Orexin 和P物质对顺铂诱发大鼠异食癖的影响

目的:观察食欲素(Orexin)和P物质(SP)对顺铂诱发大鼠异食癖的影响。方法:雄性Wistar大鼠被随机分为对照组和顺铂处理组,顺铂处理组给予大鼠顺铂(3或6 mg/kg,腹腔注射),对照组给予等量生理盐水。记录顺铂大鼠摄食高岭土量、摄食量的改变;Real-time PCR法观察顺铂对大鼠下丘脑Orexin和延髓中SP前体-前速激肽原A(PPT-A)m RNA表达的影响;分别和联合应用SP受体(NK1受体)拮抗剂阿瑞匹坦和Orexin-A对顺铂大鼠异食癖和摄食量的作用。结果:皮下注射3 mg/kg(低剂量组)的顺帕后大鼠高岭土摄入量和摄食量与对照组相比无明显差异(P0.05),而注射6 mg/kg(高剂量组)顺铂后,大鼠高岭土摄入量与对照组和低剂量组相比显著增加(P0.05);高剂量的顺铂作用12 h时,大鼠延髓内PPT-A的m RNA表达有轻微增加,但无统计学差异(P0.05),24 h后,延髓内PPT-A的m RNA表达量显著增加(P0.05)。在此后持续观察的5天中,顺铂可持续引起延髓中PPT-A的mRNA表达增高,在第5天时PPT-A的m RNA仍维持166.23±16.92%的高表达。高剂量顺铂抑制大鼠下丘脑中Orexin的mRNA表达,24 h时Orexin降低幅度最明显,为对照组的34.81±7.22%(P0.05)。此后检测的5天,Orexin浓度均低于对照组;将阿瑞匹坦和orexin联合应用,大鼠高岭土摄入量较单独应用阿瑞匹坦或orexin明显减少,摄食量显著增加(P0.05)。结论:P物质和orexin通路对顺铂化疗大鼠的异食癖和摄食量调控具有协同作用。     

DVC orexin-A通过调控ghrelin受体信号通路改善顺铂所致大鼠胃功能紊乱

目的:探讨迷走神经复合体(Dorsal vagal complex,DVC)内orexin-A对顺铂所致胃功能紊乱的影响及可能机制。方法:随机选取30只大鼠并将其分为3组(n=10):对照组(NS组);24 h顺铂治疗组;48 h顺铂治疗组。24 h顺铂治疗组和48 h顺铂治疗组大鼠分别在腹腔注射顺铂后24 h和48 h处死大鼠,对照组大鼠腹腔注射生理盐水(Normal saline,NS)。采用定量实时PCR检测各组大鼠下丘脑orexin-A mRNA的表达,ELISA测量大鼠脑脊液中P物质水平;DVC内微量注射orexin-A和ghrelin受体拮抗剂后,检测大鼠食物和高岭土的摄入量。结果:顺铂可显著减少大鼠下丘脑orexin-A mRNA表达,增加其脑脊液内P物质的浓度。外源性orexin-A可改善顺铂引起的厌食症和异食癖。orexin-A以上的效应可被DVC内预先注射ghrelin受体拮抗剂部分逆转。结论:orexin-A可能通过ghrelin神经肽系统改善顺铂在化疗过程中诱导的胃功能紊乱。     

Efficacy of Nimotuzumab Combined with Docetaxel–Cisplatin–Fluorouracil Regimen in Treatment of Advanced Oral Carcinoma

The present study aimed to evaluate efficacy and adverse effects of Nimotuzumab combined with docetaxel–cisplatin–fluorouracil regimen in the treatment of advanced oral carcinoma. Nine patients with advanced oral carcinoma were treated with Nimotuzumab combined with docetaxel–cisplatin–fluorouracil regimen (test group). The treatment was given as follows: Nimotuzumab 200 mg, given as intravenous infusion once a week for 6 weeks; docetaxel and cisplatin, 75 mg/m² each, on day 1 only; 5-fluorouracil, 750 mg/m² infused continually for 8 h, used from day 1 to 5; the total cycle was for 21 days. Another eight patients comprised control group (docetaxel–cisplatin–fluorouracil regimen alone). Study patients from both groups were evaluated for objective response. The response rate was significantly (p = 0.044) higher in test group (88.9 vs. 37.5 % in control group). The disease control rate also tended to be higher in test group (100 vs. 62.5 % in control group; p = 0.083). The major adverse effects were bone marrow suppression, nausea, vomiting, and alopecia. The incidence of adverse effects was similar between both study groups. In conclusion, Nimotuzumab combined with docetaxel–cisplatin–fluorouracil regimen is effective and safe in the treatment of advanced oral carcinoma.     

