The effect of rosiglitazone on novel atherosclerotic risk factors in patients with type 2 diabetes mellitus and hypertension - An open-label observational study

Thiazolidinediones are antidiabetic agents that decrease insulin resistance. Emerging evidence indicates that they present beneficial effects for the vasculature beyond glycemic control. The aim of this open-label observational study was to determine the effect of the thiazolidinedione rosiglitazone on novel cardiovascular risk factors, namely, lipoprotein(a) [Lp(a)], C-reactive protein (CRP), homocysteine, and fibrinogen in patients with type 2 diabetes and hypertension. A total of 40 type 2 diabetic patients already on treatment with 15 mg of glibenclamide daily and with poorly controlled or newly diagnosed hypertension were included in the study. Twenty of them received 4 mg of rosiglitazone daily as added-on therapy, whereas the rest remained on the preexisting antidiabetic treatment for 26 weeks. At baseline and the end of the study, subjects gave blood tests for the determination of Lp(a), CRP, homocysteine, fibrinogen, serum lipids, apolipoprotein (apo) A-I, and apo B. At the end of the study, rosiglitazone treatment was associated with significant reductions in Lp(a) (10.5 [8.9-54.1] to 9.8 [8.0-42.0] mg/dL, P <.05) and CRP levels (0.33 [0.07-2.05] to 0.25 [0.05-1.84] mg/dL, P <.05) vs baseline. Homocysteine levels were not affected but plasma fibrinogen presented a significant increase (303.5 +/- 75.1 to 387.5 +/- 70.4 mg/dL, P <.01) with rosiglitazone. Although no significant changes were observed in the rosiglitazone group for triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein (LDL) cholesterol, both apo A-I and apo B presented small significant reductions and the LDL-apo B ratio was significantly increased. None of the above parameters were changed in the control group. In conclusion, rosiglitazone treatment had a beneficial impact on Lp(a), CRP, and LDL particles ' lipid content in type 2 diabetic hypertensive patients but not on homocysteine and fibrinogen. The overall effect of rosiglitazone on cardiovascular risk factors seems positive but must be further evaluated

Radiographic total disc replacement angle measurement accuracy using the Oxford Cobbometer: precision and bias

Total disc replacement (TDR) clinical success has been reported to be related to the residual motion of the operated level. Thus, accurate measurement of TDR range of motion (ROM) is of utmost importance. One commonly used tool in measuring ROM is the Oxford Cobbometer. Little is known however on its accuracy (precision and bias) in measuring TDR angles. The aim of this study was to assess the ability of the Cobbometer to accurately measure radiographic TDR angles. An anatomically accurate synthetic L4–L5 motion segment was instrumented with a CHARITE artificial disc. The TDR angle and anatomical position between L4 and L5 was fixed to prohibit motion while the motion segment was radiographically imaged in various degrees of rotation and elevation, representing a sample of possible patient placement positions. An experienced observer made ten readings of the TDR angle using the Cobbometer at each different position. The Cobbometer readings were analyzed to determine measurement accuracy at each position. Furthermore, analysis of variance was used to study rotation and elevation of the motion segment as treatment factors. Cobbometer TDR angle measurements were most accurate (highest precision and lowest bias) at the centered position (95.5%), which placed the TDR directly inline with the x-ray beam source without any rotation. In contrast, the lowest accuracy (75.2%) was observed in the most rotated and off-centered view. A difference as high as 4° between readings at any individual position, and as high as 6° between all the positions was observed. Furthermore, the Cobbometer was unable to detect the expected trend in TDR angle projection with changing position. Although the Cobbometer has been reported to be reliable in different clinical applications, it lacks the needed accuracy to measure TDR angles and ROM. More accurate ROM measurement methods need to be developed to help surgeons and researchers assess radiological success of TDRs

An extract of Urtica dioica L. mitigates obesity induced insulin resistance in mice skeletal muscle via protein phosphatase 2A (PP2A)

The leaf extract of Urtica dioica L. (UT) has been reported to improve glucose homeostasis in vivo, but definitive studies on efficacy and mechanism of action are lacking. We investigated the effects of UT on obesity- induced insulin resistance in skeletal muscle. Male C57BL/6J mice were divided into three groups: low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with UT. Body weight, body composition, plasma glucose and plasma insulin were monitored. Skeletal muscle (gastrocnemius) was analyzed for insulin sensitivity, ceramide accumulation and the post translational modification and activity of protein phosphatase 2A (PP2A). PP2A is activated by ceramides and dephosphorylates Akt. C2C12 myotubes exposed to excess free fatty acids with or without UT were also evaluated for insulin signaling and modulation of PP2A. The HFD induced insulin resistance, increased fasting plasma glucose, enhanced ceramide accumulation and PP2A activity in skeletal muscle. Supplementation with UT improved plasma glucose homeostasis and enhanced skeletal muscle insulin sensitivity without affecting body weight and body composition. In myotubes, UT attenuated the ability of FFAs to induce insulin resistance and PP2A hyperactivity without affecting ceramide accumulation and PP2A expression. UT decreased PP2A activity through posttranslational modification that was accompanied by a reduction in Akt dephosphorylation