Synergistic effect of surface phosphorylation and micro-roughness on enhanced osseointegration ability of poly(ether ether ketone) in the rabbit tibia.

This study was aimed to investigate the osseointegration ability of poly(ether ether ketone) (PEEK) implants with modified surface roughness and/or surface chemistry. The roughened surface was prepared by a sandblast method, and the phosphate groups on the substrates were modified by a two-step chemical reaction. The in vitro osteogenic activity of rat mesenchymal stem cells (MSCs) on the developed substrates was assessed by measuring cell proliferation, alkaline phosphatase activity, osteocalcin expression, and bone-like nodule formation. Surface roughening alone did not improve MSC responses. However, phosphorylation of smooth substrates increased cell responses, which were further elevated in combination with surface roughening. Moreover, in a rabbit tibia implantation model, this combined surface modification significantly enhanced the bone-to-implant contact ratio and corresponding bone-to-implant bonding strength at 4 and 8 weeks post-implantation, whereas modification of surface roughness or surface chemistry alone did not. This study demonstrates that combination of surface roughness and chemical modification on PEEK significantly promotes cell responses and osseointegration ability in a synergistic manner both in vitro and in vivo. Therefore, this is a simple and promising technique for improving the poor osseointegration ability of PEEK-based orthopedic/dental implants.

Pelvic tilt and movement during total hip arthroplasty in the lateral decubitus position.

OBJECTIVES: Total hip arthroplasty (THA) is often performed in the lateral decubitus (lateral) position. In this position, the pelvis may have various degrees of tilt leading to implant malposition. We sought to quantify the pelvic tilt in lateral position and further pelvic movement during surgery. METHODS: In 95 cases with primary THA, three-dimensional pelvic tilts were quantified by superimposing images reconstructed from CT data onto antero-posterior radiographs taken in lateral position at set-up and after cup placement. Pelvises were fixed with a device compressing anterior superior iliac spines and sacrum. RESULTS: Various degrees of pelvic tilt occurred compared to the supine position; sagittal: -3.1° (-25.5° to 10.2°), axial: 3.9° (-8.4° to 17°), coronal: 0.9° (-11.9° to 13.2°). Absolute changes more than 5° were observed 43%, 47%, and 12% in the sagittal, axial, and coronal planes, respectively. The more preoperative posterior pelvic tilt resulted in the more change in the sagittal plane. Further pelvic movement of about 3° in three planes were observed ranging from -11° to 20° after cup placement. CONCLUSION: This study showed various pelvic tilt and movement during THA. As pelvic tilt directly alters the cup orientation, its changes should be well understood. Improved tools for positioning and holding the pelvis are required.

High prevalence of cam deformity in dysplastic hips: A three-dimensional CT study.

Cam deformity could lead to suboptimal articulation by causing secondary femoroacetabular impingement after periacetabular osteotomy; however, the inherent femoral head-neck morphology in dysplastic hips and the effect of an additional osteoarthritic deformity have not been well described. We compared femoral head-neck morphology using three-dimensional imaging of normal and dysplastic hips in pre/early (Tönnis grade 0 and 1) and advanced stage osteoarthritis (Tönnis grade 2). Using computed tomography, we measured the circumferential α-angle and head-neck offset ratio in 68 dysplastic hips and 24 normal hips. Locations of the head-neck junction were represented by the clock position. In the pre/early group, the α-angle was significantly larger at the anterosuperior and inferior aspects (1, 2, and 5-7 o'clock) and head-neck offset ratio was smaller at the anterosuperior aspect (2 o'clock) than in the control group. The α-angle was significantly larger at the anterior aspects (1-4 o'clock) in the advanced group than in the pre/early group. The maximum α-angle was most commonly found at 2 o'clock (60%, 41/68 hips) in dysplastic hips. The prevalence of cam deformity (maximum α-angle >55°) was 4.2% (1/24 hips) in the control group, 22% (11/50 hips) in the pre/early group, and 50% (9/18 hips) in the advanced group. Cam deformity, inherent in the pre/early group, was found with relatively high frequency. The higher prevalence in the advanced group reflected degeneration-modified changes. When performing periacetabular osteotomy, preoperative radiographic assessments should include the femoral head-neck junction to prevent secondary femoroacetabular impingement, especially in patients with advanced stage osteoarthritis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1613-1619, 2016.

Atorvastatin upregulates nitric oxide synthases with Rho-kinase inhibition and Akt activation in the kidney of spontaneously hypertensive rats.

