MPO Concentrations Research Articles

Umbilical Cord Stem Cell Lysate: A New Biologic Injection for Treatment of Temporomandibular Joint Inflammation

PurposeProgressive degenerative diseases that affect the TMJ, such as osteoarthritis (OA), juvenile idiopathic arthritis (JIA), and idiopathic condylar resorption (ICR), are characterized by ongoing loss of articular fibrocartilage, subchondral bone remodeling, and synovitis.1 These structures can be preserved by reducing inflammation and thereby slowing the progressive catabolic cellular processes underlying the pathogenesis of these conditions.1 Given that mesenchymal stem cells and their derivatives have now been employed in the treatment of numerous systemic pro-inflammatory conditions with promising outcomes, the goal of this study was to investigate the anti-inflammatory effects of human umbilical cord perivascular mesenchymal cells (HUCPVCS) and a cell lysate (CL) derived therefrom in an established hind-paw model of carrageenan-induced inflammation, then further evaluate their anti-inflammatory potential in a model of temporomandibular joint inflammation.2 MethodsFemale CD1 mice (n = 8 per group) underwent hind-paw injections of carrageenan for induction of inflammation, followed by treatment with saline (control), 1% CL, or HUCPVCS. Tissue edema was assessed by measuring paw circumference prior to injections and 48 hours later. Hind paws were excised post-sacrifice to assess MPO and TNF-alpha concentrations. Male Wistar rats (n = 8 per group) underwent intra-articular TMJ injections of either saline followed by carrageenan (control), 1% CL, or viable HUCPVCS. Rats were sacrificed at 4 and 48 hours post-injection. Articular tissue as well as synovial aspirates were obtained for histologic analysis and to assess leukocyte infiltration. The effects of CL and HUCPVCS on TNF-alpha and MPO concentrations were analyzed using 1-way ANOVA and post-hoc Tukey tests for pairwise comparisons between means of groups, while linear regression modeling was utilized to assess differences in leukocyte infiltration. ResultsFor the results, 1% CL and HUCPVC-treated hind paws demonstrated a reduction tissue edema and significantly lower concentrations of MPO and TNF-alpha 48 hours post-injection compared to controls. Treated TMJs demonstrated lower concentrations of leukocytes in the synovium post-Injection compared to controls. Histologic analysis of the TMJs from treatment groups demonstrated a reduction in signs of acute inflammation when compared to controls. ConclusionHUCPVCs and their CL derivatives reduced tissue edema, levels of pro-inflammatory mediators, leukocyte infiltration, while modulating signs of TMJ inflammation histologically.

Chitosan-chelated zinc modulates ileal microbiota, ileal microbial metabolites, and intestinal function in weaned piglets challenged with Escherichia coli K88.

This study was to investigate the effects of chitosan-chelated zinc on ileal microbiota, inflammatory response, and barrier function in weaned piglets challenged with Escherichia coli K88. Piglets of the chitosan-chelated zinc treatment (Cs-Zn; 100mg zinc + 766mg chitosan/kg basal diet, from chitosan-chelated zinc) and the chitosan treatment (CS, 766mg chitosan/kg basal diet) had significantly increased ileal villus height and the ratio of villi height to crypt depth. CS-Zn group piglets had a higher abundance of Lactobacillus in the ileal digesta, while the abundance of Streptococcus, Escherichia shigella, Actinobacillus, and Clostridium sensu stricto 6 was significantly decreased. The concentrations of propionate, butyrate, and lactate in the CS-Zn group piglets were significantly increased, while the pH value was significantly decreased. Furthermore, the concentrations of IL-1β, TNF-α, MPO, and INF-γ in the ileal mucosa of the CS-Zn and the H-ZnO group (pharmacological dose of 1600mg Zn/kg basal diet, from ZnO) were significantly lower than those of the control group fed with basal diet, and the mRNA expression of TLR4, MyD88, and NF-κB of the CS-Zn group was also reduced. In addition, the mRNA expression of IGF-1 was increased, the protein expression of occludin and claudin-1 was enhanced, while the mRNA expression of caspase 3 and caspase 8 was decreased in the CS-Zn group. These results suggest CS-Zn treatment could help modulate the composition of ileal microbiota, attenuate inflammatory response, and maintain the intestinal function in weaned piglets challenged with Escherichia coli K88. KEY POINTS: • Chitosan-chelated zinc significantly modulated ileal microbiota. • Chitosan-chelated zinc can improve ileal health. •The ileal microbiota plays an important role in host health.

