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Metabolic reprogramming is typical in cancerous cells and is required for proliferation and cellular survival. In addition, oncoproteins of high-risk human papillomavirus (HR-HPV) are involved in this process. This study evaluated the relationship between glucose transporter I (GLUT1), lactate dehydrogenase A (LDHA), and monocarboxylate transporter type 4 (MCT4) expression and cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma (ICC) with HR-HPV infection. The protein expression was evaluated in women with CIN I ( n=20), CIN II/III ( n=16), or ICC ( n=24) by immunohistochemistry. The protein expression was analyzed qualitatively by van Zummeren score and quantitatively by Image ProPlus 6 software. LDHA expression increases in HPV-16 infection. In the CIN I group, GLUT1 immunostaining has a 35% protein expression at the membrane level at more than two thirds of the epithelium, which increased by 21.25% more in CIN II/III in more than two thirds of the epithelium. While LDHA and MCT4 in CIN I mostly do not present immunostaining, or this was only limited to the basal stratum, this expression is increased in CIN II/III and ICC cases. The GLUT1, LDHA, and MCT4 expression increased in ICC. The overexpression in high-grade CIN with HR-HPV infection shows a higher risk for cervical carcinoma progression.

The aim of this report was to evaluate the morphological and biochemical changes in the liver by the inhalation of vanadium and consumption of sweetened beverages in a subchronic murine model. Forty CD-1 male mice were randomly divided into four groups: control, vanadium (V), sucrose 30% (S), and vanadium–sucrose (V + S). V was inhaled (1.4 mg/m3) for 1h, twice/week; 30% sucrose solution was given orally ad libitum. Blood samples were obtained for AST, ALT, and LDH determination. Liver samples were processed for histological and oxidative stress immunohistochemical evaluation with 4-hydroxynonenal at weeks 4 and 8 of exposure. Regarding liver function tests, a statistically significant increase ( P < 0.05) was observed in groups V, S, and V + S at weeks 4 and 8 compared to the control group. A greater number of hepatocytes with meganuclei and binuclei were observed in V and V + S at week 8 compared to the other groups. Steatosis and regenerative changes were more extensive in the eighth week V + S group. 4-Hydroxynonenal immunoreactivity increased in the V + S group at both exposure times compared to the other groups; however, the increment was more evident in the V + S group at week 4 compared to the V + S group at week 8. An increase in De Ritis ratio (>1) was noticed in experimental groups at weeks 4 and 8. Findings demonstrate that in the liver, V, S, and V + S induced oxidative stress and regenerative changes that increased with the length of exposure. Results support possible potentiation of liver damage in areas with high air pollution and high-sweetened beverage consumption.

Aims To search for biochemical indicators that can identify symptomatic patients with COVID-19 whose nucleic acid could turn negative within 14 days, and assess the prognostic value of these biochemical indicators in patients with COVID-19. Patients and methods We collected the clinical data of patients with COVID-19 admitted to our hospital, by using logistic regression analysis and AUC curves, explored the relationship between biochemical indicators and nucleic acid positive duration, the severity of COVID-19, and hospital stay respectively. Results A total of two hundred and thirty-three patients with COVID-19 were enrolled in the study. We found patients whose nucleic acid turned negative within 14 days had lower LDH, CRP and higher ALB ( P 31days with statistical significance ( P 35.8 g/L) was about 4 times higher than that in patients with high LDH, CRP and low ALB ( P Conclusions LDH, CRP and ALB are useful prognostic marker for predicting nucleic acid turn negative within 14 days in symptomatic patients with COVID-19.

Early recognition of severe clinical outcomes in children with pneumonia-related bacteremia is vitally important because of the high mortality. This study aims to explore risk factors for severe clinical outcomes in children with pneumonia-related bacteremia and evaluate the value of time to first positive blood cultures (TTFP) in predicting prognosis. Children with pneumonia-related bacteremia in Children's Hospital of Chongqing Medical University were included (January 2013-May 2019), respectively. TTFP and clinical parameters were collected and analyzed. The area under the curve (AUC)-receiver operating characteristic was used to evaluate the discrimination ability of TTFP. Multivariate logistic regression tests were performed to evaluate the association between TTFP and severe clinical outcomes. A total of 242 children with pneumonia-related bacteremia were included. The least absolute shrinkage and selection operator (LASSO) regression analysis identified TTFP, serum albumin (ALB) and lactic dehydrogenase (LDH) as predictors of in-hospital mortality. Multivariate logistic regression analysis showed that shorter TTFP (OR 0.94; 95% CI 0.89 to 0.97; p

Di-2-ethylhexyl phthalate (DEHP) has been widely used as a plasticizer in industry and can affect memory; however, the underlying mechanism remains unclear. In the present study, mouse HT22 cells, an immortalized hippocampal neuronal cell line, was utilized as an in vitro model. We showed that DEHP dramatically inhibited cell viability and increased lactate dehydrogenase (LDH) release from the cells in a dose-dependent manner, suggesting that DEHP could cause cytotoxicity of mouse HT22 cells. The protein levels of cleaved Caspase-8, cleaved Caspase-3, and Bax markedly increased in the DEHP-treated cells, whereas there was a significant decrease in the Bcl-2 protein level, implying that DEHP could induce apoptosis of mouse HT22 cells. DEHP exposure significantly increased the content of malondialdehyde, whereas it markedly decreased the level of glutathione and the activities of glutathione peroxidase and superoxide dismutase, suggesting that DEHP induced oxidative stress of the cells. Compared with the DEHP-treated group, the inhibition of cell viability and the release of LDH were rescued in the N-acetyl-l-cysteine plus DEHP group. Furthermore, inhibition of oxidative stress could rescue the induction of apoptosis by DEHP. Collectively, our results indicated that DEHP could induce apoptosis of mouse HT22 cells via oxidative stress.

Introduction: Lactate dehydrogenase (LDH) is widely used as an indicator of pump thrombosis in a centrifugal pump. However, due to the low specificity of LDH, pump thrombosis is difficult to detect in the clinical environment. We measured plasma free hemoglobin (pfHb) with the portable device in ICU. The goal of this investigation is to evaluate its diagnostic ability for pump thrombosis. Methods: We enrolled 31 consecutive patients who needed Extracorporeal Membrane Oxygenation (ECMO) therapy and pfHb was determined with HemoCue® plasma/Low Hb photometer. Pump thrombosis was analyzed macroscopically at the timing of pump explantation or exchange. Also, we divided the pump thrombosis into a grading scale by the place of thrombosis. Results: The median of peak pfHb was significantly lower in the none thrombus group (0.03 g/dL) than that of in the thrombus group (0.05g/dL) ( p = 0.01). In our grading criteria, pfHb was significantly higher when the thrombus is existing near the shaft ( p = 0.015). Contrary, no significant difference was found for LDH. The ROC analysis of pfHb revealed an AUC of 0.77 for detecting pump thrombosis with the best statistical cutoff value at 0.05 g/dL (specificity, 78%; sensitivity, 77%). Also, ROC analysis of LDH was performed (AUC, 0.44; cutoff value, 1200 IU/L; specificity, 59%; sensitivity, 54%) and compared with pfHb. AUC was significantly higher in pfHb ( p = 0.04). Conclusion: Our results showed the efficacy of pfHb for detecting centrifugal pump thrombosis.

