Serum Myeloperoxidase Activity Research Articles

Effects of a mitochondria-targeted antioxidant (MitoQ) in murine experimental acute pancreatitis

Effects of a mitochondria-targeted antioxidant (MitoQ) in murine experimental acute pancreatitis

Abstract 124: Increased Selective Clearance of Cholesteryl-Ester in Patients with Rheumatoid Arthritis is Reversed by Treatment with Tofacitinib

Inflammation is associated with dysfunctional HDL. Rheumatoid arthritis (RA) is a chronic inflammatory disease with significantly elevated cardiovascular risk in spite of low LDL and HDL cholesterol (C) levels. Using stable isotope methods, we examined underlying metabolic mechanisms for the reduced cholesterol levels in active RA and for the changes with tofacitinib (tofa) treatment. Apolipoprotein and cholesterol kinetics were assessed in 36 RA patients at baseline and following 6 weeks of tofa treatment compared to baseline values in 33 non-RA controls matched for age, gender, and menopausal status. All subjects received constant IV infusions of [3,4] 13 C 2 cholesterol and U- 13 C 6 leucine with collection of fasting blood samples hourly for 22 hours. Whole-body cholesterol efflux and cholesteryl ester (CE) and apolipoprotein production and fractional catabolic rates (FCR) were determined by modeling isotope enrichments. At baseline, total-C, HDL-C, LDL-C, CE and apoA-I concentrations were lower and CE FCR was elevated in RA. No differences were seen in CE production rate, whole body cholesterol efflux or HDL-apoA-I and LDL-apoB production and FCRs. RA patients had elevated serum HDL-SAA, myeloperoxidase and reduced in vitro LCAT activity and mass. Following 6 weeks of tofa therapy, cholesterol and apoAI approached levels of controls and apoB concentrations increased. Tofa treatment reduced CE FCR, increased HDL-apoA-I production rate with no changes in LDL-apoB production rates or LDL-apoB and HDL-apoA-I FCRs. Increased CE FCR in the absence of changes in HDL-apoA-I or LDL-apoB particle clearance suggest increased selective CE uptake, presumably by SR-B1, which was normalized by tofa. Change in CE FCR with treatment was negatively correlated with changes in HDL size and concentration of large HDL particles, but not with LDL size or composition. Change in CE production rate with treatment was positively correlated with change in LCAT mass. This is the first study to evaluate the effect of chronic inflammation on in vivo cholesterol and lipoprotein kinetics in humans. Inflammation increases selective CE uptake explaining the reduced cholesterol levels in RA. Reducing inflammation with tofa restored selective CE uptake to normal rates.

Therapeutic Effects of Alpha Lipoic Acid and Vitamin C on Alveolar Bone Resorption After Experimental Periodontitis in Rats: A Biochemical, Histochemical, and Stereologic Study

Alpha lipoic acid (ALA) and vitamin C (Vit-C) are very important and powerful antioxidants that have been used for the treatment of many diseases. The present study aims to investigate the role of ALA and Vit-C substances in the treatment of alveolar bone resorption in periodontal diseases. Thirty-six male Wistar albino rats were randomly divided into four groups as follows: 1) control rats; 2) rats with experimental periodontitis (PED); 3) rats with PED treated with ALA (ALA); and 4) rats with PED treated with ALA+Vit-C (ALA+Vit-C). PED was simulated by placing ligatures around the neck of teeth for 5 weeks. After ligature removal, the PED group was given a single intragastric dose of 1 mL saline, and the ALA and ALA+Vit-C groups were treated with an intragastric dose of 50 mg/kg ALA and ALA+Vit-C for 15 days, respectively. Levels of serum bone alkaline phosphatase (B-ALP) and myeloperoxidase (MPO) activity in gingival tissues were analyzed. To evaluate the osteoclast activation, expression of activated receptor activator nuclear factor-kappa B ligand (RANKL) and bone density index (BDI) were determined stereologically in the bone sections obtained from the mandibles of the rats. The results showed statistically significant differences between the PED group and groups treated with antioxidant according to B-ALP, MPO, RANKL, and BDI values (P <0.05). ALA and ALA+Vit-C treatments showed beneficial effects on the mesial/distal periodontal bone support at the ligature-induced periodontitis tooth areas. This study shows that ALA and Vit-C treatment provides therapeutic effects on inhibition of alveolar bone resorption and periodontal tissue destruction.