异氟烷对化疗性大鼠异食癖恶心呕吐模型神经功能及呕吐相关神经递质的影响

摘要 目的：研究异氟烷预处理对化疗性大鼠异食癖恶心呕吐模型神经功能及呕吐相关神经递质的影响。方法：选用SD大鼠作为研究对象,腹腔注射顺铂以建立化疗性大鼠异食癖恶心呕吐模型（Model组）,腹腔注射等量生理研究作为对照组（Control）,在腹腔注射顺铂前1 h和12 h吸入异氟烷预处理作为异氟烷治疗组（Isoflurane）。记录腹腔注射顺铂0~12 h和12~24 h内各组大鼠摄入高岭土量;在腹腔注射顺铂0 h、12 h和24 h后,通过神经功能缺损评分法对各组大鼠神经功能进行评分;并在腹腔注射顺铂24 h后处死大鼠,收集大鼠回肠和延髓组织以检测5-羟色胺(5-Hydroxytryptamine,5-HT)、5-羟基-吲哚乙酸（5-hydroxy-indole acetic acid,5-HIAA）、色氨酸羟化酶（Tryptophan hydroxylase,TPH）以及单胺氧化酶（Monoamine oxidase,MAOA）含量。结果：与Control组相比,Model组和Isoflurane组大鼠在腹腔注射顺铂0~12 h,12~24 h以及0~24 h内摄入的高岭土量均显著升高（P<0.05）,并且Isoflurane组大鼠均显著Model组。三组大鼠在腹腔注射顺铂0 h、12 h和24 h后,神经功能评分均无显著差异（P>0.05）。与Control组大鼠相比,Model组和Isoflurane组大鼠在腹腔注射顺铂24 h后回肠/延髓组织内5-HT和TPH含量均显著升高,并且Isoflurane组大鼠显著低于Model组大鼠（P<0.05）;与Control组相比,Model组大鼠回肠和延髓组织中5-HIAA/5-HIT比值和MAOA含量均显著降低（P<0.05）;与Model组大鼠相比,Isoflurane组大鼠回肠5-HIAA含量、回肠/延髓5-HIAA/5-HT比值和MAOA含量均显著升高（P<0.05）。结论：异氟烷预处理可用于预防腹腔注射顺铂诱导的恶性呕吐,其机制可能与下降THP含量和提高MAOA含量,抑制5-HT合成以及促进5-HT代谢有关。     

The Effects of Dietary Chromium(III) Picolinate on Growth Performance, Vital Signs, and Blood Measurements of Pigs During Immune Stress

This experiment used 24 pigs (26.0 kg) to investigate the effects of dietary chromium (Cr) on pigs challenged with lipopolysaccharide (LPS). Following 35 days of diet exposure, the immune stress treatments were: (1) phosphate-buffered saline (PBS) injection and no Cr, (2) LPS injection and no Cr, (3) LPS injection and Cr 1,000 ppb, and (4) LPS injection and Cr 2,000 ppb. At 0 h, PBS or LPS was injected intraperitoneally in each pig. During the first 12 h post-injection, pigs challenged with LPS lost 951 g, while the PBS group gained 170 g (p?<?0.001). Compared with the PBS group, LPS-challenged pigs consumed less feed (p?<?0.01) during the first 24 h. The LPS group had higher rectal temperature at 2 and 4 h and higher respiratory rate at 1.3 and 8.5 h than the PBS group (p?<?0.05). Plasma collected at 3 h had higher cortisol (p?<?0.001) and lower glucose (p?<?0.05) concentrations in the LPS group than the PBS group. However, supplemental Cr did not affect the response variables. Overall, the LPS challenge affects growth performance, vital signs, and plasma variables, but dietary Cr is unable to moderate stress-related effects associated with an LPS challenge.     