Background The differential diagnosis of ovarian cancer is important, and there has been ongoing research to identify biomarkers with higher performance. This study aimed to evaluate the diagnostic utility of combinations of cancer markers classified by machine learning algorithms in patients with early stage ovarian cancer, which has rarely been reported. Methods In total, 730 serum samples were assayed for lactate dehydrogenase (LD), neutrophil-to-lymphocyte ratio (NLR), human epididymis protein 4 (HE4), cancer antigen 125 (CA125), and risk of ovarian malignancy algorithm (ROMA). Among them, 53 were diagnosed with early stage ovarian cancer, and the remaining 677 were diagnosed with benign disease. Results The areas under the receiver operating characteristic curves (ROC-AUCs) of the ROMA, HE4, CA125, LD, and NLR for discriminating ovarian cancer from non-cancerous disease were .707, .680, .643, .657, and .624, respectively. ROC-AUC of the combination of ROMA and LD (.709) was similar to that of single ROMA in the total population. In the postmenopausal group, ROC-AUCs of HE4 and CA125 combined with LD presented the highest value (.718). When machine learning algorithms were applied to ROMA combined with LD, the ROC-AUC of random forest was higher than that of other applied algorithms in the total population (.757), showing acceptable performance. Conclusion Our data suggest that the combinations of ovarian cancer-specific markers with LD classified by random forest may be a useful tool for predicting ovarian cancer, particularly in clinical settings, due to easy accessibility and cost-effectiveness. Application of an optimal combination of cancer markers and algorithms would facilitate appropriate management of ovarian cancer patients.

The aim of this study was to examine whether a peroxisome proliferator-activated receptor (PPAR)-γ agonist could affect cadmium (Cd)-induced cytotoxicity via the increased expression of megalin, one of the uptake pathways, using renal epithelial LLC-PK1 cells. The treatment with 1 µM Cd for 24 h was not cytotoxic; however, when the cells were pretreated with 0.1 µM pioglitazone for 12 h and then exposed to 1 µM Cd for 24 h, significant accumulation of Cd and cytotoxicity were detected, with an increase in megalin mRNA expression. In addition, pretreatment with pioglitazone significantly increased the Cd-induced generation of hydrogen peroxide and cell apoptosis. The augmented Cd-induced cytotoxicity and apoptosis on preincubation with pioglitazone were inhibited by prior treatment with GW 9662 (PPAR-γ antagonist). These findings suggest that a PPAR-γ agonist could augment Cd-induced oxidative injury and cell apoptosis, possibly dependent on the expression level of the uptake pathway.

The current study was aimed to investigate the ameliorative effect of lycopene against gentamicin-induced testicular toxicity in adult rat testes. Pretreatment with lycopene (4 mg/kg/day) significantly prevented the decrease in the absolute testes weight and relative testes weight and the reduction in sperm count, motility, viability, and daily sperm production in gentamicin (100 mg/kg/day)-treated rats. Gentamicin significantly decreased the level of serum testosterone and testicular lactate dehydrogenase-X and G6PDH activities but a marked increase was observed upon pretreatment with lycopene. Testicular caspase-3 and -9 activities were significantly increased but lycopene showed significant protection from gentamicin-induced apoptosis. Oxidative stress was induced by gentamicin treatment as evidenced by increased hydrogen peroxide level and lipid peroxidation and decreased the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities and glutathione content. These alterations were effectively prevented by lycopene pretreatment. Histopathological examination showed loss of spermatogenesis and morphological abnormalities of the testis after treatment with gentamycin. These abnormalities were effectively normalized by pretreatment with lycopene. In conclusion, gentamicin decreases rat testes weight and inhibits spermatogenesis. It induces oxidative stress and apoptosis by possible mitochondrial dysfunction. These data provide insight into the mode of action of gentamicin-induced testicular toxicity and the beneficial role provided by lycopene to restore the suppressed spermatogenesis.

The aim of the present study was to determine the protective and therapeutic effects of linalool (LIN) against doxorubicin (DOX)-induced cardiotoxicity in rats histologically and biochemically. In experiments, 64 male Wistar albino rats were randomly divided into eight groups ( n = 8). These groups were control (C) (0.9% saline solution), DOX (20 mg/kg DOX), LIN50 (50 mg/kg LIN), LIN100 (100 mg/kg LIN), DOX + LIN50 (20 mg/kg DOX and 50 mg/kg LIN), DOX + LIN100 (20 mg/kg DOX and 100 mg/kg LIN), LIN50 + DOX (50 mg/kg LIN and 20 mg/kg DOX), and LIN100 + DOX (100 mg/kg LIN and 20 mg/kg DOX). It was determined that necrosis and extensive inflammatory cell infiltration were observed in the DOX group. It was determined that histopathological changes significantly decreased in groups treated with LIN after DOX administration. While the caspase-3 immunostaining was highly evident in DOX group apoptotic cells ( p < 0.001, for all), the intensity of caspase-3 immunostaining in the treatment groups decreased ( p < 0.05). While DOX administration resulted in a significant increase in malondialdehyde (MDA) levels and plasma Creatine kinase (CK) and lactate dehydrogenase (LDH) levels in cardiac tissue when compared to the C groups, it was observed that DOX + LIN administration led to a significant decrease in MDA, plasma CK and LDH levels and a significant increase in glutathione (GSH), superoxide dismutase, and catalase enzyme levels. Finally, it was concluded that DOX led to heavy cardiotoxicity and DOX + LIN administration could remove cardiomyopathy symptoms.

Background: Bone marrow metastasis occurs in lung adenocarcinoma patients with a poor prognosis due to the late course and lack of definitive treatments, although reports on this are limited. This study analyzed the clinical manifestation, laboratory examination, treatment, and prognosis of patients with lung adenocarcinoma with bone marrow metastasis. Methods: All patients were confirmed to have bone marrow infiltration by bone marrow aspiration. The clinical data of 12 patients with lung adenocarcinoma with bone marrow metastasis were analyzed retrospectively. The prognostic factors were analyzed by Kaplan-Meier statistics. Results: The common biomarker abnormalities in 12 patients were elevated carcinoembryonic antigen in 12 cases (100%), elevated lactate dehydrogenase in 9 cases (75%), increased alkaline phosphatase and anemia in 8 cases each (66.7%), and thrombocytopenia in 4 cases (33.3%). After diagnosis of bone marrow metastasis, 5 patients were treated with platinum-based chemotherapy, 3 patients received chemotherapy and targeted drug tyrosine kinase inhibitor (TKI) therapy, 2 patients received simple TKI therapy, and 2 patients received only best supportive care (BSC) therapy. The median duration of survival after the diagnosis of bone marrow involvement was 422 days. The survival time of patients receiving TKI therapy after bone marrow metastasis was significantly better than that of patients receiving only BSC and chemotherapy (χ2=4.636, P=0.031). Conclusions: The survival period of patients with lung adenocarcinoma with bone marrow metastasis is short, and targeted drug TKI treatment can prolong the survival time for patients with EGFR mutation–carrying lung adenocarcinoma with bone marrow metastasis.

