The role of nitric oxide on bone metabolism in ovariectomized rats following chronic ethanol intake

This experimental study was designed to examine the effect of nitric oxide (NO) on bone metabolism in ovariectomized rats following chronic ethanol treatment. Chronic ethanol intake was produced by gradual substitution (within 3 weeks) of tap water in diet with 5,10,15 and finally 20% of ethanol. Thereafter, the rats were maintained under these conditions for a duration of 4 months. The rats were divided into two groups. The first group received sham operation (SHAM) and the rats in Group II were ovariectomized (OVX). Five weeks after the SHAM and ovariectomy, the rats were treated with ethanol for 4 months. After this period of ethanol administration, the NOS inhibitor N(W)-nitro-L-arginine methyl ester (L-NAME) was given for three weeks along with ethanol to the same rats. Serum interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, NO, calcium (Ca), phosphorous (P), parathyroid hormone (PTH), 25 HydroxyvitaminD3 [25(OH)D3], alkaline phosphatase (ALP), bone alkaline phosphatase (b-ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), gamma-glutamyltransferase (GGT) levels were measured in different stages of the experiment. IL-1beta, IL-6, TNFalpha and NO levels increased after ethanol administration in SHAM and OVX rats.The decrease in serum Ca was significant while the changes in P, PTH and 25 (OH)D3 levels were not. ALP and b-ALP levels were significantly decreased; ALT, AST and GGT levels were significantly increased. In ovariectomized and SHAM rats, administration of L-NAME together with ethanol, produced a significant increase in IL-1beta, IL-6 and TNFalpha levels. In this group, Ca and P levels were significantly increased, PTH and 25 (OH)D3 levels were significantly decreased. Also, there was a significant decrease in ALT, AST, ALP, b-ALP, and GGT levels. NO increase due to alcohol intake may function as a protective mechanism preventing bone resorption in cases of estrogen insufficiency.     

Proinflammatory liver and antiinflammatory intestinal mediators involved in portal hypertensive rats

Proinflammatory (TNF-alpha , IL-1beta, and NO) and antiinflammatory (IL-10, CO) levels were assayed in serum, liver, and small bowel in order to verify a hypothetic inflammatory etiopathogeny of portal hypertension that could be the cause of its evolutive heterogeneity. Male Wistar rats were divided into one control group (n=11) and one group with a triple stenosing ligation of the portal vein (n=23) after 28 days of evolution. In one subgroup of portal hypertensive rats, portal pressure, collateral venous circulation, mesenteric vasculopathy, and liver and spleen weights were determined. In the remaining rats with portal hypertension TNF-alpha, IL-1beta, and IL-10 were quantified in liver and ileum by enzyme-linked immunosorbent assay. NO synthase activity was studied in liver and ileum. CO and NO were measured in portal and systemic blood by spectrophotometry and Griess reaction, respectively. Portal hypertensive rats with mayor spleen weight show hepatomegaly and mayor development of collateral circulation. Ileum release of IL-10 (0.30 +/- 0.12 versus 0.14 +/- 0.02 pmol/mg protein; P< .01) is associated with a liver production of both proinflammatory mediators (TNF-alpha: 2 +/- 0.21 versus 1.32 +/- 0.60 pmol/mg protein; P< .05, IL-1beta: 19.17 +/- 2.87 versus 5.96 +/- 1.84 pmol/mg protein; P=.005, and NO: 132.10 +/- 34.72 versus 61.05 +/- 8.30 nmol/mL; P=.005) and an antiinflammatory mediator (CO: 6.49 +/- 2.99 versus 3.03 +/- 1.59 pmol/mL; P=.005). In short-term prehepatic portal hypertension a gut-liver inflammatory loop, which could be fundamental in the regulation both of the portal pressure and of its complications, could be proposed.     