Oxidant/Antioxidant Status in Cases of Snake Bite

BackgroundSnake bites are an important cause of mortality and morbidity worldwide, especially in rural areas. ObjectiveThe aim of this study was to investigate serum paraoxonase (PON), arylesterase (ARLY), ceruloplasmin (Cp), and myeloperoxidase (MPO) activity and lipid hydroperoxide (LOOH) and total sulfhydryl group (-SH) levels in patients with snake venom poisoning. MethodsThe study included 49 patients with snake bite envenomation (Group 1) and 39 healthy volunteers as the control group (Group 2). Plasma PON, ARLY, Cp, and MPO activity and LOOH and -SH levels were measured. Laboratory measurements of 20 patients with snake bite envenomation (Group 3) were performed again after treatment. ResultsPON and ARLY activity and -SH levels were significantly decreased in Group 1 compared with those in Group 2. Cp and MPO activity and LOOH levels were significantly elevated in Group 1 compared with those in Group 2. PON and ARLY activity were significantly elevated in Group 3 compared with those in Group 1. Cp and MPO activity and LOOH levels were significantly decreased in Group 3 compared with those in Group 1. ConclusionsPatients with snake bite envenomation had increased oxidants (MPO and LOOH) and decreased antioxidants (PON, ARLY, and -SH). Results obtained in this study demonstrate that snake bites are associated with a shift to oxidative status. Therapy with antioxidants can lead to an increase in the antioxidant defense system, and thus improvements in clinical symptoms.

Serum myeloperoxidase activity and serum paraoxonase-1 activity in patients with silicosis and observation subjects and their clinical significance

To investigate the serum myeloperoxidase (MPO) activity and serum paraoxonase-1 (PON-1) activity in patients with silicosis and observation subjects and their clinical significance. Seventy-two patients with silicosis (stage I: 30 cases, stage II: 22 cases, stage III: 20 cases) and 37 observation subjects were selected as a case group, and 110 healthy men were selected as a control group. Serum MPO activity was measured by double-antibody sandwich enzyme-linked immunosorbent assay, and serum PON-1 activity was measured by chemical spectrophotometry. Serum MPO activity was significantly higher in the case group than in the control group [(102.1 ± 15.7) U/L vs. (62.4 ± 11.4) U/L, P < 0.01], but serum PON-1 activity was significantly lower in the case group than in the control group [(85.4 ± 15.7) U/ml vs. (125.4 ± 13.7) U/ml, P < 0.01]. Serum MPO activity was significantly lower in patients with stages I, II, and III silicosis than in the observation subjects [(91.3 ± 13.5) U/L, (85.7 ± 14.4) U/L, and (88.6 ± 14.5) U/L vs. (128.4 ± 16.4) U/L, P < 0.01]. Serum PON-1 activity declined as the stage of silicosis increased; serum PON-1 activity was significantly lower in the patients with stages II and III silicosis than in the observation subjects and the patients with stage I silicosis [(70.4 ± 11.4) U/ml and (67.6 ± 13.7) U/ml vs. (101.5 ± 14.0) U/ml and (89.1 ± 10.1) U/ml, P < 0.01]. Serum MPO activity and serum PON-1 activity are valuable for early diagnosis of silicosis and evaluation of patient's condition.

The Role of Xanthine Oxidase in Hemodialysis-Induced Oxidative Injury: Relationship with Nutritional Status

The role of xanthine oxidase (XOD) in patients undergoing chronic hemodialysis treatment (HD) is poorly understood. Geriatric nutritional risk index (GNRI) ≤ 90 could be linked with malnutrition-inflammation complex syndrome. This study measured XOD, myeloperoxidase (MPO), superoxide dismutase (SOD), lipid hydroperoxides, total free thiol groups, and advanced oxidation protein products (AOPP) in 50 HD patients before commencing (pre-HD) and immediately after completion of HD session (post-HD) and in 22 healthy controls. Pre-HD serum hydroperoxides, AOPP, XOD, and SOD were higher and total thiol groups were lower in patients than in controls (P < 0.05, resp.). Compared to baseline values, serum MPO activity was increased irrespective of GNRI status. Serum XOD activity was increasing during HD treatment in the group with GNRI ≤ 90 (P = 0.030) whilst decreasing in the group with GNRI > 90 (P = 0.002). In a multiple regression analysis, post-HD serum XOD activity was independently associated with GNRI ≤ 90 (β ± SE: 0.398 ± 0.151; P = 0.012) and HD vintage (β ± SE: −0.349 ± 0.139; P = 0.016). These results indicate that an upregulated XOD may be implicated in HD-induced oxidative injury contributing to accelerated protein damage in patients with GNRI ≤ 90.

