgery declined with time. Late complications were observed within 20 years, but biliary carcinoma was not observed. The follow-up rate should be increased to detect late complications. Moreover, patient education on long-term follow up is essential to prevent life-threatening events after definitive surgery for CC."

"ABSTRAKBackground Aim of this research is to assess the efficacy and safety of tocilizumab in combination with methotrexate in Indonesian patients with moderate to severe active rheumatoid arthritis who have an inadequate response to non biologic DMARDs.Methods This was a interventional, prospective, single arm, multicenter, study in Indonesian male or female patients aged > 18 years old, with a diagnosis of RA for > 6 months based on ACR 1987 revised criteria with moderate to severe disease activity DAS28 score > 3.2 after > 12 weeks of non biologic DMARDs treatment. The treatment consisted of tocilizumab, 8 mg/kg, intravenous, every 4 weeks for a total of 6 infusion in combination with oral MTX 10 until 25 mg every week. Efficacy was assessed based on the percentage of patients achieving low disease activity state DAS28 < 3.2, percentage of patients achieving reduction > 1.2 point of DAS28, percentage of patients achieving remission DAS28 < 2.6, and percentage of patients with ACR20, ACR50, and ACR70 responses. Descriptive statistics will be used for presentation of results.Results 100 percent patients reached low disease activity DAS28 < 3.2 at last study visit week 24 and clinically significant improvement reduction at least 1.2 units at every visit in DAS28, both for ITT or PP patients. Remission DAS28 < 2.6 was observed in 82.1 percent ITT patients and 93.1 percent PP patients on last study visit. ACR20, ACR50, and ACR70 were achieved in 20 percent, 34 percent, and 34 percent ITT patients, and 7 percent, 24 percent, and 62 percent PP patients on week 24. There were 3 out of 39 patients 7.69 percent with adverse events and serious adverse events that resulted in discontinuation of TCZ treatment, consisting of 1 patient with SAE of sepsis ec acquired community pneumonia, 1 patient with SAE of pneumonia tuberculosis, and 1 patient with AE of candidiasis. Most common adverse events were hepatic dysfunction 30.7 percent, hypercholesterolemia 23.1 percent, followed by arthralgia 20.5 percent Twelve percent of patients needed dose modification due to elevated liver enzyme elevated ALT/SGPT level. Conclusion Tocilizumab seems to be efficacious and likely to have good safety profile in non biologic DMARD nonresponsive RA patients of PICTURE INA study. "

"Pendahuluan: Andrografolida, konstituen aktif utama diisolasi dari Andrographis paniculata yang digunakan untuk terapi artritis reumatoid. Namun, senyawa ini memiliki bioavailabilitas oral yang rendah. Masalah ini dapat diatasi dengan memformulasikan andrografolida dalam etosom melalui pemberian transdermal.Tujuan: Penelitian ini bertujuan untuk mengetahui profil farmakokinetik, bioavailabilitas relatif, dan efektivitas sediaan transdermal etosom andrografolida pada hewan model artritis reumatoid.Metode: Metode hidrasi lapis tipis digunakan untuk memformulasikan etosom andrografolida. Karakterisasi etosom meliputi ukuran partikel, indeks polidispersitas, potensial zeta, dan efisiensi penjerapan. Pada uji farmakokinetik, digunakan GE, GNE dan SO dosis 50 mg/kgbb kemudian sampel plasma diambil dari sinus retro-orbital dengan 10 titik pengambilan dalam 24 jam. Parameter farmakokinetik dianalisis dengan KCKT fase terbalik. Pada uji aktivitas antiartritis, GE dosis 25, 50, dan 100 mg/kg diberikan secara transdermal pada tikus uji yang diinduksi CFA 0,1 mL. Selama fase induksi dan setelah pemberian obat, manifestasi klinis artritis dipantau menyeluruh.Hasil: Hasil penelitian didapatkan etosom dengan ukuran partikel 76,35±0,74 nm, zeta potensial -40,17±1,03 mV dan efisiensi penjerapan 97,87±0,23%. Studi farmakokinetik menghasilkan Cmax pada GE, GNE, dan SO berturut-turut adalah 53,07±4,73; 27,34±1,48; dan 11,72±0,74 μg/mL, AUC0-∞ masing-masing 152,10±16,53; 77,15±12,28; dan 23,20± 3,46 μg.jam/mL. Tmax rute transdermal dicapai jam ke-6 sementara rute oral jam ke-2 setelah pemberian sediaan. Hasil uji aktivitas antiartritis mengungkapkan, GE 50 dan 100 mg/kgbb menunjukkan persentase penghambatan edema hampir serupa dengan metotreksat 0,135 mg, subkutan.Kesimpulan: Hasil penelitian disimpulkan bahwa GE 50 mg/kgbb menghasilkan peningkatan Cmax, Tmax dan AUC0-∞. Bioavailabilitas relatif dicapai sebesar 655,60% pada rute transdermal dibandingkan dengan rute oral. Hasil uji aktivitas antiartritis, GE 50 mg/kg secara efektif mengurangi volume edema, diameter kaki, dan skor artritis tikus model yang diinduksi CFA.

