Simvastatin Reduces the Expression of Adhesion Molecules in Circulating Monocytes From Hypercholesterolemic Patients Atorvastatin has hypolipidemic and anti-inflammatory effects in apoE/LDL receptor-double-knockout mice. Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery Influence of a hydrophobic resin coating on the immediate and 6-month dentin bonding of three universal adhesives. Effects of Losartan and Simvastatin on Monocyte-Derived Microparticles in Hypertensive Patients With and Without Type 2 Diabetes Mellitus In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid Reduction of epidural scar adhesion by topical application of simvastatin after laminectomy in rats. Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study. Anterior abdominal wall adhesions after laparotomy or laparoscopy. Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial. Effect of vitamin D supplementation on inflammation: protocol for a systematic review High, but not moderate frequency and duration of exercise training induces downregulation of the expression of inflammatory and atherogenic adhesion molecules Prevention of post-surgical adhesion formation using aspirin in a rodent model: a preliminary report.
Objective —The intercellular adhesion molecule-1 ( ICAM-1/CD54 ) and its lig and , CD11a/CD18 , mediate endothelial adhesion of leukocytes and their consecutive transmigration . Anti-inflammatory effects of statins are considered to be exerted in part through inhibition of leukocyte – endothelial interactions . We investigated the in vivo effects of simvastatin treatment in hypercholesterolemic patients and the influence of various statins on expression of cellular adhesion molecules in vitro . Methods and Results —A total number of 107 hypercholesterolemic patients were treated with 20 mg ( n=52 ) or 40 mg ( n=55 ) of simvastatin daily . After 6 weeks of treatment , peripheral blood mononuclear cells ( P BMC s ) expressed lower amounts of CD54- , CD18- , and CD11a-mRNA compared with pretreatment values . Surface expression of CD54 and CD18/CD11a on CD14 + -monocytes also decreased significantly in both groups of patients . Moreover , simvastatin , atorvastatin , and cerivastatin were found to downregulate tumor necrosis factor (TNF)-&agr ;– induced expression of CD54 and CD18/CD11a in isolated P BMC s obtained from normal donors as well as TNF-&agr ;– dependent expression of these CAMs in cultured human umbilical vein endothelial cells ( HUVECs ) . Furthermore , all three statins were found to reduce the binding of P BMC s to TNF-&agr ;– stimulated HUVECs in vitro . Conclusions —Statin-induced inhibition of expression of CD54 and CD18/CD11a in P BMC s and HUVECs with consecutive loss of adhesive function may contribute to the anti-inflammatory effects of these drugs and some of their beneficial clinical activities Statins are first-line pharmacotherapeutic agents for hypercholesterolemia treatment in humans . However the effects of statins in animal models of atherosclerosis are not very consistent . Thus we wanted to evaluate whether atorvastatin possesses hypolipidemic and anti-inflammatory effects in mice lacking apolipoprotein E/low-density lipoprotein receptor ( apoE/LDLR-deficient mice ) . Two-month-old female apoE/LDLR-deficient mice ( n=24 ) were r and omly subdivided into 3 groups . The control group of animals ( n=8 ) was fed with the western type diet ( atherogenic diet ) and in other two groups atorvastatin was added to the atherogenic diet at the dosage of either 10 mg/kg or 100 mg/kg per day for a period of 2 months . Biochemical analysis of lipids , ELISA analysis of monocyte chemotactic protein-1 ( MCP-1 ) in blood , quantification of lesion size and expression of vascular cell adhesion molecule-1 ( VCAM-1 ) and intercellular cell adhesion molecule-1 ( ICAM-1 ) in the atherosclerotic lesion by means of immunohistochemistry and Western blot analysis were performed . The biochemical analysis showed that administration of atorvastatin ( 100 mg/kg/day ) significantly decreased level of total cholesterol , lipoproteins ( VLDL and LDL ) , triacylglycerol , and moreover significantly increased level of HDL . ELISA analysis showed that atorvastatin significantly decreased levels of MCP-1 in blood and immunohistochemical and Western blot analysis showed significant reduction of VCAM-1 and ICAM-1 expression in the vessel wall after atorvastatin