Background: The predominance of neutrophils in pleural effusions of patients with different serious impairments of the pleural cavity organs is often found. The aim of this study was to identify the type of injury using the cytological-energy analysis of pleural effusions. Methods: We analysed 635 samples of pleural effusions with predominance of neutrophils. We compared the values of the coefficient of energy balance (KEB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) catalytic activities in the following subgroups of patients: with transudative effusions, purulent pneumonia, chest empyema and after chest surgery with and without purulent complications. Statistical analysis was performed using the ANOVA Kruskal–Wallis test ( p Results: We found the lowest KEB values in pleural effusions of patients with chest empyema and their gradual increases in patients with purulent pneumonia and with transudative effusions. We observed the highest LDH and AST enzymes activity in patients with chest empyema and their gradual decrease in patients with purulent pneumonia and with transudative effusions. LDH and AST enzymes activity was significantly higher in pleural effusions of patients after chest surgery with purulent complications compared with non-purulent cases. Conclusion: The most intensive inflammation and the most extensive tissue destruction in the pleural cavity were found in patients with chest empyema. Significantly better parameters were observed in patients with purulent pneumonia. The absence of serious inflammation and the absence of tissue destruction were typical for patients with transudative effusions. Finally, our results confirmed an anticipated higher tissue destruction in patients after chest surgery. Significantly worse injury was found in surgical patients with purulent complications compared with non-purulent ones. The reviews of this paper are available via the supplemental material section.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in more than five hundred million infected cases worldwide. The current study aimed to screen the correlation of different laboratory findings with disease severity and clinical outcomes of coronavirus disease (COVID-19) among Egyptian patients to obtain prognostic indicators of disease severity and outcome. A total of 112 laboratory-confirmed COVID-19 patients were examined. According to the severity of the disease, these patients were divided into three main groups: mild, moderate and severe cases. In addition, clinical characteristics and laboratory findings, including Hb, platelet count, white blood cell count, lymphocyte percentage, neutrophil percentage, neutrophil lymphocyte ratio (NLR), D-dimer, highly sensitive C-reactive protein (HS-CRP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine, were measured. The presence of hypertension and/or diabetes was found to be a significant risk factor for disease severity and poor outcome. Increased respiratory rate, levels of SpO2, HS-CRP, D-dimer, NLR, ALT, LDH, lymphopenia and neutrophilia, as well as changes in chest computed tomography (CT), were associated with increased disease severity and fatal consequences. Highly sensitive C-reactive protein, D-dimer, NLR and LDH constituted excellent predictors for both disease severity and death. Laboratory biomarkers, such as HS-CRP, D-dimer, NLR and LDH, are excellent predictors for both disease severity and death. They can predict mortality in patients at the time of admission secondary to SARS-CoV-2 infection and can help physicians identify high-risk patients before clinical deterioration.

Background. The cardioprotective effects of Persea americana extract was investigated on biochemical activities of high salt–fed adult Wistar rats in this study. Method. Forty healthy Wistar rats of both sexes weighing 120 to 150 g were randomly assigned into 8 groups of 5 rats each (groups A, B, C, D, E, F, G, and H). Rats in groups A, F, G, and H were fed with standard laboratory pellets, while groups B, C, D, and E were fed on the high-salt diet for 4 weeks. Concomitantly, daily administration of 50, 100, and 150 mg/kg of the P americana extract were given orally to groups C and F, D and G, and E and H, respectively, while rats in groups A and B were administered distilled water. Blood samples were taken by cardiac puncture; concentration of sodium ion, potassium ion, nitric oxide, and activity of lactate dehydrogenase were determined. One-way analysis of variance was used to analyze data, followed by Student-Newman-Keuls (SNK) test for multiple comparison. Results. Results revealed that concentration of potassium ion and nitric oxide was significantly lower ( P < .05) in high salt–fed groups. Sodium ion concentration and activity of lactate dehydrogenase were higher in high salt–fed group while P americana prevented biochemical perturbations in other experimental groups. Conclusion. In conclusion, high salt–diet induced biochemical alterations which were significantly protected by oral administration of P americana extract.

Background: Nitric oxide (NO) is an effective mediator of ischemic preconditioning (IPC)-induced cardioprotection. Atrial natriuretic peptide (ANP) is downregulated after ovariectomy, which results in reduction in the level of NO. The present study deals with the investigation of the role of ANP in abrogated cardioprotective effect of IPC in the ovariectomized rat heart. Methods: Heart was isolated from ovariectomized rat and mounted on Langendorff’s apparatus, subjected to 30 min of ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Krebs–Henseleit solution. The myocardial infract size was estimated employing triphenyltetrazolium chloride stain, and coronary effluent was analyzed for creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) release to consider the degree of myocardial injury. The cardiac release of NO was estimated by measuring the level of nitrite in coronary effluent. Results: IPC-mediated cardioprotection was significantly attenuated in ovariectomized rat as compared to normal rat, which was restored by perfusion with ANP. However, this observed cardioprotection was significantly attenuated by perfusion with L-NAME, an endothelial nitric oxide synthase inhibitor, and Glibenclamide, a KATP channel blocker, alone or in combination noted in terms of increase in myocardial infract size, release of CK-MB and LDH, and also decrease in release of NO. Conclusion: Thus, it is suggested that ANP restores the attenuated cardioprotective effect of IPC in the ovariectomized rat heart which may be due to increase in the availability of NO and consequent increase activation of mitochondrial KATP channels.

Diabetes patients suffer from chronic disorders in the metabolism due to high blood sugar caused by anomalies in insulin excretion. Recently, vanadium compounds have been prepared and functionalized to decrease the level of hyperglycemia. Vitamin A boosts beta cell activity; therefore, the lack of this vitamin plays a role in the development of type 2 diabetes. The aim of this article focused on the synthesis of a new anti-diabetic drug formed from the complexation of a vanadium(IV) salt with vitamin A. Vitamin A acts as a unidentate chelate through the oxygen of its –OH group. The vanadium(IV) compound is surrounded by two vitamin A molecules. The [VO(vitamin A)2(H2O)2] compound was synthesized in a binary solvent system consisting of MeOH/H2O (1:1 ratio) in alkaline media at pH = 8. This compound was characterized using Fourier transform infrared spectra (FT-IR), electronic spectra (UV–vis), effective magnetic moment, electron spin resonance (ESR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermal analysis (thermogravimetry (TG)–differential thermal analysis (DTA)). Anti-diabetic efficiency for the vanadium(IV) compound was assessed in streptozotocin (STZ)-induced diabetic mice. The results of the animal studies demonstrate the ability of the vanadium(IV) complex to act as an anti-diabetic agent, as measured by improvements of lipid profile, antioxidant activity (superoxide dismutase), malondialdehyde (MDA), glutathione, methionine synthase, and kidney and liver functions.

Hemorrhagic stroke is a devastating disease that lacks effective therapies. In the present investigation, we tested 6-bromoindirubin-3′-oxime (BIO) as a selective glycogen synthase kinase-3β (GSK-3β) inhibitor in a mouse model of intracerebral hemorrhage (ICH). ICH was induced by injection of collagenase IV into the striatum of 8- to 10-week-old C57BL/6 mice. BIO (8 μg/kg, IP) was administered following either an acute delivery (0–2 h delay) or a prolonged regimen (every 48 h starting at 3 days post-ICH). At 2 days post-ICH, the acute BIO treatment significantly reduced the hematoma volume. In the perihematoma regions, BIO administration blocked GSK-3β phosphorylation/activation, increased Bcl-2 and β-catenin levels, and significantly increased viability of neurons and other cell types. The prolonged BIO regimen maintained a higher level of β-catenin, upregulated VEGF and BDNF, and promoted neurogenesis and angiogenesis in peri-injury zones at 14 days after ICH. The BIO treatment also promoted proliferation of neural stem cells (NSCs) and migration of nascent DCX+ neuroblasts from the subventricular zone (SVZ) to the lesioned cortex. BIO improved functional outcomes on both the neurological severity score and rotarod tests. The findings of this study corroborate the neuroprotective and regenerative effects of BIO and suggest that the Wnt/GSK-3β/β-catenin pathway may be explored for the treatment of acute or chronic ICH.

