The influence of lipoic acid on caveolin-1-regulated antioxidative enzymes in the mouse model of acute ulcerative colitis

AimThis study was undertaken to verify if two-weeks treatment of lipoic acid (LA) influence colon damage and pro-inflammatory cytokine synthesis during DSS-induced acute colitis. Moreover, as LA has anti-oxidative properties, we analyzed its influence on the level of antioxidative enzymes, HO-1 and eNOS, and their regulator- caveolin-1.MethodsLA was administrated to male C57/BALBc mice at a dose of 25 or 50 mg/kg/day (i.p.) for 21 days. Acute colitis was induced by administration of 4% DSS (w/v) in drinking water for 5 days, followed by 2 days of normal drinking water. Mice in LA + DSS groups were treated with LA (25 or 50 mg/kg/day; i.p.) starting 14 days prior to 4% DSS. Control group received saline for 21 days. In the colon tissue we measured myeloperoxidase activity (MPO), IL-1β, IL-6, IL-17A, IL-23 (ELISA method), and tissue level of cav-1, phospho-eNOS, total eNOS and HO-1 (Western blot).ResultsAdministration of DSS significantly increased total colon damage (p < 0.001), myeloperoxidase (MPO) activity (p < 0.05) and pro-inflammatory IL-6 (p < 0.05). There was also a tendency towards higher IL-1β, IL-17A, and IL-23 in the colon. LA alone did not influence total colon damage, MPO activity, and pro-inflammatory cytokines concentration compared to control (p < 0.05). Notably, mice treated with LA and DSS had significantly decreased total colon damage score (p < 0.001), despite augmented colon MPO activity (p < 0.01), but similar (IL-17A) or even significantly higher level (IL-1β, IL-23) as compared to the DSS group (p < 0.05). IL-6 was insignificantly decreased after LA treatment at a dose of 50 mg/kg.In acute colitis there was a tendency towards an increase in cav-1 and HO-1 and a decrease p-eNOS/total eNOS ratio. Moreover, the LA + DSS groups had higher expression of HO-1 and p-eNOS/total eNOS (p < 0.05) compared to the DSS group, and a tendency towards higher cav-1 level. The changes did not depend on LA dose.ConclusionOur study indicated that LA, at lower doses, may influence cav-1-regulated antioxidative enzyme levels (HO-1 and p-eNOS/total eNOS) despite an increase in colon pro-inflammatory cytokine levels during acute colitis. Hence, LA treatment may be – to some extent – beneficial in attenuation of acute colitis.     

Endostatin gene therapy inhibits intratumoral macrophage M2 polarization

BackgroundRenal cell carcinoma (RCC) is a highly vascularized cancer resistant to chemotherapy and radiotherapy. RCC is frequently infiltrated with immune cells, with macrophages being the most abundant cell type. Alternatively activated M2 macrophages are known to contribute to tumor progression. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we investigated the impact of ES gene therapy on the polarization of tumor-associated macrophages (TAMs) in lung metastases from tumor-bearing mice.MethodsBALB/c mice divided into three groups: Normal, Control and ES-treated. Tumor-bearing mice were treated with ES-transduced cells or control cells over ten days. At the end of the study, plasma was collected, and pulmonary macrophages were isolated and used for FACS or RT-PCR. ELISA tests were used to analyze plasma and cell culture supernatant cytokines.ResultsES treatment significantly reduced the levels of anti-inflammatory and pro-angiogenic cytokines, including IL4, IL-10, IL-13 and VEGF. Gene expression of M2 markers, such as IL-10, Arg-1, VEGF and YM-1, declined significantly. Flow cytometry showed a reduction in the number of M2 F4/80 + CD36 + CD206 + CD209+ macrophages and in IL-10 secretion by these cells. Reduced levels of IL-10 were also found in the culture supernatants of the ES-treated group.ConclusionsOur research corroborates previous observations that ES has an important anti-tumoral role. However, aside from promoting interferon-ɤ secretion and an effective T cell response, we show here that this switch is extended to TAMs, complicating the maintenance of pro-tumorigenic M2 macrophages and thus favoring tumor elimination.     