treatment ( 100 mg/kg/day ) . In conclusion , we demonstrated here for the first time strong hypolipidemic and anti-inflammatory effects of atorvastatin in apoE/LDLR-deficient mice . Thus , we propose that apoE/LDLR-deficient mice might be a good animal model for the study of statin effects on potential novel markers involved in atherogenesis and for the testing of potential combination treatment of new hypolipidemic substances with statins Objectives : Systemic inflammatory response occurs frequently after coronary artery bypass surgery , and it is strongly correlated with the risk of postoperative morbidity and mortality . Recent studies demonstrate that treatment with statin is associated with a significant and marked decrease in inflammation-associated variables such as the C-reactive protein , cytokines , and adhesion molecules . Therefore , we investigated the effects of preoperative atorvastatin treatment on systemic inflammatory response and perioperative morbidity after cardiopulmonary bypass . Design : Double-blinded , placebo-controlled , r and omized study . Setting : University hospital . Patients : Forty patients were r and omized to treatment with atorvastatin ( 20 mg/day , group A , n = 20 ) or placebo ( group B , n = 20 ) 3 wks before surgery . Interventions : Three-week treatment by atorvastatin 20 mg/day . Measurement and Main Results : Postoperative serum levels of both interleukin-6 and interleukin-8 increased significantly over baseline , but the peak levels observed 4 hrs postoperatively were significantly lower in the atorvastatin group . In the same fashion , CD11b expression on neutrophils was significantly lower in the statin group at 4 and 24 hrs postoperatively . Finally , neutrophil-endothelial adhesion was significantly reduced in the statin patients compared with controls . The operation time , blood loss , need for inotropic support , intubation time , and length of intensive care unit or hospital stay did not differ significantly between the two groups . The systemic inflammatory response syndrome score on postoperative days 1 and 2 was comparable in both groups . Conclusions : Pretreatment with atorvastatin significantly reduces cytokine release and neutrophil adhesion to the venous endothelium in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass OBJECTIVE To test the influence of a hydrophobic resin coating ( HC ) on the immediate ( 24h ) and 6-month ( 6 m ) microtensile dentin bond strengths ( μTBS ) and nanoleakage ( NL ) of three universal adhesives applied in self-etch ( SE ) or in etch- and -rinse ( ER ) mode . METHODS Sixty caries-free extracted third molars were assigned to 12 experimental groups result ing from the combination of the factors " adhesive system " ( Scotchbond Universal Adhesive [ SBU ] , 3 M ESPE ; All-Bond Universal [ ABU ] , Bisco Inc. ; and G-Bond Plus [ GBP ] , GC Corporation ) ; " adhesive strategy " ( SE or ER ) ; " hydrophobic resin coating " [ HC ] ( with or without Heliobond , Ivoclar Vivadent ) ; and " storage time " ( 24h or 6 m ) . Specimens were prepared for μTBS testing - ( 24h ) half of the beams were immediately tested under tension ; and ( 6 m ) the other half was stored in distilled water ( 37 ° C ) for 6 m prior to testing . For each tooth , two beams were r and omly selected for NL evaluation for both evaluation times . Data were analyzed for each adhesive system using three-way ANOVA and Tukey 's post-hoc test ( α=0.05 ) . RESULTS μTBS : ( 24h ) : In SE mode , HC result ed in statistically greater mean μTBS for all adhesives . ( 6 m ) : When HC was not used the mean μTBS for SBU/ER , ABU/ER , GBP/ER and SBU/SE decreased significantly . NL : ( 24h ) : SBU/ER , ABU/ER and GBP/SE result ed in a significant reduction in NL when HC was applied . ( 6 m ) : No significant reduction was observed for SBU/ER or for SBU/SE regardless of the use of HC . SIGNIFICANCE The application of a hydrophobic resin coating improved the 24h and the 6 m performances of all three adhesives systems in SE mode Monocyte-derived microparticles play an important role in the pathogenesis of diabetic vasculopathy , and angiotensin II receptor blocker and statin have been shown to have a beneficial effect on the angiopathies of hypertension and hyperglycemia in patients with type 2 diabetes mellitus . However , the interaction between angiotensin II receptor blocker and statin , and