89Zr-pro-MMP-9 F(ab\u2032)2 detects colitis induced intestinal and kidney fibrosis

Intestinal fibrosis is a common complication of inflammatory bowel disease but remains difficult to detect. Matrix metalloproteases (MMPs) have key roles in fibrosis and are therefore potential targets for fibrosis detection. We determined whether immunoPET of F(ab′)2 antibody fragments targeting MMPs detects colitis induced colonic fibrosis. Mice were administered 2% dextran sulfate sodium treated water for 1 cycle (inflamed) or 3 cycles (fibrotic), or were untreated (control). Colonic and kidney collagen, innate cytokine, MMPs and fecal MPO concentrations were analyzed by multiplex/ELISA. α-pro-MMP-9 F(ab′)2 fragments were engineered and conjugated to 89Zr for PET imaging, ex-vivo Cherenkov analysis and bio-distribution. Colonic innate cytokine concentrations and fecal myeloperoxidase were increased in inflamed mice but not fibrotic mice, while collagen concentrations were increased in fibrotic mice. MMPs were increased in inflamed mice, but only pro-MMP-9 remained increased in fibrotic mice. 89Zr-pro-MMP-9 F(ab′)2 uptake was increased in the intestine but also in the kidney of fibrotic mice, where collagen and pro-MMP-9 concentrations were increased. 89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal fibrosis and associated kidney fibrosis.

Antiedematogenic and Anti-Inflammatory Activity of the Monoterpene Isopulegol and Its β-Cyclodextrin (β-CD) Inclusion Complex in Animal Inflammation Models.

Isopulegol (ISO) is an alcoholic monoterpene widely found in different plant species, such as Melissa officinalis, and has already been reported to have a number of pharmacological properties. Like other terpenes, ISO is a highly volatile compound that is slightly soluble in water, so its inclusion into cyclodextrins (CDs) is an interesting approach to increase its solubility and bioavailability. Thus, our aim was to evaluate the antiedematogenic and anti-inflammatory activity of isopulegol and a β-cyclodextrin–isopulegol inclusion complex (ISO/β-CD) in rodent models. For the anti-inflammatory activity evaluation, antiedematogenic plethysmometry and acute (peritonitis and pleurisy), as well as chronic (cotton pellet-induced granuloma) anti-inflammatory models, were used. The docking procedure is used to evaluate, analyze, and predict their binding mode of interaction with H1 and Cox-2 receptors. The animals (n = 6) were divided into groups: ISO and ISO/β-CD, negative control (saline), and positive control (indomethacin and promethazine). ISO and ISO/β-CD were able to reduce acute inflammatory activity by decreasing albumin extravasation, leukocyte migration, and MPO concentration, and reducing exudate levels of IL-1β and TNF-α. ISO and ISO/β-CD significantly inhibited edematogenic activity in carrageenan- and dextran-induced paw edema. Moreover, both significantly reduced chronic inflammatory processes, given the lower weight and protein concentration of granulomas in the foreign body granulomatous inflammation model. The results suggest that the inclusion of ISO in β-cyclodextrins improves its pharmacological properties, with the histamine and prostaglandin pathways as probable mechanisms of inhibition, and also reinforces the anti-inflammatory profile of this terpene.

Anti-inflammatory effects of ginsenoside Rg3 on the hypertrophic scar formation via the NF-κB/IκB signaling pathway in rabbit ears.