Xylaria nigripes ( XN) is a medicinal fungus that was used traditionally as a diuretic, nerve tonic, and for treating insomnia and trauma. In this study, we elucidated possible mechanisms of neuroprotective effects of XN mycelia extracts. XN mycelia were produced by fermentation. Hot water extract and 70% ethanol extract of XN mycelia were evaluated on hydrogen peroxide (H2O2)-induced apoptosis in PC12, a rat pheochromocytoma cell line. Both XN extracts effectively protected PC12 cells against H2O2-induced cell damage by inhibiting release of lactate dehydrogenase, decreasing DNA damage, restoring mitochondrial membrane potential, and arresting abnormal apoptosis through upregulation of Bcl-2 and downregulation of Bax and caspase 3. Compared to water extract, ethanol extract showed not only greater neuroprotective effects but also a higher antioxidant activity by scavenging DPPH radicals, inhibiting lipid peroxidation, and reducing power. High phenolic content and antioxidant activity may provide the neuroprotective properties of XN ethanol extract.

Background The most common way to validate a pneumatic tube system is to compare pneumatic tube system-transported blood samples to blood samples carried by hand. The importance of measuring the forces inside the pneumatic tube system has also been emphasized. The aim of this study was to define a validation protocol using a mini data logger (VitalVial, Motryx Inc., Canada) to reduce the need for donor samples in pneumatic tube system validation. Methods As an indicator of the total vibration, the blood samples are exposed to under pneumatic tube system transportation; the area under the curve was determined by a VitalVial for all hospital Tempus600 lines using a five-day validation protocol. Only the three lines with the highest area under the curves were clinically validated by analysing potassium, lactate dehydrogenase and aspartate aminotransferase. A month after pneumatic tube system commissioning, a follow-up on laboratory data was performed. Results Mean area under the curve of the six lines ranged between 347 and 581. The variability of the area under the curve was between 1.51 and 11.55%. In the laboratory data follow-up, an increase in lactate dehydrogenase haemolysis was seen from the three lines with the highest area under the curve and the emergency department, which was not detected in the clinical validation. When the Tempus600 system was in commission, a higher mean area under the curve was measured. Conclusion A three-day validation protocol using VitalVials is enough to determine the stability of a Tempus600 system and can greatly reduce the need for donor samples. When in commission, the stability of the pneumatic tube system should be verified and lactate dehydrogenase haemolysis should be routinely checked.

Background:Attenuated cardioprotective effect of ischemic preconditioning (IPC) by reduced nitric oxide (NO) is a hallmark during diabetes mellitus (DM). Recently, we reported that the formation of caveolin–endothelial nitric oxide synthase (eNOS) complex decreases the release of NO, which is responsible for attenuation of IPC-induced cardioprotection in DM rat heart. Heme oxygenase-1 (HO-1) facilitates release of NO by disrupting caveolin–eNOS complex. The activity of HO-1 is decreased during DM. This study was designed to investigate the role of hemin (HO-1 inducer) in attenuated cardioprotective effect of IPC in isolated diabetic rat heart.Methods:DM was induced in male Wistar rat by single dose of streptozotocin. Cardioprotective effect was assessed in terms of myocardial infarct size and release of lactate dehydrogenase and creatine kinase in coronary effluent. The release of NO was estimated indirectly by measuring the release of nitrite in coronary effluent. Perfusion of sodium nitrite, a precursor of NO, was used as a positive control.Result:IPC-induced cardioprotection and increased release of nitrite were significantly attenuated in a diabetic rat as compared to a normal rat. Pretreatment with hemin and daidzein, a caveolin inhibitor, alone or in combination significantly restored the attenuated cardioprotection and increased the release of nitrite in diabetic rat heart. Zinc protoporphyrin, a HO-1 inhibitor, significantly abolished the observed cardioprotection and decreased the release of nitrite in hemin pretreated DM rat heart.Conclusion:Thus, it is suggested that hemin restores the attenuated cardioprotective effect in diabetic rat heart by increasing the activity of HO-1 and subsequently release of NO.

Cyclosporine-A (CsA) is an immunosuppressive drug which has been used to prevent rejection after organ transplantation and to treat certain autoimmune diseases. However, its therapeutic use is limited by nephrotoxicity. In this study, the modulator effect of allicin on the oxidative nephrotoxicity of CsA in rats was investigated. Furthermore, the effect of allicin on CsA-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was estimated. Rats were divided into three groups, control, CsA (15 mg/kg, subcutaneously), and CsA/allicin (50 mg/kg, orally). At the end of the study, all rats were killed and then blood, urine samples, and kidneys were taken. CsA administration caused a severe nephrotoxicity which was evidenced by elevated kidney/body weight ratio, serum creatinine (Cr), blood urea nitrogen, lactate dehydrogenase, and urinary protein with a concomitant reduction in serum albumin and Cr clearance as compared with control. A significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione, superoxide dismutase activities, and nitric oxide (NOx) content was detected upon CsA administration. Exposure to CsA increased the sensitivity of isolated urinary bladder rings to ACh. Histological analysis revealed that CsA caused tubular necrosis and moderate diffuse tubular atrophy. Allicin protected kidney tissue against the oxidative damage and the nephrotoxic effect of CsA and significantly reduced the responses of isolated bladder rings to ACh. Our study indicates that allicin administration has the potential to protect against CsA-induced renal injury by reducing oxidative stress and inflammation and restoring NOx level.

Atorvastatin is considered to be one of the most commonly used of all statins anti-hyperlipidemic drugs despite the fact that there is much controversy about its safety. Its therapeutic use becomes severely limited by the hazards of inducing myotoxicity. Curcumin is one of the safe spices that have chemoprotection and cytoprotection effects against endogenous and exogenous noxious stimuli. This study investigates the effect of curcumin on atorvastatin sub-chronic use-induced myotoxicity in rats by the assessment of serum creatinine phosphokinase, lactic acid dehydrogenase, myoglobin, troponin, potassium, creatinine, and histopathological changes of skeletal, smooth, and cardiac muscles by light and electron microscope examination. Eighty adult albino rats were divided into four groups; each group consists of 20 rats. The control group received water, the second group received atorvastatin, the third group received curcumin, and the fourth group received curcumin with atorvastatin for 90 days by gastric gavage. The prolonged use of atorvastatin induced significant abnormalities of all myotoxicity biomarkers associated with histopathological and ultrastructural changes in the different types of the muscles. Co-administration of curcumin with sub-chronic use of atorvastatin led to an improvement in myotoxicity manifestations.

