Anti-inflammatory Effects In Patients Research Articles

Effect of beinaglutide treatment on weight loss in Chinese patients with type 2 diabetes mellitus and overweight/obesity.

To evaluate the effect of beinaglutide on weight loss and plasma protein patterns of inflammation/obesity relevant cytokines and biomarkers. This study involved 36 adult patients with a body mass index (BMI) of ≥ 24 kg/m2 and T2DM. Beinaglutide was administered for three months. Changes in body weight, fasting plasma glucose (FPG) level, 2 h postprandial plasma glucose (2h-PG) level, glycosylated hemoglobin (HbA1c) level, BMI and visceral and subcutaneous fat areas were measured at baseline and after three months of treatment. In addition, relevant inflammation/obesity cytokines and biomarkers were measured. After three months, beinaglutide treatment led to significant changes, including in body weight, BMI, FPG level, HbA1c level, visceral and subcutaneous fat areas. In addition, serpin E1, leptin, C-reaction protein (CRP) and tumor necrosis factor-α (TNF-α) also decreased significantly. The plasma protein concentrations of CRP (Log2 transformed) were found to be positively correlated with the percentage of weight loss (R = 0.514 and p-value = 0.021). Beinaglutide treatment resulted in weight loss, plasma glucose control and anti-inflammatory effects in patients with T2DM and overweight/obesity.

Levosimendan as a therapeutic strategy to prevent neuroinflammation after aneurysmal subarachnoid hemorrhage?

BackgroundPoor patient outcomes after aneurysmal subarachnoid hemorrhage (SAH) occur due to a multifactorial process, mainly involving cerebral inflammation (CI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia, followed by neurodegeneration....

A 4-strain probiotic supplement influences gut microbiota composition and gut wall function in patients with ulcerative colitis

Symprove, a multi-strain probiotic, has been shown to exert a mild anti-inflammatory effect in patients with ulcerative colitis (UC). We examined stool samples from 3 patients with UC in order to create microbiotas in an in-vitro gut model. The effects of Symprove on bacterial diversity and metabolic activity in the microbiotas was evaluated over 48h. In addition, the influence of probiotic dosing on epithelial tight-junction integrity, production of inflammatory markers and wound healing were evaluated in cell culture models. The relative proportions of the main bacterial phyla in UC patients differed from those of healthy subjects studied previously; levels of Firmicutes were lowered and levels of Bacteroidetes were raised. Addition of Symprove changed the bacterial composition in the microbiotas over a 48h period. Several other factors generally implicated in good gut health changed after dosing with probiotic; production of short chain fatty acids (SCFAs) and lactate was stimulated, levels of anti-inflammatory cytokines (IL-6, IL-10) increased, levels of pro-inflammatory cytokines and chemokines (MCP-1 and IL-8) decreased, epithelial tight junction integrity improved and wound healing occurred faster than a control. The results imply it is not the simple addition of probiotic bacteria that improves gut health. Rather, the probiotic bacteria generate lactate, which then stimulates growth of commensal gut bacteria, raising SCFA levels (particularly butyrate). The increased butyrate concentration positively influences inflammation response and time of wound healing.