Protective effect of bilberry (Vaccinium myrtillus L.) on cisplatin induced ovarian damage in rat

Cisplatin is one of the most effective chemotherapeutic agents but injury may occur at higher doses. The aim of this study was to investigate the effect of bilberry on cisplatin induced toxic effects in rat ovary. Twenty-one female Wistar–Albino rats were utilized to form three groups: In group 1 (control group), each rat received intraperitoneal injection of 1 mL of 0.9 % NaCl saline solution during 10-days. In group 2 (cisplatin group), a single dose of 7.5 mg/kg b.w. cisplatin was given. In group 3 (cisplatin + bilberry group), a single dose of 7.5 mg/kg cisplatin and bilberry at 200 mg/kg b.w. were given for 10 days. Ovaries were surgically removed in all groups and prepared for biochemical and light microscopic investigations at the examination times. Malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) of tissue samples were measured. Histopathological damages in cisplatin administrated rats were seen such as severe edema, vascular congestion, hemorrhage and follicular degeneration in the ovary tissue. Moderate pathological alterations were observed in rats treated with bilberry plus cisplatin. Cisplatin administration significantly increased MDA production and decreased SOD, CAT, GPx and GST activities in the ovarian tissue when compared to the control group (p < 0.05). Cisplatin + bilberry administration increased antioxidant enzymes activities and reduced MDA levels. Bilberry administration seems to reduce the cisplatin induced ovarian toxicity thus it alleviates free radical damage. But it dose not protect completely rat ovary tissues.     

Chemotherapy-induced pica and anorexia are reduced by common hepatic branch vagotomy in the rat

Anticancer agents, such as cisplatin, induce vomiting, nausea, and anorexia. Cisplatin primarily acts on vagal afferents to produce emesis, but little is known about how this drug generates nausea and anorexia. Electrophysiology indicates that cisplatin activates vagal afferents of the common hepatic branch (CHB). Rats lack an emetic response but do ingest kaolin clay (a pica response) when made sick by toxins, and this behavior can be inhibited by antiemetic drugs. It has been postulated that pica may serve as a proxy for emesis in the rat. The goal of this study was to assess the effect of CHB or ventral gastric (Gas) or celiac (Cel) branch vagotomies on pica and anorexia produced by cisplatin in the rat. The effects of apomorphine, a dopamine receptor agonist, which induces emesis via a central mechanism, were also assessed. Cisplatin-induced pica was suppressed by CHB vagotomy (a 61% reduction) but not by Gas and Cel vagotomy. Suppression of daily food intake and body weight following cisplatin treatment was also blunted by CHB ablation but not by Gas or Cel vagotomy. No vagotomy condition exhibited altered apomorphine-induced pica. The results indicate that the CHB, which innervates primarily the duodenum, plays an important role in cisplatin-induced malaise. These data suggest that pica has sensory pathways similar to emetic systems, since a vagotomy condition inhibited cisplatin-induced pica but had no effect on apomorphine-induced pica. This investigation contributes to the delineation of the physiology of pica and neural systems involved in malaise in the nonvomiting rat.     

Effects of Intracavitary Administration of Endostar Combined with Cisplatin in Malignant Pleural Effusion and Ascites

This study evaluated the efficacy and safety of intracavitary administration of recombinant human endostatin (Endostar) combined with cisplatin chemotherapy in treating malignant pleural effusion and ascites. Forty-five patients with malignant pleural effusion and ascites were divided into the EP group (n = 23), who received Endostar and cisplatin intracavitarily, and P group (n = 22), who were intracavitarily treated with cisplatin only. Pleural effusion and ascites were completely drained before treatments. The treatment was administered once a week; two treatments were considered as one course. The outcome quality of life as well as toxicity were evaluated. The objective overall response and disease control rates were, respectively, 78.3 % (18/23) and 87.0 % (20/23) in EP group. In contrast, these parameters were significantly (p < 0.05) lower in P groups: 40.9 % (9/22) and 59.1 % (13/22), respectively. The improvement rate of Karnofsky Performance Status was 87.0 % (20/23) in EP group versus 59.1 % (13/22) in P group (p < 0.05). All patients tolerated the combined treatment well, and no severe adverse effects were observed. Intracavitary injection of Endostar combined with cisplatin is effective and safe to treat malignant pleural effusion and ascites.     