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial

BackgroundCytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS.MethodsThis study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1 g/day) or a matched placebo for a period of 8 weeks.ResultsOne hundred and seventeen subjects were assigned to either curcumin (n = 59) or placebo (n = 58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p < 0.001). In the placebo group, serum levels of TGF-β were decreased (p = 0.003) but those of IL-6 (p = 0.735), TNF-α (p = 0.138) and MCP-1 (p = 0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines.ConclusionResults of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.     

15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy

ObjectiveIn this study, we confirmed a protective effect of 15d-PGJ2 in concanavalin A (ConA)-induced fulminant hepatitis in mice and investigated the potential mechanism.Materials and methodsBalb/C mice were injected with ConA (25 mg/kg) to induce acute fulminant hepatitis, and 15d-PGJ2 (2.5–10 μg) was administered 30 min after the ConA injection. The histological grade, pro-inflammatory cytokine and ROS levels, apoptosis and autophagy activity, the expression of HO-1, Nrf2, JNK and Bcl-2 activity were determined 2, 4, and 8 h after the ConA injection.ResultsFollowing ConA challenge, the expression of cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) was up-regulated. Treatment with 15d-PGJ2 reduced the pathological effects of ConA-induced fulminant hepatitis and significantly reduced the levels of TNF-α, IL-1β and ROS after injection. 15d-PGJ2 inhibited apoptosis and autophagic cell death, facilitated Nrf2 nuclear translocation, increased HO-1 expression and suppressed the JNK activation.Conclusion15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating the anti-oxidative stress factor HO-1 and reducing the production of cytokines and ROS, thereby inhibiting hepatic cell autophagy probably induced by ROS.     

Pro-inflammatory cytokine profile of critically ill septic patients following therapeutic plasma exchange

Severe sepsis involves a generalized inflammatory response, mediated by a number of various cytokines and factors. Plasma exchange (PE) has been proposed as a therapeutic approach to improve survival of patients with severe sepsis and septic shock. The theory is that removing harmful excessive endogenous inflammatory mediators is beneficial. Upon establishment of a diagnosis of severe sepsis, twelve patients received PE plus conventional sepsis treatment. Interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α were assayed before and after each session of PE.ResultsThere were no significant changes in cytokine plasma levels after each PE session compared to pre-procedure levels. Among measured pro-inflammatory cytokines, only the plasma levels of IL-6 before the 2nd and 3rd PE sessions were lower than baseline levels (p = 0.011 and p = 0.012, respectively). All patients tolerated PE therapy well without any adverse effects or homodynamic instability. The results of this study showed that PE does not have a direct and rapid effect on plasma level of TNF-α, IL-1β and IL-6.     

Changes of serum adhesion molecules and cytokines in post-ERCP pancreatitis: Adhesion molecules and cytokines in acute pancreatitis

ObjectivesTo assess the early changes of soluble IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-α, TNF-β, IL-17A, IL-22, soluble (s) P-Selectin, sE-Selectin and sICAM-1 in post-ERCP pancreatitis (PEP).MethodsSingle center, prospective study of 318 ERCP procedures. Serum samples were acquired from all patients prior to ERCP, 6 hours and 24 hours after the procedure. For every PEP case, another patient was chosen as a control, matched for gender, age and time period in which ERCP took place.ResultsTotally, 28 cases and 28 controls were studied. Except for significantly higher IL-1b levels in cases at baseline, no significant differences were observed between cases and controls after Bonferroni corrections. An increase in IL-6 was noted between baseline and 6 h in cases alone (p = 0.016). There was a significant fall in sP-selectin levels at 6 and 24 hours compared to baseline in all patients (corrected p = 0.008 and 0.016 for cases and 0.016 and 0.048 for controls respectively). An increase of sE-selectin in cases was observed between 6 and 24 hours post-ERCP (corrected p = 0.03).ConclusionsSoluble forms of cytokines and adhesion molecules studied seem not to play a major role in PEP.     