EFFICIENCY OF PROTEASE INHIBITOR ULINASTATIN IN PATIENTS WITH ACUTE PANCREATITIS

Introduction. Acute pancreatitis is one of the most common acute gastroenterological diseases in the world. A key element of its pathogenesis is “pancreatic self-digestion” by pancreatic enzymes. In recent years, the use of protease inhibitors has attracted considerable interest as a pathogenetic therapy of acute pancreatitis.Objective: To study the effect of ulinastatin on the severity of acute pancreatitis.Materials and methods. A total of 50 patients with acute pancreatitis were examined. Group 1 (n = 25) received standard therapy, group 2 (n = 25) additionally received intravenous ulinastatin infusion in a dose of 100,000 IU 1 time per day for 3 days. Indicators of pancreatic inflammation and mortality were studied.Results and discussion. On admission, patients had enzymatic ascites, an acute increase in blood levels of α-amylase and diastase in the urine, neutrophilic leukocytosis with a left shift and relative lymphocytopenia. Compared to standard therapy, ulinastatin reduced the frequency of abdominal drainage from 68.0% to 40.0%. Blood α-amylase and urine diastase levels in the ulinastatin group decreased 2-6 times as compared with the control group and normalized on day 5, whereas in the control group they did not reach the norm. The number of leukocytes in the ulinastatin group on day 5 decreased by 38.1% from the baseline, and in the control group – only by 26.0%. On the 5th day the left shift, LII and lymphocytopenia decreased in the ulinastatin group, but not in the control group. In the first 3 days of the disease, the diagnosis of severe acute pancreatitis was confirmed in 80.0% of patients in the control group and 48.0% in the ulinastatin group. Mortality in the control group was 20.0%, and there were no fatal cases in ulinastatin group. Ulinastatin decreased duration of treatment in ICU from 3.6 ± 1.0 to 2.3 ± 0.9 days and did not affect total hospital stay.Conclusions. Ulinastatin has a significant anti-inflammatory effect in patients with acute pancreatitis. This is manifested by a rapid and reliable reduction of signs of inflammation in the pancreas, which prevents the development of pancreatic necrosis, reduces pancreatitis severity, accelerates SIRS resolving and reduces mortality.

Active Hexose Correlated Compound Has Protective Effects in Ischemia–Reperfusion Injury of the Rat Small Intestine

BackgroundIschemia–reperfusion (IR) injury of the small intestine is a serious problem in abdominal aortic aneurysm surgery or small intestine transplantation. Active hexose correlated compound (AHCC) is a popular anti-inflammatory drug in complementary and alternative medicine. The aim of this study was to examine whether pretreatment with AHCC reduces intestinal IR injury. MethodsRats were given a normal diet (IR group) or normal diet supplemented with 2% AHCC (IR + AHCC group) ad libitum for 10 d. After 1 d of fasting, the superior mesenteric artery was occluded by clipping for 45 min. Intestinal and blood samples were collected for 1-6 h after reperfusion. The messenger RNA (mRNA) and protein levels of inflammatory factors were analyzed. ResultsThe IR + AHCC group had reduced mucosal abrasion and significantly increased mucosal thickness of the intestinal tissues 6 h after reperfusion, compared with the IR group. AHCC decreased mRNA expression of inducible nitric oxide synthase (iNOS), cytokine-induced neutrophil chemoattractant 1 and interleukin 6 in the mucosa of the small intestine. AHCC also decreased expression of iNOS protein. Serum levels of cytokine-induced neutrophil chemoattractant 1 and tumor necrosis factor α were decreased in the IR + AHCC group compared with the IR group. Electrophoretic mobility shift assay of mucosal nuclear extracts revealed that AHCC inhibited the activation of nuclear factor kappa B. AHCC also inhibited the expression of iNOS antisense transcript, which stabilizes iNOS mRNA. ConclusionsOur findings suggest that AHCC reduces expression of inflammatory mediators, in part, by inhibiting nuclear factor kappa B activation. AHCC may have anti-inflammatory effect in patients with intestinal IR injury.

Effect of long-term remote ischemic conditioning on inflammation and cardiac remodeling

