Effects of ovariectomy and growth hormone administration on body composition and vascular function and structure in old female rats

Aging and estrogen-deprivation induce deleterious effects on body composition and vascular function in females. On the other hand, growth hormone (GH), whose production is reduced by age, exerts several vascular effects. The aim of this study was to investigate the effect of long-term estrogen deprivation and GH administration on body composition, vascular function and structure in aged female rats. Methods: Twelve female Wistar rats were ovariectomized at 10 months of age. At 20 months of age, half of the ovariectomized rats were treated with GH for 4 weeks. The remaining ovariectomized rats animals and one group of six intact females were used as control groups. After the treatment period, animals were sacrificed and Specific Gravity Index (SGI) and periuterine fat weigh, as well as vascular reactivity and morphometry in aortic rings, were studied. Results: No significant differences were found in SGI and periuterine fat weigh between ovariectomized and intact control rats. SGI was significantly increased by GH, and periuterine fat was reduced by the treatment. Dose-dependent relaxing responses to acetylcholine and isoproterenol were significantly diminished in ovariectomized rats as compared with intact animals, and GH treatment improved these responses. Ovariectomized animals showed significantly higher contracting responses to phenylephrine, acetylcholine + L-NAME and angiotensin-I than intact rats, and treatment with GH reduced them significantly. Media cross-sectional area was increased in ovariectomized rats as compared to intact animals, and GH reduced this area, but differences did not reach significance. Conclusion: GH has beneficial effects in body composition and endothelial function in old ovariectomized female rats.     

Validity of the ischemic score in degenerative and vascular dementia and depression in old age

Thirty six male and 45 female patients (mean age 66 years) suffering from either dementia of Alzheimer type (DAT) or dementia of vascular type (DVT) with comparable severity and suffering from depression in old age were included in the investigation. The study was performed to evaluate the diagnostic value of Ischemic Score, EEG and CT scan of the brain in differentiating dementia types and depression in old age. The patients underwent physical, psychiatric, psychometric, neurological, neurophysiological and CT scan examinations. Clinical diagnosis and diagnosis related to Ischemic Score were consistent in 86% of DAT and in 65% of DVT. Patients suffering from DVT showed significantly higher incidence of distinct Ischemic Scale items than was found in DAT patients. The Ischemic Scale items were found to be of major importance in differentiating vascular dementia from both DAT and depression. However, it was insufficient to distinguish between the latter two. In EEG, general slowing predominated in DAT (68%), and focal disturbances in DVT (71%). Patients with DAT and depression could not be differentiated on the basis of their EEG findings. CT scans of the brain yielded a higher incidence of brain atrophy in patients with DAT (71%) and DVT (70%) as compared to depressive patients (37%). In DAT, ventricular enlargement seems to be rather disease- than age-related. Psychological testing showed abnormalities in attention and memory performance in DAT and DVT to a significantly greater extent as compared to depression. This study demonstrated that the combination of Ischemic Score and EEG was found to be most valid in differentiating DAT from DVT. Additional cranial computerized tomography and the psychological testing of attention and memory were able to confirm the diagnosis of dementia and to differentiate dementia from depression in old age.     

肝硬化患者QTc间期与QT离散度变化机制及临床意义

目的 探讨肝硬化患者QTc间期及QT离散度(QTd)变化的机制与临床意义.方法 116例肝硬化患者与50例对照组行同步12导联心电图,测定QTc及QTd,同时检测凝血酶原活动度(PTA)、白蛋白(Alb)、总胆红素(Tbil),观察腹水和肝性脑病情况.结果 肝硬化组的QTc延长发生率显著高于对照组(41.4%Vg 4.0%,P＜0.01),肝硬化组QTd显著高于对照组(48.7±18.6ms Vg 34.6±11.1ms,P＜0.05),QTc延长的发生率与Child分级、Tbil、腹水量呈正相关,与PTA、Alb、肝性脑病无相关性.结论 肝硬化患者QTc延长及QTd增加是多因素共同作用的结果,QTc延长及QTd增加是引起室性心律失常的常见诱因,可能也是肝硬化患者出现猝死的原因之一.     