Takotsubo cardiomyopathy: serious early complications and two-year mortality – a 101 case study

Background

Takotsubo cardiomyopathy (TTC) is characterised by transient contractility disturbances of the apex of the left ventricle.

Methods

We enrolled 101 patients from the northern-eastern part of Poland in the years 2008–2012 who were hospitalised for TCC. The control group consisted of female patients diagnosed with anterior myocardial infarction with ST-segment elevation (anterior STEMI) (n = 101).

Results

89?% of the study group were women. Patients with TTC had diabetes (12.6?% vs 29.7?%; p = 0.002) and hyperlipidaemia (36.8?% vs 64.4?%; p = 0.0001) significantly less frequently, and better kidney function assessed by estimated glomerular filtration rate versus patients with anterior STEMI (74.52?% vs 64.30?%; p = 0.004). In the TTC group there were more patients with chronic obstructive pulmonary disease (11.6?% vs 1.0?%; p = 0.002) and thyroid disturbances, especially hyperthyroidism (23.4?% vs 11.0?%; p = 0.021). In patients with TTC sudden cardiac arrest, pulmonary oedema and cardiogenic shock were observed less frequently than in the control group (14.7?% vs 30.7?%; p = 0.0078). Hospitalisations in TTC patients were less frequently complicated by pneumonia (20.0?% vs 35.6?%; p = 0.0148) and urinary infection (4.2?% vs 21.8?%; p = 0.0003). Cardiac rupture occurred in 3 patients with TTC and in 1 with anterior STEMI. In-hospital mortality was significantly lower in the group with TTC. Also, mortality at 30 days, 3 months, 1 year and 2.5 years was significantly lower in patients with TTC than in patients with MI (p = 0.035; p = 0.0226; p = 0.0075; p = 0.009).

Conclusions

Previously considered to be a benign syndrome, TTC should be reconsidered as a clinical condition at risk for serious complications such as cardiac arrest, cardiogenic shock, pulmonary oedema and cardiac rupture leading to death and causing substantial early hazard. The prognosis in TTC is significantly better than in patients with anterior STEMI.

     

姜黄素对顺铂所致胃组织ICC损伤的保护作用及机制

目的:探索顺铂对胃组织Cajal间质细胞(Cajal interstitial cells,ICCs)结构和功能的损伤以及姜黄素的保护作用。方法:选用成年雄性昆明种小鼠,随机分为对照组、顺铂组和顺铂+姜黄素组,每组各10只。姜黄素(200 mg/kg/d)混悬液连续灌胃15天。顺铂于实验结束前5天开始腹腔注射(2 mg/kg/d)共5天。计算每只小鼠最后5天的体重增减值,停药24 h后测量小鼠的胃排空率。电镜检测胃组织ICC超微结构,并测定特异性反映ICC功能变化的Ano1蛋白和m RNA的表达情况。结果:注射顺铂后各组小鼠的体重和胃排空率均显著降低(P0.01);与顺铂组相比,姜黄素预先灌胃组小鼠体重下降较少(P0.01),胃排空率有所回升(P0.05)。注射顺铂后,胃组织中ICCs受损,尤其与周围神经和肌肉间的缝隙连接增大甚至断裂,而姜黄素可以减轻这种损伤。同时,顺铂组胃组织中Ano1 m RNA和蛋白表达均下降(P0.01),加姜黄素组有所改善(P0.05)。结论:而姜黄素可通过减轻顺铂所致胃组织ICC结构损伤以及增强Ano1表达进而增强ICC慢波起博功能。     

A neurokinin-1 receptor antagonist that reduces intra-abdominal adhesion formation decreases oxidative stress in the peritoneum