Background. Remote ischemic conditioning (RIC) protects against acute ischemia-reperfusion injury and may have beneficial effects in patients with stable cardiovascular disease. We investigated the effect of long-term RIC treatment in patients with chronic ischemic heart failure (CIHF). Methods. Prespecified post-hoc analysis of a prospective, exploratory and outcome-assessor blinded study. Twenty-one patients with compensated CIHF and 21 matched controls without heart failure or ischemic heart disease were treated with RIC once daily for 28 ± 4 days. RIC was conducted as 4 cycles of 5 minutes upper arm ischemia followed by 5 minutes of reperfusion. We evaluated circulating markers of inflammation and cardiac remodeling at baseline and following long-term RIC. Results. RIC reduced C-reactive protein from 1.5 (0.6–2.5) to 1.3 (0.6–2.1) mg/l following long-term RIC treatment (p = .02) and calprotectin from 477 (95% CI 380 to 600) to 434 (95% CI 354 to 533) ng/ml (p = .03) in patients with CIHF, but not in matched controls. Overall, RIC did not affect circulating markers related to adaptive or innate immunology or cardiac remodeling in patients with CIHF. Among patients with CIHF and N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels above the geometric mean of 372 ng/l, long-term RIC treatment reduced soluble ST2 (n = 9) from 22.0 ± 3.7 to 20.3 ± 3.9 ng/ml following long-term RIC treatment (p = .01). Conclusion. Our findings suggest that long-term RIC treatment has mild anti-inflammatory effects in patients with compensated CIHF and anti-remodeling effects in those with increased NT-proBNP levels. This should be further investigated in a randomized sham-controlled trial.

Meta-analysis of the benefit of sitagliptin treatment in patients with type 2 diabetes complicated with incipient nephropathy.

The purpose of this meta-analysis was to evaluate the evidence of the clinical efficacy and safety of sitagliptin in diabetic patients with incipient nephropathy. PubMed, Ovid, Cochrane library, Chinese National Knowledge Infrastructure, and Wanfang databases were searched in September 2017 to identify randomized controlled trials (RCTs) of sitagliptin in diabetic patients with incipient nephropathy. Study selection, data extraction and study quality assessment were performed independently by two investigators, while disagreements were resolved by a third reviewer. The treatment effect was estimated by calculating the mean difference (MD) or standard mean difference (SMD). Heterogeneity was assessed with the χ2 and I2 tests. Additionally, risk of bias graphs and summaries were used to assess the quality of the included trials. Thirteen RCTs were included in this review; their results suggested that sitagliptin has obvious advantages in lowering the 24-hour urinary albumin excretion [MD, −25.71; 95% confidence interval (CI), −30.75 to −20.66; P<0.00001], serum cystatin C (MD, −0.59; 95% CI, −0.64 to −0.54; P<0.00001), inflammation (MD, −0.81; 95% CI, −1.20 to −0.42; P<0.0001), and total cholesterol (MD, −0.13; 95% CI, −0.22 to −0.03; P=0.009). However, sitagliptin did not appear to influence serum creatinine, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin A1c, or triglyceride levels, although these results may have been influenced by biases in the included trials. The most common adverse effects of sitagliptin were gastrointestinal tract reaction and hypoglycemia, although these symptoms resolved quickly. Sitagliptin appears to be effective in reducing proteinuria, ameliorating renal function, and producing an anti-inflammatory effect in patients with early-stage diabetic nephropathy. The present analysis provides important guidance for the clinical application of sitagliptin.

Effect of fish and olive oil on mitochondrial ATPase activity and membrane fluidity in patients with relapsing-remitting multiple sclerosis treated with interferon beta 1-b.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with increased oxidative stress (OS) and mitochondrial alterations. Fish oil consumption has neuroprotective, antioxidant and anti-inflammatory effects in patients with relapsing-recurrent MS (RR-MS). To evaluate changes in the hydrolytic activity of ATP synthase and mitochondrial membrane fluidity in patients with RR-MS who receive fish oil or olive oil as a dietary supplement. Clinical, controlled, randomized, double-blind trial. Patients consumed fish oil or olive oil for one year. The hydrolytic activity of ATPase and the fluidity of the mitochondrial membrane of platelets were quantified. In patients with RR-MS, a decrease in the fluidity of mitochondrial membranes and an increase in the hydrolytic activity of ATP synthase was observed in comparison with healthy controls. After 6 or 9 months of treatment with fish oil or olive oil, respectively, these values were normalized. The consumption of fish oil and olive oil increases the fluidity of the mitochondrial membranes and decreases the catabolic activity of ATP synthase in platelets from patients with RR-MS.