Protective Effect of Phosphatidylcholine on Lipopolysaccharide-Induced Acute Inflammation in Multiple Organ Injury

Soybean polyunsaturated phosphatidylcholine (PC) is thought to exert anti-inflammatory activities and has potent effects in attenuating acute renal failure and liver dysfunction. The aim of this study was to investigate the effects of PC in protecting multiple organ injury (MOI) from lipopolysaccharide (LPS). Six groups of rats (N=8) were used in this study. Three groups acted as controls and received only saline, hydrocortisone (HC, 6 mg/kg, i.v.) or PC (600 mg/kg, i.p.) without LPS (15 mg/kg, i.p.) injections. Other 3 groups, as the test groups, were administered saline, HC or PC in the presence of LPS. Six hours after the LPS injection, blood and organs (lung, liver and kidney) were collected from each group to measure inflammatory cytokines and perform histopathology and myeloperoxidase (MPO) assessment. Serum cytokines (TNF-α, IL-6 and IL-10) and MPO activities were significantly increased, and significant histopathological changes in the organs were observed by LPS challenge. These findings were significantly attenuated by PC or HC. The treatment with PC or HC resulted in a significant attenuation on the increase in serum levels of TNF-α and IL-6, pro-inflammatory cytokines, while neither PC nor HC significantly attenuated serum levels of IL-10, anti-inflammatory cytokine. In the organs, the enhanced infiltration of neutrophils and expression of ED2 positive macrophage were attenuated by PC or HC. Inductions of MPO activity were also significantly attenuated by PC or HC. From the findings, we suggest that PC may be a functional material for its use as an anti-inflammatory agent.

Effect of Echium amoenum Fisch. et Mey a Traditional Iranian Herbal Remedy in an Experimental Model of Acute Pancreatitis

Acute pancreatitis is a morbid inflammatory condition of pancreas with limited specific therapy. Enhanced oxidative stress plays an important role in induction and progression of acute pancreatitis. So reducing oxidative stress may relieve this pathogenic process. Echium amoenum Fisch. and Mey has been implemented in Iranian folk medicine for several centuries. Antioxidant, analgesic, immunomodulatory, and anxiolytic properties of E. amoenum suggest that this plant may have beneficial effects in the management of acute pancreatitis. The aim of this study was to evaluate the protective effect of petals of E. amoenum extract (EAE) on a murine model of pancreatitis. Acute pancreatitis was induced by five intraperitoneal (i.p.) injection of cerulein (50 μg/kg) with 1h intervals which was characterized by pancreatic inflammation and increase in the serum level of digestive enzymes, in comparison to normal mice. EAE (100, 200, and 400 mg/kg) was administered i.p., 30 minutes before induction of pancreatitis. Pretreatment with EAE (400 mg/kg) reduced significantly the inflammatory response of cerulein-induced acute pancreatitis by ameliorating pancreatic edema, amylase and lipase serum levels, proinflammatory cytokines, myeloperoxidase activity, lipid peroxidation and pathological alteration. These results show that EAE attenuates the severity of cerulein-induced acute pancreatitis with an anti-inflammatory, immunomodulatory and antioxidant effects.

Biochemical Study of Myeloperoxidase in Blood and it's Relation to Atherosclerosis

