Muscular strength,aerobic capacity,and adipocytokines in obese youth after resistance training: A pilot study

Background

Exercise has shown positive training effects on obesity-related inflammation, however, resistance training has shown mixed results concerning adipocytokine levels.

Aims

The purpose of this pilot study was to explore the effects of resistance training on blood adipocytokine concentrations in obese youth, with specific examination of the relationship between these biomarkers and improved fitness (i.e., aerobic capacity, muscular strength).

Methods

Fourteen obese adolescents (16.1 ±1.6 y; BMI: 32.3 ±3.9 kg/m²) participated in a 16-week resistance training intervention. Body composition, fasting blood concentrations of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-ɑ), adiponectin, and leptin were measured pre- and post-training. Aerobic capacity was assessed via a maximal discontinuous exercise test. The rate of gain in muscular strength was calculated as the slope of progression in 1-repetition maximum throughout the intervention.

Results

Resistance training increased lean mass (total, trunk) and decreased per cent body fat (total, trunk). The training also caused moderate clear decreases in IL-6 and TNF-ɑ concentrations. A small increase in adiponectin was also observed before and after intervention. When the group was stratified by changes in aerobic capacity, there were substantially larger decreases in leptin levels for those with improved capacity. Correlation analyses also revealed a negative relationship between log-transformed leptin and aerobic capacity at rest. Improvement in quadriceps strength was positively correlated with IL-6 and TNF-ɑ, while improvement in shoulder adductor strength was positively correlated with IL-6 only.

Conclusion

Resistance training improved adipocytokine markers, which were partially associated with improved physical fitness. Specifically, the relationship between strength improvements and IL-6 and TNF-ɑ suggests an exercise-induced signalling pathway that results in overall adaptive decreases in systemic inflammation in obese youth.     

Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial Cells

Background:

Salvianolic acid B (Sal B) is a bioactive water-soluble compound of Salviae miltiorrhizae, a traditional herbal medicine that has been used clinically for the treatment of cardiovascular diseases. This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 (MMP-9) and on the underlying mechanisms in tumor necrosis factor-α (TNF-α)-activated human coronary artery endothelial cells (HCAECs), a cell model of Kawasaki disease.

Methods:

HCAECs were pretreated with 1–10 μmol/L of Sal B, and then stimulated by TNF-α at different time points. The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay, respectively. Nuclear factor-κB (NF-κB) activation was detected with immunofluorescence, electrophoretic mobility shift assay, and Western blot assay. Protein expression levels of mitogen-activated protein kinase (c-Jun N-terminal kinase [JNK], extra-cellular signal-regulated kinase [ERK], and p38) were determined by Western blot assay.

Results:

After HCAECs were exposed to TNF-α, 1–10 μmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity. Furthermore, Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min. In addition, Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.

Conclusions:

The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB, JNK, and ERK1/2 signaling pathways.     

Short term effects of periodontal therapy on inflammatory markers in patients with type-2 diabetes

Objectives:

To evaluate the influence of periodontal therapy on glycosylated hemoglobin and fasting blood glucose and serum levels of interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) in chronic periodontitis (CP) patients with type-2 diabetes mellitus (T2DM) and in controls.

Methods:

A total of 30 periodontal patients, 15 of which were systemically healthy (control group), and 15 were T2DM patients (test group) were included in this study. This prospective study was carried out at Istanbul University, Istanbul, Turkey between February 2011 and December 2013. Plaque index, gingival index, bleeding on probing, periodontal probing depth, and clinical attachment level were assessed and recorded at baseline, one, and 3 months after therapy. Serum samples were collected at the same time-points and analyzed using Luminex assay for the levels of IL-4, IL-6, IL-8, IL-10, and TNF-α. The change in the metabolic control was also monitored.

Results:

All clinical parameters were significantly improved after the periodontal therapy in both groups (p<0.001). Glycosylated hemoglobin levels were decreased; however, the difference was not significant (p>0.05). Fasting blood glucose levels were decreased one month after therapy, and increased at 3 months. Patients with T2DM had significantly higher levels of circulating IL-8 at each time point, and TNF-α (p<0.05) at baseline. The IL-4 and IL-10 levels were decreased at one month after therapy (p>0.05).