Enhanced cortical reperfusion protects coagulation factor XII-deficient mice from ischemic stroke as revealed by high-field MRI

Intrinsic coagulation factor XII deficient (FXII^?/?) mice are protected from ischemic stroke. To elucidate underlying mechanisms we investigated the early ischemic period in vivo by multimodal magnetic resonance imaging (MRI) at 17.6 Tesla.Cerebral ischemia was induced by either transient (60 min) or permanent occlusion of the middle cerebral artery (t/pMCAO). 10 FXII^?/? mice underwent t- , 10 FXII^?/? mice p- and 10 Wildtype (Wt) mice tMCAO. Cerebral blood flow (CBF), diffusion-weighted-imaging (DWI) and T2-relaxometry were measured at 2 h and 24 h after MCAO. Outcome measures were evaluated after motion correction and normalization to atlas space. 2 h after tMCAO CBF reduction was similar in FXII^?/? and Wt mice extending over cortical (CBF (ml/100 g/min) 33.6 ± 6.9 vs. 35.3 ± 4.6, p = 0.42) and subcortical regions (25.7 ± 4.5 vs. 31.6 ± 4.0, p = 0.17). At 24 h, recovery of cortical CBF by +36% was observed only in tMCAO FXII^?/? mice contrasting a further decrease of – 30% in Wt mice after tMCAO (p = 0.02, F_(1,18) = 6.24). In FXII^?/? mice in which patency of the MCA was not restored (pMCAO) a further decrease of ? 75% was observed. Cortical reperfusion in tMCAO FXII^?/? mice was related to a lower risk of infarction of 59% vs. 93% in Wt mice (p = 0.04). Subcortical CBF was similarly decreased in both tMCAO groups (Wt and FXII^?/?) relating to a similar risk of infarction of 89% (Wt) vs. 99% (FXII^?/?, p = 0.17).Deficiency of FXII allows neocortical reperfusion after tMCAO and rescues brain tissue by this mechanism. This study supports the concept of FXII as a promising new target for stroke prevention and therapy.     

Tumor necrosis factor alpha (TNF-α) polymorphisms in Chinese patients with Graves' disease

ObjectivesTumor necrosis factor alpha (TNF-α) may play a central role in the development of Graves' disease (GD). The aim of this study was to investigate the association of TNF-α polymorphisms with GD in Chinese population.Design and methodsGenomic DNA was extracted from peripheral blood lymphocyte of 436 GD patients and 316 control subjects. TNF-α polymorphisms at positions ? 308 (G-308A, rs1800629), ? 238 (G-238A, rs361525), and + 419 (G + 419A, rs3093661) were genotyped.ResultsThe distribution of TNF-α ? 238 and + 419 allelic frequencies between GD and control individuals was significantly different. Both the G alleles of TNF-α ? 238 (OR 2.385, 95%CI 1.359–4.184) and + 419 (OR 2.293, 95%CI 1.303–4.035) SNPs conferred higher risk of GD as compared with A alleles. No significant difference of ? 308 allelic frequency was observed. Further haplotype analysis revealed that the haplotype GGG was associated with an increased risk of GD (OR 1.554, 95%CI 1.125–2.146), whereas the haplotype GAA was found to be protective (OR 0.419, 95%CI 0.239–0.736).ConclusionsThis study demonstrated the association of TNF-α gene with GD in Chinese patients.     

Comparison of the effects of lidocaine pre-administration and local warming of the intravenous access site on propofol injection pain: Randomized,double-blind controlled trial