The anti-inflammatory effects of Rg3 on the hypertrophic scar (HS) formation remain relatively obscure. Hence, this study aimed to explore the anti-inflammatory effects of Rg3 on the HS formation using a rabbit ear model and we assessed the involvement of the NF-κ B/IκB signaling pathway in this process. We constructed the Newland white rabbit ear HS model and treated it with Rg3. Using histological analyses, we evaluated scar hypertrophy based on the hematoxylin and eosin staining. The degree of scarring was evaluated using the scar elevation index (SEI). In addition, collagen I and collagen III expression levels were assessed by immunohistochemistry, while fibroblast apoptosis was examined using TUNEL assays. While MPO, IL-1β, IL-6, and TNF-α concentrations were quantified using ELISA, NF-κB and p-IκB activities were respectively measured using electrophoretic mobility shift assays (EMSAs) and western blots. SEI measurements and histological characteristics revealed that Rg3 could suppress the HS formation. Moreover, Rg3 could inhibit the HS formation by decreasing collagen I and collagen III synthesis and inducing fibroblast apoptosis. Besides, Rg3 treatment markedly inhibited the inflammatory cytokine production and ameliorated neutrophil infiltration. Notably, this study revealed that Rg3 inhibited NF-κB activation and the activity of p-IκB. Furthermore, this study suggested that the ability of Rg3 to decrease the scar formation might result from its ability to inhibit inflammation by modulating the NF-κB/IκB signaling. Overall, the findings of this study could support the use of Rg3 to prevent the HS formation.

Crosstalk between inflammation and coagulation in pancreatitis-induced renal injury in experimental and clinic acute pancreatitis

Background: The pathogenesis of organ failure in AP is complicated. Proteases, inflammatory cells and its mediators which secreted from pancreas into blood circulation and impairment of blood coagulation, microcirculations are explaining as the main contributed factors for organ failure in AP. Acute renal failure is a serious early complication in patients with AP significantly increases mortality rates. Materials and Methods: For the experiment were used 42 Wistar albino rats. We examined 98 patients with moderately severe AP, and 57 patients with severe AP. Disorders of kidney function were in 48 patients. We determined the creatinine level, indicators of hemostasis and inflammation. Results: In the kidneys characteristic of experimental acute necrotizing pancreatitis were: edema, inflammatory infiltration of the parenchyma, parenchymal congestion and dilation of capillaries, tubular necrosis. The concentration of creatinine in serum is increase at 86.86%. It was noticed that the level of creatinine significantly directly correlated with the concentration of MPO and activity of iNOS in the tissue of pancreatic, amylase in serum blood, reverse with the concentration of H2S in serum. Renal failure in rats was accompanied by a hypercoagulation. Analysis of the relationship of inflammation and hemostasis in patients with acute pancreatitis and renal dysfunction is accompanied by decreased of activated partial thrombolastin time, increased of thrombin time, fibrinogen concentration, D-dimers level, and level of soluble fibrin-monomer complexes, lack of activity of antithrombin III, increased synthesis of C-reactive protein, excessive production of proinflammatory cytokines IL-2, IL-6, and TNF-α. Was shown a direct correlation between severity of renal failure (SOFA score) and concentrations of IL-6, CRP, D-dimers, soluble fibrin-monomer complexes, and duration of thrombin time. Conclusion: The mechanism of the acute renal injury following severe necrotizing pancreatitis is complicated. The inflammatory cascades and hypercoagulative state are initiated this pathological process.

Experimental study of ginsenoside Rg3 in the treatment of acute radiation proctitis in rat models

Objective To evaluate the efficacy of ginsenoside Rg3(GRg3) in the treatment of acute radiation proctitis in rat models. Methods On the 7th day after 21.5 Gy irradiation, 100 rats were divided into the control group (normal saline, n=20), GRg3 group (gavage of 20 mg/kg, 40 mg/kg and 80 mg/kg GRg3, n=20 for each dose) and Smecta mixture enema group (n=20). After 2 weeks, all rats were anesthetized with chloral hydrate (3 ml/kg) and approximately 5 ml of blood sample was collected from the abdominal aorta prior to sacrifice. The rectal tissues were taken and prepared for detection of Bax and NF-κB contents and HE staining to observe the pathological changes of the rectal tissues. After the blood samples were centrifuged, the supernatants were collected for ELISA to detect the serum levels of IL-2, IL-6, TNF-α and MPO in each group. Results In the GRg3 group, the serum inflammatory cytokines, serum MPO concentration and the concentration of Bax and NF-κB in the intestinal tissues of rats were decreased along with the increasing dose of GRg3. These parameters in the high-dose GRg3 group were significantly lower than those in the saline group (all P 0.05), suggesting that GRg3 exerted good therapeutic effect on acute radiation proctitis in rat models. Conclusions GRg3 can significantly reduce the concentration of inflammatory cytokines, Bax and NF-κB in the intestinal tissues of rat models with acute radiation proctitis, which is more efficacious than the normal saline. GRg3 can be used to treat acute radiation proctitis in rat models. Key words: Ginsenoside Rg3; Acute radiation proctitis; Rat

Cesarean section increases sensitivity to oxazolone-induced colitis in C57BL/6 mice.