Glycogen overload by postexercise insulin administration abolished the exercise-induced increase in GLUT4 protein

Summary To elucidate the role of muscle glycogen storage on regulation of GLUT4 protein expression and whole-body glucose tolerance, muscle glycogen level was manipulated by exercise and insulin administration. Sixty Sprague-Dawley rats were evenly separated into three groups: control (CON), immediately after exercise (EX0), and 16 h after exercise (EX16). Rats from each group were further divided into two groups: saline- and insulin-injected. The 2-day exercise protocol consisted of 2 bouts of 3-h swimming with 45-min rest for each day, which effectively depleted glycogen in both red gastrocnemius (RG) and plantaris muscles. EX0 rats were sacrificed immediately after the last bout of exercise on second day. CON and EX16 rats were intubated with 1 g/kg glucose solution following exercise and recovery for 16 h before muscle tissue collection. Insulin (0.5 μU/kg) or saline was injected daily at the time when glucose was intubated. Insulin injection elevated muscle glycogen levels substantially in both muscles above saline-injected group at CON and EX16. With previous day insulin injection, EX0 preserved greater amount of postexercise glycogen above their saline-injected control. In the saline-injected rats, EX16 significantly increased GLUT4 protein level above CON, concurrent with muscle glycogen supercompensation. Insulin injection for EX16 rats significantly enhanced muscle glycogen level above their saline-injected control, but the increases in muscle GLUT4 protein and whole-body glucose tolerance were attenuated. In conclusion, the new finding of the study was that glycogen overload by postexercise insulin administration significantly abolished the exercise-induced increases in GLUT4 protein and glucose tolerance.     

Interleukin-6 gene expression is increased in insulin-resistant rat skeletal muscle following insulin stimulation

IL-6 expression in skeletal muscle is stimulated by contractions. We sought to examine whether hyperinsulinaemia increases IL-6 mRNA in skeletal muscle and whether any increase is modified in insulin resistant muscle. We hypothesized that intramuscular IL-6 mRNA would be increased in response to insulin, but such an affect would be unaffected by insulin resistance because the primary insulin sensitive signalling protein responsible for activating IL-6 functions normally in insulin resistant muscle. Transgenic rats over-expressing the gluconeogenic regulatory enzyme phosphoenolpyruvate carboxykinase (PEPCK) were studied. White gastrocnemius muscle samples were obtained under hyperinsulinaemic, euglycaemic clamp (4 mU kg(-1)min(-1) insulin, plasma glucose concentration 4-6 mmol L(-1)) and basal conditions in both PEPCK (basal n=4; insulin n=5) and wild-type (CON) (basal n=5; insulin n=4) rats, which were previously injected with a bolus of 2-[1-14C]deoxyglucose (2-DG) into the carotid artery. Muscle samples were assayed for 2-DG uptake and IL-6 mRNA. No differences in 2-DG uptake or IL-6 mRNA were observed when comparing groups under basal conditions. Under clamp conditions, 2-DG uptake was lower (P<0.05) in PEPCK compared with CON. Insulin stimulation in CON did not change IL-6 mRNA compared with basal levels. In contrast, there was an approximately 8-fold increase (P<0.05) in IL-6 mRNA in insulin-stimulated PEPCK compared with CON basal levels. Insulin stimulation increases IL-6 gene expression in insulin resistant, but not healthy, skeletal muscle, suggesting that IL-6 expression in skeletal muscle is sensitive to changes in insulin in circumstances of insulin resistance. It is likely that the differences observed when comparing healthy with insulin resistant muscle are due to the differential activation of insulin sensitive signalling proteins responsible for activating IL-6.     

Intracerebroventricular interleukin-6 treatment decreases body fat in rats

Recently we found that interleukin-6 (IL-6) knockout mice develop mature-onset obesity and that a single intracerebroventricular (ICV) injection of IL-6 increases energy expenditure. In the present study we investigated if chronic ICV treatment with IL-6 can suppress body fat mass. IL-6 was injected ICV daily for two weeks to rats fed a high-fat diet. IL-6 treatment but not saline treatment decreased body weight by 8.4% and decreased the relative weights of mesenteric and retroperitoneal fat pads. Consistent with this, circulating leptin levels were decreased by 40% after IL-6 treatment but not after saline treatment. Average food intake per day was decreased in the IL-6 treated group compared to the saline treated rats. IL-6 treatment did not change hepatic expression of the acute-phase protein haptoglobin, serum levels of insulin or insulin-like growth factor-I, or the weights of the heart, liver, kidneys, adrenals, and spleen. We conclude that centrally administered IL-6 can decrease body fat in rats without causing acute-phase reaction.     