Conclusion:

Periodontal therapy has limited impact on the serum levels of IL-4, IL-6, IL-8, IL-10, and TNF-α. Metabolic control levels were not influenced by periodontal therapy.Chronic periodontitis (CP) is an infectious disease resulting in inflammation in periodontal tissues, progressive attachment, and bone loss. Chronic periodontitis is the most common type of periodontitis, and its prevalence and severity increases with age.1 Microbial dental plaque is the main etiological agent; however, progression from gingivitis to periodontitis is associated with host response and immunity. Presence of systemic disease such as diabetes, stress, and genetic factors are among the factors related to host response.2 Bone loss occurs with the influence of local factors, which are expressed from inflammatory mediators. Interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), IL-6 are the cytokines favoring bone loss around the teeth. It has been reported that patients with chronic periodontitis present with increased systemic inflammation and raised levels of various inflammatory markers compared with healthy controls.3 The local tissue produces inflammatory cytokines, as well as elevates their systemic circulating levels. Type-2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and protein metabolism. Defects in insulin secretion (b-cell dysfunction), insulin action (insulin resistance), or both cause T2DM.4 Type-2 diabetes is regarded as a low-grade inflammatory disease because some inflammatory cytokines are involved in the mechanism. Functions of specific immune system cells are impaired in patients with DM. Diabetes mellitus causes dysfunction in the adhesion, chemotaxis, and phagocytosis capacity of neutrophils. As a result, they cannot kill periodontopathogens, and cannot destroy their toxins resulting in the destruction of periodontal tissues,5-7 which may explain in part the increased incidence of periodontitis among diabetic patients. The glycosylated hemoglobin (HbA1c) levels reflect the glycemic level over the previous one to 3 months. Whether periodontal therapy reduces HbA1C levels in periodontitis patients remains controversial.8-14 In patients with periodontitis, diabetes is associated with elevated levels of several cytokines and other mediators in serum, saliva, and gingival crevicular fluid (GCF). It was reported that monocytes in peripheral blood of patients with DM produce higher amounts of TNF-α when encountered with Porphyromonas gingivalis.15The TNF-α, which is a pro-inflammatory cytokine was first reported by Hotamisligil et al16 to cause insulin-resistance. The TNF-α produced by the adipose tissues acts as a risk factor for periodontal disease; likewise, TNF-α produced due to periodontal inflammation may be an additional risk factor influencing insulin sensitivity.17 The TNF-α, IL-6, resistin, and other pro-, and anti-inflammatory cytokines activate intracellular pathways, which causes the development of insulin resistance and T2DM.18 Interleukin-4 reduces secretion of IL-1, IL-6, and TNF-α from monocytes.19 It was reported by a series of studies that patients with diabetes have a lower concentration of GCF IL-4 compared with healthy subjects.20-22 It was indicated that periodontal therapy reduces serum IL-6 concentration significantly in patients with CP.23 Interleukin-8 is a chemo attractive proinflammatory cytokine that affects neutrophil migrations in thetissue and circulation. Interleukin-1β and TNF-α has a role on IL-8 production.24 Substantial data has been accumulated on metabolic measures and serum levels of cytokines on T2DM patients with periodontitis. A systematic review has shown that non-surgical periodontal treatment results in a mean reduction in HbA1C of 0.36% (95% confidence interval [CI]: 0.19-0.54) at 3 months.25 However, the results from different reports are not consistent to demonstrate the potential effects of non-surgical periodontal therapy on Hba1C and specific cytokines in T2DM patients with CP.9-14We hypothesized that non-surgical periodontal therapy will reduce the levels of proinflammatory cytokines, HbA1c, and fasting blood glucose (FBG) levels in T2ßDM patients with CP, and this group of patients can benefit from periodontal therapy, as well as non-diabetics. Thus, the aim of this study was to evaluate the influence of periodontal therapy on HbA1C and FBG and serum levels of IL-4, IL-6, IL-8, IL-10, and TNF-α in CP patients with T2DM and in controls.     

Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction

Background:

Tumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases. The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (GLP-1) or its analogue exhibits protective effects on the cardiovascular system. The objective of the study was to assess the effects of exenatide, a GLP-1 analogue, on oxidative stress, and apoptosis in TNF-α-treated cardiomyocytes in vitro.