The research included studying of myeloperoxidase in human serum, The normal value of myeloperoxidase activity was found (27.71±0.74 U/ml) in control group for both sexes at (19-70 year), with no sex difference, while it was affected by age and smoking. The study also showed a significant increase in myeloperoxidase activity (38.95±1.01 U/ml) in serum of atherosclerosis patients group for both sexes at (31-80 year) in comparison with control, on the other hand, myeloperoxidase activity in serum of patients group was affected by sex, age, smoking and the intake of statins. The results also indicated a significant increase in the concenteration of total cholesterol, low density lipoprotein -cholesterol, C-reactive protein and troponin. While a significant decrease in high density lipoprotein -cholesterol, total protein, albumin, globulin, chloride and arylesterease in serum of patients group in comparison with control. Correlation study was performed between the measured biochemical parameters and myeloperoxidase activity in serum by linear correlation coefficient, The results also showed that there was a significant positive correlation between myeloperoxidase activity and troponin in atherosclerosis patients. Also, the research included the isolation of myeloperoxidase from normal human serum using different biochemical techniques, including: precipitation by ammonium sulfate, dialysis, gel filtration chromatography on sephadex G-100. The results predicted that spicefic activity and the number of fold of purification were (8.865 U/ml) and (25) respectively for partially purified enzyme. Furthermore, the comparative molecular weight of the partially isolated myeloperoxidase was (151±1.8 kDa) using gel filtration chromatography. The results were predicted also that myeloperoxidase containing heam group, zinc and calcium elements, which indicated that the enzyme is glycoproteins type. The study showed that the optimum conditions of myeloperoxidase were obtained at the first minute using sodium citrate (0.1 M) as buffer at pH (5.0), at a temperature (45 ºC) and (12 mM) of ο-dianisidin as substrate. It was found that Vmax and Km have the values of (24.27 U/ml) and (2.443 mM) respectively. Ethylene diamine tetraacetic acid, sodium azide, 2-mercaptoethanol and sodium chloride showed inhibition on the activity of myeloperoxidase, where sodium azide had more inhibition in the activity and in an irreversible non competitive inhibition type.

Clinical Study of Myeloperoxidase and some Biochemical Parameters in Diabetes Mellitus Patients

The research included a clinical studying of Myeloperoxidase enzyme and some biochemical parameters in serum. The normal value of Myeloperoxidase activity in control group was (30.27 U/ml) for both sexes in age group (15-77 year). The results showed that Myeloperoxidase activity in the serum of control group was not affected by sex and marital status, while it was affected by age, smoke and body mass index. The study also showed a significant decrease in serum Myeloperoxidase activity of Diabetes Mellitus patients group (19.17 U/ml) for both sexes at in age group (31-80 year) comparison with control, and the enzyme activity in serum of patients group was not affected by sex, marital status and type of disease, while it was affected by age, smoke and body mass index. The results indicated a significant decrease in serum Myeloperoxidase activity in type Ι, type Π Diabetes Mellitus male in comparison with control male, and enzyme activity in type Ι, type Π Diabetes Mellitus female in comparison with control female. Also the results showed a significant decrease in enzyme activity in age groups of type Ι, type Π patients in comparison with age groups of control, so that in comparison the body mass index for type Ι patients with control. The results also predicted a significant decrease in serum Myeloperoxidase activity in type Ι, type Π Diabetes Mellitus smokers in comparison control smokers, and nonsmokers in comparison control nonsmokers. The study also showed a significant increase in the level of Glucose, Total Cholesterol and Low Density lipoprotein, while a significant decrease in the level of Total protein, Albumin, Globulin and High Density lipoprotein in serum of type Ι Diabetes Mellitus patients in comparison control. Also noticed a significant increase in the level of Glucose, Triglyceride, Total Cholesterol, Low Density lipoprotein, Very Low Density lipoprotein, while a significant decrease in the level of Total protein, Albumin, Globulin and High Density lipoprotein in serum of type Π Diabetes Mellitus patients in comparison control.

Inflammatory Response Patterns in ICSI Patients: A Comparative Study Between Chronic Anovulating and Normally Ovulating Women

The aim of this study was to evaluate inflammatory response in chronic anovulating infertility women undergoing intracytoplasmic sperm injection. Thirteen infertile women with chronic anovulation and 23 normally ovulating women were prospectively evaluated. N-acetylglucosaminidase (NAG), myeloperoxidase (MPO), monocyte chemoattractant protein 1 (MCP-1), and C-reactive protein (CRP) concentrations were evaluated in serum and follicular fluid. Women with chronic anovulation presented higher NAG and MPO activity in follicular fluid when compared with normally ovulating women. Serum MPO activity was higher in the control group compared to the chronic anovulation group. Both serum and follicular fluid CRP concentrations were higher in women with chronic anovulation in comparison with the control group. Higher MCP-1 follicular fluid concentrations and serum levels of CRP were associated with the occurrence of ovarian hyperstimulation syndrome. Patients with chronic anovulation exhibited significantly higher follicle macrophage/neutrophil activation as well as unspecific inflammatory response by comparison with normally ovulating women.

