Long-term (up to 20 years) effects of 50-Hz magnetic field exposure on immune system and hematological parameters in healthy men

ObjectivesThe relationship between exposure to 50-Hz magnetic fields and human health is of increasing interest since associations have been found in brain cancer in adults and childhood leukemia. In this study we investigate the possible chronic (up to 20 years) effects of exposure to magnetic fields in humans.Design and methodsWe examined the nocturnal profiles of red blood cells, hemoglobin, hematocrit, platelets, mean platelet volume, total white blood cells, lymphocytes, monocytes, eosinophils, basophils, neutrophils, Ig (Immunoglobulin) A, IgM, IgG, CD (cluster of differentiation) 3, CD4, CD8, natural killer cells, B cells, total CD28, CD8 + CD28+, activated T cells, interleukin (IL)-2, IL-6, and IL-2 receptor, in 15 men exposed chronically and daily for a period of 1–20 years, in the workplace and at home, to a 50-Hz magnetic field. The weekly geometric mean of individual exposures ranged from 0.1 to 2.6 μT. The results are compared to those of 15 unexposed men age-matched, with the same synchronization and physical activity that served as controls (individual exposures ranged from 0.004 to 0.092 μT). Blood samples were taken hourly from 20:00 h to 08:00 h.ResultsExposure over a long period and on a daily basis to magnetic fields resulted in no changes in the levels or patterns of hematological and immune system variables.ConclusionsOur data show that a long-term exposure to 50-Hz magnetic fields does not affect the hematological and immune system functions or their profile in healthy men, at least for the variables studied, and suggest that magnetic fields have no cumulative effects on these functions.     

Ketamine delays mortality in an experimental model of hemorrhagic shock and subsequent sepsis

BackgroundIn previous studies ketamine was reported to improve survival and decrease serum interleukin-6 (IL-6) concentration after sepsis alone and after burn injury followed by sepsis. The aim of this study was to determine whether ketamine alters survival and/or IL-6 after hemorrhagic shock alone or hemorrhagic shock followed by sepsis.Materials and methodsRats were subjected to hemorrhagic shock with or without subsequent Gram-negative bacterial sepsis and were either treated with ketamine 5 mg/kg or were not treated. Blood was sampled for IL-6 determination prior to hemorrhage, at the completion of resuscitation, and at 6 and 30 h later. Mortality was recorded for 7 days following hemorrhage or hemorrhage + sepsis.ResultsAfter hemorrhage + sepsis the time to median mortality was significantly later in the ketamine-treated group (36 h) than in the control group (12 h). At 12 h the survival rate of the ketamine-treated group (100%) was significantly higher than in the control group (55%). There were no significant differences between groups with respect to IL-6 or 7-day survival after either hemorrhage + sepsis or hemorrhage alone.ConclusionKetamine improved 12 h survival and delayed mortality after hemorrhage + sepsis without significantly altering IL-6, and did not alter survival or IL-6 after hemorrhage alone.     

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.     

Quantifying loss of CD34+ cells collected by apheresis after processing for freezing and post-thaw

Introduction: CD34⁺ cells collected for autologous bone marrow transplantation (BMT) are usually quantified in the apheresis product after collection, but the necessity to repeat these measures post-thaw is controversial.Methods: We examined the loss of CD34⁺ cells after collection, preparation for freezing and post-thaw in apheresis products collected for BMT.Results: Median number of CD34⁺ cells collected per unit was 1.61 × 10⁶/kg, viability: 97–100%. This number decreased to 1.38 × 10⁶/kg, viability: 96–100% before freezing and was 1.17 × 10⁶/kg post-thaw. Viability decreased to 86–98%. The relative loss of viable PBHPC showed an inverse correlation with the ratio “CD34⁺ cells/total nucleated cells” (r = ?0.45; p = <0.0005). This relative loss was largest in patients with Hodgkin’s lymphoma.Conclusion: Cryopreservation and thawing of PBHPCs in leukapheresis products provokes a small but significant stem cell loss. So, quantification of viable CD34⁺ cells post-thaw is important, especially in poorly mobilizing patients. Besides, the ratio “CD34⁺ cells/total nucleated cells” after leukapheresis is an important parameter for prediction of neutrophil recovery after BMT.     

