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.     

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.     

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.     

大鼠脑损伤局部谷氨酸的异常释放对乳酸含量变化的影响

目的探讨谷氨酸(Glu)在大鼠脑损伤局部的异常释放以及其对乳酸(Lac)含量变化的影响。方法采用大鼠局部脑损伤动物模型,分为对照组、损伤组、干预组。伤前15min干预组注射Riluzole(一种Glu突触前释放抑制剂),损伤组注射等容量的生理盐水,对照组仅开骨窗不损伤脑。应用微透析技术检测各组伤后不同时间透析液中Glu含量([Glu]d)及Lac含量([Lac]d)变化。结果[Glu]d及[Lac]d在伤后15min、30min和45min干预组明显低于损伤组(P<0.05),而明显高于对照组(P<0.05);在伤后60min,损伤组仍明显高于对照组(P<0.05)。伤后不同时间[Glu]d和[Lac]d变化呈显著正相关(P<0.01)。结论脑损伤后受损脑组织细胞液中Glu水平的升高是Glu神经元末梢大量释放Glu所致,并继而引起了Lac的含量升高。     

Multidimensional analysis of metabolism contributions involved in running track tests

It is difficult to interpret the training induced changes in middle-distance running, since numerous aerobic and anaerobic determinants of the performance are interdependent. Several aerobic and anaerobic tests are available but their results, particularly those from anaerobic tests, may be discordant, not providing univocal interpretation of training. The purpose of this study is to use a multidimensional approach to distinguish aerobic and anaerobic capacities assessed by two running tests on a track: the maximal anaerobic running test (MART) and V(O2max) tests. Eleven runners carried out two maximal tests on a synthetic track before and after a 4-week training period: (i) a maximal test to determine V(O2max), the velocity associated with V(O2max) (vV(O2max)) and the velocity at the lactate threshold (v(LT)), (ii) a maximal anaerobic running test to estimate anaerobic capacity. An all-out test run at v(LT)+50% of the difference between v(LT) and vV(O2max), known to be affected by both aerobic and anaerobic energy production, was used to test this approach. A principal components analysis (PCA) shows that two components (i.e., aerobic and anaerobic) explained 79% of the variation in the physiological variables. The PCA suggests that V(O2max) and MART tests assess the aerobic and the anaerobic capacities, respectively. In contrast, the performance in the all-out test is affected by both aerobic and anaerobic energy production. The PCA shows that v(LT) and DeltaP (difference between the maximal power of the MART and V(O2max)) are clear markers of the long-term endurance and the anaerobic capacity, respectively. This multidimensional approach can be a useful way to disentangle the aerobic and anaerobic components of track tests.     

用ROC曲线评价肿瘤标志物LDH在急性白血病早期诊断中的临床价值

目的 探讨肿瘤标志物乳酸脱氢酶（LDH）在急性白血病早期诊断中的临床价值。方法 应用受试者工作特性曲线（ROC曲线）及其曲线下面积（AUC）抛物线估算法（以金标准计算准确度和敏感度），对51例急性白血病的早期患者及部分经治疗后缓解的患者、61例非急性白血病患者、61例健康体检者进行了LDH的检测及分析。结果 AUC为0．954，其可信区间为0．935－0．973，其下限0．935远离0．5，经治疗缓解的白血病患者LDH检验结果与治疗前数据经t检验证实＜0．0001。结论 LDH对急性白血病的早期诊断以及治疗效果与预后的评估均有着重要及较好的临床价值。     

多器官功能衰竭患儿血糖血乳酸血渗透压的改变

对５０例ＭＯＦ患儿血糖血乳酸血渗透压进行了检测，并与３５名健康儿童进行比较。结果显示危重患儿血糖血乳酸明显高于对照组，血糖血乳酸呈正相关，提示高血糖是危重患儿应激状态下的主要代谢改变。当患儿血糖＞１５ｍｍｏｌ／Ｌ血乳酸）５ｍｍｏｌ／Ｌ时，其死亡率明显增加，因此血糖血乳酸的变化可作为ＰＩＣＵ的常规监测指标。     