Oxidative stress has been implicated in intra-abdominal adhesion formation. Substance P, a neurokinin-1 receptor (NK-1R) ligand, facilitates leukocyte recruitment and reactive oxygen species (ROS) generation. We have shown in a rat model of adhesion formation that intraperitoneal administration of a NK-1R antagonist at the time of abdominal operation reduces postoperative adhesion formation. Thus we determined the effects of NK-1R antagonist administration on peritoneal leukocyte recruitment and oxidative stress within 24 h of surgery. Adhesions were induced in Wistar rats randomly assigned to receive the antagonist or vehicle intraperitoneally. Peritoneal tissue was isolated at 2, 4, 6, and 24 h after surgery for analysis of the oxidative stress biomarkers 8-isoprostane (8-IP), protein carbonyl, NADPH oxidase, myeloperoxidase (MPO), and ICAM-1 and VCAM-1 mRNAs. Total antioxidant capacity of peritoneal fluid was also determined. MPO, NADPH oxidase, 8-IP, and protein carbonyl were elevated (P < 0.05) by 6 h. ICAM-1 mRNA was elevated (P < 0.05) by 2 h, whereas VCAM-1 levels decreased (P < 0.05) at 24 h. The NK-1R antagonist delayed the MPO rise and reduced (P < 0.05) 8-IP levels by 6 h and ICAM-1 mRNA, VCAM-1 mRNA, and protein carbonyl at 2 h. The antagonist also increased (P < 0.05) the antioxidant capacity of peritoneal fluid at all time points. These data further support a role for oxidative stress in adhesion formation and suggest that the NK-1R antagonist may limit adhesions, in part, by reducing postoperative oxidative stress through an inhibition of neutrophil recruitment and an increase in peritoneal fluid antioxidant capacity.     

Chronic Alcoholism-Mediated Impairment in the Medulla Oblongata: A Mechanism of Alcohol-Related Mortality in Traumatic Brain Injury?

Alcohol-related traumatic brain injury (TBI) is a common condition in medical and forensic practice, and results in high prehospital mortality. We investigated the mechanism of chronic alcoholism-related mortality by examining the effects of alcohol on the synapses of the medulla oblongata in a rat model of TBI. Seventy adult male Sprague–Dawley rats were randomly assigned to either ethanol (EtOH) group, EtOH-TBI group, or control groups (water group, water-TBI group). To establish chronic alcoholism model, rats in the EtOH group were given EtOH twice daily (4 g/kg for 2 weeks and 6 g/kg for another 2 weeks). The rats also received a minor strike on the occipital tuberosity with an iron pendulum. Histopathologic and ultrastructure changes and the numerical density of the synapses in the medulla oblongata were examined. Expression of postsynaptic density-95 (PSD-95) in the medulla oblongata was measured by ELISA. Compared with rats in the control group, rats in the chronic alcoholism group showed: (1) minor axonal degeneration; (2) a significant decrease in the numerical density of synapses (p < 0.01); and (3) compensatory increase in PSD-95 expression (p < 0.01). Rats in the EtOH-TBI group showed: (1) high mortality (50 %, p < 0.01); (2) inhibited respiration before death; (3) severe axonal injury; and (4) decrease in PSD-95 expression (p < 0.05). Chronic alcoholism induces significant synapse loss and axonal impairment in the medulla oblongata and renders the brain more susceptible to TBI. The combined effects of chronic alcoholism and TBI induce significant synapse and axon impairment and result in high mortality.     

Autologous cytokine-induced killer cell immunotherapy in lung cancer: a phase II clinical study

Objective

Cytokine-induced killer (CIK) cells have the ability to kill tumor in vitro and in vivo. This study was designed to evaluate the clinical efficacy of CIK cell immunotherapy following regular chemotherapy in patients with non-small cell lung cancer (NSCLC) after surgery.

Methods

A paired study, with 87 stage I–IV NSCLC patients in each group, was performed. Patients received either chemotherapy (arm 2) or chemotherapy in combination with autologous CIK cell immunotherapy (arm 1). Progression-free survival (PFS) and overall survival (OS) were evaluated.