Peripheral blood progenitor cell collection without close monitoring of peripheral blood CD34+ cells: A feasible strategy for multiple myeloma or pre-treated Non-Hodgkin’s Lymphoma patients mobilized with low-dose cyclophosphamide plus G-CSF

BackgroundDaily monitoring of peripheral blood CD34+ cells may not be necessary for all patients with hematologic malignancies for adequate peripheral blood progenitor cells (PBPC) mobilization and harvesting. We therefore designed a regimen for PBPC mobilization in patients with multiple myeloma or pre-treated Non-Hodgkin’s lymphoma based on a combination of low-dose cyclophosphamide (Cy) plus granulocyte colony-stimulating factor (G-CSF) without daily monitoring of peripheral blood CD34+ cells.Study design and methodsA prospective study was performed on patients with multiple myeloma (n = 22) or pre-treated Non-Hodgkin’s lymphoma (n = 17) whose PBPC were harvested according to the following regimen: 1.5 g/m² Cy at day 1, 12 μg/kg/day G-CSF from day +7 to +11 avoiding daily monitoring of peripheral blood CD34+ cells and two consecutive leukapheresis at days +12 and +13. The optimum threshold of 2 × 10⁶ CD34+ cells per kg was established.ResultsThe proportion of patients with higher CD34+ cell yield after two leukapheresis was similar: multiple myeloma (16/22–72.7%) and Non-Hodgkin’s lymphoma (12/17–70.6%). Exposure to radiotherapy and greater than two prior chemotherapy regimens were significantly associated with lower yield in multiple myeloma (p = 0.002) and Non-Hodgkin’s lymphoma patients (p = 0.002), respectively.ConclusionOur data suggested that adequate yields of CD34+ cells may be achieved in multiple myeloma or pre-treated Non-Hodgkin’s lymphoma mobilized with low-dose Cy plus G-CSF regardless of the daily monitoring of peripheral blood CD34+ cells.     

Clinical analysis of 95 cases of pulmonary sarcomatoid carcinoma

ObjectivesTo collect data on the clinical characteristics, pathologic presentation, and prognosis of patients with pulmonary sarcomatoid carcinoma.MethodsFrom September 24, 2008 to June 3, 2014, 95 patients were hospitalized at the Shanghai Chest Hospital for the treatment of pulmonary sarcomatoid carcinoma. We retrospectively collected patient gender, age, smoking history, time of initial diagnosis, diagnostic methods, tumor location, pathohistological subtype, tumor size, TNM stage, immunohistochemical results, subsequent treatments, and patient survival.ResultsOf the 95 patients included in this study, 80 were male and 15 were female. Median patient age was 64 years (range: 43–80 years). There were 29 cases of pleomorphic carcinoma, one case of giant cell carcinoma, six cases of spindle cell carcinoma, and six cases of carcinosarcoma. The other 53 cases were not subtyped. The median survival was 11.54 months (range: 0.9-100.9 months). 1-, 2-, 3-, and 5-year survival was 32%, 30%, 25%, and 21%, respectively. Univariate analysis showed that tumor size, stage, T1 + T2 vs T3 + T4 stage, N stage, and M stage were prognostic factors for survival. Multivariate regression analysis showed that T stage and lymph node metastases were independent prognostic factors.ConclusionPulmonary sarcomatoid carcinoma is an uncommon, aggressive cancer. T1 + T2 vs T3 + T4 stage and lymph node metastases were independent prognostic factors. Our results underscore the importance of early detection and early diagnosis. Effective treatments for this disease are lacking.     

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.     