Role of VEGF in small bowel adaptation after resection: the adaptive response is angiogenesis dependent

Previous work in our group has demonstrated that mouse salivary gland has the highest concentration of salivary-derived VEGF protein compared with other organs and is essential for normal palatal mucosal wound healing. We hypothesize that salivary VEGF plays an important role in maintaining the integrity of the gastrointestinal mucosa following small bowel resection (SBR). Thirty-five 8- to 10-wk-old C57BL/6 female mice were divided into seven treatment groups: 1) sham (transaction and anastomosis, n = 5); 2) SBR (n = 8); 3) sialoadenectomy and small bowel resection (SAL+SBR, n = 8); 4) sialoadenectomy and small bowel resection with EGF supplementation (SAL+SBR+EGF, n = 9); 5) sialoadenectomy and small bowel resection with VEGF supplementation (SAL+SBR+VEGF, n = 9); 6) sialoadenectomy and small bowel resection supplemented with EGF and VEGF (SAL+ SBR+VEGF+EGF, n = 6); 7) selective inhibition of VEGF in the submandibular gland by Ad-VEGF-Trap following small bowel resection (Ad-VEGF-Trap+SBR, n = 7). Adaptation was after 3 days by ileal villus height and crypt depth. The microvascular response was evaluated by CD31 immunostaining and for villus-vessel area ratio by FITC-labeled von Willebrand factor immunostaining. The adaptive response after SBR was significantly attenuated in the SAL group in terms of villus height (250.4 +/- 8.816 vs. 310 +/- 19.35, P = 0.01) and crypt depth (100.021 +/- 4.025 vs. 120.541 +/- 2.82, P = 0.01). This response was partially corrected by orogastric VEGF or EGF alone. The adaptive response was completely restored when both were administered together, suggesting that salivary VEGF and EGF both contribute to intestinal adaptation. VEGF increases the vascular density (6.4 +/- 0.29 vs. 6.1 +/- 0.29 vs. 5.96 +/- 0.20) and villus-vessel area ratio (0.713 +/- 0.01 vs. 0.73 +/- 0.01) in the adapting bowel. Supplementation of both EGF and VEGF fully rescues adaptation, suggesting that the adaptive response may be dependent on VEGF-driven angiogenesis. These results support a previously unrecognized role for VEGF in the small bowel adaptive response.     

Ghrelin and glucagon-like peptide-2 increase immediately following massive small bowel resection

Children with short bowel syndrome face life-threatening complications. Therefore, there is an urgent need for a new therapy to induce effective adaptation of the remnant intestine. Adaptation occurs only during feeding. We focused on preprandial acyl ghrelin and des-acyl ghrelin, and postprandial glucagon-like peptide-2 (GLP-2), which are known to have active orexigenic and trophic actions. This study aims to clarify the secretion trends of these hormones after massive small bowel resection and to obtain basic data for developing a new treatment. Sixty-three growing male rats were used: 3 were designated as controls receiving no operation and 60 were randomized into the 80% small bowel resection (80% SBR) group and the transection and re-anastomosis group. Changes in body weight, food intake, and remnant intestine morphology were also assessed for 15 days after the operation. Acyl ghrelin and des-acyl ghrelin levels increased immediately, equivalently in both operation groups (P = 0.09 and 0.70). Interestingly, in 80% SBR animals, des-acyl ghrelin peaked on day 1 and acyl ghrelin peaked on day 4 (P = 0.0007 and P = 0.049 vs controls). GLP-2 secretion was obvious in 80% SBR animals (P = 2.25 × 10⁻⁶), which increased immediately and peaked on day 4 (P = 0.009 vs. controls). Body weight and food intake in 80% SBR animals recovered to preoperative levels on day 4. Morphological adaptations were evident after day 4. Our results may suggest a management strategy to reinforce these physiological hormone secretion patterns in developing a new therapy for short bowel syndrome.     