Naringenin is a naturally occurring flavanones and has been found to exhibit free radical scavenging, enzyme inhibition, antioxidants, anti-inflammatory, and anticancer activities. Present study was designed to evaluate the protective role of naringenin against benzo[a]pyrene (B[a]P)-induced oxidative stress and pulmonary toxicity. Rats were treated with naringenin at a dose of 100 mg/kg body weight (b. wt.), by oral gavage. B[a]P in a single dose of 50 mg/kg b. wt. was given intraperitoneally. Total protein, total cell counts, lactate dehydrogenase, lipid peroxidation, reduced glutathione, antioxidant enzymes activities, lung histology and expression of nuclear factor kappa B (NF-κB), and cyclo-oxygenase-2 (COX-2) was assessed to evaluate protective effects of naringenin. Histopathological and immunohistochemical studies were also carried out to observe lung toxicity and inflammation. B[a]P administration enhanced the levels of lung injury markers and reduced antioxidant enzymes activities. Naringenin treatment attenuated the levels of oxidative stress by restoring antioxidant enzymes, further improved lung histological damage and significant decrease in inflammatory responses. Naringenin also effectively decreased the expression of NF-κB, and COX-2 induced by B[a]P. These findings suggest that naringenin supplementation is beneficial in maintaining the integrity of alveoli and the epithelium that may be used as a protective agent in B[a]P-induced oxidative stress and lung damage. However, further studies are warranted to elucidate the potential mechanism of action of naringenin.

Objective: To investigate the characteristics of central nervous system (CNS) involvement in children with non-Hodgkin’s lymphoma (NHL) and the value of flow cytometry (FC) in the diagnosis of CNS disease in pediatric NHL. Methods: The data of 56 newly diagnosed pediatric NHL patients with CNS involvement (CNS+/mass, CNS+/palsy, CNS+/CSF) were analyzed. The proportions and formats of CNS disease in different pathological types were compared. In addition, FC and conventional cytology (CC) of cerebrospinal fluid (CSF) were carried out in 383 newly diagnosed NHL cases. Results: A total of 383 children with NHL were enrolled. Among these patients, 56 (14.6%) were diagnosed with positive CNS involvement (CNS+), 33 had bulky disease (tumor diameter >10 cm), 32 had bone marrow invasion, 32 had lactate dehydrogenase levels >1000 U/L, and 25 had invasion of more than 4 organs at the time of diagnosis. There were 14 patients with T lymphoblastic lymphoma (T-LBL), 9 with B lymphoblastic lymphoma (B-LBL), 26 with Burkitt’s lymphoma (BL), and 2 with Epstein-Barr virus-positive diffuse large B cell lymphoma (EBV + DLBCL). Among the 56 CNS+ patients, 35 were CSF-positive (CSF+); there were 2 patients who were CSF+ via CC detection and 35 who were CSF+ via FC detection. The difference between CC and FC was statistically significant ( P < 0.01). In the T-LBL group, 14 patients were CNS+/CSF, and in the B-LBL group, 8 were CNS+/mass. In the BL group, 22 patients were CNS+/mass and 15 were CNS+/CSF. In the anaplastic large-cell lymphoma group, 5 patients were CNS+/mass. Nine of the 56 CNS+ patients had events. The 2-year overall survival rate was 87% ± 0.046%, and the 2-year event-free survival rate was 76.2% ± 0.07%. Conclusion: CNS+ diagnoses were more common in pediatric NHL patients with bulky disease and/or bone marrow involvement and/or involvement of more than 4 organs at the time of diagnosis, and they were also common in the EBV + DLBCL and BL groups. FC of CSF showed important clinical significance in the diagnosis of CNS disease in pediatric NHL patients, and it can be used to significantly improve the CNS+ detection rate.

In the 1920s, Otto Warburg observed the phenomenon of altered glucose metabolism in cancer cells. Although the initial hypothesis suggested that the alteration resulted from mitochondrial damage, multiple studies of the subject revealed a precise, multistage process rather than a random pattern. The phenomenon of aerobic glycolysis emerges not only from mitochondrial abnormalities common in cancer cells, but also results from metabolic reprogramming beneficial for their sustenance. The Warburg effect enables metabolic adaptation of cancer cells to grow and proliferate, simultaneously enabling their survival in hypoxic conditions. Altered glucose metabolism of cancer cells includes, inter alia, qualitative and quantitative changes within glucose transporters, enzymes of the glycolytic pathway, such as hexokinases and pyruvate kinase, hypoxia-inducible factor, monocarboxylate transporters, and lactate dehydrogenase. This review summarizes the current state of knowledge regarding inhibitors of cancer glucose metabolism with a focus on their clinical potential. The altered metabolic phenotype of cancer cells allows for targeting of specific mechanisms, which might improve conventional methods in anti-cancer therapy. However, several problems such as drug bioavailability, specificity, toxicity, the plasticity of cancer cells, and heterogeneity of cells in tumors have to be overcome when designing therapies based on compounds targeted in cancer cell energy metabolism.

Electromagnetic field at extremely low frequencies plays a significant role in the physiological function of human tissues and systems. It is shown that electromagnetic field inhibits production of reactive oxygen species which are involved in heart injury triggered by oxidative stress. We hypothesize that low frequency electromagnetic field protects function of cardiac cells from ischemia–reperfusion injury. Human cardiac myocytes, endothelial cells, and cardiac fibroblast underwent ischemia–reperfusion conditions in the presence or in the absence of low frequency electromagnetic field. LDH and MMP-2 activities (as markers of cell injury), and cell metabolic activity (by fluorescein diacetate staining) were measured to determine the protective role of low frequency electromagnetic field. Our data showed that short courses of low frequency electromagnetic field protect cardiac cells from cellular damage and preserve their metabolic activity during ischemia–reperfusion. This study demonstrates the possibility to use of low frequency electromagnetic field as strategy for the prevention or therapy of ischemia–reperfusion injury. Impact statement In our study, we showed that LF-EMF may be protective for heart during ischemia–reperfusion (I/R). Following is the short description of the main findings: (a) the response to the I/R injury was different for endothelial cells, fibroblasts, and cardiomyocytes; (b) I/R decreases MMP-2 activity in cardiac myocytes and fibroblasts; (c) I/R increases MMP-2 activity in endothelial cells; (d) LF-EMF reverses these changes; (e) LF-EMF protects cells from injury and preserves their metabolic activity.

The effect of hybrid material—graphene flakes with Fe3O4 nanospheres (GO-Fe3O4), graphene oxide (GO) and magnetite nanospheres (Fe3O4) in rotating magnetic field on mammalian cells metabolism has been studied. Several reports shown that exposure to magnetic field may have influence on cellular membrane permeability. Thus, the aim of presented study was to determine the cellular response of L929 fibroblast cells to nanomaterials and rotating magnetic field for 8-h exposure experiment. The GO had tendency to adsorb proteins, thus cell metabolism was decreased and the effect of that mechanism was enhanced by impact of nanospheres and rotating magnetic field. The highest reduction of cellular metabolism was recorded for WST-1 and NR assays at concentration 100 µg/mL of all tested nanomaterials and magnetic induction value 10.06 mT. The lactate dehydrogenase leakage assay has shown significant changes in membrane permeability. Further studies need to be carried out to precisely determine the mechanism of that process.