Assessment of stability of CD34+ cell products enriched by immunoselection from peripheral blood mononuclear cells during refrigerated storage

Durable engraftment of transplanted CD34+ cells largely depends on the quality of the cell product. Limited data are currently available about extended storage of immunoselected CD34+ cells. The aim of our study was to assess the stability of CD34+ cell product with the cells stored in high concentration (80 × 10⁶ in 6 mL) in small bags intended for cell implantation. Cell products were prepared by leukapheresis and immunoselection (Clinimacs^plus procedure) from 13 patients with chronic dilated cardiomyopathy. CD34+ cell products were stored at 2–8 °C and analyzed at time 0 (fresh products), 24, 48 h, 4 and 6 days. Product viability, absolute number of viable CD34+ cells and apoptosis were determined by flow cytometry. Microbiological contamination of the cell products was tested by BACTEC system. The mean viability of CD34+ cells decreased by 2.7% within 24 h, by 13.4% within 48 h and by 37.5% within 6 days. The mean recovery of viable CD34+ cells was 91.1%, 74.8%, 66.3% and 56.2% at 24, 48 h, 4 and 6 days, respectively. The mean fraction of early apoptotic cells in fresh and stored products was 4.9 ± 3.5% at 0 h, 5.9 ± 3.8% at 24 h, 4.2 ± 3.1% at 48 h, 6.3 ± 2.6% at 4 days and 9.3 ± 4.6% at 6 days. All products were negative for microbial contamination.     

Bidis — hand-rolled,Indian cigarettes: Induced biochemical changes in plasma and red cell membranes of human male volunteers

ObjectiveTo investigate the effect of bidi smoking on erythrocyte antioxidant status, membrane fluidity.Design and methodsThirty experimental and control subjects (mean age 35 ± 5) were selected for the study. Experimental subjects smoke 22 ± 4 bidis per day for 8–10 years.ResultsIncrease in plasma total cholesterol, LDL-cholesterol, triglycerides, lipid peroxidation, protein carbonyls with a decrease in HDL-cholesterol, thiol groups as well as increased erythrocyte catalase (CAT), superoxide dismutase (SOD), decreased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) content was observed in bidi smokers. Increase in the erythrocyte membrane lipid peroxidation, cholesterol phospholipids (C/P) ratio as well as decrease in protein and Na⁺/K⁺-ATPase activity was observed. Increase in nitrite/nitrate (NOx) levels of plasma, red cell lysate was positively correlated with C/P ratio (r = 0.614) and Na⁺/K⁺-ATPase (r = 0.435) in bidi smokers.ConclusionsBidi smoke alters antioxidant status, red cell membrane fluidity and increases atherogenicity.     

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.     

Tanshinone IIA protects against myocardial ischemia reperfusion injury by activating the PI3K/Akt/mTOR signaling pathway

ObjectiveTo determine the mechanism by which Tanshinone IIA (Tan IIA) relieves myocardial ischemia reperfusion injury (MIRI) in rats via the PI3K/Akt/mTOR signaling pathway.MethodsSprague-Dawley (SD) rats received an intravenous injection of Tan IIA and LY294002 and were divided into the sham, control (myocardial ischemia reperfusion), Tan-L (low-dose Tan IIA), Tan-H (high-dose Tan IIA), Tan-L + LY (low-dose Tan IIA + LY294002), Tan-H + LY (high-dose Tan IIA + LY294002) and LY (LY294002) groups. Cardiomyocytes obtained from neonatal rats were treated with hypoxia reoxygenatin, Tan IIA and LY294002 and divided into the blank, control, Tan-L, Tan-H, Tan-L + LY, Tan-H + LY and LY groups. Creatine kinase MB isoenzyme (CK-MB) and lactic dehydrogenase (LDH) levels in serum and cardiomyocytes were measured. Area of necrosis/area at risk (AN/AAR) was determined with double staining of TTC and Evan’s blue; viability and apoptosis of cardiomyocytes with MTT and TUNEL assays; SOD, MDA, H₂O₂, SDH and COX levels in heart mitochondria together with PI3K/Akt/mTOR and eNOS expressions and phosphorylation with Western blotting.ResultsThe Tan-L and Tan-H groups showed a remarkable decrease in AN/AAR, serum CK-MB and LDH, mitochondrial MDA and H₂O₂ levels but an increase in SOD activity, SDH and COX levels compared with the control group. However, compared with the Tan-L and Tan-H groups, the Tan-L + LY, Tan-H + LY and LY groups indicated an inverse tendency of those indicators. As shown by MTT and TUNEL, the control group had more severe cell damage than the blank group. Furthermore, cell damage and apoptosis were less severe in the Tan-L and Tan-H groups than in the control group, while the Tan-L + LY, Tan-H + LY and LY groups showed an opposite tendency when compared with the Tan-L and Tan-H groups. Meanwhile, the Tan-L and Tan-H groups showed significantly higher expression levels of PI3K, p-Akt/Akt, mTOR and p-eNOS/eNOS than the control group, whereas the Tan-L + LY, Tan-H + LY and LY groups had lower expression levels than the Tan-L and Tan-H groups.ConclusionOur study provided evidence that Tan IIA could activate the PI3K/Akt/mTOR signaling pathway to relieve MIRI in rats.     