Methods:

Isolated neonatal rat cardiomyocytes were divided into three groups: Control group, with cells cultured in normal conditions without intervention; TNF-α group, with cells incubated with TNF-α (40 ng/ml) for 6, 12, or 24 h without pretreatment with exenatide; and exenatide group, with cells pretreated with exenatide (100 nmol/L) 30 mins before TNF-α (40 ng/ml) stimulation. We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, measured ROS production and mitochondrial membrane potential (MMP) by specific the fluorescent probes, and assessed the levels of proteins by Western blotting for all the groups.

Results:

Exenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay at 12 h and 24 h. Also, exenatide inhibited excessive ROS production and maintained MMP. Furthermore, declined cytochrome-c release and cleaved caspase-3 expression and increased bcl-2 expression with concomitantly decreased Bax activation were observed in exenatide-pretreated cultures.

Conclusion:

These results suggested that exenatide exerts a protective effect on cardiomyocytes, preventing TNF-α-induced apoptosis; the anti-apoptotic effects may be associated with protection of mitochondrial function.     

Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients

Background:

Studies of interleukin (IL)-4 and IL-6 in the exhaled breath condensate (EBC) of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid (ICS) treatment on IL-4 and IL-6 in the EBC of asthmatic patients.

Methods:

In a prospective, open-label study, budesonide 200 μg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma (mean age 42.7 years) for 12 weeks. Changes in asthma scores, lung function parameters (forced expiratory volume in 1 s [FEV₁], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEF₅₀], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate) and the concentrations of IL-4 and IL-6 in EBC were measured.

Results:

Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmol/L after 8 weeks of treatment (P < 0.05) and 1.54 ± 0.81 pmol/L after 12 weeks of treatment (P < 0.01). However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEV₁, PEF and FEF₅₀ values (correlation coefficients −0.468, −0.478, and −0.426, respectively).

Conclusions:

The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.     

Subclinical haemorrhagic tendency exists in patients with β-thalassaemia major in early childhood

Background

Alterations of coagulation profile have been reported in patients with β-thalassaemia major (β-TM).

Method

To investigate this in the paediatric population, we studied haemostatic parameters in pre-transfusion blood samples from 50 non-splenectomised transfusion-dependent children with β-TM (mean age 6±2.5 years) and in blood from 25 healthy controls.

Results

Laboratory evaluation showed thrombocytopenia in 40%, prolongation of prothrombin time (PT) in 12% and prolongation of activated partial thromboplastin time (APTT) in 6% of the patients. Mean values for PT, APTT and platelet count (PC) were all raised in the patient population compared with the controls. The alteration of coagulation status was significant for PT (p value <0.005) and APTT (p value <0.0001). However, the change for PC was not significant (p value <0.05). No significant liner correlation could be identified between PT, APTT, PC of the patients and interval between transfusions (in days) or days since last transfusion.

Conclusion

The findings from this study suggest that a subclinical haemorrhagic tendency exists in patients with β-TM at a very early age. The intrinsic pathway appears to be more affected than the extrinsic pathway.     

Meta-analysis for the Association of Apolipoprotein E ε2/ε3/ε4 Polymorphism with Coronary Heart Disease

Background:

Coronary heart disease (CHD) is a multifactorial disease and is thought to have a polygenic basis. Apolipoprotein E (APOE) gene is one such candidate with its common ε2/ε3/ε4 polymorphism in CHD. In recent years, numerous case-control studies have investigated the relationship of APOE polymorphism with CHD risk. However, the results are confusing.

Methods:

To clarify this point, we undertook a meta-analysis based on 14 published studies including 5746 CHD cases and 19,120 controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for association using a random-effects or fixed-effects model using STATA version 10 (StataCorp LP, College Station, TX, USA).

Results:

Overall, the analysis showed that carriers of APOE ε2 allele decreased risk for CHD (ε2 allele vs. ε3 allele: OR = 0.82, 95% CI: 0.75–0.90, P < 0.001; ε2 carriers vs. ε3 carriers: OR = 0.81, 95% CI: 0.73–0.89, P < 0.001), compared with those carrying ε3 allele, especially in Caucasian population. However, those with ε4 allele had a significant increased risk for CHD (ε4 allele vs. ε3 allele: OR = 1.34, 95% CI: 1.15–1.57, P < 0.001), especially in Mongoloid population. Potential publication bias was observed in the genetic model of ε4 versus ε3, but the results might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results were not materially alerted, suggesting the stability of our results.