Dietary supplements containing plant materials of Annonaceae species ( Annona muricata L., A. squamosa L., A. mucosa JACQ., A. squamosa × cherimola Mabb.) were extracted by hot, pressurized ethyl acetate and analyzed for their effect in vitro on Lund human mesencephalic neurons. Cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell death was determined by lactate dehydrogenase levels. Three supplements strongly decreased the cell viability at extract concentrations of 1 µg/mL, of which 1 decreased cell viability at 0.1 µg/µL. Also, strong neuronal toxicities of these supplements were found. Cell death was observed at concentrations of 10 µg/mL. The degree of toxicity was comparable to the ones found in Annonaceous fruit extracts. Two fruit pulps of Annonaceae ( A. muricata and A. squamosa) showed a reduction in cell viability at lower concentrations. The fruit pulp extract of A. muricata revealed the strongest neurotoxic effect, with 67% cell death at a concentration of 1 µg/mL. A high reduction in cell viability coupled with pronounced cell death was found at 0.1 µg/mL for an Annonaceous seed extract. These results demonstrate that the intake of dietary supplements containing plant material from Annonaceae may be hazardous to health in terms of neurotoxicity.

This study investigates the possible protective effects of montelukast (MNT) against lipopolysaccharide (LPS)-induced cardiac injury, in comparison to dexamethasone (DEX), a standard anti-inflammatory. Male Sprague Dawley rats (160–180 g) were assigned to five groups ( n = 8/group): (1) control; (2) LPS (10 mg/kg, intraperitoneal (i.p.)); (3) LPS + MNT (10 mg/kg, per os (p.o.)); (4) LPS + MNT (20 mg/kg, p.o.); and (5) LPS + DEX (1 mg/kg, i.p.). Twenty-four hours after LPS injection, heart/body weight (BW) ratio and percent survival of rats were determined. Serum total protein, creatine kinase muscle/brain (CK-MB), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities were measured. Heart samples were taken for histological assessment and for determination of malondialdehyde (MDA) and glutathione (GSH) contents. Cardiac tumor necrosis factor α (TNF-α) expression was evaluated immunohistochemically. LPS significantly increased heart/BW ratio, serum CK-MB, ALP, and LDH activities and decreased percent survival and serum total protein levels. MDA content increased in heart tissues with a concomitant reduction in GSH content. Immunohistochemical staining of heart specimens from LPS-treated rats revealed high expression of TNF-α. MNT significantly reduced percent mortality and suppressed the release of inflammatory and oxidative stress markers when compared with LPS group. Additionally, MNT effectively preserved tissue morphology as evidenced by histological evaluation. MNT (20 mg/kg) was more effective in alleviating LPS-induced heart injury when compared with both MNT (10 mg/kg) and DEX (1 mg/kg), as evidenced by decrease in positive staining by TNF-α immunohistochemically, decrease MDA, and increase GSH content in heart tissue. This study demonstrates that MNT might have cardioprotective effects against the inflammatory process during endotoxemia. This effect can be attributed to its antioxidant and/or anti-inflammatory properties.

Cerebral ischemia induces a complex transcriptional response with global changes in gene expression. It is essentially regulated by transcription factors as well as epigenetic players. While it is well known that the inhibition of transcriptionally repressive histone deacetylases leads to neuroprotection, the role of histone methyltransferases in the postischemic transcriptional response remains elusive. We investigated the effects of inhibition of the repressive H3K9 histone methyltransferases SUV39H1 and G9a on neuronal survival, H3K9 promoter signatures and gene expression. Their inhibition either with the specific blocker chaetocin or by use of RNA interference promoted neuronal survival in oxygen glucose deprivation (OGD). Brain-derived neurotrophic factor (BDNF) was upregulated and BDNF promoter regions showed an increase in histone marks characteristic for active transcription. The BDNF blockade with K252a abrogated the protective effect of chaetocin treatment. In conclusion, inhibition of histone methyltransferases SUV39H1 and G9a confers neuroprotection in a model of hypoxic metabolic stress, which is at least in part mediated by BDNF.

Objective: Diabetes mellitus (DM) and hypercholesterolemia (HC) when poorly controlled lead to debilitating central nervous system complications including cognitive deficits and memory impairment. In the present study, we investigated the mechanisms that may be responsible for such deficits. Methods: Both diabetes and HC were induced in two groups of rats independently using alloxan and high cholesterol diet, respectively. Results: Acetyl cholinesterase was significantly increased in brain of diabetic rats. Also, brain malondialdehyde level was extremely elevated in both diabetic and hypercholesterolemic groups. Meanwhile, brain albumin was markedly decreased in both of them. However, the brain iron level was significantly increased in DM with concomitant increase in total antioxidant capacity in the same group as compared to the normal control. The concentration of brain calcium was noticeably increased in HC group. Our results were confirmed by the increased activity of lactate dehydrogenase in both DM and HC groups, indicating major brain cytotoxicity. Conclusions: Overall, our results suggested that both DM and HC have deleterious effects on the brain which may be attributed to oxidative stress and dysregulation of both cholinergic function and calcium level. Administration of antioxidant is recommended in both cases.

This research studied the extraction from Microcystis aeruginosa using hydrochloric acid method as a potentially valuable protein resource from eutrophic lakes. Amino acid composition, residual algal toxins, and heavy metals of the acidolysis product were studied. After 18 h of hydrochloric acid treatment, the product of M. aeruginosa contained 17 amino acids, 51.34% of total amino acid requirements, and 30.25% of the livestock and poultry essential amino acid (Eaa). The residual microcystin-LR (MC-LR) was 0.94 µg kg−1, which was less than WHO drinking water limit of microcystins. The removal ratio of microcystins was higher than 99.99% during the process of hydrolysis. The concentration of heavy metals of the product was in compliance with feed standards. Furthermore, using Horn’s method, Mouse Micronucleus Test and Sperm Shape Abnormality Test were conducted to study the forage safety of the product. Half lethal dose (LD50) of acidolysis product in mice was >9.09 g kg−1 body weight, actually belonging to non-toxic grade. Every dose treatment did not significantly increase activities of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyltransferase (γ-GT). The results of both micronucleus test and sperm shape abnormality test were negative, which suggested the product with no mutagenicity and sperm malformation effects. This study indicated that the acidolysis product of M. aeruginosa was safe to be used as a feed ingredient.

Mitogen-activated protein kinase (MAPK) signaling has been implicated in a wide range of neuronal processes, including development, plasticity, and viability. One of the principal downstream targets of both the extracellular signal-regulated kinase/MAPK pathway and the p38 MAPK pathway is M itogen- and S tress-activated protein K inase 1 (MSK1). Here, we sought to understand the role that MSK1 plays in neuroprotection against excitotoxic stimulation in the hippocampus. To this end, we utilized immunohistochemical labeling, a MSK1 null mouse line, cell viability assays, and array-based profiling approaches. Initially, we show that MSK1 is broadly expressed within the major neuronal cell layers of the hippocampus and that status epilepticus drives acute induction of MSK1 activation. In response to the status epilepticus paradigm, MSK1 KO mice exhibited a striking increase in vulnerability to pilocarpine-evoked cell death within the CA1 and CA3 cell layers. Further, cultured MSK1 null neurons exhibited a heighted level of N-methyl-D-aspartate-evoked excitotoxicity relative to wild-type neurons, as assessed using the lactate dehydrogenase assay. Given these findings, we examined the hippocampal transcriptional profile of MSK1 null mice. Affymetrix array profiling revealed that MSK1 deletion led to the significant (>1.25-fold) downregulation of 130 genes and an upregulation of 145 genes. Notably, functional analysis indicated that a subset of these genes contribute to neuroprotective signaling networks. Together, these data provide important new insights into the mechanism by which the MAPK/MSK1 signaling cassette confers neuroprotection against excitotoxic insults. Approaches designed to upregulate or mimic the functional effects of MSK1 may prove beneficial against an array of degenerative processes resulting from excitotoxic insults.