Effects of physical training on IL-1beta, IL-6 and IL-1ra concentrations in various brain areas of the rat

There is increasing evidence that voluntary physical activity and exercise training have beneficial effects on brain function by facilitating neurovegetative, neuroadaptative and neuroprotective processes. Cytokines are chronically expressed at elevated levels within the CNS in many neurological disorders and may contribute to the histopathological, pathophysiological, and cognitive deficits associated with such disorders. In the present study, we examined the influence of seven weeks of physical training on IL-1b, IL-6 and IL-1ra concentrations in hypothalamus, pituitary, hippocampus, cerebellum and frontal cortex in rats. We determined circulating concentrations of cytokines, corticosterone, prolactin and leptin. Two groups of 10 rats were investigated: one group (trained rats) was progressively trained (5 days/week); the other group (sedentary rats) was used as a sedentary group. The training program induced a decrease of (i) IL-1b concentration in the hippocampus (0.7 +/- 0.16 versus 0.99 +/- 0.14 pg/mg protein; p < 0.05), (ii) IL-6 concentration in the cerebellum (10.7 +/- 1.00 in trained rats versus 14.8 +/- 1.34 pg/mg protein in sedentary rats; p < 0.05), (iii) IL-1ra concentration in the pituitary (245 +/- 14.31 versus 328 +/- 17.73 pg/mg protein; p < 0.01). We also found positive correlations between (i) serum prolactin and the concentration of IL-6 in the cerebellum, (ii) serum leptin and the concentration of IL-1ra in the pituitary. There was no effect of physical training on IL-1b, IL-6, and IL-1ra serum levels. These findings suggest that the decrease in particular pro-inflammatory, central cytokines such as IL-1b and IL-6 induced by the training program may play a role in the positive effects of regular physical activity on the central nervous system.     

Swimming training promotes cardiac remodeling and alters the expression of mRNA and protein levels involved in calcium handling in hypertensive rats

Aim

The aim of this study was to identify the effects of swimming training on the mRNA expression and protein levels of the calcium handling proteins in the hearts of renovascular hypertensive rats submitted to swimming protocol during 6 weeks.

Main methods

Fischer rats with renovascular hypertension 2-kidney 1-clip (2K1C) and SHAM groups were divided among sedentary and exercised groups. The exercise protocol lasted for 6 weeks (1 h/day, 5×/week), and the mean arterial pressure, cardiomyocytes hypertrophy parameters, mRNA expression and protein levels of some calcium handling proteins in the left ventricle were evaluated.

Key findings

Swimming training was able to reduce the levels of mean arterial pressure in the hypertensive group compared to 2K1C SED, and to promote cardiac hypertrophy in SHAM EX and 2K1C EX groups in comparison to the respective control groups. The mRNA levels of B-type natriuretic peptide were reduced in the 2K1C EX when compared to 2K1C SED. The mRNA and protein levels of the sarcoplasmic reticulum Ca^2 +-ATPase increased after the swimming training in SHAM and 2K1C groups. The mRNA and protein levels of phospholamban, displayed an increase in their levels in the exercised SHAM and in hypertensive rats in comparison to their respective controls; while mRNA levels of Na⁺/Ca^2 + exchanger was reduced in the left ventricle comparing to the sedentary hypertensive rats.

Significance

Taken altogether, we provide evidence that the aerobic training may lead to cardiac remodeling, and modulate the calcium handling proteins expression in the heart of hypertensive rats.     