Results

Of the 87 paired patients, 50 had early-stage disease (stage I–IIIA) and 37 had advanced-stage disease (stage IIIB–IV). Among early-stage patients, the distribution of 3-year PFS rate and median PFS time showed no statistical difference between the two groups (p = 0.259 and 0.093, respectively); however, the 3-year OS rate and median OS time in arm 1 were significantly higher than those in arm 2 (82 vs. 66 %; p = 0.049 and 73 vs. 53 months; p = 0.006, respectively). Among the advanced-stage patients, the 3-year PFS and OS rates of arm 1 were significantly higher than those of arm 2 (6 vs. 3 %; p < 0.001 and 31 vs. 3 %; p < 0.001, respectively); the median PFS and OS times in arm 1 were also significantly longer than those in arm 2 (13 vs. 6 months; p = 0.001 and 24 vs. 10 months; p < 0.001, respectively). Multivariate analyses indicated that the frequency of CIK cell immunotherapy was significantly associated with prolonged PFS (HR = 0.91; 95 % CI 0.85–0.98; p = 0.012) and OS (HR = 0.83; 95 % CI, 0.74–0.93; p = 0.001) in the arm 1.

Conclusions

The data suggested that CIK cell immunotherapy could improve the efficacy of conventional chemotherapy in NSCLC patients, and increased frequency of CIK cell treatment could further enhance the beneficial effects. A multi-center randomized trial is being carried out in our hospital to further validate these findings.     

Correlation of Chronic Renal Dysfunction and Albuminuria with Severity of Coronary Artery Lesions in Patients with Coronary Artery Disease

This study was conducted to investigate the possible correlation of chronic renal dysfunction and albuminuria with the severity of coronary artery lesions in patients with coronary artery disease (CAD). Two-hundred and ninety-nine patients who had undergone coronary angiography for suspected CAD were stratified into three groups according to the glomerular filtration rate (GFR): group I included 144 patients with normal renal function GFR >90 ml/(min × 1.73 m²), group II included 97 patients with mild renal impairment GFR 60–89 ml/(min × 1.73 m²), and group III included 58 patients with moderate renal impairment GFR <60 ml/(min × 1.73 m²). Patients were then stratified into two groups according to the albuminuria level (0; minimal, 1+, 2+, 3+): the albuminuria negative group (negative = 0) included 171 patients and the albuminuria positive group (positive = minimal, 1+, 2+, 3+) included 128 patients. Clinical features and coronary lesion characteristics were compared among these groups. Patients with more severe renal dysfunction and positive albuminuria had a higher incidence of CAD (66.7 vs. 70.1 vs. 72.4 %, p = 0.025 and 64.2 vs. 75.0 %, p = 0.032), more multi-vessel disease (31.2 vs. 41.2 vs. 53.4 %, p = 0.004 and 33.3 vs. 46.1 %, p = 0.015), more left anterior descending branch lesions (50.7 vs. 56.7 vs. 60.3 %, p = 0.012 and 49.1 vs. 61.7 %, p = 0.009), and a higher Gensini score (42.3 ± 14.7 vs. 46.1 ± 19.9 vs. 52.8 ± 21.2, p = 0.026 and 44.0 ± 16.0 vs. 50.5 ± 20.2, p = 0.017). In conclusion, chronic renal dysfunction and albuminuria may be important factors determining the occurrence and the severity of CAD. Albuminuria was an especially significant indicator at the early stage of renal dysfunction.     

Synergic Effect of Exercise and Lipoic Acid on Protection Against Kainic Acid Induced Seizure Activity and Oxidative Stress in Mice

Anti-convulsant effects of physical exercise and lipoic acid (LA), also referred to as thioctic acid with antioxidant activity, were investigated using chemical induced seizure model. We investigated the synergic effect of physical exercise and LA on kainic acid-induced seizure activity caused by oxidative stress. After 8 weeks of swimming training, body weight decreased and endurance capacity increased significantly compared to sedentary mice. Kainic acid (30 mg/kg, i.p.) evoked seizure activity 5 min after injection, and seizure activity peaked approximately 80 min after kainic acid treatment. Median seizure activity score in KA only treated group was 4.55 (range 0.5–5), 3.45 for “LA + KA” group (range 0.5–4.3), 3.12 for “EX + KA” group (range 0.05–3.4, p < 0.05 vs. “KA only” group), 2.13 for “EX + LA + KA” group (range 0.5–3.0, p < 0.05 vs. “EX + KA” group). Also, there was a synergic cooperation of exercise and LA in lowering the mortality in kainic acid treated mice (χ² = 5.45, p = 0.031; “EX + KA” group vs. “LA + EX + KA” group). In addition, the synergic effect of exercise and LA was found in PGx activity compared to separated treatment (“LA + EX + KA”: 37.3 ± 1.36; p < 0.05 vs. “LA + KA” and “EX + KA” group). These results indicate that physical exercise along with LA could be a more efficient method for modulating seizure activity and oxidative stress.     