Differential effects of GdCl3- or MDP treatment on rat liver microcirculation and gene expression in the hepatic non-parenchymal cell fraction in LPS shock

Background: Dichloromethylenebisphosphonate (MDP) and gadolinium chloride (GdCl₃) are substances frequently used for experimental depletion of Kupffer Cells (KC) in models of endotoxin shock. The aim was to determine whether depletion of KC through pretreatment with GdCl₃ or MDP alters the hepatic microcirculation during lipopolysaccharide (LPS)‐induced shock in rats and to test if there are substance‐specific differences. Methods: Rats received either MDP or GdCl₃ or saline prior to induction of LPS shock. Hepatic microcirculation was evaluated by intravital microscopy (sinusoidal diameter, sinusoidal bloodflow, leukocyte adhesion), and the gene expression in the hepatic non‐parenchymal cell fraction was determined by RT‐PCR. Results: GdCl₃ pretreatment prevented sinusoidal narrowing but did not restore sinusoidal blood flow and did not normalize leukocyte‐endothelial interaction time after LPS. In contrast, MDP pretreatment improved hepatic microcirculation consistently for all parameters measured compared to GdCl₃ pretreated animals. In the non‐parenchymal cell fraction, eNOS gene expression was preserved and gene expression of TNF‐α was blocked after MDP but not after GdCl₃ application prior to LPS shock. Conclusions: The results show that GdCl₃ and MDP cannot be used equivalently for experimental KC depletion in the condition of LPS‐induced shock. These findings should be taken into consideration in studies that evaluate the role of Kupffer cells in models of endotoxin‐induced shock.     

Effect of in situ hypothermic perfusion on intrahepatic pO2 and reactive oxygen species formation after partial hepatectomy under total hepatic vascular exclusion in pigs

Abstract: Aim: This study examined attenuation of ischemia and reperfusion (I/R) induced liver injury during liver resections by hypothermic perfusion of the liver under total hepatic vascular exclusion (THVE). Method: Reactive oxygen species (ROS) formation, microcirculatory integrity and endothelial cell damage were investigated. Left hemihepatectomy (LHX) was performed without in situ perfusion (control‐LHX, n = 5) or with concomitant in situ perfusion with hypothermic (4 °C) Ringer‐glucose (cold‐LHX, n = 5) or normothermic (38 °C) Ringer‐glucose (warm‐LHX, n = 5). Glutathione (GSH) and malondialdehyde (MDA) concentrations, tissue pO₂ levels and hyaluronic acid (HA) uptake capacity were determined. Results: After cold, warm and control‐LHX, 24 h survival was 5/5, 0/5 and 3/5, respectively. GSH levels were best preserved after cold‐LHX during reperfusion. MDA levels increased in all groups without significant differences between the groups during reperfusion. Tissue pO₂ levels increased after cold‐LHX whereas after warm‐LHX and control‐LHX, pO₂ levels decreased during reperfusion. HA uptake capacity remained normal after cold‐LHX. After warm‐LHX and control‐LHX, HA uptake capacity decreased after 6 h of reperfusion but recovered after 24 h of reperfusion in the control‐LHX group. Conclusion: Moderate hypothermic perfusion protects the liver from I/R injury during LHX under THVE. This protective effect depended on maintenance of liver microcirculation rather than a reduction in ROS formation.     

老年大鼠血管功能及能量代谢改变及机制

目的:探讨老年大鼠血管功能的特点及其能量代谢和线粒体功能变化.方法:将16只大鼠分为两组(n=8),即老年大鼠组和成年大鼠组.禁食12 h后,测量大鼠全血血糖水平和血浆胰岛素的水平.取大鼠胸主动脉制作成2-3 mm的血管环,连接到离体血管灌流及记录系统记录血管的舒张变化情况.取血管灌流液测定NO的含量.用Western...     

