У многих пациентов с остеоартритом (ОА) имеются коморбидные заболевания. Причем эта ассоциация чаще наблюдается по мере старения. Одной из коморбидных патологий ОА является сахарный диабет 2-го типа (СД2). В связи с увеличением распространенности и случаев сосуществования этих двух заболеваний предполагается, что гипергликемия, свойственная СД2, может неблагоприятно влиять на ткани сустава и увеличивать тяжесть ОА. Однако молекулярные механизмы возникновения СД у больных ОА неясны. Цель работы-проследить динамику развития СД2 у больных ОА на уровне экспрессии генов, ассоциированных с метаболизмом глюкозы, деструкцией суставов и общей регуляцией метаболических процессов. Пациенты и методы. Наблюдение 3 больных ОА проводили в течение 4-6 лет, включая год начала СД2. Клиническое состояние больных анализировали раз в год. Общую РНК ежегодно выделяли из крови и использовали для определения уровня экспрессии генов в полимеразной цепной реакции в режиме реального времени. Результаты и обсуждение. Показано, что развитие СД2 у больных ОА сопровождалось увеличением экспрессии генов гликолиза, цикла Кребса, пентозофосфатного пути, матриксных металлопротеиназ и регуляторов метаболизма АМРК и mTOR. Напротив, уровень регулятора гипоксии HIF1α и генов гексозаминового пути снижался. Выводы. Возникновение СД2 на фоне ОА, вероятно, связано с увеличением потребности клеток в энергии АТФ и сопровождается активацией путей ассимиляции глюкозы, а также увеличением экспрессии генов, ответственных за разрушение внеклеточного матрикса. Это может быть вызвано нарушением гликозилирования белков вследствие ингибирования гексозаминового пути.
for 15 min with the above mentioned drugs, and [1-14C] arachidonic acid was added and incubated for 2 min. After the extraction using organic solvent from the reaction solution, PGE2 was measured with a liquid scintillation counter. Study2 This was in vivo rat skin absorption study. SFPP, ketoprofen and loxoprofen patches, size of 1.4 cm  2.5 cm each, were applied to the dorsal skin of SD rat. After 24 h, the patches were peeled off. The active ingredient remained in the each patch was extracted from the patch and the concentrations were determined by high-performance liquid chromatography. Study3 This was a study to investigate anti-inflammatory effect of SFPP by measuring PGE2 of the inflamed paw exudate and by quantifying pain of AIA model. Arthritis was induced in Lewis rats by injecting adjuvant into left hind footpad (day 0). On day 20, SFPP, ketoprofen and loxoprofen patches (1.0  0.88 cm, considering the difference in body weight between human and rat) were applied to the right paw. Inflammatory exudate from the right paw was collected at 15, 30 min and 1, 2, 3, 4, 5 and 6 hours after patch application. The PGE2 was measured with EIA kit. Pain response was measured by counting the number of squeaking vocalizations induced by five consecutive gentle flexion of the right ankle joint. Results: Study1 IC50 values of SFP against COX-1 and COX-2 activities were 8.97 and 2.94 nM, respectively, whereas those of the conventional NSAIDs were: ketoprofen, 38.2 and 26.1 nM; loxoprofen-SRS, 1470 and 25.9 nM; diclofenac Na, 13.0 and 4.0 nM; felbinac, 14.0 and 12.0 mM; flurbiprofen, 17.5 and 4.59 nM; indomethacin, 33.4 and 48.9 nM, respectively. SFP showed the strongest effects to inhibit COX-1 and COX-2 activities. Study2 Skin absorption of SFPP 24h after application was 92.9% which was significantly greater than those of ketoprofen (67.8%) and loxoprofen (32.4%) patches, respectively.
Objectives
To assess the efficacy and safety of Rceclofenac (200mg/day) versus Diclofenac (100mg/day) therapy during three month in patients with knee osteoarthritis (OA).
Methods
200 outpatients (each group consists of 100 patients) with knee OA (mean age 62,6±7,1), with Kelgren and Lawrence radiograhic grade II-III, pain >40mm at a 100mm visual analog scale (VAS) were studied. WOMAC and EQ-5D questionnairies, and “stand up and go” test were served as criteria of treatment efficacy.
Results
There was no difference between groups regarding baseline characteristics. The significant decrease of pain and joint function improvement was observed in both groups after the first month of each treatment. This was maintained during the whole period of the follow-up. Significant decrease in stiffness was observed after one month of Aceclofenac and after two months of Diclofenac treatments. Significant improvement of general health and EQ-5D questionnaire results as well as decreased “stand up and go” test accomplishment time were observed in both groups after one month of treatment. After the first month significant “improvement” was observed in 86.3% in Aceclofenac patients and in 66% patients from Diclofenac group and after three month of treatment, in 95.8% and 76.2% patients, respectively (p<0.05). Therapy tolerance was satisfactory. Adverse effects were noted in 3% of Aceclofenac treated OA patients and in 12% subjects treated with Diclofenac.
Conclusions
Our results show that both drugs were effective in the treatment of OA. Rceclofenac is capable of decreasing pain faster than Diclofenac. In addition Rceclofenac use is associated with a decreased risk of gastroenterological side effects.
Disclosure of Interest
None Declared
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