The aim is to estimate the prognostic value of lactate dehydrogenase (LDH) in patients undergoing surgical resection for laryngeal squamous cell carcinoma (LSCC). A total of 640 resected LSCC patients were included. Preoperative lactate dehydrogenase (LDH) was assessed. Kaplan-Meier survival analysis and Cox regression analysis were conducted for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis, univariate analysis and multivariate analysis demonstrated significant prognostic value for preoperative LDH. Although LDH was predictor of OS, it failed to be a predictor of RFS. The univariate HR and 95% CI of LDH were 0.484 and 0.357-0.658 (P < 0.0001). The multivariate analysis showed that LDH (HR = 0.518, 95% CI: 0.380-0.705, p < 0.0001) was related to OS. Elevated preoperative LDH >132 IU/L was significantly associated with better survival. Preoperative LDH might be an independent prognostic marker of OS in LSCC patients undergoing surgical resection.

Introduction: We compared the systemic inflammatory response of the MCPB system to the CCPB system with cell salvage and phosphorylcholine-coated tubing amongst Asian patients undergoing coronary artery bypass grafting. Methods: Seventy-eight patients were randomly assigned to the MCPB or the CCPB groups equally and followed up in a prospective, single-blinded, randomised, controlled trial. Levels of TNF-α, IL-6, CRP and LDH were measured peri-operatively. Results: The systemic inflammatory response was similar in both groups (TNF-α: p=0.222; IL-6: p=0.991; CRP: p=0.258). Only haemolysis was significantly higher in the CCPB group (LDH: p=0.011). The MCPB system was twice more expensive, but had a near 4-fold cost saving in tranfusions. Overall, the MCPB system cost 20% more than the modified CCPB system. Conclusion: These results corroborate with studies that demonstrated the avoidance of cardiotomy suction rather than the MCPB system, itself, leads to an attenuated inflammatory response. The absence of obvious clinical benefit and the higher costs involved with the MCPB system would preclude its routine use.

The protective effect of quercetin (QT) on atrazine (ATZ)-induced testicular damage in rats was investigated. Sexually mature male Wistar rats (weighing 220–250 g) divided into four groups with six animals in each group were given ATZ (120 mg kg−1; 1/16 of the median lethal dose for an oral dose) and/or QT (10 mg kg−1) daily via gavage for 16 days. By the end of day 16, rats given ATZ alone had significantly lower sperm counts, daily spermatozoa production, and sperm motility and significantly higher abnormal sperm numbers than the untreated control rats. The rats given ATZ alone also had significantly decreased 3β-hydroxtsteroid dehydrogenase (HSD) and 17β-HSD activities than the control rats. Lactate dehydrogenase activity and malondialdehyde levels were significantly increased, whereas superoxide dismutase activity decreased but glutathione levels remain unaffected after ATZ exposure. These changes were reversed toward control values in the QT + ATZ-treated animals, though the sperm motility was 28% below the control levels but was still higher than in the ATZ-treated rats. The results indicate that QT might improve testicular function of rats exposed to ATZ, but its protective effect on sperm motility might be partial.

The 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) is an environmental contaminant toxicant that mediates carcinogenic effects associated with oxidative DNA damage. Docosahexaenoic acid (DHA) with antioxidant functions has many biochemical, cellular, and physiological functions for cells. The present study assessed, for the first time, the ameliorative effect of DHA in alleviating the toxicity of TCDD on primary cultured rat hepatocytes (HEPs). In vitro, isolated HEPs were incubated with TCDD (5 and 10 μM) in the presence and absence of DHA (5, 10, and 20 μM) for 48 h. The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release. DNA damage was analyzed by liver micronucleus assay and 8-oxo-2-deoxyguanosine (8-OH-dG) level. In addition, total antioxidant capacity (TAC) and total oxidative stress (TOS) were assessed to determine the oxidative injury in HEPs. The results of MTT and LDH assays showed that TCDD decreased cell viability but not DHA. On the basis of increasing treatment concentrations, the dioxin caused significant increases of micronucleated HEPs and 8-OH-dG as compared to control culture. TCDD also led to significant increases in TOS content. On the contrary, in cultures treated with DHA, the level of TAC was significantly increased during treatment in a concentration-dependent fashion. DHA showed therapeutic potential against TCDD-mediated cell viability and DNA damages. As conclusion, this study provides the first evidence that DHA has protective effects against TCDD toxicity on primary cultured rat hepatocytes.

One of the main challenges for clinical implementation of small diameter vascular grafts (SDVGs) is their limited hemocompatibility. Important design specifications for such grafts include features that minimize the long-term risks of restenosis, fouling, and thrombus formation. In our lab, we have developed elastomeric hollow fiber membranes (HFMs), using a phase inversion method, as candidates for SDVGs. Here, we present our results for in vitro hemocompatibility testing of our HFM under flow and static conditions. Our results showed that the polymer-based HFMs do not damage the integrity of human red blood cells (RBCs) as shown by their low hemolytic extent (less than 2%). When analyzed for blood cell lysis using lactate dehydrogenase (LDH) activity as an indicator, no significant differences were observed between blood exposed to our HFMs and uncoagulated blood. Analysis of protein adsorption showed a low concentration of proteins deposited on the surfaces of HFM after 24 h. Platelet adhesion profiles using human platelet-rich plasma (PRP) showed that a low level of platelets adhered to the HFMs after 24 h, indicating minimal thrombotic potential. Under the majority of conditions, no significant differences were observed between medical-grade polymers and our HFMs. Eventual optimization of hemocompatible elastomeric HFM vessel grafts could lead to improved tissue vascularization as well as vascularized, tissue-engineered scaffolds for organ repair.

Chemotherapy-related hepatotoxicity is a limitation for the continuation of chemotherapy in patients with advanced colorectal cancer (CRC). This prospective study determined the efficacy of tiopronin infusion in chemotherapy-induced hepatoxicity.One hundred and fifty patients having advanced CRC treated with first-line palliative chemotherapy were included, of whom 86 were treated with mFOLFOX7 plus supplementation of tiopronin and 64 were treated with the same regimen without tiopronin. Aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), total bilirubin (TBIL), gamma-glutamyl transferase (γ-GT), alkaline phosphatase (ALP), and albumin (ALB) were recorded before treatment and during every therapy cycle. In addition, course discontinuations, dose reductions, and chemotherapy efficacy were evaluated.The age and gender of the two groups were comparable (P0.05). The proportions of abnormal mean ALT (P = 0.042), AST (P = 0.045), TBIL (P = 0.044) and ALB (P = 0.043) were significantly lower in the tiopronin group than the control group. Course discontinuations (P = 0.002), dose reductions (P = 0.005) and efficacy (P = 0.012) were significantly different between the two groups. Multivariate logistic regression analysis showed that the hepatoprotective drug played an important role in clinical outcome (OR = 6.837; 95% CI, 1.845 to 25.333; P = 0.004).Tiopronin tends to decrease the incidence of chemotherapy-induced hepatoxicity, enhance patients' tolerance to mFOLFOX7 treatment, and even benefit the efficacy of chemotherapy.