Dipeptidyl peptidase-4 inhibitors have adverse effects for the proliferation of human T cells

Dipeptidyl peptidase-4 (DPP-4) is a critical molecule for the metabolism of incretins. In addition, DPP-4 is known as CD26, the receptor of T cells, and plays important role in activation of T cells. Recently, DPP-4 inhibitors (DPP4i) are reported to have several immunologic effects beyond glycemic control. DPP4i seem to have anti-inflammatory effects in patients with type 2 diabetes. This might be direct effects on T cells. However, the close mechanism is not clear. To evaluate the possibility, we performed ex vivo assays by using primarily human CD4+ T cells (CD4) and CD8+ T cells (CD8). We purified primary naïve CD4 and CD8 from human peripheral blood. Then, we evaluated the effect of DPP4i on the proliferation of naïve T cells and the cytokine production in ex vivo experiments. The proliferation of CD4 and CD8 were suppressed by adding DPP4i in a dose dependent manner. However, DPP4i did not inhibit cytokine production from CD4. It was revealed by phospho-flow that the T cell receptor (TCR) signaling was attenuated in the presence of DPP4i. Taken together, DPP4i modulated TCR signaling, which contributed to attenuate the proliferation of CD4 and CD8. DPP4i have adverse effects for the proliferation of human T cells.

Colchicine Therapy and Plaque Stabilization in Patients With Acute Coronary Syndrome: A CT Coronary Angiography Study

ObjectivesThe authors sought to evaluate the plaque-modifying effects of low-dose colchicine therapy plus optimal medical therapy (OMT) in patients post-acute coronary syndrome (ACS), as assessed by coronary computed tomography angiography (coronary CTA). BackgroundColchicine therapy has been postulated to have beneficial anti-inflammatory effects in patients with ACS, translating into reduction in future adverse cardiovascular events. However, whether favorable plaque modification underpins this is yet unproven. MethodsIn this prospective nonrandomized observational study of 80 patients with recent ACS (<1 month), patients received either 0.5 mg/day colchicine plus OMT or OMT alone and were followed for 1 year. Our primary outcome was change in low attenuation plaque volume (LAPV), a marker of plaque instability on coronary CTA and robust predictor of adverse cardiovascular events. Secondary outcomes were changes in other coronary CTA measures and in high-sensitivity C-reactive protein (hsCRP). ResultsMean duration of follow-up was 12.6 months; mean age was 57.4 years. Colchicine therapy significantly reduced LAPV (mean 15.9 mm3 [−40.9%] vs. 6.6 mm3 [−17.0%]; p = 0.008) and hsCRP (mean 1.10 mg/l [−37.3%] vs. 0.38 mg/l [−14.6%]; p < 0.001) versus controls. Reductions in total atheroma volume (mean 42.3 mm3 vs. 26.4 mm3; p = 0.28) and low-density lipoprotein levels (mean 0.44 mmol/l vs. 0.49 mmol/l; p = 0.21) were comparable in both groups. With multivariate linear regression, colchicine therapy remained significantly associated with greater reduction in LAPV (p = 0.039) and hsCRP (p = 0.004). There was also a significant linear association (p < 0.001) and strong positive correlation (r = 0.578) between change in LAPV and hsCRP. ConclusionsOur findings suggest, for the first time, that low-dose colchicine therapy favorably modifies coronary plaque, independent of high-dose statin intensification therapy and substantial low-density lipoprotein reduction. The improvements in plaque morphology are likely driven by the anti-inflammatory properties of colchicine, as demonstrated by reductions in hsCRP, rather than changes in lipoproteins. Colchicine may be beneficial as an additional secondary prevention agent in patients post-ACS if validated in future studies.