Frailty has a stronger association with inflammation than age in older veterans

Background

Upregulation of pro-inflammatory cytokines has not only been associated with increased morbidity and mortality in older adults but also has been linked to frailty. In the current study we aimed to compare the relative relationship of age and frailty on inflammation and thrombosis in older veterans.

Results

We analyzed 117 subjects (age range 62–95 years; median 81) divided into 3 cohorts: non-frail, pre-frail and frail based on the Fried phenotype of frailty. Serum inflammatory markers were determined using commercially available ELISA kits. Frail and pre-frail (PF) subjects had higher levels than non-frail (NF) subjects of IL-6 (NF vs. PF: p?=?0.002; NF vs. F: p?<?0.001), TNFR1 (NF vs. F: p?=?0.012), TNFRII (NF vs. F: 0.002; NF vs. PF: p?=?0.005) and inflammatory index: = 0.333*log(IL-6)?+?0.666*log(sTNFR1) (NF vs. F: p?=?0.009; NF vs. PF: p?<?0.001). Frailty status explained a greater percent of variability in markers of inflammation than age: IL-6 (12 % vs. 0.3 %), TNFR1 (5 % vs. 4 %), TNFR2 (11 % vs. 6 %), inflammatory index (16 % vs. 8 %). Aging was significantly associated with higher fibrinogen (p?=?0.04) and D-dimer levels (p?=?0.01) but only among NF subjects.

Conclusion

In conclusion, these data suggest that among older veterans, frailty status has a stronger association with inflammation and the inflammatory index than age does. Larger studies, in more diverse populations are needed to confirm these findings.

     

Role of angiotensin II and vasopressin in cisplatin-induced emesis

Cisplatin-containing chemotherapy regimens are known to produce intense nausea and vomiting. Angiotensin II (AII) and vasopressin (AVP) have been shown to have emetic properties. The role of these two peptides on cisplatin-induced vomiting was investigated in beagle dogs. Cisplatin (2 mg/kg, IV over 5 min) produced consistent emesis in all dogs after a mean latency time of 144 +/- 4 min. Serum Angiotensin Converting Enzyme (ACE) and plasma AII levels did not significantly change 3 hr after cisplatin administration (at the time of nausea and emesis) in control animals. AVP levels rose from 0.3 pg/ml to 7.5 pg/ml 3 hrs after cisplatin. Complete inhibition of ACE with enalapril (given at 3 mg/kg p.o., 3 hrs prior to cisplatin) reduced AII levels by 70%, but failed to significantly modify the increase in AVP levels (7.2 +/- 2.2 pg/ml), the latency time to emesis (149 +/- 2 min) and the number of emetic episodes induced by cisplatin. These results suggest that AII does not mediate cisplatin-induced emesis, nor does it mediate the increase in AVP observed at the time of emesis. We propose that AVP may be a good marker for nausea and emesis, and that increases in AVP may be neurally-mediated. The large increase in circulating AVP may represent a desirable water conservation response in anticipation of fluid losses induced by vomiting.     

