Effect of Hyperglycemia to The mRNA Level and Protein Expression of Perlecan at Rat Model of Osteoarthritis with Diabetes Mellitus Type 1.

INTRODUCTION: Previous research found that diabetes mellitus capable to aggravate osteoarthritis disease. In brief, the hyperglycemia condition in diabetes mellitus has an impact on protein glycation of all joint components, including molecule, such as perlecan. The protein expression of perlecan reflects the presence amount of perlecan in the matrix of articular cartilage. However, the impact of hyperglycemia on articular perlecan has not been explained. Moreover, the role of perlecan as a mechanotransducer for chondrocytes in type 1 Diabetes mellitus remains unclear. AIM: This research aims to analyze the effect of hyperglycemia in type 1 Diabetes mellitus to the mRNA level and protein expression of perlecan. METHODS: Thirty-five adult male rats were divided into seven groups, such as three groups of rat model with anterior cruciate ligament transection (ACLT) at right knee (ACLT1, ACLT2, ACLT3); three groups of rats with ACLT at right knee which followed by Streptozotocin injection for diabetic mice model (DM1, DM2, DM3); and control group (N). Rat sacrificed at the third week, fourth week, and sixth week after two months of maintenance. The mRNA level and protein expression were analyzed by using PCR and Western blot. All of data was analyzed by ANOVA. RESULTS: Protein expression of perlecan in ACLT mice with diabetes mellitus (DM1, DM2, DM3 group) was gradually decreased according to the increased hyperglycemia duration. Whilst, protein expression of perlecan within ACLT mice without diabetes mellitus (ACLT1, ACLT2, ACLT3 group) was increased. The similar result also demonstrated by the mRNA level of perlecan. Group of DM1, DM2, DM3 exhibited decreased mRNA level of perlecan over the hyperglycemia duration. While, ACLT1, ACLT2, and ACLT3 group had a gradually increased of perlecan mRNA level. CONCLUSION: Hyperglycemia on osteoarthritic condition decreased mRNA level and protein expression of perlecan which increased the severity of osteoarthritis disease.

Chondrocyte Intracellular Matrix Strain Fields of Articular Cartilage Surface in Hyperglycemia Model of Rat: Cellular Morphological Study.

INTRODUCTION: Chondrocyte is one cell in articular cartilage was products many proteins, molecules, and other factors. The external influence of cartilage, such as: hyperglycemia was entering joint capsule and impact to the chondrocytes and the cartilage. Hyperglycemia caused modification of heparan sulfate proteoglycan 2 (perlecan) proteins through glycation process. AIM: The aim of this study was to analyze morphological changing of chondrocytes pericellular matrix by the influence of hyperglycemia. MATERIAL AND METHODS: Eighteen adult male rats were divided into six groups: control, rat treated with sugar intake was 0.5 mg/kg, 0.75 mg/ kg, 1mg/kg, 1.5 g/kg and 2 mg/kg of body weight. The animal model was dislocated and left knee was taken to observe changing of chondrocytes pericellular matrix strain fields by Scanning Electron Microscope (SEM) from perpendicular to femoral condylus cartilage. RESULTS: Changing of chondrocytes intracellular matrix strain fields as changing of cell diameters and cell distances at group control and group I to group V, which cell diameters was lower level and cell distances was the highest level at over diet 2. This changing of intracellular matrix strain fields was corresponding to changing chondrocytes morphology in hyperglycemia condition, due to hypertrophic stage as adaptive responses. This research as based on next research for accomplish of hyperglycemia influence to morphology articular cartilage changing to prevent degeneration of cartilage towards osteoarthritis. CONCLUSIONS: Present study concludes that hyperglycemia influence to chondrocyte intracellular matrix strain fields changing.

An RCT Investigating Patient-Driven Versus Physician-Driven Titration of BIAsp 30 in Patients with Type 2 Diabetes Uncontrolled Using NPH Insulin.