Vitamin E (α-tocopherol) enhances the PDT action of hematoporphyrin derivatives on cervical cancer cells

ObjectiveThe effect of antioxidant vitamin E (VE) on PDT (a mainly reactive oxygen species-driven process) has in the past shown contradicting results. Hence, we studied the effect of different concentrations and different incubation periods of VE on the PDT cytotoxicity of the cervical adenocarcinoma HeLa cell line.Materials and methodsHeLa cells were incubated with 25 μg/ml of hematoporphyrin derivatives (HpD) for 25 min (1st PDT regimen) or 24 h (2nd PDT regimen), then irradiated with visible light (total light dose of 10 J/cm²) either with or without different concentrations of VE (1–1000 μM) which had been incubated with the cells for 1 h or 24 h prior to PDT. After irradiation, viability was measured using MTT assay.ResultsThe results obtained showed that PDT is effective against cervical cancer cells. Incubation of HpD for 24 h leads to improved PDT action. Higher concentrations of VE incubated in HeLa cells for 1 h before the 2nd PDT regimen significantly enhanced cytotoxicity of PDT and the maximal enhancement was at 1000 μM of VE. The cytotoxic effect of VE on HeLa cells after incubation for 24 h before PDT is enhanced by the PDT action.ConclusionIn conclusion 1000 μM of VE can be used 1 h before PDT to enhance its effect on cervical adenocarcinoma, a disease which is steadily increasing in young women. It is well-known that the cervical adenocarcinoma is resistant to anticancer agents and radiotherapy and it was previously considered to be HpD-PDT resistant.     

Alterations of Na+/K+-ATPase,cholinergic and antioxidant enzymes activity by protocatechuic acid in cadmium-induced neurotoxicity and oxidative stress in Wistar rats

BackgroundThis study assessed the possible protective mechanisms of protocatechuic acid (PCA) against cadmium (Cd)-induced oxidative stress and neurotoxicity in rats.MethodsMale wistar strain rats weighing between 150–160 g were purchased and acclimatized for two weeks. The rats were divided into seven groups of seven each; NC group received normal saline, CAD group received 6 mg/kg of Cd-solution, CAD + PSG group received Cd-solution and prostigmine (5 mg/kg), CAD + PCA-10 and CAD + PCA-20 groups received Cd-solution and PCA (10 mg/kg and 20 mg/kg) respectively, PCA-10 and PCA-20 groups received 10 mg/kg and 20 mg/kg PCA each. Animals were administered normal saline, Cd and PCA daily by oral gavage for 21 days. After which the animals were sacrificed, the brain excised, homogenized and centrifuged. The activities of enzymes (Na⁺/K⁺-ATPase, cholinesterases, catalase, glutathione peroxidase, superoxide dismutase) and levels of oxidative stress markers (lipid peroxidation and reduced glutathione) linked to neurodegeneration were subsequently assessed.ResultsSignificant (p < 0.05) alterations in the enzyme activities and levels of oxidative stress markers were observed in CAD group when compared to the NC group. However, the activities of the enzymes were reversed in CAD + PSG and CAD + PCA groups.ConclusionsPCA may protect against cadmium-induced neurotoxicity by altering the activities of Na⁺/K⁺-ATPase, acetylcholinesterase, butyrylcholinesterase and endogenous antioxidant enzymes.     