BackgroundLidocaine reduces pain that occurs upon the intravenous injection of propofol. But, there are few non-pharmacological nursing interventions to reduce propofol injection pain.ObjectiveTo compare the effects of lidocaine pre-administration and local warming of the intravenous access site on propofol injection pain.DesignProspective, double-blind, randomized controlled trial.SettingThe 555 bed, non-teaching National Cancer Center in Kyunggido, South Korea.ParticipantsA total of 96 patients who underwent thyroidectomy under total intravenous general anesthesia with propofol were randomly allocated to the control, lidocaine pre-administration (LA) or local warming (LW) group.MethodsAll three groups received 2% propofol with an effect-site target at 3 μg/mL for induction dose. The control group received 2% propofol with no intervention. The lidocaine pre-administration group received 2% propofol 30 s after 1% lidocaine 30 mg. The local warming group received 2% propofol after warming of the intravenous access site for 1 min using 43 °C forced air. Propofol injection pain was assessed by four-point verbal categorial scoring (VCS), numerical rating scale (NRS) and surgical pleth index (SPI).ResultsPain VCS of the LA group (mean ± SD, 1.11 ± 0.45) was significantly reduced (U = −3.92, p < .001) compared to the control group (mean ± SD, 1.71 ± 0.74). Pain VCS of the LW group (mean ± SD, 0.76 ± 0.44) was significantly reduced (U = −5.17, p < .001) compared to the control group (mean ± SD, 1.71 ± 0.74). Pain VCS of the LW group was significantly reduced compared to the LA group (U = −3.33, p = .001]. Pain NRS of the LA group (mean ± SD, 4.31 ± 2.32) was significantly reduced (mean difference, 1.82; 95% CI, 0.63–3.00; p = .003) compared to the control group (mean ± SD, 6.13 ± 2.39). Pain NRS of the LW group (mean ± SD, 3.06 ± 2.37) was significantly reduced (mean difference, 3.07; 95% CI, 1.63–4.51; p < .009) compared to the control group. There were significant differences in pain NRS between the LA group and the LW group (mean difference, 1.25; 95% CI, 0.09–2.42; p = .035). SPI of the LA group (mean ± SD, 64.1 ± 16.3) was significantly reduced (mean difference control versus LA, 8.36; 95% CI, 1.64–15.1; p = .016) compared to the control group (mean ± SD, 72.5 ± 9.56). SPI of the LW group (mean ± SD, 55.0 ± 16.2) was significantly reduced (mean difference control versus LW, 17.4; 95% CI, 10.8–24.0; p < .001) compared to the control group. There was a significant difference in SPI between the LA group and LW group (mean difference, 9.06; 95% CI, 1.02–17.1; p = .028).ConclusionLocal warming of the intravenous access site by 43 °C forced air for 1 min is slightly more effective in reducing propofol injection pain compared to lidocaine pre-administration.     

Effect of notch1,2,3 genes silicing on NF-κB signaling pathway of macrophages in patients with atherosclerosis

BackgroundNotch and NF-κB signaling pathways both play important roles in the regulation of atherosclerosis (AS). However, the mechanisms of notch and NF-κB signaling pathways on AS are still unclear. In this study, we aimed to investigate the effects of notch1,2,3 genes silicing by siRNA on notch and NF-κB signaling pathways of macrophages in patients with atherosclerosis (AS), so as to seek the treatment of AS from genetic perspective.MethodsPeripheral blood mononuclears of 31 patients with AS were isolated by density gradient centrifugation and transformed by PMA to macrophages. Then macrophages were transfected with notch1-siRNA (notch1-siRNA group), notch2-siRNA (notch2-siRNA group), notch3-siRNA (notch3-siRNA group), negative control siRNA (NC group) and none (control group). RT-PCR and Western blot analysis were applied to assess the expression level of Delta-like-4 (DLL4), Jagged-1 (JAG1), IκBα and P52. Electrophoretic mobility shift assay (EMSA) was used to observe the NF-κB DNA binding activity. Subcellular distributions of NF-κB/P52 were detected through immunofluorescence. mRNA expression levels of TNF-α, IL-6 and IL-6 in macrophages were also determined with RT- PCR. The expression of 20S proteasome was detected by Western blot.ResultsAfter transfected with siRNA, there was no difference in the expression of DLL4, JAG1, IκBα and P52 between NC group and control group (p > 0.05). Compared with NC group and control group, the expression of DLL4, P52 and JAG1 in notch1-siRNA group, notch2-siRNA group and notch3-siRNA group was significantly downregulated (p < 0.05 or p < 0.01, respectively), whereas the expression of IκBα was significantly increased (P < 0.05 or p < 0.01, respectively), especially in notch1-siRNA group. The binding activity of NF-κB DNA was lower in notch1- siRNA group, notch2-siRNA group and notch3-siRNA group compared with NC group and control group (p < 0.05), especially in notch1-siRNA group. The fluorescence intensity of p52 was decreased significantly both in the nucleus and cytoplasm in notch1-siRNA group, notch2-siRNA group and notch3-siRNA group compared with NC group and control group (p < 0.05), which decreased more obviously in the nucleus, especially in notch1-siRNA group. The TNF-α, IL-1 and IL-6 expression of notch1-siRNA group, notch2-siRNA group and notch3-siRNA group was lower compared to NC group and control group (p < 0.05 or p < 0.01, respectively), also especially in notch1-siRNA group. 20S proteasome level was significantly lower in notch1-siRNA group, notch2-siRNA group and notch3-siRNA group than in NC group and control group (p < 0.05 or p < 0.01, respectively), especially in notch1-siRNA group.ConclusionsThere was a positive regulation between Notch and NF-κB signaling pathway in patients with AS. Notch1 may play a more important role than notch2 and notch 3 in the regulation of NF-κB signaling pathway in AS.     