INTRODUCTION: The aim of this study was to confirm the efficacy of patient-driven titration of BIAsp 30 in terms of glycemic control, by comparing it to physician-driven titration of BIAsp 30, in patients with type 2 diabetes in North Africa, the Middle East, and Asia. METHODS: A 20-week, open-label, randomized, two-armed, parallel-group, multicenter study in Egypt, Indonesia, Morocco, Saudi Arabia, and Vietnam. Patients (n = 155) with type 2 diabetes inadequately controlled using neutral protamine Hagedorn (NPH) insulin were randomized to either patient-driven or physician-driven BIAsp 30 titration. RESULTS: The noninferiority of patient-driven compared to physician-driven titration with respect to the reduction in HbA1c was confirmed. The estimated mean change in HbA1c from baseline to week 20 was -1.27% in the patient-driven arm and -1.04% in the physician-driven arm, with an estimated treatment difference of -0.23% (95% confidence interval: -0.54; 0.08). After 20 weeks of treatment, the proportions of patients achieving the target of HbA1c <7.5% were similar between titration arms; the proportions of patients achieving the target of ≤6.5% were also similar. Both titration algorithms were well tolerated, and hypoglycemic episode rates were similar in both arms. CONCLUSION: Patient-driven titration of BIAsp 30 can be as effective and safe as physician-driven titration in non-Western populations. Overall, the switch from NPH insulin to BIAsp 30 was well tolerated in both titration arms and led to improved glycemic control. A limitation of the study was the relatively small number of patients recruited in each country. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01589653. FUNDING: Novo Nordisk A/S, Denmark.

Diabetes and stroke.

Diabetes mellitus is a well-established independent risk factor for stroke and is associated with high mortality. Risk factors or risk markers for a first stroke were classified according to their potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented or less well documented). Modifiable risk factors include hypertension, exposure to cigarette smoke, diabetes, atrial fibrillation and certain other cardiac conditions, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, physical inactivity, and obesity and body fat distribution. Some of parameters are usefull as screening test to predict the incidence of stroke in diabetic patients in the future, such as UKPDS Risk Engine, incidence of carotid bruit featuring the stenosis of carotid artery, QTc interval prolongation and proteinuria. The real action must be taken to prevent the stroke when high risk patient is found. The modifiable and potentially modifiable risk factors that have been recommended by numbers of expert committee have to be modified immediately. In case with stenosis of carotid artery, the endarterectomy and carotid stenting have become popular and acceptable treatment in USA and Europe. It must be considered by Indonesian physicians to decrease the incidence of stroke.

Effects of high-carbohydrate and high fat diet on formation of foam cells and expression of TNF-alpha in Rattus novergicus.

AIM: to examine the role of high carbohydrate and high fat diet on formation of foam cells and expression of TNFalpha, an early stage of atherosclerosis. METHOD: three months old male Rattus Novergicus strain Wistar were allocated into 3 groups, normal diet group (GI, n=8), high carbohydrate diet group (GII, n=8), and high fat diet group (G III, n=8). Those groups received an isoenergetic diet but contained different percentage of carbohydrate and fat for 12 weeks. The rest of the food was measured daily to calculate the calorie intake. The body weight was measured weekly. At the end of study, blood samples were taken using cardiac puncture to examine lipid profiles and random blood sugars. RESULTS: levels of blood glucose significantly increased in GII compared to the GI (281.87 +/- 39.66 mg/dl vs 192.5 +/- 1.4 mg/dl, p=0.002). Group II and G III showed increased of triglyseride compared to GI (138.0 +/- 47.15 vs 85.5 +/-20.3, p=0.02; 163.62 +/- 41.77 vs 85.5 +/- 20.3, p=0.00, respectively). Level of LDL significantly increased in G III compared to GI (72 +/- 35.6 vs 27.0 +/- 8.9, p=0.00). No statistical difference in level of HDL among the three groups. Level of TNFalpha significantly increased in GII and G III compared to GI (19.13 +/- 3.68 vs 2.5 +/- 1.4, p=0.00; 23.6 +/- 5.58 vs 2.5 +/- 1.4, p=0.00, respectively). The number of foam cells was significantly increased in GII and G III compared to GI (7.18 +/- 5.28 vs 1.2 +/- 1.4, p=0.00; 9.91 +/- 6.26 vs 1.2 +/- 1.4, p=0.00, respectively). The foam cell had strong correlation with triglyseride level and TNFalpha (r=0.696, p=0.00; r=0.618, p=0.00, respectively). CONCLUSION: this result shows that high carbohydrate and high fat diet potentially increase the risk factor of atherosclerosis. Both diets induced the inflammatory process and increase foam cells formation, are in the early stage of atherosclerosis.

Rickettsia felis in Xenopsylla cheopis, Java, Indonesia.

Rickettsia typhi and R. felis, etiologic agents of murine typhus and fleaborne spotted fever, respectively, were detected in Oriental rat fleas (Xenopsylla cheopis) collected from rodents and shrews in Java, Indonesia. We describe the first evidence of R. felis in Indonesia and naturally occurring R. felis in Oriental rat fleas.