Haematological and innate immune responses in Puntius sarana: normal range and seasonal variation

Abstract A study was conducted to measure the normal ranges, seasonal and annual variations in haematological and immune parameters of juvenile healthy Puntius sarana (weighing 75–100 g) during three major seasons over two consecutive years. Significantly (P&lt;0.05) lower serum myeloperoxidase and ceruloplasmin activities, superoxide production, plasma glucose level, packed cell volume and haemoglobin concentration were detected in winter as compared to the summer season. However, serum lysozyme activity, antiprotease activity, total erythrocyte count (TEC) and TLC profiles were consistent during all seasons. The reference intervals (25th–75th) of each parameter were estimated and a range was established. The annual changes in immune parameters with minimum and maximum values were measured and a significant variation was noticed in myeloperoxidase, antiprotease, total protein levels and TEC over two consecutive years. The lower levels in haematological and innate immune status of fish during winter possibly indicate a higher disease risk period for the species.

Serum myeloperoxidase activity and oxidative stress in patients with acute brucellosis

The role of infection in the pathogenesis of atherosclerosis has been increasingly discussed. Previous studies have suggested that increased myeloperoxidase activity plays an important role in the pathogenesis of atherosclerosis. The aim of this study was to investigate the serum myeloperoxidase activity and catalase activity along with lipid hydroperoxide (LOOH) levels in patients with acute brucellosis. Thirty-two patients with brucellosis and 33 healthy controls were enrolled. Serum myeloperoxidase activity, catalase activity and LOOH levels were determined. Serum myeloperoxidase activity and LOOH levels were significantly higher in patients with brucellosis than controls (p<0.05, p<0.001), while catalase activity were significantly lower (p<0.001). LOOH levels were found to be significantly positively correlated with MPO activity (r=0.297, p=0.016) in patients. These results indicate that increased myeloperoxidase activity and decreased catalase activity is associated with increased oxidative stress, which may have a role in atherosclerotic processes in brucellosis patients.

Elevated Serum Myeloperoxidase Activities are Significantly Associated with the Prevalence of ACS and High LDL-C Levels in CHD Patients

Recent researches have shown that myeloperoxidase (MPO) is a potential inflammatory risk factor for coronary heart disease (CHD). In the present study, the possible associations of MPO with acute coronary syndrome (ACS), low density lipoprotein cholesterol (LDL-C) and other risk factors in CHD patients were investigated. Five hundred thirty-six CHD patients [363 ACS and 173 stable angina pectoris (SAP)] and 181 non-CHD patients confirmed by coronary angiography were enrolled in this study. The association study was performed by logistic regression analysis. ACS patients had significantly higher MPO activities than SAP and non-CHD patients (p < 0.001). The area under the receiver operating characteristic (ROC) curve of MPO for diagnosing ACS was 0.84 (95% CI: 0.80-0.88, p < 0.001). The optimal cut-off value (sensitivity; specificity) of MPO was 164.77 ng/mL (79.1% and 82.1%). LDL-C (III versus I tertile, OR: 3.24, 95% CI: 1.67-6.29, p = 0.001) and ACS (yes versus no, OR 2.74, 95% CI: 1.71-4.39, p < 0.001) were significantly associated with elevated serum MPO activities, which had the highest odds ratio in quantitative and qualitative variables, respectively. There were significant increase trends in the prevalence of ACS and high LDL-C levels from I to III MPO tertile, which were 46.4% and 8.9% for I, 68.0% and 31.5% for II, 88.8% and 59.8% for III tertile, respectively (p < 0.001). The present study provides epidemiological evidence that elevated serum MPO activities are significantly associated with the prevalence of ACS and high LDL-C levels in CHD patients, and MPO may be a potential early warning marker for ACS.

Protective effect of andrographolide against concanavalin A-induced liver injury

This study was designed to investigate the hepatic protective effect and the molecular mechanisms of andrographolide in concanavalin A-induced liver injury model. Results showed that andrographolide (Ag) attenuated concanavalin A (Con-A)-induced liver injury and inhibited hepatocyte apoptosis. Further results showed that oxidative stress response genes were significantly elevated during the pathogenesis induced by Con-A. Meanwhile, gadolinium chloride and N-acetyl-L-cysteine (NAC) treatment, which inactivates Kupffer cells or reduces reactive oxygen species, respectively, prevented the liver injury. So the messenger RNA levels of the oxidative response genes mentioned above were detected, and the following results showed that Ag treatment reduced their expression. Besides, serum lactate dehydrogenase and myeloperoxidase activity was significantly reduced by Ag. Finally, Ag treatment did not further reduce serum tumor necrosis factor-α production compared with NAC treatment alone. Thus, our results indicate that Ag prevents Con-A-induced liver injury and reduced the hepatic oxidative stress response. The hepatic protective effect of Ag indicates that Ag supplementation may be beneficial in the treatment of immune-mediated liver injury.