陈旧性心肌梗死侧支循环对左心室功能及QT离散度的影响

目的 探讨陈旧性心肌硬死患者侧支循环对冠状动脉病变程度、左心室功能及QT离散度及其内在关系的影响。方法 56例陈旧性心肌梗死者,冠状动脉造影主要分支狭窄≥70％血管作Leaman计分,左心室造影检测左心室射血分数,左心室壁运动作Cortina记分,研究侧支循环对Leaman 记分与左心室射血分数、Cortina记分及QT离散度及其相互关系的影响。结果 全组Leaman冠状动脉计分与左心室射血分数及Cortina左心室壁运动记分无相关,与QT离散度呈弱正相关;而无侧支循环建立的亚组,Leama冠状动脉记分与左心室射血分数呈负相关（r＝－0．59,P＜0．01）,与Cortina 左心室壁运动计分呈显著正相关（r=0．77,P＜0．01）,与QT离散度呈正相关（r＝0．53,P＜0．05）,Cortina左心室壁运动计分与QT离散度呈正相关（r＝0．63,P＜0．05）。结论 陈旧性心肌梗死冠状动脉病变程度与左心室功能及心肌电稳定性之间的关系,一定程度上取决于严重病变的冠状动脉有无侧支循环的建立,侧支循环对陈旧性心肌梗死的左心室功能有保护作用并可以减小心室肌复极的不均一性及电不稳定性。     

Effects of age and estrogen status on the skeletal IGF regulatory system

Human marrow was obtained as material discarded during total hip replacement and was established in culture with phenol red-free α-MEM with 10% fetal bovine serum (FBS) and antibiotics. Insulin-like growth factor I (IGF-I) and its binding proteins were secreted by human marrow cells, in amounts that increased with time in culture. Western ligand blotting showed that insulin-like growth factor binding protein-3 (IGFBP-3) accounted for the majority (∼75%) of the secreted binding proteins. Evidence for marrow secretion of BP-3 protease was found by electrophoretic analysis of mixtures of radiolabeled IGFBP-3 and marrow-conditioned media. The amount of constitutive secretion of IGFBP-3 increased with age of the subject (r=0.97,p=0.0058). A notable exception was marrow from a postmenopausal women on estrogen replacement therapy (ERT) at the time of surgery; her marrow secreted 89.3 ng/mL after 14 d in vitro, only 38% of the IGFBP-3 that was secreted by cultures from two age-matched peers (208.8 and 285.2 ng/mL). This in vivo effect of estrogen was matched by an in vitro experiment in which 10⁻⁸ M 17-β estradiol suppressed IGFBP-3 to 60% of the constitutive level. In all cultures of marrow from postmenopausal women, IL-1β suppressed IGFBP-3 secretion to either undetectable levels or levels between 11% and 35% of control. Thus, human bone marrow cultures demonstrate components of the skeletal IGF regulatory system: IGF-I, IGF-binding proteins, and evidence of IGFBP-3 proteolysis. These results provide evidence of regulation by both systemic (age, estrogen status) and cytokine (IL-1β) factors.     

The effect of old age on liver oxygenation and the hepatic expression of VEGF and VEGFR2

In old age, the liver contains less ATP and hypoxia-responsive genes are upregulated. Age-related changes in hepatic perfusion and the liver sinusoidal endothelial cell (LSEC) could contribute to this altered hepatic oxygen-dependent metabolism by causing intrahepatocytic hypoxia. Furthermore, age-related changes in the LSEC ('pseudocapillarization') have been partially induced by ATP depletion. To investigate whether there is intracellular hypoxia in the old rat liver, pimonidazole immunohistochemistry in intact livers and ATP levels in isolated LSECs were studied from young and old rats. There were no age-related changes. To determine whether defenestration of the LSEC could impair oxygen diffusion, pimonidazole immunohistochemistry was performed in rats treated with poloxamer 407. Despite defenestration, there was no change in pimonidazole staining. Immunohistochemistry was then performed to determine whether there are age-related changes in VEGF and VEGFR2. VEGF staining was not associated with age. However, there was an increase in perisinusoidal VEGFR2 expression with increasing age. In conclusion, liver hypoxia does not occur in old age and LSEC pseudocapillarization does not constitute an oxygen-diffusion barrier. There are no age-related changes in VEGF expression but an increase in perisinusoidal VEGFR2 expression, which has implications for the effects of aging on the hepatic sinusoid.     