Conclusions:

Taken together, our meta-analysis supported a genetic association between APOE gene and CHD. ε4 increased the risk of CHD, whereas ε2 decreased the risk of CHD.     

Follow-up of N400 in the Rehabilitation of First-episode Schizophrenia

Background:

The N400 component of event-related potentials (ERP) has recently drawn widespread attention at home and abroad. This study was to explore the relationship between N400 changes and risperidone treatment and rehabilitation in first-episode schizophrenia (FES).

Methods:

ERP component N400 was recorded by Guangzhou Runjie WJ-1 ERP instruments, in 58 FES before and 6 months, 15 months after risperidone treatment, and in 62 normal controls. The patients’ syndromes were assessed by Positive and Negative Syndrome Scale (PANSS). And the stimuli are Chinese sentences with matching (congruent) or mismatching (incongruent) ending words.

Results:

N400 latencies were prolonged, and amplitudes were decreased in Cz, Pz, Fz, C3, C4, in FES compared with in NC, before treatment. The prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients’ positive scale and total scale of PANSS. There are significant differences of N400 amplitudes and latencies in 6 months and 15 months follow-up after treatment. Before treatment, 6 months and 15 months after treatment, N400 latencies are 446 ± 35 ms, 440 ± 37 ms, 414 ± 31 ms (F = 9.72, P < 0.01) in incongruent situation; N400 amplitudes are 5.2 ± 4.6 μV, 5.7 ± 4.8 μV, 7.3 ± 5.0 μV (F = 2.06, P > 0.05) in congruent situation, and 8.5 ± 5.9 μV, 10.1 ± 5.0 μV, 11.9 ± 7.0 μV (F = 3.697, P < 0.05) in incongruent situation.

Conclusions:

N400 could be used to predict the effects of treatment of schizophrenia to some degree. The linguistic and cognitive impairment in schizophrenia can be improved by antipsychotic drugs.     

Wnt/Glycogen Synthase Kinase 3β/β-catenin Signaling Activation Mediated Sevoflurane Preconditioning-induced Cardioprotection

Background:

Sevoflurane preconditioning (SP) has been shown to invoke potent myocardial protection in animal studies and clinical trials. However, the mechanisms underlying SP are complex and not yet well understood. We investigated the hypothesis that the cardioprotection afforded by SP is mediated via the Wnt/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway.

Methods:

Two models were established: A Langendorff perfused rat heart model and the H9C2 cell hypoxia/reoxygenation model. Both rats and H9C2 cells were randomly divided into 6 groups as follows: S group, ischemia-reperfusion (I/R) group, DMSO group, IWP group, SP group, and SP + IWP group. Hemodynamic parameters, lactate dehydrogenase (LDH) activity in coronary effluent and cell culture supernatant, and the infarct size were measured to evaluate myocardial ischemia-reperfusion injuries. To determine the activity of Wnt/GSK3β/β-catenin signaling pathway, the expressions of Wnt3a, phospho-GSK3β, and β-catenin were measured by Western blotting.

Results:

SP improved cardiac function recovery, reduced infarct size (18 ± 2% in the SP group compared with 35 ± 4% in the I/R group; P < 0.05), decreased LDH activity in coronary effluent, and culture supernatant. IWP-2, an inhibitor of Wnt, abolished the cardioprotection by SP. In addition, Western blotting analysis demonstrated that the expressions of Wnt3a, phospho-GSK3β, and β-catenin significantly (P < 0.05) increased in the I/R group, compared with the S group; and compared to I/R group, SP significantly (P < 0.05) increased Wnt3a, phospho-GSK3β, and β-catenin expressions. Pretreatment with IWP-2 significantly (P < 0.05) abolished SP-induced Wnt/GSK3β/β-catenin signaling activation.

Conclusions:

The results showed for the first time that cardioprotection afforded by SP may be mediated partly via the Wnt/GSK3β/β-catenin signaling pathway.     

Could Intrathymic Injection of Myelin Basic Protein Suppress Inflammatory Response After Co-culture of T Lymphocytes and BV-2 Microglia Cells?

Background:

The interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory response. This study aimed to investigate whether intrathymic injection of myelin basic protein (MBP) in mice could suppress the inflammatory response after co-culture of T lymphocytes and BV-2 microglia cells.