Luminal transport step of para-aminohippurate (PAH): transport from PAH-loaded proximal tubular cells into the tubular lumen of the rat kidney in vivo

 Proximal tubular cells were loaded for 10 s with [³H]para-aminohippurate ([³H]PAH) by microperfusing the peritubular capillaries with Ringer solution containing 0.05 mmol/l PAH. Immediately thereafter [³H]PAH influx from cells into a column of equilibrium solution injected into the oil-filled tubular lumen was measured by re-aspirating the fluid after 1–10 s of contact time. The rise of luminal PAH concentration within 2 s of contact time was almost linear, reaching a luminal / capillary concentation ratio of 1.6 after 2 s and of 3.2 after 5 s. The 2-s PAH concentration ratio was not changed when different manoeuvres were applied to depolarize proximal tubular cells. Also, the 2-s PAH concentration ratio was not influenced by varying the luminal pH from 6.0 to 8.0 or the luminal Cl^–concentration from zero to 134 mmol/l or when either 5 mmol/l urate or 25 mmol/l lactate was in the luminal perfusate. A decrease in the 2-s PAH concentration ratio, i.e. trans-inhibition, was observed when 25 or 50 mmol/l HCO₃ ^–(–50%) was in the luminal perfusate. Trans-inhibition was also seen with 5 mmol/l of the following substituted benzoates: 2-hydroxy-benzoate (–58%), 2-methoxy-benzoate (–46%), 2-hydroxy-benzoate-acetyl ester (–36%), 2-hydroxy-3,5-dinitro-benzoate (–48%), 3,5-dichloro-benzoate (–49%), and 2,3,5-trichloro-benzoate (–45%). No effect was seen with benzoate, 3-hydroxy-benzoate, 2-chloro-benzoate, 2-nitro-benzoate, 2,5-dinitro-benzoate, 3-sulfamoyl-benzoate and 4-sulfamoyl-benzoate. However, analogues of the latter two compounds possessing two additional side groups, such as furosemide and piretanide, or a hydrophobic moiety, such as probenecid, were inhibitory (by –62, –41 and –49% respectively). Phenoxyacetate had no effect; however, it inhibited if in addition it had three chloro groups, as in 2,4,5-trichlorophenoxyacetate (–71%) or a hydrophobic carbamoyl side group, as in mersalylic acid (salyrgan, –75%). Benzene-sulfonate trans-inhibited (–33%), as did phenolsulfonphthalein (phenol red, –39%) and sulfofluorescein (–55%). However, the trans-inhibitory effect of the corresponding carboxy-compounds was absent (phenolphthalein) or weaker (fluorescein, –42%). The trans-inhibitory effect of the uricosurics ethacrynic acid (–53%), tienilic acid (–55%) indacrinone (–72%) and benzbromarone (–42%) could be attributed to two chloro or bromo side groups on the benzene ring. Other trans-inhibiting uricosuric substances were indomethacin (–42%), sulfinpyrazone (–38%), losartan (–80%) its metabolite EXP 3174 (–55%), and AA 193 (–65%). These organic acids, with pKa values between 2.8 and 4.9, possess chloro and sulfin groups, as well as heterocyclic 5-ring and hydrophobic ring or chain areas. No significant effect was seen with 5 mmol/l PAH, 2-oxo-glutarate, DIDS, cGMP, prostaglandin E₂, cortisol, benzylamiloride, pyrazinoic acid and 25 mmol/l lactate. Our data indicate that in situ the secretory luminal PAH transport proceeds in a non-rheogenic fashion, per exclusionem by anion exchange. The observed trans-inhibition of PAH secretion seems to correlate with the affinity for the luminal PAH transporter and, for uricosuric substances, with their uricosuric potency. Received: 15 October 1996 / Received after revision: 17 December 1996 / Accepted: 18 December 1996