Garlic Extract Ameliorates Renal and Cardiopulmonary Injury in the Rats with Chronic Renal Failure

Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species and cytokine release. We aimed to investigate the possible protective and antioxidant effects of aqueous garlic extract (AGE) in a rat model of CRF. Male Sprague-Dawley rats were randomly assigned as either CRF group with 5/6 reduction in the renal mass or sham-operated control group. CRF group received either saline or AGE (250 mg/kg/day/1 mL) orally for 3 weeks. At the end of the 3 weeks, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) activity, and TNF-α and IL-1β levels were measured in the serum samples, while malondialdehyde (MDA), glutathione (GSH) levels, and myeloperoxidase (MPO) activity were determined in the kidney, lung, and heart samples. CRF caused significant decreases in tissue GSH, which were accompanied with significant increases in MDA levels and MPO activities, while the circulating levels of the LDH activity, creatinine, BUN, TNF-α, and IL-1β were elevated. AGE treatment alleviated CRF-induced oxidative changes in the injured tissues, while CRF-induced elevations in the blood levels of the pro-inflammatory cytokines and LDH were reduced. In conclusion, CRF-induced oxidative tissue injury occurs via the activation of pro-inflammatory mediators and by neutrophil infiltration into tissues and that the protective effects of garlic on CRF-induced injury can be attributed to its ability to inhibit neutrophil infiltration and pro-inflammatory mediators. These findings suggest that garlic, as a supplementary to diet, may have a potential therapeutic use in delimitating the systemic oxidant effects of CRF on remote organs.

Serum myeloperoxidase and adenosine deaminase activities in polycystic ovary syndrome

Objective: To evaluate serum myeloperoxidase (MPO) and adenosine deaminase activities and to investigate whether there was a correlation between these and sex hormones, and lipids in polycystic ovary syndrome. Design and methods: Forty-five women with polycystic ovary syndrome and 40 healthy controls were included in this study. Leukocyte counts, serum MPO and adenosine deaminase activities, and high-sensitive C-reactive protein (hs-CRP), sex hormone and lipid levels were assessed. Results: Leukocyte counts and serum MPO activities were higher (p < 0.01 and p < 0.05, respectively) and there was a significant correlation between serum adenosine deaminase and hs-CRP level in women with polycystic ovary syndrome (r = 0.853, p < 0.01). Serum MPO and adenosine deaminase levels did not correlate with sex hormones or lipid profiles in these patients. Conclusion: Polycystic ovary syndrome may involve an inflammatory process by increasing serum MPO activity independent of sex hormones, body mass index and lipid profiles.

Advanced glycation end products in diabetic cardiomyopathy: An alternative hypothesis

Advanced glycation end products (AGEs) are chemically heterogeneous structures and include such specific forms as carboxy (methyl)lysine, pentosidine and others, and were previously measured in heart failure patients as serum AGE, skin AGE, and AGE in cardiomyocytes and vascular cells within the heart. The study by Nozynski et al.1 adds to this body of knowledge as it examines AGE expression directly in explanted hearts: 22 with cardiomyopathy (CMP) and diabetes (DM), 114 with CMP without DM, 20 healthy heart donors, and 14 with DM without CMP. One of the main findings in this study was equally increased AGE accumulation in intramyocardial veins, arterioles and venules in diabetic subjects with and without CMP. This is an unexpected finding, since it is believed that AGE may contribute to mechanical (stiffness) as well as molecular (inflammation) changes contributing to myocardial dysfunction. However, we would like to offer a hypothesis for this unexpected result not raised by the authors. The diabetic cohort without CMP consists of patients who died in the first 24 hours after admission to the intensive care unit due to cerebral injury, and therefore represent a very sick cohort. It is well established that trauma is associated with a high burden of systemic inflammation, oxidative stress and for instance serum myeloperoxidase activity is highest in the first 6 hours in non-surviving patients with head trauma2. Moreover, inflammation, reactive oxygen species and myeloperoxidase enzymatic activity promotes protein glycation and AGE formation as rapidly as in 60 minutes3. AGE formation in human tissue is a dynamic process as recently demonstrated by the rapid decline of AGEs in myeloperoxidase-positive inflammatory cells in carotid endarterectomy tissue after treatment with simvastatin prior to surgery4. We speculate that the increased accumulation of AGE in the heart of diabetic subjects without CMP found in the study by Nozynski et al. may be largely explained by the circumstances of this study. The authors cannot exclude the possibility of rapid AGEs formation as a result of enhanced oxidative stress and myeloperoxidase activity associated with lethal trauma in this diabetic control group without CMP. Further studies examining AGE in cardiac tissue are needed to dissect the role of AGE in heart failure. Most importantly, more in-depth analysis of the specific AGEs and their concentrations in these tissues must be performed. Indeed, the concept of the heterogeneous nature of AGEs is underscored in Nyzynski’s study population and design.