Pioglitazone ameliorates glomerular NLRP3 inflammasome activation in apolipoprotein E knockout mice with diabetes mellitus

ObjectiveThe NLRP3 inflammasome plays an important role in the pathogenesis of inflammation in diabetic nephropathy (DN). Pioglitazone (PIO) has been found to exert an anti-inflammatory effect in patients with diabetes mellitus, but it is still unclear whether PIO exhibits a similar effect in DN. We aimed to explore the effect and underlying mechanism of PIO on DN, as well as investigate if NLRP3 is a pharmacologic target of PIO.MethodsWe divided 48 apolipoprotein E (apoE) (-/-) mice into 4 groups: apoE (-/-), apoE (-/-) with PIO, diabetic apoE (-/-), and diabetic apoE (-/-) with PIO. Wild type male C57BL/6 mice were used as controls (n = 8 per group). After 8 weeks of PIO treatment, we examined the baseline characteristics and metabolic parameters of each group, and we used enzyme-linked immunosorbent assay (ELISA), western blot, and immunohistochemical staining to evaluate the expression levels of advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE), NLRP3, nuclear factor—kappa B (NF-κB), caspase-1, interleukin (IL)-18, and IL-1β in each group.ResultsCompared to the diabetic apoE (-/-) group, PIO treatment decreased blood glucose, cholesterol, serum blood urea nitrogen (BUN), and creatinine levels. It also depressed the glomerular mesangial expansion. PIO down-regulated expression of AGEs, RAGE, and NF-κB, all of which further depressed NLRP3, caspase-1, IL-18, and IL-1β levels.ConclusionPioglitazone can ameliorate diabetic renal damage, and this effect is related to the inhibition of renal AGE/RAGE axis activation and the down-regulation of NF-κB expression. These effects lead to a decline in NLRP3 levels and downstream secretion of inflammatory cytokines.

Lutein exerts anti-inflammatory effects in patients with coronary artery disease

Background and aimsMany coronary artery disease (CAD) patients exhibit chronic low-grade inflammation. Carotenoids are anti-oxidants with potential anti-inflammatory properties. Here, we first assessed relationships between interleukin (IL)-6 and individual carotenoids in plasma from CAD patients. Based on the results, we proceeded to assess anti-inflammatory effects of one carotenoid, lutein, in peripheral blood mononuclear cells (PBMCs) from CAD patients. MethodsLutein + zeaxanthin (isomers with lutein being dominant), β-cryptoxanthin, lycopene, α- and β-carotene and IL-6 were measured in plasma from 134 patients with stable angina (SA) and 59 patients with acute coronary syndrome. In 42 patients, plasma measurements were also performed 3 months after coronary intervention. PBMCs from SA patients were pre-treated with lutein (1, 5 and 25 μM) for 24 h followed by 24 h incubation ± lipopolysaccharide (LPS). Cell pellets were collected for IL-6, IL-1β and TNF mRNA and intracellular lutein. Cytokine secretion was measured in cell media. ResultsOnly lutein + zeaxanthin were inversely correlated with IL-6 in SA patients at baseline (r = −0.366, p < 0.001) and follow-up (r = −0.546, p < 0.001). Ex vivo, lutein was taken up by PBMCs from SA patients in a dose- and time-dependent manner. Pre-treatment with lutein dose-dependently lowered LPS-induced secretion of IL-6, IL-1β (p < 0.01) and TNF (p < 0.05), and also reduced IL-6, IL-1β and TNF mRNA expression (p < 0.05). ConclusionsClinical findings highlighted the inverse association between lutein and IL-6 in CAD patients. Anti-inflammatory effects of lutein in PBMCs from CAD patients were consolidated in ex vivo experiments. Taken together, these results show that lutein has the potential to play a role in resolution of chronic inflammation in CAD patients.

Fluid resuscitation with lactated Ringer's solution vs normal saline in acute pancreatitis: A triple-blind, randomized, controlled trial.