Methods:

Totally, 72 male C57BL/6 mice were randomly assigned to three groups (n = 24 in each): Group A: intrathymic injection of 100 μl MBP (1 mg/ml); Group B: intrathymic injection of 100 μl phosphate-buffered saline (PBS); and Group C: sham operation group. Every eight mice in each group were sacrificed to obtain the spleen at postoperative days 3, 7, and 14, respectively. T lymphocytes those were extracted and purified from the spleens were then co-cultured with activated BV-2 microglia cells at a proportion of 1:2 in the medium containing MBP for 3 days. After identified the T lymphocytes by CD3, surface antigens of T lymphocytes (CD4, CD8, CD152, and CD154) and BV-2 microglia cells (CD45 and CD54) were detected by flow cytometry. The expressions of pro-inflammatory factors of BV-2 microglia cells (interleukin [IL]-1β, tumor necrosis factor-α [TNF-α], and inducible nitric oxide synthase [iNOS]) were detected by quantitative real-time polymerase chain reaction (PCR). One-way analysis of variance (ANOVA) and the least significant difference test were used for data analysis.

Results:

The levels of CD152 in Group A showed an upward trend from the 3^rd to 7^th day, with a downward trend from the 7^th to 14^th day (20.12 ± 0.71%, 30.71 ± 1.14%, 13.50 ± 0.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The levels of CD154 in Group A showed a downward trend from the 3^rd to 7^th day, with an upward trend from the 7^th to 14^th day (10.00 ± 0.23%, 5.28 ± 0.69%, 14.67 ± 2.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The ratio of CD4⁺/CD8 + T in Group A showed a downward trend from the 3^rd to 7^th day, with the minimum at postoperative day 7, then an upward trend from the 7^th to 14^th day (P < 0.05). Meanwhile, the levels of CD45 and CD54 in Group A were found as the same trend as the ratio of CD4⁺/CD8 + T (CD45: 83.39 ± 2.56%, 82.74 ± 2.09%, 87.56 ± 2.11%; CD54: 3.80 ± 0.24%, 0.94 ± 0.40%, 3.41 ± 0.33% at postoperative days 3, 7, and 14, respectively, P < 0.05). The expressions of TNF-α, IL-1β, and iNOS in Group A were significantly lower than those in Groups B and C, and the values at postoperative day 7 were the lowest compared with those at postoperative days 3 and 14 (P < 0.05). No significant difference was found between Groups B and C.

Conclusions:

Intrathymic injection of MBP could suppress the immune reaction that might reduce the secondary immune injury of brain tissue induced by an inflammatory response.     

An Appreciation for the Rabbit Ladderlike Modeling of Radiation-induced Lung Injury with High-energy X-Ray

Background:

To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury (RILI) for the future investigation of computed tomography perfusion.

Methods:

A total of 72 New Zealand rabbits were randomly divided into two groups: 36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung; 36 rabbits in the control group were sham-radiated. All rabbits were subsequently sacrificed at 1, 6, 12, 24, 48, 72 h, and 1, 2, 4, 8,1 6, 24 weeks after radiation, and then six specimens were extracted from the upper, middle and lower fields of the bilateral lungs. The pathological changes in these specimens were observed with light and electron microscopy; the expression of tumor necrosis factor-α (TNF-a) and transforming growth factor-β1 (TGF-β₁) in local lung tissue was detected by immunohistochemistry.

Results:

(1) Radiation-induced lung injury occurred in all rabbits in the test group. (2) Expression of TNF-a and TGF-β₁ at 1 h and 48 h after radiation, demonstrated a statistically significant difference between the test and control groups (each P < 0.05). (3) Evaluation by light microscopy demonstrated statistically significant differences between the two groups in the following parameters (each P < 0.05): thickness of alveolar wall, density of pulmonary interstitium area (1 h after radiation), number of fibroblasts and fibrocytes in interstitium (24 h after radiation). The test group metrics also correlated well with the time of postradiation. (4) Evaluation by electron microscopy demonstrated statistically significant differences in the relative amounts of collagen fibers at various time points postradiation in the test group (P < 0.005), with no significant differences in the control group (P > 0.05). At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups (each P < 0.05), correlating well with the time postradiation (r = 0.99318).