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium (Cr(VI)), is widely recognized as potentially hepatotoxic in humans and animals. Its toxicity is associated with overproduction of free radicals, which induces oxidative damage. This study focused on the possible protective effect of propylthiouracil (PTU) against potassium dichromate (K2Cr2O7). Female mice were divided into four groups (groups I–IV) with seven animals in each group. Group I served as a control, which received tap water; group II received K2Cr2O7 alone (75 mg kg−1 body weight (b.w.)) via drinking water; group III received both K2Cr2O7 via drinking water and PTU by intramuscular injection at a dose 2.5 mg/100 g−1 b.w. twice a week, and group IV received PTU alone twice a week for 30 days. Exposure of mice to Cr promoted oxidative stress with an increase in malondialdehyde, protein carbonyl, and advanced oxidation protein product levels. Nonenzymatic antioxidants such as glutathione, nonprotein thiol, vitamin C levels and enzymatic antioxidant activities such as glutathione peroxidase and superoxide dismutase were decreased, while catalase activity was increased. Biomarkers of liver injury such as aspartate and alanine transaminases, lactate dehydrogenase activities, bilirubin, albumin, and glucose levels were increased, while triglyceride and cholesterol levels decreased. Coadministration of PTU restored the above-mentioned parameters to near-normal values. The histological findings confirmed the biochemical results.

α-Pinene (α-pinene), a bicyclic monoterpene, is present in the oils of many species of coniferous trees, most notably the pine, and is known for its diverse biological properties such as antimicrobial, anti-inflammatory, antiproliferative and antioxidant. However, there are limited data on the cytogenetic and antioxidant effects of α-pinene in cultured human blood cells ( n = 5) for the first time. The purpose of this study was to investigate the genetic, oxidative, and cytotoxic effects of α-pinene in cultured human blood cells ( n = 5) for the first time. Human blood cells were treated with α-pinene (0 to 200 mg/L) for 24 and 48 h, and then cytotoxicity was detected by lactate dehydrogenase (LDH) release and (3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide) (MTT) assay, while DNA damage was also analyzed by micronucleus (MN) assay, chromosomal aberration (CA) assay and 8-oxo-2-deoxyguanosine (8-OH-dG). In addition, biochemical parameters (total antioxidant capacity (TAC) and total oxidative stress (TOS)) were examined to determine oxidative effects. The results of LDH and MTT assays showed that α-pinene (at 200 mg/L) decreased cell viability. In our in vitro test systems, it was observed that α-pinene did not cause any statistically important changes in the rates of studied genotoxicity endpoints but dose-dependent alterations were observed in TAC and TOS levels. α-Pinene treatment caused increases in TAC levels (at 25 and 50 mg/L) and decreases in TOS levels (only at 200 mg/L) on human lymphocytes. In conclusion, the findings of the present study confirm for the first time that α-pinene could be a significant source of natural antioxidant compound that may have beneficial health effects.

The present study was designed to investigate the protective effects of carvacrol against thioacetamide (TAA)-induced oxidative stress, inflammation and apoptosis in liver of Wistar rats. In this study, rats were subjected to concomitant prophylactic oral pretreatment of carvacrol (25 and 50 mg kg−1 body weight (b.w.)) against the hepatotoxicity induced by intraperitoneal administration of TAA (300 mg kg−1 b.w.). Efficacy of carvacrol against the hepatotoxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, histopathological changes, and expressions of inflammation and apoptosis. Carvacrol pretreatment prevented deteriorative effects induced by TAA through a protective mechanism in a dose-dependent manner that involved reduction of oxidative stress, inflammation and apoptosis. We found that the protective effect of carvacrol pretreatment is mediated by its inhibitory effect on nuclear factor kappa B activation, Bax and Bcl-2 expression, as well as by restoration of histopathological changes against TAA administration. We may suggest that carvacrol efficiently ameliorates liver injury caused by TAA.

Background Current sampling and transport conditions of samples in general practice can result in pseudohyperkalaemia. This study was undertaken to determine, in a general practice setting, whether there is any difference in haemolysis obtained when using BD Vacutainer® Rapid Serum Tubes (BD RST) compared with using BD Vacutainer® SST™ II Advance Blood Collection Tubes (BD SSTII). Methods Blood was collected from 353 patients requiring blood sampling who were attending 31 general practitioner practices in Belgium. For each patient, two BD SSTII tubes and two BD RST tubes were drawn in a randomized order. One of each pair of tubes was inverted five times, the other was not. Serum potassium concentration, serum LDH activity and haemolysis index were measured in each sample. Results There was no significant difference in measured potassium concentration according to tube type ( P = 0.16). Measured LDH activities were 1.7% higher in serum collected into BD SSTII tubes compared to BD RST tubes ( P = 0.02). When comparing serum from unmixed BD RST with BD SSTII tubes, there was a slight reduction in the haemolysis index but no significant difference in measured potassium concentration or LDH activity. Risk of hyperkalaemia was 4.8 times higher in serum from tubes that were incompletely filled compared to those that were filled with the correct amount of blood. Conclusion Both types of blood tubes are suitable for the measurement of serum potassium and LDH in patients from general practice. Tube inversion does not improve the accuracy of either serum potassium or LDH measurement. Blood tubes should be filled to the level recommended by the manufacturer to avoid artefactual increases in measured serum potassium concentration and LDH activity.

Ascorbic acid (AA) is a naturally occurring phenolic compound with antioxidant properties used in food, cosmetics, and pharmaceutical products. In this study, the effect of AA on ferric nitrilotriacetate (Fe-NTA)-induced hepatotoxicity in rats has been examined. Fe-NTA alone enhances ornithine decarboxylase activity to 4.5-fold and tritiated thymidine incorporation in DNA to 3.6-fold in livers compared with the corresponding saline-treated controls. The enhanced ornithine decarboxylase activity and DNA synthesis showed a reduction to 3.02- and 1.88-fold, respectively, at a higher dose of 2 mg AA per day per animal, compared with the Fe-NTA-treated groups. Fe-NTA treatment also enhanced the hepatic microsomal lipid peroxidation to 1.7-fold compared to saline-treated controls. These changes were reversed significantly in animals receiving pretreatment of AA. The present data shows that AA can reciprocate the toxic effects of Fe-NTA and can serve as a potent chemopreventive agent to suppress oxidant-induced tissue injury and hepatotoxicity in rats.

Alcohol intoxication and psychiatric medication overdoses, including antidepressants, are common emergency room events. Heavy alcohol and antidepressant exposure are able to induce changes in cytokines disturbing normal physiology. We examined the inflammatory and physiological effects of selective serotonin reuptake inhibitor (SSRI) medication after heavy alcohol exposure. Rats were randomly divided into Alc (EtOH 5g/kg, intravenous infusion for 3 h), SSRI (paroxetine oral intake) and Alc+SSRI groups. Serum samples were collected to measure blood ethanol, aspartate transferase, alanine transferase, creatine phosphokinase, lactate dehydrogenase, amylase, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels. Lactate dehydrogenase levels in bronchoalveolar lavage fluid were also examined. Liver, pancreas and lungs were removed after sacrifice and any pathological changes were catalogued. Ethanol infusion resulted in blood levels of ethanol of >100 mg/dL after ethanol infusion. Serum levels of aspartate transferase, alanine transferase, creatine phosphokinase, lactate dehydrogenase, amylase, TNF-α and IL-6 in the Alc+SSRI group were lower than in the Alc group. Moreover, pathological damages to the liver, pancreas and lungs were slightly lower in the Alc+SSRI group than in the Alc group. These findings suggested that SSRI is able to decrease the release of pro-inflammatory cytokines and thereby reduce liver and pancreas damage after heavy alcohol exposure.