Antioxidant and anti-inflammatory activities of lycopene against 5-fluorouracil-induced cytotoxicity in Caco2 cells

5-fluorouracil (5FU) is widely used to treat colorectal cancer (CC) and its main mechanisms of anticancer action are through generation of ROS which often result in inflammation. Here, we test the effect of Lycopene against 5FU in Caco2 cell line. Caco2 cells were exposed to 3 µg/ml of 5FU alone or with 60, 90, 120 µg/ml of lycopene. This was followed by assessment of cytotoxicity, oxidative stress, and gene expression of inflammatory genes. Our findings showed that Lycopene and 5FU co-exposure induced dose-dependent cytotoxic effect without compromising the membrane integrity based on the LDH assay. Lycopene also significantly enhanced 5FU-induced SOD activity and GSH level compared to control for all mixture concentrations (p < 0.01). Lycopene alone and combination with 5FU-induced expression of IL-1β, TNF-α, and IL-6. Furthermore, IFN-γ expression was significantly enhanced by only mixture of lycopene (90 µg/ml) and 5FU (p < 0.05). In conclusion, Lycopene supplementation with 5FU therapy resulted in improvement in antioxidant parameters such as catalase and GSH levels giving the cell capacity to cope with 5FU-mediated oxidative stress. Lycopene also enhanced IFN-γ expression in the presence of 5FU, which may activate antitumor effects further enhancing the cancer killing effect of 5FU.     

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

Cyanide and lactate levels in patients during chronic oral amygdalin intake followed by intravenous amygdalin administration

The natural compound amygdalin has gained high popularity among tumor patients as a complementary or alternative treatment option. However, due to metabolization of amygdalin to cyanide (HCN) following oral consumption, there could be a high risk of lactic acidosis caused by cyanide intoxication. The present retrospective study was undertaken to evaluate cyanide blood and lactate plasma levels of tumor patients (n = 55) before and after intravenous (i.v.) amygdalin infusion. All patients had also continuously ingested amygdalin tablets (3 x 500 mg/day), excepting on the days of i.v. administration. Each patient received one to five intravenous amygdalin treatments. The time period between each i.v. application ranged between 4–6 days. The initial i.v. dose was 6 mg (n = 28), 9 mg (n = 1), 15 mg (n = 1) or 18 mg (n = 25). The mean cyanide blood level before i.v. amygdalin administration was 34.74 μg/L, which increased significantly to a mean value of 66.20 μg/L after i. v. amygdalin application. In contrast, lactate decreased significantly from 1266 μmol/L pre-infusion to 868 μmol/L post-infusion. Increasing i.v. amygdalin by 1 mg was also associated with a significant increase in the cyanide level, while the lactate blood level significantly decreased. This is the first study evaluating cyanide levels under conditions employed by amygdalin administrators, i.e. after chronic oral amygdalin intake and then again after a closely subsequent intravenous amygdalin administration. Since lactate decreased, whilst cyanide increased, it is concluded that elevation of cyanide does not induce metabolic acidosis in terms of an increased lactate level.     

穴位埋线治疗进行性肌营养不良的疗效观察

目的观察穴位埋线联合糖皮质激素及神经营养药物治疗进行性肌营养不良的临床疗效。方法 50例进行性假肥大性肌营养不良患者,随机分为治疗组和对照组,每组25例。对照组采用糖皮质激素及神经营养药物治疗,治疗组在对照组基础上采用穴位埋线治疗。观察两组治疗前后10米步行时间和登梯时间及血清肌酸磷酸激酶(CPK)、乳酸脱氢酶(LDH)水平的变化,并比较两组临床疗效。结果两组治疗后及随访10米步行时间和登梯时间与同组治疗前比较,差异有统计学意义(P<0.05);两组治疗后及随访10米步行时间和登梯时间比较,差异有统计学意义(P<0.05)。两组治疗后及随访血清CPK、LDH水平较同组治疗前明显下降,差异有统计学意义(P<0.01);治疗组治疗后及随访血清CPK和LDH水平低于对照组(P<0.01)。治疗组总有效率为96.0%,对照组总有效率为72.0%,治疗组总有效率高于对照组(P<0.05)。结论穴位埋线联合糖皮质激素治疗进行性肌营养不良的临床疗效显著,可作为临床治疗进行性肌营养不良方案的优选方法。     

Comparison of Salivary and Serum Alkaline Phosphates Level and Lactate Dehydrogenase Levels in Patients with Tobacco Related Oral Lesions with Healthy Subjects - A Step Towards Early Diagnosis

Aim: To evaluate and compare salivary and serum levels of Alkaline Phosphates and Lactate Dehydrogenase in patients without the habit of tobacco, in patients with the habit of tobacco, in patients with benign oral lesions and in patients with oral premalignant lesions and oral malignant lesions. Material and Methodology: This study was comprised of 500 subjects, Group I: 100 healthy individuals without the habit of tobacco usage formed the control group. Group II: 100 patients with the habit of tobacco/ smoking consumption without any oral lesion. Group III: 100 patients with benign oral lesions. Group IV: 100 patients having the history of tobacco consumption and having apparent precancerous lesions like leukoplakia, erythroplakia. Group V:100  patients having frank oral cancer. The grade of dysplasia in these patients was statically correlated with the levels of serum and salivary ALP and LDH. Results: This study revealed that there was high expression of both serum and salivary ALP and LDH  in group IV and Group V as compared with the other groups and mean difference showed a statistically significant p value of less than 0.01. This study revealed that the in group V, the highest level of serum and salivary ALP was found in those patients who were reported with poorly differentiated oral cancer. Conclusion: Both Alkaline phosphates and Lactate dehydrogenase could be considered a sensitive markers for the detection of dysplasia with already existing precancancerous and cancerous lesions.     