紫杉醇对培养的兔血管平滑肌细胞和内皮细胞增生与迁移的影响及其相互关系

目的 观察不同浓度紫杉醇对兔血管平滑肌细胞和内皮细胞增生、迁移的影响及其相互关系。方法 培养兔血管平滑肌细胞及内皮细胞,建立细胞共培养体系,模拟紫杉醇对血管壁平滑肌细胞及内皮细胞的作用方式,观察不同浓度紫杉醇对兔血管平滑肌细胞及内皮细胞DNA合成、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)蛋白表达的影响,测定不同浓度紫杉醇对兔血管平滑肌细胞及内皮细胞的迁移率,用直线回归法推算紫杉醇对平滑肌细胞及内皮细胞增生迁移的半数有效抑制浓度(IC50)。结果 溶剂对照组平滑肌细胞及内皮细胞氚-胸腺嘧啶脱氧核苷(3H-TdR)掺入、PCNA蛋白表达和迁移与对照组相比差异均无显著性。在1 nmol/L～1μmoL/L之间,紫杉醇呈浓度依赖地抑制平滑肌细胞3H-TdR掺入、PCNA蛋白表达和迁移(n=6,P<0.05);在10nmol/L-1 μmol/L之间,紫杉醇呈浓度依赖地抑制内皮细胞3H-TdR掺入、PCNA蛋白表达和迁移(n=6,P<0.05);1 nmol/L的紫杉醇对内皮细胞3H-TdR掺入和PCNA蛋白表达有抑制倾向,但与对照组相比差异无显著性,而1 nmol/L的紫杉醇却显著抑制内皮细胞迁移(n=6,P<0.05)。紫杉醇对兔血管平滑肌细胞增生、迁移抑制的IC50分别为(10.09±0.47)和(9.16±0.54)nmol/L,对内皮细胞增生、迁移抑制的IC50分别为(19.05     

丁基苯酞对血管性痴呆大鼠记忆及海马Bcl-2、Bax的影响

目的 研究丁基苯酞(NBP)对血管性痴呆(VD)大鼠记忆、海马病理变化及抗凋亡蛋白(Bcl-2)和促凋亡蛋白(Bax)蛋白表达的影响.方法 采用永久性结扎双侧颈总动脉方法制备VD大鼠模型.SD大鼠被随机分成假手术组、VD模型组、NBP治疗组、尼莫地平治疗组.应用Morris水迷宫检测大鼠记忆能力,苏术精-伊红(HE)染色观察海马神经元形态,免疫组化检测海马Bcl-2和Bax的表达.结果 VD模型组与假手术组大鼠比较记忆能力显著下降,逃避潜伏期分别为(78.79±21.93) s与(16.96±7.44) s (P＜0.05),海马神经元病理改变严重,免疫阳性细胞数量显著增加,其中Bax变化更为显著 (43.00±6.72与6.00±1.29,P＜0.05),Bcl-2与Bax的比值较对照组明显降低;NBP治疗组与模型组比较记忆能力显著改善,逃避潜伏期分别为(47.13±21.75) s与(78.79±21.93) s (P＜0.05),海马神经元病理形态明显改善,Bcl-2免疫阳性细胞数显著增多(33.14±8.05与21.81±4.97,P＜0.05),Bax免疫阳性细胞数显著减少(32.93±4.99与43.00±6.72,P＜0.05).NBP治疗组与尼莫地平治疗组之间比较,各项指标均无显著差异 (P＞0.05).结论 NBP能改善VD大鼠记忆能力,抑制海马细胞凋亡,对VD大鼠有一定的治疗作用.