Little is known regarding the optimal type of fluid resuscitation in acute pancreatitis (AP). The objective of this article was to compare the effect of lactated Ringer's solution (LR) vs normal saline (NS) in the inflammatory response in AP. We conducted a triple-blind, randomized, controlled trial. Patients ≥ 18 admitted with AP were eligible. Patients were randomized to receive LR or NS. Primary outcome variables were number of systemic inflammatory response syndrome (SIRS) criteria at 24 hours, 48 hours and 72 hours and blood C-reactive protein (CRP) levels at 48 hours and 72 hours. Invitro complementary experiments were performed to further explore the interaction between pH, lactate and inflammation. Nineteen patients receiving LR and 21 receiving NS were analyzed. The median (p25-p75) number of SIRS criteria at 48 hours were 1 (1-2) for NS vs 1 (0-1) for LR, p = 0.060. CRP levels (mg/l) were as follows: at 48 hours NS 166 (78-281) vs LR 28 (3-124), p = 0.037; at 72 hours NS 217 (59-323) vs LR 25 (3-169), p = 0.043. Invitro, LR inhibited the induction of inflammatory phenotype of macrophages and NF-κB activation. This effect was not observed when using Ringer's solution without lactate, suggesting a direct anti-inflammatory effect of lactate. Lactated Ringer's is associated with an anti-inflammatory effect in patients with acute pancreatitis.

Anti-inflammatory effect of factor-Xa inhibitors in Japanese patients with atrial fibrillation.

Activated factor-X (FXa) plays an important role not only in the coagulation cascade, but also in pro-inflammatory responses. However, few data exist regarding the anti-inflammatory effect of FXa inhibitors in clinical practice. The aim of this study was to evaluate the anti-inflammatory and anti-atherosclerotic effects of FXa inhibitors in Japanese patients with non-valvular atrial fibrillation (NVAF). Eighty-three patients with NVAF were treated with FXa inhibitors from March 2013 to March 2015 at our institution. Of these, 55 patients who were not pretreated with warfarin or dabigatran (rivarixaban in 23 patients and apixaban in 32) were included in this study. We measured various inflammatory and coagulation markers at baseline and at 6 months after treatment. Plasma concentrations of pentraxin 3 (PTX3) (from 2.45 ± 1.31 to 1.97 ± 1.00ng/mL, p = 0.0009) and fibrin and fibrinogen degradation products (FDP) D-dimer (from 1.18 ± 0.70 to 0.74 ± 0.32μg/mL, p < 0.0001) decreased, while those of TM (from 2.9 ± 0.8 to 3.2 ± 0.9 FU/mL, p = 0.003) increased significantly at 6 months. Interestingly, change of each marker denoted the same tendency in both rivaroxaban and apixaban. In conclusion, the present study suggests that FXa inhibitors have not only an anti-coagulant effect but also anti-inflammatory effects in patients with NVAF. Further large-scale prospective study is necessary to evaluate whether changes in these markers will be associated with a lower risk for future cardiovascular events.

Effects of Pitavastatin on Lipid-rich Carotid Plaques Studied Using High-resolution Magnetic Resonance Imaging

PurposeThis study evaluates the effectiveness of pitavastatin in patients with atherosclerosis. MethodsSixty patients with atherosclerosis with lipid-rich carotid plaques were included and allocated into low-dose (2 mg/d) and high-dose (4 mg/d) pitavastatin groups with 48 weeks of treatment. Total cholesterol, LDL-C, HDL-C, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein (a), and the inflammation-related factors interleukin 6, high-sensitivity C-reactive protein, and homocysteine were determined. High-resolution (3.0-T) magnetic resonance imaging was used to evaluate the lipid core area, plaque thickness, total vessel area, lumen area, wall area, and normalized wall index. FindingsAfter the treatment period, the blood serum values were improved in both groups, but the improvement was significantly better for total cholesterol (P < 0.009), HDL-C, LDL-C, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein (a), and homocysteine (all P < 0.001) in the high-dose group. The high-resolution magnetic resonance images revealed great improvements in both groups, although significantly better for the lipid core area (P < 0.001), plaque thickness (P < 0.001), wall area (P < 0.05), normalized wall index (P < 0.001), and lumen area (P < 0.05) in the HD group. Further analyses revealed a close correlation between lipid-rich plaques and changes in blood lipid components. ImplicationsPitavastatin had significant lipid-lowering and anti-inflammatory effects in patients with atherosclerosis. It also reduced the lipid components and plaques of lipid rich carotid plaques. The effect was obviously stronger in the high-dose than in the low-dose group.