Elevación del lactato en el postoperatorio como marcador de isquemia mesentérica aguda. Descripción de dos casos

Serum lactate is a non-specific marker of tissue hypoperfusion. Elevated serum lactate is used in the differential diagnosis of acute intestinal ischemia. Although this practice is controversial, in the absence of other validated markers lactate is still used because of its high sensitivity.We present the cases of two patients who developed acute mesenteric ischemia as a post-surgical complication. The patients reported moderate abdominal pain —a non-specific symptom in the postoperative context— and tests showed progressively increasing serum lactate levels, which facilitated suspicion and subsequent diagnostic confirmation through an imaging test.These cases highlight the physiopathological importance of lactate elevation in the perioperative context and of performing a differential diagnosis of its possible causes, including mesenteric ischemia. Although the outcome was negative in the first case, early suspicion allowed us to make an effective diagnosis and administer appropriate treatment in the second patient.     

Correlation between initial serum levels of lactate after return of spontaneous circulation and survival and neurological outcomes in patients who undergo therapeutic hypothermia after cardiac arrest

ObjectivesWe analysed the relationship between serum levels of lactate within 1 h of return of spontaneous circulation (ROSC) and survival and neurological outcomes in patients who underwent therapeutic hypothermia (TH).MethodsThis was a multi-centre retrospective and observational study that examined data from the first Korean Hypothermia Network (KORHN) registry from 2007 to 2012. The inclusion criteria were out-of-hospital cardiac arrest (OHCA) and examination of serum levels of lactate within 1 h after ROSC, taken from KORHN registry data. The primary endpoint was survival outcome at hospital discharge, and the secondary endpoint was poor neurological outcome (Cerebral Performance Category, CPC, 3–5) at hospital discharge. Initial lactate levels and other variables collected within 1 h of ROSC were analysed via multivariable logistic regression.ResultsData from 930 cardiac arrest patients who underwent TH were collected from the KORHN registry. In a total of 443 patients, serum levels of lactate were examined within 1 h of ROSC. In-hospital mortality was 289/443 (65.24%), and 347/443 (78.33%) of the patients had CPCs of 3–5 upon hospital discharge. The odds ratios of lactate levels for CPC and in-hospital mortality were 1.072 (95% confidence interval (CI) 1.026–1.121) and 1.087 (95% CI = 1.031–1.147), respectively, based on multivariate ordinal logistic regression analyses.ConclusionHigh levels of lactate in serum measured within 1 h of ROSC are associated with hospital mortality and high CPC scores in cardiac arrest patients treated with TH.     

Nitric oxide donors offer protection to RBC from storage lesion

BackgroundRed blood cell (RBC), which is the most commonly transfused blood component, due to its ability to save a life in absence of any other blood components, can be stored up to maximum 6 weeks by following standard preservation procedure. During storage, RBC undergoes various biophysical and biochemical changes (commonly known as storage lesion) for which blood transfusion with “old RBC” shows a lot of clinical problems especially relevant to critically ill patients. Recent research on S-nitrosylation of haemoglobin to improve oxygen delivery of banked blood revealed the important role of nitric oxide (NO) in protecting storage lesion.Materials and methodsIn the present study, we used various “NO donating” chemicals with different NO release dynamics and chemistries in RBC storage cocktails to test the effects of NO on storage lesion. Changes in different storage markers were evaluated after 7 days storage of pre-treated RBC.ResultsAll the NO donors have shown protection against hemolysis. However, S-nitroso glutathione (GSNO) ranks first in shielding RBCs from storage lesion and additionally, it helps in elevating the value of 2, 3-di phosphoglycerate (2, 3-DPG), improving the RBC membrane fluidity and decreasing the adhesion towards endothelial monolayer.DiscussionPresent study reveals that NO released from NO donors confers protection against storage lesions of the RBC. Further, the study confirms that pre-treatment with GSNO, a NO donor and a nitrosylating agent, ensures the best protection to RBC during low temperature storage, when compared to other NO donor treatments.     

Performance of a new rapid diagnostic test the lactate/glucose ratio of synovial fluid for the diagnosis of septic arthritis

ObjectiveTo evaluate the diagnostic performance of the synovial lactate, glucose and lactate/glucose ratio assay for the diagnosis of septic arthritis.MethodsIn this monocentric cross-sectional study, synovial fluids were prospectively obtained from patients with acute joint effusion (<30 days) on native joint. Septic arthritis was defined using Newman's criteria. To evaluate diagnostic performance, Receiver Operating Characteristic (ROC) curves with Area under the curve (AUC), Sensitivities (Se), Specificities (Sp), LR+ their 95% confidence intervals were calculated. Synovial fluid cultures with gram staining, crystal analyses, synovial fluid white blood cell counts (WBC), lactate and glucose assays were performed.ResultsA total of 233 synovial fluids were included. 25 patients had septic arthritis and 208 had non-septic arthritis (104 crystal-induced arthritis, 15 RA, 8 SpA, 6 reactive arthritis, and 75 acute arthritis of undifferentiated origin). Synovial lactate/glucose ratio performed higher than the synovial lactate or glucose assay separately (AUC: 0.859 [0.772–0.945]). Best synovial lactate/glucose ratio threshold to differentiate septic arthritis from non-septic arthritis was 5 Se 52% [0.34–0.7], Sp 98.1% [0.95–0.99], LR+ 27.0[9.50–76.00]).ConclusionThe diagnostic performance of synovial lactate/glucose allows septic arthritis to be effectively and very quickly distinguished from other types of arthritis.