Abstract：

Objective To study the effects of butylphthalide (NBP) on memory and apoptosis related protein as well as neuronal pathology in hippocampus of vascular dementia (VD) rats. Methods VD model was generated by the permanent occlusion of bilateral common carotid arteries in SD rats to produce the forebran ischemia. Male SD rats were randomly allocated into sham-operation group, VD model group, NBP treatment group and nimodipine treatment group. The function of memory was tested by the Morris water maze. The neuronal pathological changes and the expression of Bcl-2 and Bax proteins in the hippocampus were observed with hematoxylin-eosin (HE) staining and immunohistochemical staining, respectively. Results The impaired memory of VD rats was proved by the lengthened mean escape latency [(78.79±21.93)vs.(16.96±7.44),P＜0.05] and the neuron in hippocampus was severely damaged. The decveased ratio of Bcl-2/Bax resulted from the overexpression of Bax proteins in VD model group versus the sham-operation group [(43.00±6.72)vs.(6.00±1.29),P＜0.05]. The treatment of NBP notably improved the memory function of VD rats and reduced the hippocampus pathological injury (P＜0.05). The expression of Bcl-2 protein raised [(33.14±8.05)vs.(21.81±4.97),P＜0.05] along with reduced expression of Bax protein [(32.93±4.99)vs.(43.00±6.72),P＜0.05] after NBP treatment. However, there was no significant difference in the treatment effects between nimodipine and NBP group (P＞0.05). Conclusions NBP treatment could improve memory of VD rats and reduce the hippocampus pathological lesion by inhibiting the apoptosis related protein.     

bFGF基因转染对血管内皮细胞迁移的影响及机制

目的研究碱性成纤维细胞生长因子（bFGF）基因转染对人脐静脉内皮细胞（HUVECs）迁移能力的影响,并探讨其可能机制。方法通过基因亚克隆构建真核表达载体pcDNA3．1-bFGF,利用脂质体介导将bFGF基因导入HUVECs内,通过RT-PCR和ELISA法检测基因的表达;bFGF基因转染后的HUVECs通过Transwell小室法检测其迁移能力的变化;Western blot法检测转染后的细胞Raf-1、细胞外调节蛋白激酶2（ERK2）和黏着斑激酶（FAK）蛋白表达变化。结果成功构建了表达载体pcDNA3．1-bFGF,该载体转染HUVECs后,bFGFmRNA和蛋白均显著增加。转染bFGF基因可使HUVECs的体外迁移能力增强,上调ERK2和FAK蛋白的表达,但对Raf-1蛋白表达无影响。结论bFGF基因转染能促进血管内皮细胞的迁移,其作用机制可能与上调ERK2和FAK蛋白表达有关。     

静息心率对老年人群心脑血管事件及全因死亡的影响

目的探讨老年人群(≥60岁)静息心率(RHR)水平对心脑血管事件及全因死亡的影响。方法本前瞻性队列研究于2006年和2007年进行,参加者为101 010名开滦集团的员工,选择其中年龄≥60岁、无心律失常、无心脑血管病史、未服用β受体阻滞剂的18 924例职工为研究对象。按RHR四分位数值分为以下4组:<67次/min、68~71次/min、72~79次/min、≥80次/min。随访期间收集心脑血管疾病及全因死亡事件,应用Cox比例风险模型评估RHR与全因死亡及CVD的风险。结果 (1)中位随访11.18年,4组发生心脑血管事件例数和累积发病率分别为[536(11.32%)、479(12.38%)、686(12.53%)、618(12.76%)],差异无统计学意义(P>0.05);4组发生全因死亡例数和累积全因死亡率分别为1 086(22.93%)、940(24.30%)、1 330(24.28%)、1 462(30.19%)例,差异有统计学意义(P<0.01)。(2)校正传统心血管疾病危险因素后多因素分析显示,与RHR最低四分位数组相比,最高四分位组发生心脑血管事件及全因死亡的HR值分别为1.06(95%CI 0.93~1.20)、1.07(95%CI 0.95~1.20)、1.07(95%CI 0.94~1.21);1.14(95%CI 1.04~1.25)、1.12(95%CI 1.03~1.22)、1.37(95%CI 1.26~1.49)。结论 RHR升高是开滦研究老年人群全因死亡的危险因素。     

Effects of spermine and sodium butyrate on the in vitro phosphorylation of HMG non-histone proteins of the liver of young and old rats