Effect of cardiac rehabilitation on left atrial functions in patients with acute myocardial infarction

BackgroundThe objective of this study was to analyze the effects of cardiac rehabilitation (CR) on the atrial function of patients with acute myocardial infarction (AMI) who had been successfully revascularized through percutaneous coronary intervention (PCI).MethodsForty-two AMI patients having undergone CR were enrolled in this observational study. Assessments were performed before and after 6 weeks of CR. Left atrial strain analysis was carried out by two-dimensional speckle tracking echocardiography. Left ventricular ejection fraction (LVEF) was measured by the biplane Simpson's method. Pulsed-wave Doppler at the tip of mitral valve leaflets enabled us to measure early (E) and late (A) diastolic filling velocities, deceleration time (DT) of early filling velocity and isovolumic relaxation time (IVRT). Left ventricle tissue velocity was measured by tissue Doppler imaging of the lateral mitral annulus (e’) and E/e’ was subsequently calculated. Ratio of E/e’ to left atrium (LA) peak strain was used to estimate LA stiffness.ResultsFollowing CR, LVEF (P = 0.010), LA strain (P < 0.001) and LA stiffness (P = 0.013) all showed improvement, while other parameters remained unchanged.ConclusionPost-AMI cardiac rehabilitation and revascularization by PCI might have favourable effects on LA function.     

Hydrogen sulfide inhibits development of atherosclerosis through up-regulating protein S-nitrosylation

Hydrogen sulfide (H₂S) is an important gaseous signaling molecule that serves many important regulatory roles in physiological and pathophysiological conditions. H₂S exerts an anti-atherosclerotic effect through mediating the biological functions of nitric oxide (NO). However, its mechanism of action is unclear. The purpose of this study is to explore the effect mechanism of H₂S on the development of atherosclerosis with regard to protein S-nitrosylation. A total of 45 male apoE^−/− mice were randomly divided into three groups. Atherosclerosis was induced by Western diet (21% fat and 0.15% cholesterol) with/without administration of a H₂S donor (NaHS) or an endogenous cystathionine γ-lyase inhibitor (d, l-propargylglycine) for 12 weeks. After 12 weeks, plasma lipid and plasma NO levels were measured. Aortic gross lesion area and histopathological features of aortic lesion were determined. Additionally, the level of S-nitrosylated proteins in vascular smooth muscle cells (VSMCs) was detected using immunofluorescence in aorta. Rat VSMCs were performed in an in vitro experiment. Inducible nitric oxide synthase (iNOS) protein expression, NO generation, protein S-nitrosylation, and cell proliferation and migration were measured. We found that H₂S significantly reduced the aortic atherosclerotic lesion area (P = 0.006) and inhibited lipid and macrophage accumulation (P = 0.004, P = 0.002) and VSMC proliferation (P = 0.019) in apoE^−/− mice. H₂S could up-regulate levels of plasma NO and protein S-nitrosylation in aorta VSMCs. However, d, l- propargylglycine had the opposite effect, increasing the lesion area and the content of lipids and macrophages in the lesions of apoE^−/− mice and down-regulating plasma NO levels and protein S-nitrosylation in aorta VSMCs. In vitro experiments, H₂S could significantly reverse the reduction of iNOS expression and NO generation induced by oxidized low-density lipoprotein in VSMCs. Moreover, H₂S could increase the protein S-nitrosylation level of VSMCs in a dose-dependent manner, and the effect could be inhibited by iNOS inhibitors. In addition, proliferation and migration of VSMCs could be inhibited by H₂S in a dose-dependent manner, which could be blocked by an iNOS inhibitor or protein S-nitrosylation removal agent. Our data suggest that H₂S could inhibit the development of atherosclerosis by up-regulating plasma NO and protein S-nitrosylation, thereby inhibiting the proliferation and migration of VSMCs.     