Physical activity and inactivity among different body composition phenotypes in individuals with moderate to very severe chronic obstructive pulmonary disease

BackgroundThe phenotype profiling of individuals with chronic obstructive pulmonary disease (COPD) according to impairments in body composition and level of physical activity in daily life (PADL) needs to be determined.ObjectiveTo verify if individuals with COPD classified as physically active/inactive present different characteristics within different body composition phenotypes.MethodsIndividuals with COPD were cross-sectionally stratified into four groups according to fat-free and fat mass indexes: Normal Body Composition (NBC), Obese (Ob), Sarcopenic (Sarc), and Sarcopenic/Obese (Sarc/Ob). Additionally, individuals had their PADL level objectively assessed through activity monitoring during two weekdays for at least 10 h/day, and then were classified as physically active (Act) or inactive (Inact) according to international recommendations. Lung function (spirometry), exercise capacity (6-minute walking test [6MWT]) and peripheral muscle strength (1-repetition maximum [1RM]) were also assessed.Results176 individuals with COPD (mean ± standard deviation age: 67 ± 8 years, body mass index 26 ± 6 kg/m², FEV1 47 ± 16%predicted) were classified as: NBC + Act (17%), NBC + Inact (22%), Ob + Act (6%), Ob + Inact (10%), Sarc + Act (12%), Sarc + Inact (9%), Sarc/Ob + Act (8%) and Sarc/Ob + Inact (16%). The Sarc/Ob + Inact group presented lower 6MWT and 1RM for knee extension compared to NBC + Act, NBC + Inact, and Ob + Act groups (p < 0.05). The Sarc/Ob + Inact group also presented lower FEV1% predicted, 1RM for elbow flexion and elbow extension compared to the NBC + Act and NBC + Inact groups and lower 1RM for elbow extension compared to Ob + Inact group (p < 0.05).ConclusionThe combination of sarcopenia, obesity, and physical inactivity was shown to be detrimental in individuals with COPD. Therefore, this profile is a main therapeutic target for improving PADL level and/or body composition.     

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.     

Prestorage gamma irradiation induces oxidative injury to red cells

BackgroundGamma irradiation of blood results in the formation free radicals, which interact with lipids and proteins in the membranes of red blood cells. We have investigated oxidative injury to gamma-irradiated red cells by measuring markers of oxidative injury and its correlation with red cell membrane damage.MethodsThirty red cell blood units were irradiated at 25 Gy using Gamma Irradiator (Nordion, Canada) and stored at 4 °C for 28 days. Markers of oxidative injury such as MDA levels, methemoglobin formation and osmotic fragility and markers of membrane damage including supernatant Hb, supernatant K⁺, and LDH were studied.ResultsThere was a progressive and statistically significant increase in markers of oxidative injury such as MDA (3.76 v/s 5.01), and methemoglobin formation (1.87 v/s 3.58) in irradiated red cells compared to control non-irradiated cells. Exposure to gamma irradiation caused significant increase in markers of hemolysis such as supernatant Hb (0.087 v/s 0.363), K⁺ (35.1 v/s 51.2) and LDH (366.9 v/s 587.4) over the storage period of 28 days.ConclusionGamma irradiation increases lipid peroxidation and oxidative injury to the red cells.     