Conclusions:

A consistent and reliable rabbit model of RILI can be generated in gradient using 25 Gy of high-energy X-ray, which can simulate the development and evolution of RILI.     

Protective Effects of Salubrinal on Liver Injury in Rat Models of Brain Death

Background:

Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead (BD) rats. In this study, we observed the effect of salubrinal (Sal, Sigma, USA) on liver cells in BD rats and explored its relevant mechanisms.

Methods:

Thirty Sprague–Dawley rats were equally randomized into three groups: BD group, Sal group, and DMSO group. The BD models were established by increasing intracranial pressure in a modified, slow, and intermittent way. In the drug groups, Sal was administered 1 h before the induction of BD. After modeling was completed, the blood and liver samples were harvested. CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction. PKR-like ER kinase (PERK), P-eukaryotic translation initiation factor 2α (eIF2α), eIF2α, CHOP and caspase-12 expression was detected using western blotting (WB). CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry (IHC). Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer. Hepatic cell apoptosis was detected using TUNEL. The results were analyzed using Quantity-one v4.62 software (Bio-Rad, USA).

Results:

CHOP and caspase-12 expression and PERK, eIF2α, and P-eIF2α protein expression showed no significant difference between BD group and DMSO group. Compared with BD group, Sal group had a significantly higher P-eIF2C level and a lower P-PERK level 2 h and 6 h after BD (P < 0.05). However, eIF2α expression showed no significant difference (P > 0.05). After the Sal treatment, CHOP and caspase-12 mRNA expression significantly decreased 4 h after BD (P < 0.05). WB and IHC indicated that CHOP and caspase-12 expression also significantly decreased after Sal treatment. Sal was associated with improved liver function and decreased hepatic cell apoptosis.

Conclusions:

Sal can significantly reduce apoptosis in hepatic cells of BD rats. This protective effect may be achieved via the PERK-eIF2α signaling pathway.     

Comparison of Cerebral Metabolism between Pig Ventricular Fibrillation and Asphyxial Cardiac Arrest Models

Background:

Morbidity and mortality after resuscitation largely depend on the recovery of brain function. Ventricular fibrillation cardiac arrest (VFCA) and asphyxial cardiac arrest (ACA) are the two most prevalent causes of sudden cardiac death. Up to now, most studies have focused on VFCA. However, results from the two models have been largely variable. So, it is necessary to characterize the features of postresuscitation cerebral metabolism of both models.

Methods:

Forty-four Wuzhishan miniature inbred pigs were randomly divided into three groups: 18 for VFCA group, ACA group, respectively, and other 8 for sham-operated group (SHAM). VFCA was induced by programmed electric stimulation, and ACA was induced by endotracheal tube clamping. After 8 min without treatment, standard cardiopulmonary resuscitation (CPR) was initiated. Following neurological deficit scores (NDS) were evaluated at 24 h after achievement of spontaneous circulation, cerebral metabolism showed as the maximum standardized uptake value (SUVmax) was measured by ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography. Levels of serum markers of brain injury, neuron specific enolase (NSE), and S100β were quantified with an enzyme-linked immunosorbent assay.

Results:

Compared with VFCA group, fewer ACA animals achieved restoration of spontaneous circulation (61.1% vs. 94.4%, P < 0.01) and survived 24-h after resuscitation (38.9% vs. 77.8%, P < 0.01) with worse neurological outcome (NDS: 244.3 ± 15.3 vs. 168.8 ± 9.71, P < 0.01). The CPR duration of ACA group was longer than that of VFCA group (8.1 ± 1.2 min vs. 4.5 ± 1.1 min, P < 0.01). Cerebral energy metabolism showed as SUVmax in ACA was lower than in VFCA (P < 0.05 or P < 0.01). Higher serum biomarkers of brain damage (NSE, S100β) were found in ACA than VFCA after resuscitation (P < 0.01).

Conclusions:

Compared with VFCA, ACA causes more severe cerebral metabolism injuries with less successful resuscitation and worse neurological outcome.     

Improved Survival and Neurological Outcomes after Cardiopulmonary Resuscitation in Toll-like Receptor 4-mutant Mice

Background:

Toll-like receptor 4 (TLR4) is a crucial receptor in the innate immune system and noninfectious immune responses. It has been reported that TLR4 participates in the pathological course of ischemia/reperfusion (I/R) injury. However, the role of TLR4 in the process of I/R injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) is still unknown. In this study, we investigated the effects of TLR4 mutation on survival and neurological outcome in a mouse model of CA/CPR.