In vitro and in vivo antileishmanial properties of a 2-n-propylquinoline hydroxypropyl β-cyclodextrin formulation and pharmacokinetics via intravenous route

2-n-propylquinoline (2-n-PQ) had shown interesting in vivo antileishmanial activities after administration by oral route on leishmaniasis animal models. However, the lipophilic properties of this compound avoid its use by intravenous route, this route being indicated in cases of severe visceral leishmaniasis with vomiting. Thus, a 2-n-propylquinoline hydroxypropyl beta-cyclodextrin (2-n-PQ-HPC) formulation was set up in this aim. The formulation was active in vitro both on Leishmania donovani axenic and intramacrophage amastigotes with IC₅₀ values at 6.22 ± 0.82 μM and 20.01 ± 0.52 μM, respectively, without any toxicity on macrophages. 2-n-PQ-HPC exhibited similar activity on WT and drug-resistant parasites. Its in vitro interactions with antimonials, amphotericin B and miltefosine were found as additive both in axenic amastigotes and intramacrophage amastigotes. 2-n-PQ-HPC was not able to generate drug resistance after in vitro drug pressure since the resistance index was less than 4. 2-n-PQ-HPC was also active on the L. donovani/Balb/c mice model with an intravenous treatment regimen at 10 mg kg⁻¹ day⁻¹ on 10 consecutive days without hepatic, renal and blood toxicity. The pharmacokinetics of 2-n-PQ in rats showed that after an intravenous treatment of the formulation at 10 mg kg⁻¹, the plasma drug concentrations rapidly declined bi-exponentially with a half-life of 58.7 min and a total clearance of 18.63 l h⁻¹ kg⁻¹. The apparent volume of distribution was higher than the blood volume in rats, indicating that 2-n-PQ was well distributed in tissues, allowing parasite elimination. Such a formulation is worth of further antiparasitic and toxicological evaluations.     

Identification of local angiogenic and inflammatory markers in the menstrual blood of women with endometriosis

The aim of this study was to evaluate the presence of myeloperoxidase (MPO), N-acetyl-β-D-glucosaminidase (NAG), tumor necrosis factor alpha (TNF-α) and vascular endothelial growth factor (VEGF) in peripheral and menstrual blood in women with (n = 10) and without (n = 7) endometriosis. NAG and MPO activities were evaluated by enzymatic methods, whereas TNF-α and VEGF by immunoassay. No significant differences were found for these markers, neither in menstrual nor in peripheral blood between groups. Menstrual blood NAG (P = 0.039) and MPO (P = 0.0117) activities in the endometriosis group were significantly higher than in peripheral blood. NAG and MPO presented positive linear correlation in peripheral (P = 0.07; r = 0.641) and menstrual blood (P = 0.01; r = 0.603). These findings point to the existence of an increased local inflammatory activity in women with endometriosis.     