OBJECTIVE: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins reduce blood pressure and have beneficial effects in cardiovascular and kidney diseases. The present study examined the effect of chronic treatment with atorvastatin (ATV) on the expression of nitric oxide synthase (NOS) and the activity of Rho-kinase and Akt in the kidney of spontaneously hypertensive rats (SHRs). METHODS: SHRs were treated with ATV for 8 weeks and the SBP was measured. The expressions of endothelial, neuronal and inducible NOS (eNOS, nNOS and iNOS, respectively) proteins in the kidney were examined by immunoblot analysis. The activity of eNOS, Rho-kinase and Akt in the kidney was examined by assessing the phosphorylation of eNOS, ezrin/radixin/moesin (ERM) and Akt, respectively. RESULTS: ATV reduced the SBP without changing the plasma cholesterol levels. ATV increased eNOS expression in the cortex and medulla and nNOS expression in the medulla, whereas it did not affect iNOS expression. Although it upregulated eNOS expression in the kidney, ATV decreased the levels of phosphorylated eNOS in the cortex and did not affect the ratio of phosphorylated eNOS to total eNOS in the medulla. ATV also inhibited Rho-kinase activity and enhanced Akt activity in the kidney of SHRs. CONCLUSION: ATV upregulates eNOS and nNOS expressions with Rho-kinase inhibition and Akt activation in the kidney of SHRs. The renal nitric oxide system, Rho-kinase and Akt may contribute to the antihypertensive and renoprotective effects of statins.

Effects of estradiol, angiotensin-converting enzyme inhibitor and exercise training on exercise capacity and skeletal muscle in old female rats.

Physical fitness is closely related to cardiovascular health. We examined the effects of estradiol, angiotensin-converting enzyme inhibitor, exercise training, and their combination on exercise capacity as well as skeletal muscle fiber type and capillarity in old female rats. Twelve-month-old female Wistar-Kyoto rats were allocated to six groups: control (C), treatment with 17 beta-estradiol (0.025 mg/kg/dose, i.p. twice a week) (Est), perindopril (2 mg/kg/day) (Per), exercise training on a treadmill (15 m/min, 10 grade incline, 60 min/day, 5 days/week) (Exe), and combinations of a drug and exercise training (Exe+Est and Exe+Per). Following 6-month interventions, the rats were submitted to a stepwise exercise test on a treadmill. Moreover, fiber type and capillarity in both the soleus and gastrocnemius muscles were examined. Exercise capacity, capillary density, and the percentage of type I fiber significantly increased in Exe, Exe+Est, and Exe+Per compared to C. There were no significant differences in exercise capacity, capillary density, and percentage of type I fiber among C, Est, and Per. The combination of exercise training and perindopril further increased capillary density in both the soleus and gastrocnemius muscles, and the percentage of type I fiber in the gastrocnemius muscle compared to exercise training alone. We found that in old female rats, chronic treatment with estradiol or perindopril affected neither untrained exercise capacity nor exercise capacity acquired as a result of exercise training. However, we found that perindopril promotes adaptive changes of skeletal muscle in response to exercise such as increases in capillary density and the percentage of type I fiber.

Combination of chronic exercise and antihypertensive therapy enhances renoprotective effects in rats with renal ablation.

BACKGROUND: We assessed the renal protective effects of treatment with moderate exercise (EX), with EX plus olmesartan (OLS), with EX plus azelnidipine (AZN), and with the three together in a rat model of chronic renal failure (CRF). METHODS: Male 5/6-nephrectomized Wistar Kyoto (WKY) rats were divided into six groups according to the following treatments for: (i) no EX (C); (ii) moderate EX with treadmill running (20 m/min for 60 min/day, 5 days/week) (EX); (iii) EX+OLS (10 mg/kg/day); (iv) EX+AZN (3 mg/kg/day); (v) EX+OLS (5 mg/kg/day)+AZN (1.5 mg/kg/day); and (vi) sham operation (S). The rats were then treated for 12 weeks. RESULTS: EX, EX+OLS, EX+AZN, and EX+OLS+AZN showed decreases in the serum creatinine (Scr), an index of glomerular sclerosis (IGS), the relative interstitial volume of the renal cortex (RIV), the number of ED-1 (monoclonal antibody) positive cells (ED1(+)) and the glomerular expression score of alpha-smooth muscle actin (alpha-SMA(+)). EX+OLS, EX+AZN, and EX+OLS+AZN blocked the development of hypertension, increased the number of Wilms' tumor-1 (WT-1) positive cells (WT1(+)); EX+OLS and EX+OLS+AZN blunted the increases in proteinuria. In particular, blood urea nitrogen (BUN), ED1(+), alpha-SMA(+), WT1(+), IGS, and RIV in the EX+OLS+AZN were the lowest among all the nephrectomized groups. CONCLUSIONS: In the results, simultaneous treatment of EX, OLS, and AZN showed renal protective effects in this rat model suggesting that the treatment may affect the macrophage infiltration to the glomerulus, the fibroblast accumulation in the glomerulus, the mesangial activation, and the podocyte differentiation.