Methods:

A model of potassium-induced CA was performed on TLR4-mutant mice (C3H/HeJ) and wild-type mice (C3H/HeN). After 3 min of untreated CA, resuscitation was attempted with chest compression, ventilation, and intravenous epinephrine. Behavioral tests were performed on mice on day 3 after CPR. The morphological changes in hippocampal neurons were assessed by light and electron microscopy. Expressions of TLR4 and intercellular adhesion molecule-1 (ICAM-1) were detected by Western blot. Levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were measured with enzyme-linked immunosorbent assay (ELISA).

Results:

On day 3 after resuscitation the overall mortality was 33.33% in C3H/HeJ group compared with 53.33% in C3H/HeN group (P < 0.05). And there was much higher central tendency in C3H/HeJ group than C3H/HeN group during open field test (P < 0.05). Meanwhile, the percentage of nonviable neurons was 21.16% in C3H/HeJ group compared with 53.11% in C3H/HeN group (P < 0.05). And there were significantly lower levels of hippocampal TNF-α and MPO in C3H/HeJ mice (TNF-α: 6.85±1.19 ng/mL, MPO: 0.33±0.11 U/g) than C3H/HeN mice (TNF-α: 11.36±2.12 ng/mL, MPO: 0.54±0.17 U/g) (all P < 0.01). CPR also significantly increased the expressions of TLR4 and ICAM-1 in C3H/HeN group. However, the expression of ICAM-1 was much lower in C3H/HeJ group than in C3H/HeN group after CPR (P < 0.01).

Conclusion:

TLR4 signaling is involved in brain damage and in inflammation triggered by CA/CPR.     

Effect of infliximab against cisplatin-induced nephrotoxicity

Objectives:

To investigate whether infliximab (Ib), an inhibitor of tumor necrosis factor alpha (TNF-α), prevents cisplatin (Cis)-induced nephrotoxicity.

Methods:

The study was performed in the Department of Internal Medicine, Recep Tayyip Erdogan University, Rize, Turkey, between November 2012 and May 2013. Thirty male Wistar albino rats were divided into 3 groups, a control group, a Cis group, and a Cis+Ib group. The animals of the Cis group were injected with a single dose (7 mg/kg) of Cis intraperitoneally. The animals of the Cis+Ib group were injected with a single dose (7 mg/kg) of Ib 72 hours prior to Cis injection.

Results:

The TNF-α, interleukin-1 beta (IL-1β), nitric oxide (NO) and adenosine deaminase (ADA) levels of the Cis group were higher than both the control group TNF-α (p<0.001), IL-1a (p<0.001), NO (p<0.001) and ADA (p<0.001), and the Cis+Ib group TNF-α (p<0.001), IL-1β (p<0.001), NO (p<0.001), and ADA (p=0.003). Histopathological examination revealed extensive damage in the Cis group, while the damage in the Cis+Ib group was lower. While the carbonic anhydrase II (CA-II) level of the Cis group was lower than both groups, it was similar in the Cis+Ib and the control groups.

Conclusion:

Infliximab acts against Cis-induced nephrotoxicity by a strong inhibition of TNF-α. Additionally, the combination of these 2 drugs does not obviously change the level of CA-II.Cisplatin (Cis) is an antineoplastic drug used to treat solid tumors. Although it is used in most chemotherapy regimens, its nephrotoxic effect is a common problem. The mechanisms for Cis-induced nephrotoxicity have been attributed to renal cell apoptosis, oxidative stress, and inflammation.1,2 Cisplatin leads to the formation of reactive oxygen species (ROS) by increasing the release of pro-inflammatory cytokines such as tumor necrosis alpha (TNF-α), stimulating apoptosis through the direct effect of the cytokines, and increasing inflammation.3 Moreover, it causes nephrotoxicity by increasing the turnover of purine metabolism to its metabolites.4 Cisplatin induced nephrotoxicity is one of the important side effects that limit the use of Cis. Therefore, effective treatment is still sought to prevent it. Infliximab (Ib) is a potent TNF-α inhibitor that can safely be used to treat many chronic diseases with inflammation.5 Previous studies have shown that Ib prevents organ damage,6,7 and decreases nitric oxide (NO) and ROS formation.8 It has no nephrotoxic effect and can be used in patients with renal impairment.9 Carbonic anhydrase II (CA-II), which is a zinc metalloenzyme, catalyzes the reversible hydration reaction of carbon dioxide form carbonic acid. It is found in many tissues, mainly the kidneys.10 Over-expression of CA-II is observed in many cancers, including renal cell cancer.11 This condition leads to cancer cell growth and invasion. On the contrary, the suppression of CA-II or its deficiency leads to metabolic acidosis.12 In this study, we aimed to investigate whether Ib could prevent cis-induced nephrotoxicity, and whether this combination would affect the CA-II enzyme.     