monocyte-derived microparticles in atherosclerosis is poorly understood . The effects of losartan and simvastatin on circulating concentrations of monocyte-derived microparticles , chemokines , and soluble adhesion markers were studied in hypertensive patients with or without type 2 diabetes mellitus . Monocyte-derived microparticles were measured by flow cytometry , and levels of serum chemokines ( MCP-1 and RANTES ) and soluble adhesion markers ( sP-selectin and sVCAM-1 ) were measured by enzyme-linked immunosorbent assay . Losartan decreased both the systolic and diastolic blood pressure in hypertensive patients with and without type 2 diabetes mellitus . The concentrations of monocyte-derived microparticles , chemokines , and soluble adhesion molecules were higher in hypertensive patients who also had type 2 diabetes mellitus vs. those who did not . The administration of angiotensin II receptor blocker decreased the circulating concentration of all these markers . In addition , all markers were decreased by combination therapy , and monocyte-derived microparticles were decreased more with combination therapy with losartan and simvastatin than monotherapy with losartan . The administration of angiotensin II receptor blocker inhibited monocyte-derived microparticle generation and suggests that angiotensin II is intimately related to vascular changes that occur in type 2 diabetes mellitus . Combination therapy with a statin and angiotensin II receptor blocker might be valuable as anti-atherosclerotic therapy in patients with type 2 diabetes mellitus and nephropathy Objective —A large-scale , prospect i ve , r and omized clinical trial has recently revealed that the addition of highly purified eicosapentaenoic acid ( EPA ) to low-dose statin therapy significantly reduces the incidence of major coronary events . Here we investigated in vivo and in vitro effect of EPA on monocyte adhesion to endothelial cells and adhesion molecules . Methods and Results —A new en face immunohistochemistry of endothelial surface in combination with confocal microscopy revealed marked reduction of lipopolysaccharide (LPS)-induced monocyte adhesion to the aortic endothelium in parallel with the suppression of vascular cell adhesion molecule 1 ( VCAM-1 ) and nuclear translocation of nuclear factor-&kgr;B p65 in EPA-treated mice relative to vehicle-treated groups . In an in vitro adhesion assay system under physiological flow conditions , EPA inhibited LPS-induced monocyte adhesion and endothelial adhesion molecules . We found significant decrease in plasma concentrations of soluble intercellular adhesion molecule 1 ( sICAM-1 ) and sVCAM-1 in patients with the metabolic syndrome after a 3-month administration of highly purified EPA ( 1.8 g daily ) . Multivariate regression analysis revealed that EPA administration is the only independent determinant of sICAM-1 and sVCAM-1 . Conclusions —This study provides evidence that EPA inhibits monocyte adhesion to endothelial cells in parallel with the suppression of endothelial adhesion molecules in vivo and in vitro OBJECTIVE Epidural scar adhesion is one of the major causes of the failed back surgery syndrome after laminectomy . Recent studies have shown that simvastatin has potent anti-fibrotic and anti-inflammatory properties . This study evaluates the effect of the topical application of simvastatin on reducing epidural scar adhesion after laminectomy in rats . MATERIAL S AND METHODS Thirty-six male Sprague-Dawley rats were r and omly divided into three groups : control , chitosan and simvastatin group . After laminectomy was performed at L1 level , simvastatin and chitosan were applied to the laminectomy sites . The control group received no additional treatment . Four weeks later , the rats were killed and the epidural adhesion was evaluated by macroscopic assessment , hydroxyproline content analysis and histological analysis . The number of fibroblasts and the optical density of the collagen were also determined . RESULTS The results showed that simvastatin could reduce epidural scar adhesion in rats . Little epidural adhesions were seen in the laminectomy sites treated with simvastatin . The hydroxyproline content , the number of fibroblasts and the optical density of the collagen in the simvastatin group were significantly less than those of the chitosan and control group . However , dense epidural adhesion was found in control