Children born by cesarean section (CS) have an increased risk of developing inflammatory bowel disease (IBD), possibly due to skewed microbial colonization during birth and consequently impaired bacterial stimulation of the developing immune system. The aim of this study was to investigate the association between CS and experimental colitis in a murine model of IBD. It was hypothesized that CS aggravates colonic inflammation due to a change in gut microbiota (GM) composition. C57BL/6 mice, delivered by CS or vaginal delivery (VD), were intra-rectally challenged with oxazolone at 8 weeks of age and monitored for colitis symptoms. The results showed that CS delivered mice experienced an increased body weight loss and colon weight, together with higher colonic concentrations of TNF-α and MPO compared with VD mice. Increased infiltration of inflammatory cells was present in CS delivered mice, as well as a downregulation in expression of the gut integrity genes occludin and tight junction protein 1 indicative of an impaired barrier function. The GM from CS delivered mice without colitis partly contributed to the increase in colitis symptoms when inoculated into germ-free recipient mice. In conclusion, CS increased sensitivity to oxazolone induced colitis in mice.

Expression of eosinophilic cationic protein in neutrophils and its effect on objective evaluation of nasal inflammation

Objective:The aim of this study is to explore the expression of ECP in the neutrophils and its impact on the evaluation of nasal inflammation.Method:Neutrophils and eosinophils in nasal secretions were collected and stained with ECP immunohistochemistry to observe the staining of ECP in different cells. The concentration of ECP and MPO in nasal secretion were detected of 32 patients with allergic rhinitis (AR group), 29 patients with chronic rhinosinusitis without nasal polyps and allergic rhinitis (CRSsNP group), and 21 healthy people (control group). The percentage of neutrophils and eosinophils were calculated and analyzed as well.Result:ECP could be found in both eosinophils and neutrophils with immunohistochemical staining. The expression of ECP is much stronger in eosinophils than that in neutrophils. The ECP and MPO concentration in the nasal secretions of AR group and CRSsNP group were significantly higher than that in control group (P<0.000 1), and the ECP concentration in AR group and CRSsNP group had no difference. The expression of ECP in the AR group was not different from that in CRSsNP group, but the expression of MPO was significantly lower than that in CRSsNP group(P<0.000 1).Conclusion:ECP is expressed in neutrophils, and which is likely to have influence on the objective evaluation to nasal inflammation. Combining with the expression of ECP and MPO, we can make a more accurate judgment of local inflammation.

Effect of transpulmonary pressure-guided positive end-expiratory pressure titration on lung injury in pigs with acute respiratory distress syndrome

To investigate the effect of positive end-expiratory pressure (PEEP) guided by transpulmonary pressure or with maximum oxygenation-directed PEEP on lung injury in a porcine model of acute respiratory distress syndrome (ARDS). The porcine model of ARDS was induced in 12 standard pigs by intratracheal infusion with normal saline. The pigs were then randomly divided into two groups who were ventilated with the lung-protective strategy of low tidal volume (VT) (6 ml/kg), using different methods to titrate PEEP level: transpulmonary pressure (TP group; n = 6) or maximum oxygenation (MO group; n = 6). Gas exchange, pulmonary mechanics, and hemodynamics were determined and pulmonary inflammatory response indices were measured after 4 h of ventilation. The titrated PEEP level in the TP group (6.12 ± 0.89 cmH2O) was significantly lower than that in the MO group (11.33 ± 2.07 cmH2O) (P < 0.05). The PaO2/FiO2 (P/F) after PEEP titration both improved in the TP and MO groups as compared with that at T0 (when the criteria for ARDS were obtained). The P/F in the TP group did not differ significantly from that in the MO group during the 4 h of ventilation (P > 0.05). Respiratory system compliance and lung compliance were significantly improved in the TP group compared to the MO group (P < 0.05). The VD/VT in the TP group was significantly lower than that in the MO group after 4 h of ventilation (P < 0.05). Central venous pressure increased and the cardiac index decreased significantly in the MO group as compared with the TP group (P < 0.05), whereas oxygen delivery did not differ significantly between the groups (P > 0.05). The pulmonary vascular permeability index and the extravascular lung water index in the TP group were significantly lower than those in the MO group (P < 0.05). The TP group had a lower lung wet to dry weight ratio, lung injury score, and MPO, TNF-, and IL-8 concentrations than the MO group (P < 0.05). In summary, in a pig model of ARDS, ventilation with low VT and transpulmonary pressure-guided PEEP adjustment was associated with improved compliance, reduced dead space ventilation, increased cardiac output, and relieved lung injury, as compared to maximum oxygenation-guide PEEP adjustment.