Ivabradine and the anti-inflammatory effects in patients with ischemic heart disease

Ivabradine and the anti-inflammatory effects in patients with ischemic heart disease

Immunologic Effects of Metformin and Pioglitazone Treatment on Metabolic Syndrome and Multiple Sclerosis.

Metabolic syndrome (MetS) is thought to influence several autoimmune diseases, including multiple sclerosis (MS). Anti-inflammatory effects of treatments used for MetS, such as metformin hydrochloride and pioglitazone hydrochloride, have been demonstrated, although clinical evidence supporting use of these treatments in MS is lacking. To determine whether metformin and/or pioglitazone are associated with a reduction in disease activity as measured by brain magnetic resonance imaging in patients with MS and MetS and to evaluate the potential mechanisms underlying this anti-inflammatory effect. A prospective cohort study was conducted from March 1, 2012, to December 30, 2014, at a private MS referral center among 50 obese patients with MS who also developed MetS. Twenty patients received metformin hydrochloride, 850 to 1500 mg/d, and 10 patients received pioglitazone hydrochloride, 15 to 30 mg/d; 20 untreated patients served as controls. Groups were comparable in terms of sex, age, body mass index, Expanded Disability Status Scale score, disease duration, annual relapse rate, and treatment status. Patients were followed up for a mean (SD) of 26.7 (2.7) months (range, 24-33 months). Magnetic resonance imaging of the brain was performed at 6-month intervals, and the presence of new or enlarging T2 lesions or gadolinium-enhancing lesions was registered. Serum leptin and adiponectin levels were measured. The production of cytokines by peripheral blood mononuclear cells was assayed, as were regulatory T-cell numbers and function. Of 50 patients, after 6 months of treatment, 20 patients with MS who were treated with metformin and 10 who received pioglitazone showed a significant decrease in the number of new or enlarging T2 lesions (metformin, 2.5 at study entry to 0.5 at month 24; pioglitazone, 2.3 at study entry to 0.6 at month 24), as well as of gadolinium-enhancing lesions (metformin, 1.8 at study entry to 0.1 at month 24; pioglitazone, 2.2 at study entry to 0.3 at month 24). Compared with controls, both treatments led to a decrease in mean (SD) leptin levels (metformin, 5.5 [2.4] vs 10.5 [3.4] ng/mL, P < .001; pioglitazone, 4.1 [0.8] vs 11.0 [2.6] ng/mL, P < .001) and increase in mean (SD) adiponectin serum levels (metformin, 15.4 [5.5] vs 4.5 [2.4] μg/mL, P < .001; pioglitazone, 12.6 [3.6] vs 4.8 [0.6] μg/mL, P < .001). Mean (SD) number of myelin basic protein peptide-specific cells secreting interferon γ and interleukin (IL)-17 were significantly reduced in patients receiving metformin compared with controls (interferon γ, 30.3 [11.5] vs 82.8 [18.8], P < .001; IL-17, 212.4 [85.5] vs 553.8 [125.9], P < .001). Patients treated with pioglitazone showed significant decreases in the mean (SD) number of myelin basic protein peptide-specific cells secreting IL-6 and tumor necrosis factor compared with controls (IL-6, 361.6 [80.5] vs 1130.7 [149.21], P < .001; tumor necrosis factor, 189.9 [53.4] vs 341.0 [106.0], P < .001). Both metformin and pioglitazone resulted in a significant increase in the number and regulatory functions of CD4+CD25+FoxP3+ regulatory T cells compared with controls (metformin, 6.7 [1.5] vs 2.1 [1.0], P = .001; pioglitazone, 6.9 [0.8] vs 3.0 [0.8], P = .001). Treatment with metformin and pioglitazone has beneficial anti-inflammatory effects in patients with MS and MetS and should be further explored.

Does Pre-Treatment with High Dose Atorvastatin Prevent Microvascular Dysfunction after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome?