Interleukin-6 trans-signaling in inflammatory bowel disease

The pathogenesis of inflammatory bowel disease (IBD) is complex, involving a wide range of molecules including cytokines. Recent investigations support the important role of an interleukin-6 (IL-6) signaling pathway in the development of IBD. However, the molecular mechanisms of this pathway in the intestine remain incompletely understood. The circulating and intestinal levels of IL-6 as well as soluble IL-6 receptor (sIL-6R) are increased in patients with IBD. It is remarkable that the mucosal T cells of IBD patients are extremely resistant to apoptosis and that a large fraction of these cells express membrane-bound gp130 but not IL-6R. The accumulated evidence strongly supports the hypothesis that the development and perpetuation of IBD relies on the increased formation of IL-6/sIL-6R complexes interacting with membrane-bound gp130 on T cells via trans-signaling. These studies suggest that IL-6 trans-signaling may play a role in the development of IBD; they therefore imply the possibility of a selective therapeutic strategy to target this signaling.     

高龄患者腹腔镜结直肠癌根治术围手术期对机体应激及内脏蛋白的影响

目的:研究高龄病人(75岁以上)腹腔镜与开腹结直肠癌根治术围手术期白介素6(IL-6)、IL-10和C反应蛋白(CRP)及内脏蛋白的差异.方法:将41例行结直肠癌根治术的高龄患者按患者意愿分为腹腔镜组(n=20)和开腹组(n=21),两组患者的一般资料如年龄、性别、体重指数(BMI)等有可比性,检测两组患者术前、术后的应激指标:血清IL-6、IL-10和CRP及营养蛋白:前白蛋白(prealbumin,PRE)、转铁蛋白(transferrin,TRF)、视黄醇结合蛋(retinal-binding protein,RbP)的变化.结果:两组患者CRP在术后1、2、3d均较术前明显升高(P<0.01),术后2d达到峰值,腹腔镜组术后CRP明显低于开腹组(P<0.01);两组患者血清IL-6、IL-10术后也明显升高,腹腔镜组明显低于开腹组(P<0.01),但IL-10升高持续时间短.PRE、TRF、RbP术后两组均较术前有明显下降(P<0.01),术后1 d、2 d两组各指标无显著性差异(P>0.05),术后3 d腹腔镜组4种蛋白指标均明显高于开腹组(P<0.01).结论:对高龄病人两种不同手术方式应激水平及内脏蛋白指标的研究提示,腹腔镜结直肠癌根治术较开腹手术创伤小,应激水平低,有利于机体内脏蛋白的恢复,这对微创外科的实施是一个有力支持.     

IL-6, IL-1β及TNF-α与大鼠骨质疏松形成的关系

目的:研究白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)及肿瘤坏死因子-α(TNF-α)与大鼠骨质疏松形成的关系,为研究细胞因子与骨质疏松之间的相关作用机制提供参考。方法:选择2015年1月至2015年11月我院采购的90只雌性大鼠作为研究对象,按照数字随机法将大鼠分成观察组(n=45)以及对照组(n=45)。观察组制成骨质疏松模型,对照组不作处理,对比两组局部骨密度,成骨细胞,骨小梁以及破骨细胞在视野面积中的比例,骨组织相关细胞因子水平,分析IL-6、IL-1β以及TNF-α水平与大鼠骨质疏松的相关性。结果:观察组椎体骨密度(BD)和椎间盘BD以及小关节BD均明显低于对照组,差异均有统计学意义(P0.05);观察组骨小梁和成骨细胞在视野面积中的比例明显低于对照组,而破骨细胞在视野面积中的比例明显高于对照组,差异均有统计学意义(P0.05);观察组IL-6和IL-1β以及TNF-α均明显高于对照组,差异有统计学意义(P0.05)。IL-6、IL-1β以及TNF-α水平与大鼠椎体BD、椎间盘BD以及小关节BD均呈明显负相关。结论:去卵巢大鼠的细胞因子与其骨质疏松具有紧密联系,表现在IL-6、IL-1β以及TNF-α水平与大鼠椎体BD、椎间盘BD以及小关节BD均呈明显负相关。     