Probiotics ameliorate renal ischemia-reperfusion injury by modulating the phenotype of macrophages through the IL-10/GSK-3β/PTEN signaling pathway.

After renal ischemic reperfusion injury, a series of pathological changes, such as impaired intestinal barrier function, intestinal flora, and endotoxin translocation, are caused by intestinal ischemia and hypoxia, which then trigger systemic inflammatory responses and affect the condition and prognosis of the patients. In this study, a rat model of ischemia-reperfusion injury was established by examining changes in renal function, intestinal barrier function, inflammatory index, oxidative stress, and macrophage phenotypes to evaluate the effect of probiotic VSL#3 on renal ischemia-reperfusion injury. The results showed that, after VSL#3 intervention, the levels of BUN, Scr, Cys C, PRO, and NGAL were all significantly decreased compared with the I/R group, while the value of Ccr showed a significant increase. In addition, the concentrations of MPO, IL-1β, TNF-α, IL-6, ED-1, and PCNA were all significantly lower than those in the I/R group, while the levels of endotoxin, DOA, and D-lactic acid were significantly decreased. Furthermore, the proteins associated with intestinal barrier functions, such as ZO-1, Occludin, and Claudin-1, were significantly upregulated compared with the I/R group. Overall, the VSL#3 intervention group was able to maintain the required number of beneficial intestinal flora and to inhibit the proliferation of harmful bacteria. At the same time, the VSL#3 intervention could also prevent the decrease in the levels of CAT, GSH-PX, H2O2, and T-SOD, while downregulating the expression of Keap1 and Nrf2. After the intervention with the VSL#3, the expression levels of CD68 and CD86 proteins were significantly decreased, while the expression levels of CD163 and CD206 proteins were significantly higher. Further experiments confirmed that the expression of iNOS protein was significantly decreased after the VSL#3 intervention, and the expression of Arg-1 and Ym1 proteins was significantly increased. The VSL#3 was able to induce high expressions of p-GSK-3β and p-PTEN proteins, while the use of IL-10 antibody impaired the effect of the VSL#3. In summary, this research confirms that probiotics can alleviate renal dysfunction caused by ischemia and reperfusion by protecting the intestinal barrier function and maintaining the functions of intestinal flora. The pathway screening test of this study suggests that IL-10/GSK3β/PTEN may play an important role in the process of the prototypic VSL#3 inducing M2 transformation of macrophages.

Multivariate analysis of inflammatory endotypes in recurrent nasal polyposis in a Chinese population.

Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a challenging clinical problem due to its propensity for recurrence. However, data on the frequency of CRSwNP recurrence after surgery in China are rare. 78 CRSwNP patients undergoing functional endoscopic sinus surgery were followed-up for 8 years and classified into recurrent and non-recurrent groups. A cluster analysis of the CRSwNP based on inflammatory endotypes was performed, and the endotypes were secondarily matched with clinical phenotypes. The recurrence rate of CRSwNP in Southwest China was 21.8% over 8 years post-surgery. The CRSwNP was classified into 4 clusters: cluster 1 (higher expression of IL-5, IgE, and ECP and high positivity rate for SE-IgE); cluster 2 (higher concentrations of IL-6, IL-8 and MPO); cluster 3 (higher concentrations of TNF-alpha; and IFN-gamma); and cluster 4 (higher expression of IL-17). Cluster 1 (type-2 inflammation) exhibited the highest recurrence rate, co-morbid asthma and atopy. Notably, the ECP/MPO ratio increased significantly in patients with non-type-2 recurrent CRSwNP 8 years after the first surgery. Different inflammatory endotypes of CRSwNP exhibited clearly different prognoses. The type-2 subgroup had high recurrence and co-morbid asthma rates comparable to the rates reported in Western countries.