The in vitro phosphorylation of high mobility group (HMG) proteins and its modulation by spermine and sodium butyrate were studied in the liver of young (15 week) and old (138 week) male rats. Except HMG 1 which remained unchanged, the phosphorylation of other proteins (HMG 2, 14 and 17) decreased drastically in old age. Spermine stimulated the phosphorylation of HMG 1 and 17 in young but HMG 1, 2 and 14 in old rats. The incorporation of ³²P into total HMG proteins was enhanced by butyrate in the liver of both ages. However, the degree of stimulation was higher in young rats. Particularly, the HMG 1 and 17 of young and HMG 2 and 17 of old rats showed increased phosphorylation. Furthermore, butyrate also inhibited the phosphorylation of HMG 2 in young and HMG 1 and 14 in old rats. Such alteration in the phosphorylation of major HMG proteins modulates their interaction with DNA and other components of chromatin. This may account for changes in the higher order organization of chromatin and expression of genes during aging.     

Prognostic value of bone marrow angiogenesis in multiple myeloma: use of light microscopy as well as computerized image analyzer in the assessment of microvessel density and total vascular area in multiple myeloma and its correlation with various clinical, histological, and laboratory parameters

We studied the prognostic value of parameters of angiogenesis on bone marrow biopsies in newly diagnosed multiple myeloma (MM) patients. Angiogenesis parameters studied were the microvessel count done manually on light microscopy (MVD-A), microvessel count done by using computerized image analyzer (MVD-B), and total vascular area (TVA) measured by computerized image analyzer. One hundred ten newly diagnosed cases of MM treated at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, were analyzed with respect to clinical features, laboratory findings, histological features, angiogenesis parameters, and responses to the treatment on follow-up. Twenty age- and sex-matched controls were studied for comparing with angiogenesis of the test cases. Bone marrow microvessels were examined using immunohistochemical staining for CD34. MVD-A (range 4.9-85.2; mean 28.2; SD 19.4), MVD-B (range 2.0-26.9; mean 11.7; SD 5.9), and TVA measured in percentage (range 0.1-17.1; mean 2.4; SD 2.5) were measured for test cases (n = 110). Grading of angiogenesis parameters of the test cases were done; such that angiogenesis parameters of controls (taken as baseline) were grade I. There was a statistically highly significant correlation between (MVD-A vs MVD-B, pcc = 0.92; MVD-A vs TVA, pcc = 0.78; MVD-B vs TVA, pcc = 0.76). The myeloma cases had significantly higher angiogenesis parameters when compared with controls (Kruskall-Wallis test, P < 0.001). "Complete responders" (n = 38/110) had significant lower angiogenesis (Mann-Whitney U test, P < 0.001) than "nonresponders" (n = 72/110). On treatment follow-up "rapid disease progressors" had the highest levels of angiogenesis (mean rank for MVD-A = 84.7, MVD-B = 82.1, and TVA = 81.1). On multivariate (logistic regression) analysis, factors found to have independent prognostic significance in complete responders (adjusted odd ratio (95% CI, P value)] were: (a) MVD-B grade I [0.134 (0.10-0.16, P < 0.001)], (b) clinical substage A [0.163 (0.12-0.19, P = 0.008)], (c) Bartl's histological stage II & I [0.262 (0.2-0.32, P = 0.021)], (d) MVD-A grade I [0.28 (0.22-0.36, P = 0.03)], (e) beta2 microglobulin levels less than 3,400 ng/dl [0.31 (0.23-0.42, P = 0.04)]. Kaplan-Meier survival analysis for myeloma-related death (n = 16) shows a mean survival time (in months) of 24.75; SE = 3; 95% CI = 21-28. We conclude that MVD (particularly MVD-B) is a very good predictor for the complete response in patients of MM and should be done routinely on bone marrow biopsies.     