大鼠IgA肾病模型的建立及血清中IL-6、FN、NO的检测

目的建立大鼠IgA肾病（IgAN）模型,测定大鼠血清中的白介素-6（IL-6）、纤维结合蛋白（FN）、一氧化氮（NO）,探讨这些指标水平的变化与IgAN免疫损伤的相关性,为临床治疗提供动物实验研究依据。方法24只大鼠被随机分成3组,每组8只。模型组和治疗组用免疫复合物法复制;正常对照组用生理盐水。10周后,治疗组大鼠被给予雷公藤多甙片3周。留取所有大鼠血清测定IL-6、FN、NO;留取所有大鼠尿液测定红细胞（RBC）、总蛋白量（TPR）;留取所有大鼠肾组织作病理学检查。结果模型组中大鼠尿液中RBC、TPR含量较治疗组及正常对照组显著增高（P〈0．01）;血清中的IL-6、FN的水平较治疗组及正常对照组显著增高（P〈0．01）;血清中的NO水平较治疗组及正常对照组显著降低（P〈0．01）。治疗组的大鼠肾组织病理损伤程度较模型组明显减轻（P〈0．01）。结论血清中的IL-6、FN及NO的水平与RBC数、TPR及肾组织病理损伤程度相关,它们可作为观察IgAN治疗效果的重要指标,也可作为IgAN严重性的预测指标。下调血中的IL-6、FN及上调NO的水平,可减少IgA与FN免疫复合物的形成,从而改善肾组织的免疫损伤。     

Immunomodulatory cytokines suppress epithelial nitric oxide production in inflammatory bowel disease by acting on mononuclear cells

Inducible nitric oxide synthase (iNOS) activity in colonic epithelial HT-29 cells is modulated by the T-cell-derived cytokines IL-4 and IL-13, but is not affected by IL-10 despite its effect in models of colitis. We studied the effects of these cytokines on nitric oxide (NO) production by colonic tissue. IL-10 and IL-4 but not IL-13 suppressed the NO production and iNOS expression by inflamed tissue and cytokine-stimulated noninflamed tissue from patients with ulcerative colitis, whereas the three cytokines suppressed NO production in cytokine-stimulated biopsies from controls. To examine why colonic biopsies and HT-29 cells respond differently to immunomodulatory cytokines, a coculture of mixed mononuclear monocytes (MMC) and HT-29 cells was studied. Treatment of HT-29 cells with conditioned medium from IFN-γ/LPS-stimulated MMC produced significant amounts of NO, which suggested the presence of an MMC-derived soluble factor modifying epithelial NO production. Pretreatment of IFN-γ/LPS-stimulated MMC with IL-10 and IL-4 but not IL-13 suppressed NO production by HT-29 cells. Interestingly, pretreatment of HT-29 cells with IL-1 receptor antagonist suppressed the IFN-γ/LPS-stimulated MMC-induced NO production. These results suggest that immunomodulatory cytokines might exert an inhibitory effect on NO up-regulation by colonic epithelium via the inhibition of MMC-derived soluble mediators, such as IL-1.     

Colonic soluble mediators from the maternal separation model of irritable bowel syndrome activate submucosal neurons via an interleukin-6-dependent mechanism

Irritable bowel syndrome (IBS) is characterized by episodic bouts of abdominal pain, bloating, and altered bowel habit. Accumulating evidence has linked immune activation with IBS, including reports of increases in circulating levels of the proinflammatory cytokine interleukin (IL)-6. However, it is unknown whether IL-6 contributes directly to disease manifestation. As enteric nervous activity mediates motility and secretory function, the aims of this study were to determine the effects of IL-6 on submucosal neurons and related gastrointestinal (GI) function. In these studies, we examined the colons of maternally separated (MS) rats, which exhibit elevated circulating levels of IL-6 in addition to GI dysfunction. To our knowledge, these studies are the first to provide evidence of the sensitivity of submucosal neurons to colonic secretions from MS rats (n = 50, P < 0.05), thus recapitulating clinical biopsy data. Moreover, we demonstrated that the excitatory action is IL-6 dependent. Thereafter, the impact of IL-6 on neuronal and glial activation and absorpto/secretory function was pharmacologically characterized. Other proinflammatory cytokines including IL-8 (n = 30, P > 0.05), IL-1β (n = 56, P > 0.05), and TNF-α (n = 56, P > 0.05) excited fewer neurons. Both muscarinic and nicotinic cholinergic receptors participate in the effect and cause downstream activation of ERK, JAK-STAT, and NF-κB signaling cascades. Functionally, IL-6 increases transepithelial resistance and enhances neurally and cholinergically mediated ion transport. These data provide a role for IL-6 in colonic secretory functions and relate these effects to GI dysfunction in an animal model of IBS, thereby elucidating a potential relationship between circulating levels of IL-6 and aberrant GI function.     