Increased expression of urotensin II-related peptide and its receptor in kidney with hypertension or renal failure.

Urotensin II-related peptide (URP) is a novel vasoactive peptide that shares urotensin II receptor (UT) with urotensin II. In order to clarify possible changes of URP expression in hypertension and chronic renal failure (CRF), the expressions of URP and UT were studied by quantitative RT-PCR and immunohistochemistry in kidneys obtained from spontaneous hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and WKY with CRF due to 5/6 nephrectomy. Expression levels of URP mRNA and UT mRNA were significantly higher in the kidneys obtained from SHR compared with age-matched WKY (at 5-16 and 16 weeks old, respectively). A dissection study of the kidney into three portions (inner medulla, outer medulla and cortex) showed that the expression levels of URP mRNA and UT mRNA were highest in the inner medulla and the outer medulla, respectively, in both SHR and WKY. The expression levels of URP and UT mRNAs were greatly elevated in the remnant kidneys of CRF rats at day 56 after nephrectomy, compared with sham-operated rats (about 6.5- and 11.9-fold, respectively). Immunohistochemistry showed that URP immunostaining was found mainly in the renal tubules, vascular smooth muscle cells and vascular endothelial cells. UT immunoreactivity was localized in the renal tubules and vascular endothelial cells. These findings suggest that the expressions of URP and UT mRNAs in the kidney are enhanced in hypertension and CRF, and that URP and its receptor have important pathophysiological roles in these diseases.

Combination of exercise and losartan enhances renoprotective and peripheral effects in spontaneously type 2 diabetes mellitus rats with nephropathy.

OBJECTIVES: We assessed the renal and peripheral effects of chronic exercise in a rat model of diabetic nephropathy and the benefits of combined exercise and losartan. METHODS: Heminephrectomized Goto-Kakizaki rats were divided into four groups: (i) no exercise (control); (ii) exercise with treadmill running; (iii) losartan; (iv) exercise plus losartan, and the rats were treated for 12 weeks. RESULTS: Losartan and exercise plus losartan significantly decreased systolic blood pressure (SBP). Exercise, exercise and losartan, and losartan blunted the increases in proteinuria. The index of glomerular sclerosis (IGS) and the relative interstitial volume of the renal cortex were significantly improved in the exercise, exercise and losartan, and losartan groups. The IGS, expressions of ED-1 and alpha-smooth muscle actin in the glomerulus were the lowest, and the number of Wilms' tumour was the highest in the exercise plus losartan group. The endurance, the proportion of type I fibre and capillarization in the extensor digitorum longus muscle were greater in the trained groups. CONCLUSION: These results suggest that both exercise and losartan have renoprotective effects, and the combination of exercise and losartan provided greater renoprotective effects than losartan alone, and may affect macrophage infiltration, mesangial activation, and podocyte loss in this model of diabetic nephropathy. It is also suggested that exercise has a specific renoprotective effect that is not related to SBP reduction, and can enhance endurance without renal complications.

Effect of estrogen on pressor responses to alpha1-adrenoreceptor agonist in conscious female rats.

We examined the effect of estrogen on pressor responses to an alpha1-adrenoreceptor agonist (phenylephrine) in conscious female Wistar-Kyoto rats. At the age of 11 weeks, rats underwent ovariectomy or a sham procedure. At the age of 15 weeks, ovariectomized (OVX) rats received intramuscular injection of estradiol valerate (EV) 5 microg (OVX+EV 5 microg group; n = 6), EV 25 microg (OVX+EV 25 microg group; n=7), or placebo (OVX group; n = 8), and sham-operated rats received placebo (sham group; n = 8). After 4 days, dose-pressor response curves to phenylephrine were examined under the condition where the renin-angiotensin, vasopressin and autonomic nervous systems were pharmacologically blocked. Ovariectomy shifted the dose-pressor response curve to phenylephrine leftward with a significantly decreased log ED50 (microg/kg) (the dose needed to reach 50% of the maximal response) (sham: 0.81 +/- 0.04; OVX: 0.57 +/- 0.05; p < 0.05). Supplementation with EV 25 mircog, but not EV 5 microg, reversed the dose-pressor response curve to phenylephrine in OVX rats to the level of the curve in sham-operated rats with a significantly increased log ED50 (microg/kg) (OVX+xEV 5 microg: 0.47 +/- 0.05; OVX+EV 25 microg: 0.75 +/- 0.08). These results suggest that the physiological level of estrogen seen in intact female rats attenuates pressor responses to alpha1-adrenoreceptor agonist, while supplementation with a moderate dose of estrogen is needed to restore such effects of physiological-level estrogen within a short-term period after chronic estrogen withdrawal.