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Intoduction: The main active constituent isolated from Andrographis paniculata, andrographolide, is used to treat rheumatoid arthritis. This compound, however, has a low oral bioavailability. This issue can be solved by incorporating andrographolide into ethosomes for transdermal administration.

Aim: This study was designed to determine the pharmacokinetic profile, relative bioavailability, and efficacy of andrographolide ethosomal transdermal preparations in animal models of rheumatoid arthritis.

Method: Andrographolide was prepared into ethosomal dosage forms before being characterized in terms of particle size, polydispersity index, zeta potential, and entrapment efficiency. In the pharmacokinetic test, plasma sampels were collected from the retro-orbital sinus at 10 collection points over the course of 24 hours using GE, GNE, and SO at a dose of 50 mg/kg each. Reverse-phase HPLC was used to assess pharmacokinetic parameters. In the anti-arthritic activity test, GE doses of 25, 50, and 100 mg/kg were administered transdermally to rats induced by 0.1 mL CFA. The clinical manifestations of arthritis are closely monitored during the induction phase and after drug administration.

Result: According to the results, the ethosomes with a particle size of 76.35±0.74 nm, a zeta potential of -40.17±1.03 mV, and an entrapment efficiency of 97.87±0.23%. Pharmacokinetic studies revealed that the Cmax in GE, GNE, and SO was 53.07±4.73, 27.34±1.48, and 11.72±0.74 μg/mL, and the AUC0-∞ was 152,10±16,53; 77,15±12,28; and 23,20± 3,46 μg.jam/mL, respectively. The transdermal route had a Tmax of 6 hours, while the oral route had a Tmax of 2 hours after administration of the preparation. GE 50 and 100 mg/kg inhibited edema with nearly the same percentage as methotrexate 0.135 mg subcutaneously, according to the anti-arthritis activity test.

Conclusion: The researchers concluded that GE 50 mg/kg caused an increase in Cmax, Tmax, and AUC0-∞. The transdermal route has a relative bioavailability of 655.60% compared to the oral route. The anti-arthritis activity study showed that GE 50 mg/kg effectively reduced edema volume, paw diameter, and arthritis scores in CFA-induced rat models."

"Rheumatoid arthritis and proteus explores the idea that Rheumatoid arthritis is caused by a urinary tract infection as a result of Proteus bacteria. Rheumatoid arthritis is a severe, painful and crippling disease affecting millions of people throughout the world, especially women. Genetic studies over the last 30 years have shown that individuals who possess the white cell blood groups HLA-DR1/4 carry a susceptibility sequence and are more likely to develop the disease. This book uses the methods of Sir Karl Popper, the philosopher of science, to present 12 “Popper sequences” which have been identified to indicate that proteus is the causative agent of rheumatoid arthritis. Rheumatoid arthritis and proteus proposes that Anti-Proteus therapies should be followed as early as possible to prevent the crippling and irreversible joint deformities that occur in rheumatoid arthritis."

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LATAR BELAKANG: Berbagai studi telah menunjukkan efek potensial probiotik terhadap luaran neuropsikologis melalui aksis usus-otak. Akan tetapi, studi yang menilai efek suplementasi probiotik terhadap fungsi kognitif pada populasi anak dan remaja masih terbatas.