Selection for improved resistance to Aeromonas hydrophila in Indian major carp Labeo rohita: Survival and innate immune responses in first generation of resistant and susceptible lines

Selection for disease resistance in fish may be performed directly on basis of survival data obtained in controlled challenge trials, or indirectly using information from immunological or molecular markers linked to differential survival. In the present study, several key innate immune parameters were measured in aeromoniasis resistant and susceptible lines of rohu Labeo rohita to assess their suitability as immune markers for use in indirect selection for increased resistance. Experimental infection with Aeromonas hydrophila (9.55 × 10 6 cfu g −1 fish) through the intraperitoneal route produced higher survival in the resistant line (73.33%) as compared to the susceptible line (16.67%). Blood and liver tissue samples from both lines were collected to study some of the innate immune parameters and immune-related gene expression. The respiratory burst activity of blood phagocytes, serum myeloperoxidase activity and ceruloplasmin level were significantly ( p < 0.05) higher in the resistant line compared to the susceptible line. Lower level of blood glucose and serum natural haemolysin titre were marked in the resistant line as compared to the susceptible line. No significant difference was measured in total serum protein concentration, antiprotease activity and bacterial agglutinin level between two lines, while the expression of transferrin, complement factor C3 and TLR 22-like transcripts were significantly ( P < 0.05) higher in liver samples of the susceptible line. However, no such difference was found in β 2-microglobulin and lysozyme gene expression between lines. The study demonstrated the possibility of using some of the investigated innate immune parameters as indirect marker traits for selection for improved resistance to aeromoniasis in rohu.

Serine proteases mediate inflammatory pain in acute pancreatitis

Acute pancreatitis is a life-threatening inflammatory disease characterized by abdominal pain of unknown etiology. Trypsin, a key mediator of pancreatitis, causes inflammation and pain by activating protease-activated receptor 2 (PAR(2)), but the isoforms of trypsin that cause pancreatitis and pancreatic pain are unknown. We hypothesized that human trypsin IV and rat P23, which activate PAR(2) and are resistant to pancreatic trypsin inhibitors, contribute to pancreatic inflammation and pain. Injections of a subinflammatory dose of exogenous trypsin increased c-Fos immunoreactivity, indicative of spinal nociceptive activation, but did not cause inflammation, as assessed by measuring serum amylase and myeloperoxidase activity and by histology. The same dose of trypsin IV and P23 increased some inflammatory end points and caused a more robust effect on nociception, which was blocked by melagatran, a trypsin inhibitor that also inhibits polypeptide-resistant trypsin isoforms. To determine the contribution of endogenous activation of trypsin and its minor isoforms, recombinant enterokinase (ENK), which activates trypsins in the duodenum, was administered into the pancreas. Intraductal ENK caused nociception and inflammation that were diminished by polypeptide inhibitors, including soybean trypsin inhibitor and a specific trypsin inhibitor (type I-P), and by melagatran. Finally, the secretagogue cerulein induced pancreatic nociceptive activation and nocifensive behavior that were reversed by melagatran. Thus trypsin and its minor isoforms mediate pancreatic pain and inflammation. In particular, the inhibitor-resistant isoforms trypsin IV and P23 may be important in mediating prolonged pancreatic inflammatory pain in pancreatitis. Our results suggest that inhibitors of these isoforms could be novel therapies for pancreatitis pain.