Saccharated colloidal iron enhances lipopolysaccharide-induced nitric oxide production in vivo

We investigated the effects of iron on the production of nitric oxide (NO), inducible NO synthase (iNOS), and plasma cytokines induced by lipopolysaccharide (LPS) in vivo. Male Wistar rats were preloaded with a single intravenous injection of saccharated colloidal iron (Fesin, 70 mg iron/kg body weight) or normal saline as a control, and then given an intraperitoneal injection of LPS (5.0 mg/kg body weight). Rats, preloaded with iron, had evidence of both iron deposition and strong iNOS induction in liver Kupffer cells upon injection of LPS; phagocytic cells in the spleen and lung had similar findings. LPS-induced NO production in iron-preloaded rats was significantly higher than control rats as accessed by NO-hemoglobin levels measured by ESR (electron spin resonance) and NOx (nitrate plus nitrite) levels. Western blot analysis showed that iron preloading significantly enhanced LPS-induced iNOS induction in the liver, but not in the spleen or lung. LPS-induced plasma levels of IL-6, IL-1beta, and TNF-alpha were also significantly higher in iron-preloaded rats as shown by ELISA, but IFN-gamma levels were unchanged. We conclude that colloidal-iron phagocytosed by liver Kupffer cells enhanced LPS-induced NO production in vivo, iNOS induction in the liver, and release of IL-6, IL-1beta, and TNF-alpha.     

Does massive proximal small bowel resection influence prostaglandin E2 synthesis in the stomach and ileum during adaptive process in rats?

It is unclear whether massive small bowel resection (SBR) affects prostaglandin E2 synthesis in the gastrointestinal tracts. Thus the aim of this study was to investigate possible changes over tissue levels of prostaglandin E2 in the stomach and ileum after massive proximal SBR. Female Swiss-Albino rats underwent control operation (groups 1, 3, 5) or an 80% SBR (groups 2, 4, 6). The specimens were obtained during relaparotomy at 3 days in groups 1 and 2, at 9 days in groups 3 and 4, at 15 days in groups 5 and 6. Group 2 vs. groups 1 and 6, group 4 vs. groups 3 and 6 had significant increase in the levels of gastric acid (P < 0.01, P < 0.05, respectively). Gastric prostaglandin E2 levels markedly increased in group 2 compared to group 1 (P < 0.01). Ileal prostaglandin E2 levels showed to be significantly higher in group 6 when compared with groups 2, 4, and 5 (P < 0.05). Gastric acidity increased at 3 and 9 days, decreased thereafter at 15 days following massive proximal SBR. While resected rats had increased levels of gastric prostaglandin E2 at 3 days, ileal prostaglandin E2 was markedly elevated at 15 days. Therefore, we conclude that prostaglandin E2 may have a possible role in regulating intestinal adaptation at the end of the adaptive process, and contribute to cytoprotective barrier function in the ileum and stomach at early and late periods of the intestinal adaptation, respectively.     

Non-effect of hexamethonium, a ganglionic blocker, on the response of ileal apolipoprotein A-IV mRNA following a massive small bowel resection in rats

An intravenous infusion of hexamethonium, a ganglionic blocker, did not affect the increase in the apolipoprotein A-IV mRNA level in the residual ileum following a massive small bowel resection in unrestrained conscious rats. The result suggests that upregulation of the apolipoprotein A-IV gene in the residual ileum is not mediated by a neural pathway, including the nicotinic synapse route.