group . CONCLUSIONS Topical application of simvastatin could reduce epidural scar adhesion after laminectomy in rats . Further research is necessary to determine the optimal dosage and the safety of simvastatin OBJECTIVE In addition to lowering lipid levels , statins might reduce leukocyte-endothelial cell interactions . Therefore , we assessed whether this effect could limit the inflammatory response to cardiopulmonary bypass ( CPB ) in cardiac surgical patients . METHODS Twenty patients undergoing valve or coronary operations with tepid ( 34 degrees C ) CPB were r and omized to receive an oral dose of atorvastatin ( 40 mg the evening before and 40 mg the morning of surgery ) or to serve as controls . Pre- and post-CPB blood sample s were assayed for neutrophil CD11b surface adhesion molecule and oxidative burst . Plasma levels of interleukins 6 and 8 , P-selectin , soluble intercellular adhesion molecule-1 , and lactoferrin were measured by enzyme-linked immunosorbent assay ( ELISA ) . In addition , right atrial biopsies were taken before and at the end of CPB , and processed for the expression of the transcription nuclear factor-kappa B ( NF-kappaB ) . RESULTS The two groups did not differ with regard to pre- and intraoperative data . Except for P-selectin , postbypass values of all markers significantly increased over baseline values , but atorvastatin therapy failed to attenuate the magnitude of this increase . In the two groups , the expression of NF-kappaB significantly ( p = 0.004 ) increased over baseline without group effect . Postoperative clinical outcomes did not differ either between the two groups . CONCLUSION These data show that acute preoperative statin therapy fails to limit the inflammatory response to CPB ; however , the data also document a major upregulation of NF-kappaB during cardiac operations , thereby providing a sound rationale for interventions targeted at inactivating this key component of the inflammatory cascade STUDY OBJECTIVE To determine the frequency of postoperative adhesions to the anterior abdominal wall peritoneum that could affect safe placement of the initial laparoscopic umbilical cannula at subsequent procedures . DESIGN Prospect i ve cohort study . SETTING Reproductive endocrinology and infertility service of a tertiary care referral hospital . PATIENTS Two hundred fifteen women , 124 with prior abdominal surgery and 91 with no prior surgery . INTERVENTIONS Surgical histories were review ed , abdominal skin scars noted , and extent of anterior abdominal wall adhesions prospect ively recorded . Statistical analysis was performed with the chi2 test . MEASUREMENTS AND MAIN RESULTS No anterior abdominal wall adhesions were present in 91 patients with no previous surgery  or 45 patients with previous laparoscopy  ( 12 had more than 1 laparoscopy ; p < 0.001 vs laparotomy ) . Seventeen ( 59 % ) of 29 patients with a midline vertical incision had anterior wall adhesions ( p < 0.05 vs suprapubic transverse incision ) . Eleven ( 28 % ) of 39 with a suprapubic transverse incision had anterior wall adhesions ( p < 0.001 vs no surgery or laparoscopy ) . Ninety-six percent of adhesions involved omentum and 29 % included bowel . CONCLUSION Prior laparotomy , whether through a midline vertical or suprapubic transverse incision , significantly increased the frequency of anterior abdominal wall adhesions , and these adhesions may complicate the placement of the laparoscopic cannula through the umbilicus Although statins are being used for secondary prevention of ischemic stroke , recent experimental data have shown new pleiotropic effects of these drugs responsible for their role in neuroprotection . We conducted a pilot , double-blind , r and omized , multicenter clinical trial to study for the first time safety and efficacy of simvastatin in the acute phase of ischemic stroke . Simvastatin/placebo was given at 3 - 12 h from symptom onset to 60 patients with cortical strokes . Efficacy on the evolution of several inflammation markers [ interleukin (IL)-6 , IL-8 , IL-10 , monocyte chemoattractant protein-1 , intercellular adhesion molecule-1 , vascular cell adhesion molecule-1 , C-reactive protein , sApo/Fas , tumor necrosis factor-alpha , E-selectin , L-selectin and nitrites+nitrates ] and neurological outcome was evaluated at baseline , day 1 , 3 , 5 , 7 and 90 . No differences were found amongst the biomarkers