高静水压对内皮细胞一氧化氮合酶抑制物的影响及卡托普利的干预作用

目的 :观察高静水压培养的人脐静脉内皮细胞 (HUVECs)内源性一氧化氮 (NO)合酶抑制物———不对称二甲精氨酸 (ADMA)的影响及卡托普利的保护作用。方法 :采用改良的Jaffe法培养原代HUVECs,取生长良好的3～ 6代HUVECs用于实验 ,分为①大气压组 :加等量DMEM培养液 ;②高静水压组 ;③高压加卡托普利组。测定上清液中ADMA、左旋精氨酸 (L arg)、NO和内皮素 (ET)的浓度 ,并测定血管紧张素转化酶 (ACE)的活性。结果 :高静水压组ADMA、ET的量、细胞内钙 [Ca2 + ]i及ACE活性增加 ,而NO的量减少。卡托普利干预后 ,上清液中ADMA、ET的浓度减少 ,ACE活性降低 ,NO的量增加 ,而L arg水平无明显变化。结论 :高静水压通过增加ADMA导致内皮功能紊乱 ,卡托普利则能通过减少ADMA减轻高压导致的内皮细胞代谢功能障碍     

Effects of tumor origins and therapeutic options on the prognosis of hepatic neuroendocrine tumors: A retrospective study

Hepatic neuroendocrine tumors (HNETs) are uncommon neoplasms that can be subdivided into 2 types: primary and metastatic HNETs. Due to its rarity, heterogeneity and complexity, the diagnosis, treatment modalities and prognosis are still controversial.This retrospective study reviewed the effects of tumor origins and therapeutic options on the prognosis of gastroenteropancreatic neuroendocrine tumors with liver metastasis (GEP-NETLM) and primary hepatic neuroendocrine tumors (PHNETs), providing additional evidence for clinicians evaluating patients.HNETs consisted of PHNETs and GEP-NETLM. GEP-NETLM (76.2%, 112/147) was more common, which was mainly manifested as multiple lesions in both lobes of the liver. PHNETs were relatively rare (23.8%, 35/147) and were mainly single lesion located in the right lobe of the liver. In patients with GEP-NETLM, primary tumor resection could prolong survival (P = .044). As the most widely used treatment method, systematic therapy alone could not achieve a satisfactory survival. However, the combination with hepatectomy or liver-directed therapy improved the prognosis (P = .023). As the main treatment, patients with PHNETs treated with local therapy could achieve a better prognosis (P = .049). Compared with PHNETs patients, GEP-NETLM patients with higher ki-67 index showed higher mortality and poorer prognosis (P = .006).Therefore, patients with PHNETs can be distinguished from GEP-NETLM by comprehensive imaging examinations and long-term follow-ups. The choice of appropriate treatment strategies can improve the prognosis of HNETs patients.     

Effects of islet amyloid polypeptide on hepatic insulin resistance and glucose production in the isolated perfused rat liver

Summary The impact of (pancreatic) islet amyloid polypeptide on glucose metabolism and insulin sensitivity was examined in isolated rat livers perfused in a non-recirculating system. Continuous infusion of 10^–7mol/l islet amyloid polypeptide affected neither basal nor glucagon (10^–9 mol/l)-stimulated glucose output by livers from fed rats, but it did increase the hepatic cyclic AMP release within 44 min (7.91±12.07 vs control: 0.07±0.03 pmol·100 g body weight^–1). The effect of the peptide on the ability of insulin to inhibit glucagon-induced hepatic glycogenolysis was measured in three experimental groups (n = 6). As expected glucagon (7×10^–11 mol/l) increased integral hepatic glucose release within 84 min (763.4±161.7 vs –25.7±73.2 mol · 100 g body weight^–1 in the control group, p<0.001), while insulin (100 mU/l) decreased the glucagon-stimulated glucose production (395.2±180.0 mol·100 g body weight^–1, p<0.01). Simultaneous infusion of 10^–7 mol/l islet amyloid polypeptide however, was not able to reverse insulin-dependent inhibition of glucagon-stimulated hepatic glucose output (370.0±102.5 mol·100 g body weight^–1, NS) or to enhance lactate-induced gluconeogenesis of livers from 24 h fasted rats (n = 8). The glucose production stimulated by 10^–9 mol/l glucagon was slightly greater in islet amyloid polypeptide-pre-treated livers than in a control group without addition of islet amyloid polypeptide (5 min: 3.60±3.36 vs 1.67±1.28 mol·min^–1·100 g body weight^–1). These results suggest that islet amyloid polypeptide neither directly affects hepatic glycogenolysis nor causes insulin resistance to hormone-sensitive glucose production, but may increase the size of the hepatic glycogen pool by enhancing gluconeogenesis.