Inhibition of Myeloperoxidase and MPO Reverses Microvascular Insulin Resistance in High-Fat Diet (HFD)-Fed Rats

Chronic, low-level inflammation underlies much of the vascular and metabolic insulin resistance associated with HFD. Release of MPO by leukocytes may be an early contributor to the inflammatory process and endothelial dysfunction that accompanies HFD feeding. Plasma MPO concentrations are increased in both human obesity and diabetes and HFD-fed rats. However, the impact of MPO on microangiopathy and its relation to insulin resistance is unclear. We tested whether AZD5904 (a potent, irreversible inhibitor of MPO, AstraZeneca) improves endothelial function and vascular insulin responses in insulin resistant, adult male SD rats fed a HFD (60% calories from fat) for 2 weeks. HFD fed rats received vehicle (n=8) or AZD5904 (75 µmol/kg/day, n=10) via an Alzet Mini pump for 2 weeks. A 3rd group of rats (n=8, vehicle alone) were fed a chow diet for 2 weeks. After 2 weeks of HFD or control diet, rats were fasted overnight and received a 2-hour euglycemic insulin clamp (3 mU/kg/minutes). Hindleg muscle microvascular perfusion was assessed using contrast-enhanced ultrasound and insulin-stimulated steady-state whole body glucose disposal was determined. Insulin infusion increased muscle microvascular perfusion by 2-3 fold in chow fed rats (p&amp;lt;0.05). HFD feeding abolished insulin-induced microvascular recruitment in muscle, and decreased insulin-mediated glucose disposal by ∼45% (p&amp;lt;0.01). Simultaneous treatment with AZD5904 fully restored insulin-mediated muscle microvascular perfusion (p&amp;lt;0.05) in HFD rats, but did not improve insulin-stimulated glucose disposal in HFD-fed rats. We conclude that inhibition of MPO with AZD5904specifically reverses muscle microvascular insulin resistance in HFD rats. This implicates MPO as a significant contributor to HFD-induced endothelial inflammation and suggests a role for MPO inhibition to improve microvascular complications in patients with vascular insulin resistance. Disclosure E. Barrett: None. K.W. Aylor: None. W. Chai: None. L. Gan: Employee; Self; AstraZeneca.

DAN MYELOPEROxIDASE) DAN DISFUNGSI ENDOTEL (ASIMETRIK DIMETILARGININ) DI KEGEMUKAN (OBESITAS)

Obesity is a pathological condition in which there is an excess body fat due to imbalance energy expenditure. Its association with oxidative stress could cause other metabolic disorders such as endothelial dysfunction, atherosclerosis, and cardiovascular disease. Theaim of this study was to assess the correlation of oxidative stress (F2-Isoprostane, Superoxide dismutase and Myeloperoxidase) andendothelial dysfunction (Asymmetric dimethylarginine) which happened in central obese men. A cross sectional study was carried outin 62 central obesity male subjects with ages range between 30−60 years. The researcher determined SOD activity, concentration ofMPO as well as ADMA. In this study was found a significant correlation of F2-Isoprostan (r = 0.333, p = 0.008), MPO (r = 0.386; p = 0.008) and ADMA but not with SOD. The elevated concentration of F2-Isoprostane occur 3.5 times (p = 0.02; 95%; CI = 1.19–10.19), elevated MPO occur 3.7 times (p = 0.023; 95%; CI = 1.16–11.56) while combination of elevated F2-Isoprostane-MPO occur6.7 times (p = 0.011; 95%; CI = 1.33-33.24) will increase the risk of endothelial dysfunction. There was a significant correlation of oxidative stress with endothelial dysfunction, and the increase concentration of F2-Isoprostane and MPO indicates the occurrence of endothelial dysfunction in central obesity.