Interferon-gamma treatment kinetics among patients with active pulmonary tuberculosis

Introduction:

Interferon-γ (IFN-γ) is essential for defence against Mycobacterium tuberculosis; however, levels in patients with active tuberculosis (TB) and changes during treatment have not been documented in our tuberculosis patients in Nigeria, hence this study has been carried out.

Objective:

To determine variations, treatment kinetics, and predictive value of IFN-γ levels during treatment of active tuberculosis.

Design:

Patients with pulmonary tuberculosis were recruited and subsequently followed up for 3 months during treatment with anti-TB. Peripheral blood was collected for IFN-γ assays, C-reactive protein and others followed by a Mantoux test. IFN-γ levels produced by stimulation with TB antigens were determined by ELISA and repeated measurement of IFN-γ were done at 1 and 3 months of anti-TB therapy. Chi Associations and correlations between IFN-γ were determined. Regression analysis was done to determine association between serial IFN-γ and treatment outcome.

Results:

We recruited 47 patients with active tuberculosis with a mean age of 34.8 ± 3.6 years and M:F ratio of 1.12:1. Six (11%) were HIV positive. The mean level of IFN-γ induced by TB antigens was 629 ± 114.1 pg/ml, higher for HIV-negative PTB patients compared with HIV-positive PTB patients, 609.78 ± 723.9 pg/ml and 87.88 ± 130.0 pg/ml, respectively, P-value = 0.000. The mean level of IFN-γ induced by TB antigen increased significantly from 629 ± 114.1 pg/ml to 1023.46 + 222.8 pg/ml, P-value = 0.03 and reduced to 272.3 ± 87.7 pg/ml by the third month on anti-TB drugs, P-value = 0.001. Negative correlation was observed between the mean of baseline and chest X-ray involvement, P = 0.03. There was no significant correlation between sputum smear grade with baseline and follow-up IFN-γ levels. Three-month IFN-γ level among cured patients were higher than those with treatment failure, regression analysis showed that it does not predict outcome.

Conclusion:

IFN-γ may be useful in early detection and monitoring response; however, large scale studies are needed.     

Diverse expression of selected cytokines and proteinases in synovial fluid obtained from osteoarthritic and healthy human knee joints

Background

Osteoarthritis (OA) is defined by signs and symptoms of inflammation within the affected joint. The aim of this study is to determine the mRNA expression levels of selected cytokines and matrix-metalloproteinases of cells found in synovial fluid (SF) obtained from osteoarthritic knee joints compared to healthy controls.

Methods

SF was obtained from 40 patients undergoing total knee arthroplasty due to evident OA and from 10 healthy controls. Expression of TNF-α, IL-1β, MMP-1 and MMP-3 was assayed among both groups by performing qPCR. Patients were configured concerning age, gender and BMI.

Results

IL-1β, MMP-1 and MMP-3 showed significantly higher expression among the OA group compared to control (P < 0.001). Strong correlation appeared between expression of MMP-1 and MMP-3 among OA patients (r = 0.856); no correlation was found between age, gender or BMI and cytokine/proteinase expression. Expression of IL-1β, MMP-1 and MMP-3 within SF was elevated in OA-patients.

Conclusion

Consequently, cells within SF expressing cytokines and proteinases may play a relevant role in the progression of joint destruction. Considering the fact that SF in an OA joint comprises abnormal amounts of detrimental bioactive proteins, temporary clearance, dilution or suppression/modulation by means of lavage or disease-modifying medication may be promising to constitute interim relief or even postpone disease progression due to decreased inflammatory and/or degrading activity within the articular environment.