Background and ObjectivesThere is controversy surrounding whether or not high dose statin administration before percutaneous coronary intervention (PCI) decreases peri-procedural microvascular injury. We performed a prospective randomized study to investigate the mechanisms and effects of pre-treatment high dose atorvastatin on myocardial damage in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing PCI.Subjects and MethodsSeventy seven patients with NSTE-ACS were randomly assigned to either the high dose group (atorvastatin 80 mg loading 12 to 24 h before PCI with a further 40 mg loading 2 h before PCI, n=39) or low dose group (atorvastatin 10 mg administration 12 to 24 h before PCI, n=38). Index of microcirculatory resistance (IMR) was measured after stent implantation. Creatine kinase-myocardial band (CK-MB) and high sensitivity C-reactive protein (CRP) levels were measured before and after PCI.ResultsThe baseline characteristics were not different between the two patient groups. Compared to the low dose group, the high dose group had lower post PCI IMR (14.1±5.0 vs. 19.2±9.3 U, p=0.003). Post PCI CK-MB was also lower in the high dose group (median: 1.40 ng/mL (interquartile range [IQR: 0.75 to 3.45] vs. 4.00 [IQR: 1.70 to 7.37], p=0.002) as was the post-PCI CRP level (0.09 mg/dL [IQR: 0.04 to 0.16] vs. 0.22 [IQR: 0.08 to 0.60], p=0.001).ConclusionPre-treatment with high dose atorvastatin reduces peri-PCI microvascular dysfunction verified by post-PCI IMR and exerts an immediate anti-inflammatory effect in patients with NSTE-ACS.

Traditional Chinese Medications for Knee Osteoarthritis Pain: A Meta-Analysis of Randomized Controlled Trials.

Traditional Chinese medication (TCM) has analgesic and anti-inflammatory effects in patients with knee osteoarthritis (OA). We conducted the first systematic review of the best quantitative and qualitative evidence currently available in order to evaluate the effectiveness of TCM in relieving pain in knee OA. A comprehensive literature search was conducted using three English and four Chinese biomedical databases from their inception through March 1, 2015. We included randomized controlled trials of TCM for knee OA with intervention durations of at least two weeks. The effects of TCM on pain and other clinical symptoms were measured with the visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The total effectiveness rate, which was used to assess overall pain, physical performance and wellness, was also measured. Two researchers independently extracted data on study design, population characteristics, duration, intervention, outcomes, risk of bias, and primary results. We performed a random-effects meta-analysis when appropriate. We also explored factors that could explain the heterogeneity by conducting subgroup and meta-regression analyses. Twenty-three studies, totaling 2362 subjects, met the eligibility criteria. Treatments were formulated with an average of 8 Chinese herbs and were prescribed based on the traditional Chinese diagnostic method of syndrome differentiation. The mean treatment duration was seven weeks, with oral administration occurring one to three times a day. Compared with non-steroidal anti-inflammatory drugs and intra-articular hyaluronate injections, 18 of the studies showed significantly improved VAS pain scores (Mean Difference [MD] [Formula: see text] 0.56; 95% confidence interval [CI], 0.18 to 0.94; [Formula: see text]), six of the studies showed significantly improved WOMAC pain subscale scores (MD [Formula: see text] 2.23; 95% CI, 0.56 to 3.91; [Formula: see text]), and 16 of the trials showed significantly improved total effectiveness rates (risk ratio [Formula: see text] 1.12; 95% CI, 1.05 to 1.19; [Formula: see text] 0.0003). In addition, TCM showed a lower risk of adverse events than standard western treatments. This evidence suggests that TCM is safe and effective for improving pain, function, and wellness in treatments of knee OA. However, there is inherent clinical heterogeneity (diverse TCM formulations, controls, and treatment regimens) among the included trials. Despite these limitations, the potential analgesic effects of TCM warrant further methodologically rigorous research to determine the clinical implications of TCM on pain management in knee OA.

The Vitamin D Receptors May Function as Antiinflammatory Effects in Patients With COPD

The Vitamin D Receptors May Function as Antiinflammatory Effects in Patients With COPD