Urinary myeloperoxidase to creatinine ratio as a new marker for monitoring treatment effects of urinary tract infection

ObjectiveWe want to determine whether urinary myeloperoxidase to creatinine ratio could be served as a new marker for monitoring treatment effects of urinary tract infection or not. MethodsA total of 328 patients suspected of UTI were enrolled in present study. Patients been received antibiotic therapy within two weeks were excluded (n = 26). Patients with urine contaminated specimens (n = 49) and negative urine culture results (n = 96) were also excluded, the remaining culture positive subjects (n = 157) were followed up for 7 to 14 days, finally, a total of 49 subjects were followed up and further divided into cure (n = 35) and none-cure (n = 14) subgroups according to urine culture results. MPO concentration was determined by immunoturbidimetric method and creatinine level was measured by creatinine enzyme method. Two sided P values < 0.05 were considered statistically significant. ResultsUrinary MCR level between before and after antibiotic treatment of cure group were (1437.1 ± 1777.9 vs.48.3 ± 59.3, t = 4.608, P = 0.001), respectively. Urinary MCR level between before and after antibiotic treatment of none-cure group were (1633.1 ± 2168.7 vs. 999.4 ± 1708.0, t = 1.809, P = 0.094), respectively. ConclusionsUrinary MCR could be served as a promising marker for monitoring treatment effects of urinary tract infection.

Effect of simvastatin on sensorial, motor, and morphological parameters in sciatic nerve crush induced-neuropathic pain in rats.

The present study compares the effects of a low and high doses of simvastatin in a model of peripheral neuropathy by evaluating sensorial, motor, and morphological parameters. First, male Wistar rats were orally treated with vehicle (saline, 1mL/kg), simvastatin (2 and 80mg/kg) or morphine (2mg/kg, s.c.), 1h before 2.5% formalin injection. Neuropathic pain was induced by crushing the sciatic nerve, and mechanical and cold allodynia, nerve function, histology, MPO and NAG concentrations, as well as mevalonate induced-nociception were evaluated. Animals were orally treated with vehicle, simvastatin, or gabapentin (30mg/kg) for 18days. Simvastatin (2 and 80mg/kg) reduced the inflammatory pain induced by formalin, but failed to decrease the paw edema. Mechanical allodynia was reduced by the simvastatin (2mg/kg) until the 12thday after injury and until the 18thday by gabapentin. However, both simvastatin and gabapentin treatments failed in attenuated cold allodynia or improved motor function. Interestingly, both doses of simvastatin showed a neuroprotective effect and inhibited MPO activity without altering kidney and hepatic parameters. Additionally, only the higher dose of simvastatin reduced the cholesterol levels and the nociception induced by mevalonate. Our results reinforce the antinociceptive, antiallodynic, and anti-inflammatory effects of oral simvastatin administration, which can strongly contribute to the sciatic nerve morphology preservation. Furthermore, our data suggest that lower and higher doses of simvastatin present beneficial effects that are dependent and independent of the mevalonate pathway, respectively, without causing signs of nerve damage.

Role of Vital Trace Elements in Nanocurcumin-Centered Formulation: A Novel Approach to Resuscitate the Immune System.

The present paper described the immunomodulatory potential of novel nanocurcumin-based formulation enriched with trace elements and vitamins on cyclophosphamide-induced immunosuppression in rat model. Major immune-related assays were monitored such as hemagglutination assay, delayed-type hypersensitivity (DTH) reaction, cellular immune response, IgG, IgE, IgM, cerebrospinal fluid biomarkers, hematological study, antioxidant profile, and lipid biomarkers. Chemical characterization of novel formulation showed retention time (R t ) 18.98 of curcumin, while LC-MS data revealed the presence of the curcumin mass at m/z 369.01 [M + H]+ (calculated for C21H21O6+, 369.13). This novel formulation exhibited significantly (p≤0.001) increased primary and secondary antibody titer by 72.41% and 33.25%, respectively, while DTH response being improved by 87.50% (p≤0.01). However, CD4+, CD8+, and CD28+ counts were significantly (p≤0.05) increased by 76.46%, 68.21%, and 19.29%, respectively, while the concentrations of IgE, IgM, and IgG were significantly (p≤0.05) increased by 40%, 28.43%, and 38.75%, respectively. CSF biomarkers analysis showed a decreased level of corticosterone, dopamine, serotonin, and tau protein by 29.38%, 51.73%, 29.93%, and 4.87%, respectively. Antioxidant enzymes such as CAT, GPx, and SOD were increased by 43.74%, 49.00%, and 40.84%, respectively, and non-enzymatic component, GSH, was increased by 55.52%. Similarly, free radical LPO was significantly (p≤0.05) decreased by 40.37%, and acute inflammatory marker, MPO concentration, was reduced by 31.14%, compared with the disease control group. In addition, supportive hematology and lipid profile analysis showed promising results with improved overall animal profile. Thus, trace elements in novel formulation can be used in the various pharmacological activities and as dietary supplement due to its wide properties.