Effects of ischemic preconditioning on myocardium Caspase-3, SOCS-1, SOCS-3, TNF-α and IL-6 mRNA expression levels in myocardium IR rats

The aim of this study was to characterise the effects of ischemic preconditioning (IP) on heart function parameters (ΔST and ΔT), activities of serum creatine kinase (CK), lactate dehydrogenase (LDH), and levels of serum nitric oxide (NO), malondialdehyde (MDA), and myocardium Caspase-3 mRNA, SOCS-1, SOCS-3, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression levels and Apoptosis index in myocardium IR rats. Results showed that ΔST and ΔST values in IP group were markedly lower than those in IR group. Compared with IR group, IP significantly (p < 0.01) decreased serum CK (0.83 ± 0.09 vs 1.36 ± 0.15), LDH (5613 ± 462 vs 7106 ± 492) activities and MDA (11.32 ± 1.05 vs 15.49 ± 1.26) level, increased the serum NO (86.39 ± 7.03 vs 53.77 ± 4.27) level in IR group. The IP induced a significant decreased in myocardium Caspase-3 mRNA (0.303 ± 0.021 vs 0.515 ± 0.022) gene expression (p < 0.01) compared to IR model group. The IP induced a significant decreased in myocardium SOCS-1 (0.241 ± 0.031 vs 0.596 ± 0.036), SOCS-3 (0.258 ± 0.031 vs 0.713 ± 0.057), TNF-α (0.137 ± 0.011 vs 0.427 ± 0.035) and IL-6 (0.314 ± 0.021 vs 0.719 ± 0.064) mRNA gene expression (p < 0.01) compared to IR model group. We conclude that IP is effective in the therapy of heart disease. These findings may have implications for the clinical development of preconditioning-based therapies for ischemic heart disease.     

Critical role of spatial interaction between CD8+ and Foxp3+ cells in human gastric cancer: the distance matters

Purpose

In various cancer types, an abundance of FoxP3⁺ regulatory T cells (Treg) has been associated with an unfavorable outcome. Yet, the role of Treg on cancer immunity has been shown to be complex. In single cell marker technique, other tumor-infiltrating lymphocytes (TILs) such as cytotoxic CD8⁺ T cells (CTL) also influenced prognosis. This study for the first time investigates the concurrent spatial distribution pattern of CD8⁺ and FoxP3⁺ TILs and their prognostic impact in human gastric cancer.

Materials and methods

Tumor tissue microarrays of 50 patients with surgically treated adenocarcinoma of the cardia were studied. An immunohistochemical double staining of CD8⁺ and FoxP3⁺ TILs was performed. Cell counts and cell-to-cell distances in tumor epithelium and stroma were evaluated with image-processing software. Metastasis-free survival, no-evidence-of-disease survival, and overall survival were investigated (mean follow-up time 6.9 years).

Results

High intraepithelial infiltration of CD8⁺ and FoxP3⁺ TIL was associated with the improved 10-year metastasis-free survival (83 vs. 54 %, p = 0.04 and 85 vs. 59 %, p = 0.09, respectively). Considering cell-to-cell distance and comparing patients with functional (30–110 μm) versus nonfunctional distances of CD8⁺ and FoxP3⁺ TILs, 10-year survival rates differed between 89 and 55 % (p = 0.009), respectively.

Conclusion

Prognostic influence of tumor-infiltrating immune cells in gastric cancer critically depends on their cell-to-cell distance. FoxP3⁺ TILs must be located within a distance between 30 and 110 μm of CD8⁺ T cells to positively impact on prognosis.     

The Value of Expression of M2-PK and VEGF in Patients with Advanced Gastric Cancer

Glycolytic pyruvate kinase isoenzyme type M2 (M2-PK) plays a key role in tumor metabolism and energy production. Vascular endothelial growth factor (VEGF) is critical in regulating angiogenesis which is an essential process required for tumor growth and metastasis. These two genes may function in accordance with tumor development. The purpose of this study was to investigate the relationship between the expression of M2-PK and VEGF, and their association with clinicopathological features in patients with advanced gastric cancer. Expression of M2-PK and VEGF were examined in 142 cases of paraffin-embedded tissue blocks from patients with advanced gastric cancer. M2-PK expression was found to strongly correlate with that of VEGF (r = 0.718). In addition, expression of M2-PK and VEGF correlates with tumor size (p = 0.0001, and p = 0.0017, respectively), depth of invasion (p = 0.0024, and p = 0.0261, respectively), and lymph node metastasis (p = 0.036, and p = 0.028, respectively). The high expression levels of M2-PK and VEGF may indicate poor prognosis in patients with advanced gastric cancer.