studied regarding treatment allocation . Although simvastatin patients improved significantly by the third day ( 46.4 % vs. 17.9 % , P = 0.022 ) , a non-significant increase in mortality and greater proportion of infections ( odds ratio 2.4 , confidence interval 1.06 - 5.4 ) in the simvastatin group were the main safety concerns . Therefore , a larger clinical trial is needed to confirm the net benefit of this therapeutic approach Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 Background Lifestyle changes which include daily exercise training have been shown to slow the progression of coronary artery disease . We design ed a study to examine the effects of a multifactorial intervention on atherogenic adhesion molecules on the surface of monocytes in patients with coronary artery disease . Methods We r and omized 39 patients with coronary artery disease to ( i ) an intervention program which consisted of 4 weeks of daily 6 × 15 min ergometer training at submaximal intensity in addition to a 1 h/week group exercise session , followed by 5 months of home-based ergometer training of 30 min/day again in addition to a 1 h/week group exercise session or ( ii ) conventional therapy .  All patients received a statin .  Monocyte-bound cellular adhesion molecules LFA-1 ( CD11a ) , MAC-1 ( CD11b ) , VLA-4 ( CD49d ) and L-selectin ( CD62L ) were assessed by fluorescence activated cell sorting analysis . Results After 4 weeks the multifactorial intervention led to a significant improvement of maximal work capacity , lipid profile , body mass index , blood pressure , fasting glucose and hemoglobin A1c . This was associated with a reduced expression of MAC-1 and VLA-4 . After 5 months of a home-based intervention the beneficial effects of the cardiovascular risk profile were still apparent , whereas the effects on the expression of adhesion molecules were blunted . Conclusion In patients treated with statins , 4 weeks of high frequency and long duration exercise training led to a diminished expression of atherogenic adhesion molecules MAC-1 und VLA-4 . After 5 months of home-based exercise training of moderate frequency and duration , these effects were blunted . Our data suggest that our patients in cardiac rehabilitation programs might further benefit from the antiatherogenic effects of an even higher amount of exercise training Pelvic adhesions are one of the major factors which significantly and adversely affect surgery outcome due to intra- and postoperative morbidity and reduce future female fertility . Using a rodent model , we evaluated the efficacy of aspirin , a non-steroidal anti-inflammatory drug , in the prevention of adhesion formation . A total of 72 female Wistar rats received a st and ardized primary traumatic lesion to the right uterine horn . They were r and omly divided into eight groups : group I ( control ) had no treatment and group II received a single pre-operative 0.70 mg aspirin . All the succeeding groups ( III-VIII ) received aspirin in doses of 0.35 , 0.70 , or 1.40 mg every 6 h for either 48 or 96 h in addition to the pre-operative aspirin ( 0.70 mg ) . All animals were killed 4 weeks later and adhesions were assessed using a modified adhesion scoring scale . The lowest adhesion score was found in the group treated with 0.35 mg of aspirin for 96 h , and the highest was found among the groups treated with either 0.70 or 1.40 mg for 48 - 96 h respectively ( P < 0.05 ) . These results are in line with the hypothesis that administration of a low dose of aspirin selectively inhibits the production of thromboxane A2 , whereas basal prostacyclin bio synthesis is preserved . This phenomenon might contribute to reducing postoperative adhesion formation in a rat model . Thus , future studies into the prevention of adhesion formation may require the additional use of a non-steroidal anti-inflammatory drug , for which aspirin deserves further attention , before extrapolation into human therapy
In conclusion , statins were effective in preventing postoperative adhesion , as assessed based on gross and microscopic adhesion scores in rats
Adhesion is a significant concern after surgery .
Many research ers studied the anti-adhesive effect of statin , of which results were inconsistent .
Thus , we purpose d to perform a systematic review and meta- analysis to evaluate the effect of statins on postoperative adhesion in an experimental study .