Expression and significance of serum hepatocyte growth factor and myeloperoxidase in patients with obstructive sleep apnea hypopnea syndrome

Objective:The aim of this study is to explore the expression and significance of serum HGF and MPO in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) in adults. Method:Ninety-six cases of OSAHS patients diagnosed by PSG were divided into 3 groups: Heavy, medium and light according to the range of AHI; 32 cases of outpatients were healthy persons as the control group. The serum HGF and MPO were determined by ELISA; HGF and MPO were measured after comprehensive treat with CPAP in patients with severe OSAHS, and the correlation between HGF, MPO and PSG were analyzed. Result:①With the severity of OSAHS patients increased, the serum levels of HGF and MPO increased gradually (F=119.006, 25.138; P<0.05); The concentration of HGF and MPO in each group showed that there was no significant difference between the two groups compared with the control group (P>0.05); The rest of the two groups were significantly different (P<0.05). ②There was no correlation between serum levels of HGF, MPO, BMI and age in OSAHS patients (P>0.05). The change of serum concentration was positively related to the two. All were negatively correlated with AHI, and positively correlated with LSaO₂ (P<0.05). ③LSaO₂ of 32 patients with severe OSAHS of has significantly increased after 3 months of comprehensive treatment, AHI and peripheral blood HGF, MPO levels were significantly reduced (P<0.05). The amylin and myeloperoxidase concentrations of blood after 6 months of treatment were significantly lower than those of 3 months after treatment (P<0.05), which still increased compared with the control group. Conclusion:Surgery combined with CPAP treatment can significantly reduce the degree of hypoxia and cardiovascular damage in OSAHS patients, which was significantly correlated with the treatment time. Combined detection of serum HGF and MPO concentrations in patients with OSAHS has a certain clinical value in judging the condition and curative effect and evaluating the cardiovascular damage.

Determination and significance of serum MPO and amylin in adult patients with OSAHS after short-range noninvasive positive pressure ventilation

Objective:The aim of this study to investigate the determination and significance of serum MPO and amylin in adult patients with OSAHS after short-range noninvasive positive pressure ventilation. Method:Eighty-seven OSAHS patients were divided into severe group (30 cases), moderate group (30 cases) and mild group (27 cases) according to the AHI range. Twenty-seven outpatient health persons were selected as the control group. Serum amylin and myeloperoxidase were measured by ELISA; Amyloid and myeloperoxidase were reassessed in 30 patients with severe OSAHS after 6 months of combined therapy, and the relationship between amylin, myeloperoxidase and PSG was analyzed. Result:①With the severity of OSAHS patients increased, the serum amylin and myeloperoxidase levels gradually increased (F=22.486, 19.755;P<0.01); There was no significant difference in MPO and amylin concentration between the mild group and the control group (P>0.05), and the other groups were significantly different from each other (P<0.01). ②There was no correlation among serum amylin and myeloperoxidase level and BMI and age in OSAHS patients (P>0.05); and a negative correlation with SaO₂, and AHI was positively correlated (P<0.01). ③After 3 months of CPAP treatment, LSaO₂ increased which the AHI and peripheral blood MPO, amylin levels lower than before in 30 patients (P<0.05); The amylin and myeloperoxidase concentrations of blood after 6 months of treatment were significantly lower than those of 3 months after treatment (P<0.05), which still increased compared with the control group. Conclusion:The determination of serum amylin and MPO in patients with OSAHS has a certain reference value in predicting the condition and curative effect of diabetes mellitus and insulin resistance. CPAP treatment can significantly reduce the degree of hypoxiapatients and cardiovascular damage in OSAHS patients, which was significantly correlated with the treatment time.

Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study

Background and aimsMyeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. MethodsLevels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. ResultsAdjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12–2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27–2.85). ConclusionsIncreased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.