Application of the sheepskin mattress in clinical care for pressure relieving: a quantitative experimental evaluation

This study aimed at quantitatively evaluating the effectiveness of sheepskin mattress (SSM) in pressure relieving, and then variables of peak pressure (mmHg) (PP), average pressure (AP) and contact area (cm²) (CA) at the total, back, sacrum and heel regions of 18 students supinely lying in a control mattress (CM), standard hospital mattress (SHM), SHM + SSM, SSM + CM and AM + CM were measured and contrasted. Paired-T test with a significant level of .05 shows that: the intervention of SSM significantly increased the total CA of SHM by 395.6 cm² and lowered its PP and AP by 8.8 and 2.0 mmHg respectively; further, the pressure distribution of SSM + CM was superior to that of AM + CM. The reliability of this study, with exception of the heel area, was proven to be good. Overall, the sheepskin mattress is an effective product in pressure reliving.     

Combined creatinine-cystatin C CKD-EPI equation significantly underestimates measured glomerular filtration rate in people with type 2 diabetes mellitus

AimTo evaluate the accuracy of creatinine and cystatin C (cysC) equations to estimate glomerular filtration rate (GFR) in type 2 diabetes mellitus (DM) patients and healthy adults.MethodsCase-control study including 84 patients with type 2 DM and 100 healthy adults with measured GFR (mGFR) ≥ 60 mL/min/1.73 m². GFR was measured by ⁵¹Cr-EDTA and estimated (eGFR) by the following equations using creatinine, cysC or both markers: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Caucasian Asian Pediatrics and Adults (CAPA), CKD-EPI creatinine-cystatin C (CKDEPI-CC), and CKD-EPI cystatin C (CKDEPIcysC). Agreement was evaluated by Bland & Altman analysis.ResultsHealthy individuals were 66% females, aged 38 ± 14 years; they presented mGFR 112 ± 19 mL/min/1.73 m² and eGFR by CKD-EPI, CKDEPI-CC, CKDEPIcysC and CAPA equations, respectively, 108 ± 17, 102 ± 15, 97 ± 16 and 93 ± 16 mL/min/1.73 m². DM group were 50% females, aged 59 ± 19 years and presented mGFR 104 ± 27 and eGFR 87 ± 19, 80 ± 18, 74 ± 20 and 73 ± 18 mL/min/1.73 m², respectively. All equations significantly underestimated mGFR, excepting creatinine-based CKD-EPI in the healthy group. The performance was considerably worse for GFRs above 120 mL/min/1.73 m².ConclusionIn both healthy and type 2 DM patients, cystatin C-based equations, including the combined CKD-EPI creatinine-cystatin equation, failed to improve the accuracy of GFR estimation, especially for normal and high normal GFR values.     

Plasma high sensitivity C-reactive protein and its relationship with cytokine levels in children with newly diagnosed type 1 diabetes and ketoacidosis

BackgroundHigh-sensitivity C-reactive protein (hs-CRP) and pro-inflammatory cytokines have been suggested as sensitive markers of endothelial dysfunction. Our aim was to monitor plasma hs-CRP levels at different time-points and in different degrees of ketoacidosis severity, its association with cytokine levels and its role as a marker of severe ketoacidosis complications.Patients and methodsWe studied in 38 newly diagnosed children with type 1 diabetes and ketoacidosis, aged 7.7 ± 3.1 years, hs-CRP, white blood cell count (WBC), and plasma levels of cytokines IL-1β (interleukin-1β), IL-2, IL-6, IL-8, IL-10, TNF-α (tumor necrosis factor-α) prior to and during DKA management.ResultsOn admission, the levels of WBC, PMN, IL-6 and IL-10 were elevated, but were all reduced within 120 h after ketoacidosis management. In the group with moderate/severe ketoacidosis, but not in mild ketoacidosis, hs-CRP levels were significantly reduced at 24 h (p = 0.021), WBC and IL-6 at 120 h (p = 0.003), while IL-10 was prematurely reduced at 6–8 h (p = 0.008). Moreover hs-CRP was significantly associated with WBC (p = 0.023) and IL-6 (p = 0.028) on admission, with IL-6 (p = 0.002) and IL-8 (p = 0.014) at 24 h and with IL-10 (p = 0.027) at 120 h. The above were not observed in the group with mild ketoacidosis.ConclusionsIn the children with moderate/severe diabetic ketoacidosis of our study, increased levels of hs-CRP and IL-6 were observed, together with leukocytosis and neutrophilia, without the presence of infection. As hs-CRP was found to be strongly associated with the inflammatory IL-6, the prolonged elevation of hs-CRP levels in children with severe ketoacidosis could serve as a marker for the development of its severe complications.     

Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model

Noninvasive monitoring of β-amyloid (Aβ) plaques, the neuropathological hallmarks of Alzheimer's disease (AD), is critical for AD diagnosis and prognosis. Current visualization of Aβ plaques in brains of live patients and animal models is limited in specificity and resolution. The retina as an extension of the brain presents an appealing target for a live, noninvasive optical imaging of AD if disease pathology is manifested there. We identified retinal Aβ plaques in postmortem eyes from AD patients (n = 8) and in suspected early stage cases (n = 5), consistent with brain pathology and clinical reports; plaques were undetectable in age-matched non-AD individuals (n = 5). In APP_SWE/PS1_?E9 transgenic mice (AD-Tg; n = 18) but not in non-Tg wt mice (n = 10), retinal Aβ plaques were detected following systemic administration of curcumin, a safe plaque-labeling fluorochrome. Moreover, retinal plaques were detectable earlier than in the brain and accumulated with disease progression. An immune-based therapy effective in reducing brain plaques, significantly reduced retinal Aβ plaque burden in immunized versus non-immunized AD mice (n = 4 mice per group). In live AD-Tg mice (n = 24), systemic administration of curcumin allowed noninvasive optical imaging of retinal Aβ plaques in vivo with high resolution and specificity; plaques were undetectable in non-Tg wt mice (n = 11). Our discovery of Aβ specific plaques in retinas from AD patients, and the ability to noninvasively detect individual retinal plaques in live AD mice establish the basis for developing high-resolution optical imaging for early AD diagnosis, prognosis assessment and response to therapies.     

Serum levels of pigment epithelium-derived factor,a novel marker of insulin resistance,are independently associated with fasting apolipoprotein B48 levels in humans

ObjectivesFasting apolipoprotein B48 (apoB48) levels are associated with postprandial hyperlipidemia and carotid artery intima-media thickness (IMT), one of the markers of metabolic derangements and atherosclerosis, respectively. However, it remains unknown whether fasting serum levels of apoB48 are independently correlated with insulin resistance and vascular inflammation in humans.Design and methodsThe study involved 315 consecutive outpatients in our hospital (218 males and 97 females) with a mean age of 62.0 ± 9.2. We examined which anthropometric, metabolic and inflammatory variables, including serum levels of pigment epithelium-derived factor (PEDF), a novel marker of insulin resistance were independently associated with fasting apoB48. Moreover, we investigated whether fasting apoB48 levels were correlated with atherosclerotic plaque inflammation evaluated by [¹⁸F]-fluorodeoxyglucose positron emission tomography (FDG-PET). Carotid [¹⁸F]-FDG uptake, an index of vascular inflammation within the atherosclerotic plaques, was measured as blood-normalized standardized uptake value, known as the target-to-background ratio (TBR).ResultsMean serum levels of apoB48, PEDF, carotid IMT and TBR values were 2.77 ± 0.21 μg/mL, 13.45 ± 1.03 μg/mL, 0.71 ± 0.15 mm, and 1.43 ± 0.21, respectively. Univariate analysis revealed that apoB48 levels were weakly, but not significantly associated with TBR (p = 0.057). In multiple stepwise regression analysis, triglycerides (p < 0.001), male (p = 0.039), age (inversely, p = 0.010), uric acid (p = 0.007), medication for diabetes (p = 0.029), and PEDF (p = 0.049) were independently correlated to fasting apoB48 levels (R² = 0.371).ConclusionsThe present study reveals that serum levels of PEDF are independently associated with fasting apoB48 levels, suggesting that PEDF level is a novel biomarker that could reflect postprandial hyperlipidemia in humans.