Automated cerebrospinal fluid cell count — New reference ranges and evaluation of its clinical use in central nervous system infections

ObjectivesThe purposes of this study were to establish new reference ranges for leukocytes in the CSF and to examine if the separation of mononuclear cells into lymphocytes and monocytes could be used to differentiate between various CNS infections that present with a similar picture in manual CSF cell counts.Design and methodsThe automated cell counter Siemens ADVIA 2120i was used. For the reference range section, we analyzed CSF from 80 neurologically healthy volunteers. For the differential diagnosis section we analyzed cell counts and hospital records from 175 patients with CSF mononuclear pleocytosis.ResultsCorrelation was good between automated and manual leukocyte counts for samples with erythrocyte counts < 250 cells/μL. For the neurologically healthy volunteers studied in the reference range section, the 95th percentile was 3.0 cells/μL for lymphocytes, 1.0 cell/μL for monocytes and 1.0 cell/μL for granulocytes. In the differential diagnosis section, comparisons were done between the groups Lyme neuroborreliosis and viral CNS infection. There were no significant differences between these two groups regarding cell counts; neither for lymphocytes, median 58 cells/μL vs. 72 cells/μL (P = n.s.); nor for monocytes, median 13 cells/μL vs. 16 cells/μL (P = n.s.); nor for granulocytes, median 1 cell/μL vs. 2 cells/μL (P = n.s.)ConclusionsWe suggest new CSF cell count reference ranges of < 4 cells/μL for lymphocytes, < 3 cells/μL for monocytes and < 3 cells/μL for granulocytes. The separation of mononuclear cells into lymphocytes and monocytes did not facilitate the discrimination between Lyme neuroborreliosis and viral CNS infection.     

The comparison of Filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) as a first line peripheral blood stem cell mobilization strategy in autologous hematopoieitic stem cell transplantation: A single center experience from Turkey

Objectives and aimPatients affected by hematological malignancies can often benefit from high dose chemotherapy followed by peripheral blood stem cells (PBSCs) transplantation. Different strategies have been used to mobilize an adequate number of PBSC, including granulocyte colony-stimulating factor (G-CSF) alone or chemotherapy plus G-CSF. In this study, we aimed to compare the efficacy profile of different G-CSF agents including filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34⁺ mobilization in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT).Materials and methodsWe retrospectively analysed data of patients who underwent autoHSCT diagnosed with multiple myeloma (MM), Hodgkin Lymphoma (HL), non-Hodgkin Lymphoma (NHL) and others. Data for stem cell mobilization has been obtained from patients’ files. Patients who received Filgrastim (Neupogen®), biosimilar Filgrastim (Leucostim®, Group) and Lenograstim (Granocyte®) were evaluated mainly for total CD34⁺ cell count at the end of mobilization procedure.ResultsA total of 96 patients who underwent autoHSCT were retrospectively analyzed. 27 (28.2%) of the patients were female, and 69 (71.8%) were male. The diagnosis of the patients were; multiple myeloma (39 patients, 40.6%), Hodgkin Lyphoma (23 patients, 23.9%), non-Hodgkin lymphoma (16 patients, 16.6%), and others (18 patients, 18.9%). The median number of leukapheresis cycle necessary to harvest a minimal count of 3 × 10⁶ CD34⁺/kg was 2 in Neupogen® (min–max: 1–4) and Granocyte® (min–max: 1–3) groups and 1 (min–max: 1–2) in Leucostim® group. The median doses of G-CSF agents (μg/kg/day) in PBSC collection procedure were; 10.00 (min–max: 7.00–12.00) in the Neupogen® group, 8.00 (min–max: 7.25–9.00) in the Leucostim® group and 8.50 (6.00–9.50) in the Granocyte® group. There was no statistical significance among groups (p = 0.067). The number of total collected PB CD34⁺ cells (×10⁶/kg) was 7.64 (min–max: 4.09–13.86) in the Neupogen® group, 13.43 (min–max: 8.15–23.38) in the Leucostim® group and 5.45 (min–max: 4.28–9.40) in the Granocyte® group. The data showed that patients in the leucostim group had significantly higher PB CD34⁺ cells compared to patients in the Granocyte® group (p = 0.013).ConclusionLeucostim® was comparable to Neupogen® for PBSC mobilization in patients who underwent autoHSCT.     

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.