METODE: Peneliti melakukan studi tindak lanjut tahun ke-10 dari uji klinis teracak samar suplementasi probiotik Lactobacillus reuteri DSM 17938 atau Lactobacillus casei CRL 431 pada anak terhadap fungsi kognitif. Dari 494 anak yang mengikuti uji klinis pada 2007–2008, sebanyak 160 anak yang telah berusia 11–17 tahun mengikuti studi tindak lanjut. Pada uji klinis terdahulu, subjek diberikan susu dengan kalsium regular sebanyak 440 mg/hari (kelompok KR; n = 58), kalsium regular dengan L. reuteri DSM 17938 5x10⁸ colony-forming units (CFU) (reuteri; n= 50), atau kalsium regular dengan L. casei CRL 431 5x10⁸ CFU (casei; n= 52) selama 6 bulan pada usia 1–6 tahun. Penelitian ini bertujuan untuk menilai efek suplementasi probiotik masa kanak-kanak tersebut terhadap tingkat intelegensi berdasarkan Standard Progressive Matricesdan kadar brain-derived neurotrophic factor(BDNF) serum pada masa remaja. Berbagai faktor biomedis (kualitas diet, antropometri, kadar hemoglobin, dan lain-lain) dan faktor lingkungan sosial (status pendidikan orangtua, dukungan lingkungan rumah, depresi, dll) terkait fungsi kognitif turut dinilai sebagai variabel perancu.

HASIL:Kadar BDNF serum masa remaja pada kelompok suplementasi probiotik L. reuteri DSM 17938 lebih rendah dibandingkan kelompok kontrol yang secara statistik signifikan (p = 0,036), setelah disesuaikan dengan perancu. Tidak terdapat perbedaan proporsi tingkat intelegensi masa remaja yang bermakna berdasarkan riwayat suplementasi probiotik L. reuteri DSM 17938 maupun L. casei CRL 431 masa kanak-kanak. Pada regresi multipel, dukungan lingkungan rumah memiliki hubungan yang signifikan dan konsisten dengan tingkat intelegensi. Kadar BDNF serum berhubungan dengan status gizi dan kualitas diet.

 

KESIMPULAN: Anak yang mendapat suplementasi L. reuteri DSM 17938 memiliki kadar BDNF serum yang lebih rendah pada masa remaja. Hubungan yang konsisten antara faktor lingkungan sosial dengan fungsi kognitif menunjukkan pentingnya mengintegrasikan intervensi biomedis dengan lingkungan sosial untuk mencapai populasi berdaya.

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BACKGROUND: Available evidence have shown potential effects of probiotics on neurobehavioral outcomes through ‘gut-brain axis’ mechanism. However, studies on cognitive function in children and adolescents are lacking.

METHODS: We conducted a 10-year follow-up study of randomised controlled trial of 6-month probiotic supplementation of Lactobacillus reuteri DSM 17938 or Lactobacillus casei CRL 431 in children on cognitive function. Of 494 children enrolled in 2007–2008, we re-enrolled 160 subjects at age 11–17 years. Subjects were given regular calcium milk containing 440 mg/d (RC group; n= 58), regular calcium with L. reuteriDSM 17938 5x10⁸ colony-forming units (CFU) (reuteri; n= 50), or regular calcium with L. casei CRL 431 5x10⁸ CFU (casei; n = 52) for 6 months at the age of 1–6 years. This study aimed to investigate the effect of probiotic supplementation during childhood on cognitive function based on grade of Standard Progressive Matrices and serum brain-derived neurotrophic factor (BDNF) levels in adolescents. We assessed various biomedical factors (ie. diet quality, anthropometry, and hemoglobin level) socio-environmental factors (ie. parental educations, home environment, and depression) related to cognitive outcomes as cofounding variables.

RESULTS: Compared with the RC group, the reuteri group had a significantly lower mean serum BDNF level [adj. difference 3127.5 pg/ml (95% CI: 213,5–6041,6)]. There was no difference in grade of SPM between groups nor difference on serum BDNF level between RC and casei group. In multiple regression models, the home environment had a significant and consistent association with grade of SPM. Serum BDNF level was associated with overweight/obesity and diet quality.

CONCLUSION: L. reuteri DSM 17938 supplementation during childhood was associated with lower serum BDNF level at the age of 11–17 years compared to control. The consistent association between socio-environmental factor and grade of SPM suggests that intervention of biomedical determinants should be integrated with the improvement of socioenvironmental factors to achieve thriving populations.

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