过氧化苯甲酰对小鼠肝脏组织损伤作用

目的 探讨面粉增白剂过氧化苯甲酰(benzoyl peroxide,BPO)对小鼠肝脏组织的损伤作用.方法 64只昆明种小鼠随机分为对照组和低、中、高剂量BPO组,分别灌胃给予BPO50,100和200 mg/kg,每组16只,雌雄各半;灌胃6周后,测定各组肝脏组织中谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活力和丙二醛(MDA)含量及三磷酸腺苷(ATP)酶活力.结果 高、中剂量BPO组SOD活力分别为(40.15±7.13),(46.01±6.69)U/(mg·prot),与对照组(53.15±6.55)U/(mg·prot)比较,差异有统计学意义(P<0.05);高剂量BPO组与对照组MDA含量分别为(1.93±0.37)和(1.57±0.33)nmol/(mg·prot),差异有统计学意义(P<0.05);高剂量BPO组Mg2+-ATP、Ca2+-ATP酶活力分别为(1.58±0.11)和(1.48±0.09)μmol Pi/(mg·prot),与对照组比较明显降低,差异有统计学意义(P<0.05);各剂量BPO组GSH-Px活力与对照组比较差异无统计学意义(P>0.05).结论 BPO在一定程度上可降低小鼠肝脏抗氧化及Ca2+、Mg2+-ATP酶活力.     

海藻萜类化合物联合VE对酒精性肝损伤大鼠影响

目的 研究凹顶藻萜类化合物(Laurencia extract,LET)与维生素E(VE)合用对乙醇诱导肝损伤大鼠的影响及其作用机制.方法 70只雄性Wistar大鼠随机分为7组.除空白组每天给予蒸馏水灌胃外,其余各组均每天乙醇12 mL/(kg·bw)灌胃,各干预组分别给予不同剂量LET加VE、VE、甘利欣灌胃,6周后测定血清肝功、血脂及肝匀浆中抗氧化指标.结果 不同剂量LET合用干预组血清肝功、血脂水平与乙醇模型组比较,差异有统计学意义(P<0.05);LET中、高剂量合用干预组谷胱甘肽过氧化物酶(GSH-Px)活力分别为(59.523±11.015),(59.541±13.724)U/(mg·prot);丙二醛含量(MDA)分别为(5.018±1.239),(4.799±1.628)nmol/(mg·prot);高剂量合用干预组超氧化物歧化酶活力(SOD)为(147.690±9.989)U/(mg·prot),与乙醇模型组GSH-Px(45.624±10.589)U/(mg·prot)、MDA含量(10.593±1.716)nmol/(mg·prot)、SOD活力(100.153±13.632)12/(mg·prot)比较,差异有统计学意义(P<0.05).结论 LET与VE合用能调整酒精性肝损伤大鼠体内脂质代谢,改善肝功能,减少脂质过氧化产物,对酒精造成的机体损伤表现出相应的保护效应.     

原卟啉钠对急性肝损伤小鼠肝脏氧化酶影响

目的 探讨原卟啉钠对四氯化碳((CCI4)致急性肝损伤小鼠肝组织过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)活力影响.方法 60只ICR小鼠随机分为正常对照、模型组、联苯双酯、原卟啉钠低、中、高剂量组;原卟啉钠组每天灌胃给药;造模16 h后,剖腹取肝进行病理组织学检查,计算肝脏指数,测定肝组织匀浆液CAT和GSH-Px活力.结果 模型组小鼠肝组织CAT和GSH-Px活力分别为(19.67±4.46),(193.39±42.36)U/(mg·prot),与正常对照组比较明显降低(P<0.01);联苯双酯组、原卟啉钠低、中、高剂量组CAT和GSH-Px活力分别为(29.98±4.79),(27.74±6.11),(28.13±5.67),(33.82±6.00)U/(mg·prot)和(265.72±48.42),(200.24±39.30),(231.73±46.70),(257.64±37.11)U/(mg·prot),明显高于模型组(P<0.05);病理切片显示,原卟啉钠各剂量组小鼠肝损伤有不同程度减轻.结论 原卟啉钠具有一定抗氧化作用,能有效阻止CCl4致急性肝损伤小鼠肝组织CAT和GSH-Px活性降低.     

尼莫地平对皮质神经元缺糖缺氧性损伤的保护作用

目的:探讨尼莫地平对缺糖缺氧培养的小鼠大脑皮质神经元的保护作用.方法:新生1～2 d小鼠的大脑皮质神经元原代培养8 d,用含连二亚硫酸钠的无糖.Earle's液模拟体内缺血性损伤,检测乳酸脱氢酶(IJDH)的漏出量,细胞生存率(M3Tr法)及细胞超氧化物歧化酶的活性,观察尼莫地平对神经元缺糖缺氧损伤的保护作用.结果:1.经缺糖缺氧培养后,细胞培养液中的乳酸脱氢酶(LDH)漏出增多,细胞超氧化物酶(SOD)活性和细胞生存率显著降低(P＜0.05);2.尼莫地平组LDH的漏出低于缺氧缺糖组,SOD活性及细胞生存率明显提高(P＜0.05).结论:尼莫地平对小鼠大脑皮质神经元缺糖缺氧性损伤具有一定的保护作用.     

牛磺酸对锰致海马神经元损伤影响

目的 探讨牛磺酸对锰致海马神经元损伤的影响.方法 新生Wistar大鼠海马神经元细胞原代培养后随机分为空白组、牛磺酸组、低、中、高剂量锰组、牛磺酸+低、中、高剂量锰组,检测乳酸脱氢酶(LDH)活力、流式细胞仪定量凋亡率和观察神经元超微结构变化.结果 LDH活力低、中、高剂量锰组分别为(1 048.063 0±55.459 8)、(1 004.1233±65.339 4)、(1 405.303 3±163.311 5)U/L,明显高于空白组(895.203 3±53.228 6) U/L(F=31.802,P＜0.001),牛磺酸+低剂量锰组(834.595 0±173.445 5)U/L明显低于低剂量锰组(1 048.063±55.459 8) U/L(t=2.871,P=0.017);神经元凋亡率中、高剂量锰组分别为(44.6±4.0)％和(57.7±6.2)％,均明显高于空白组(17.5±2.5)％ (F=159.05,P＜0.001),牛磺酸+中剂量锰组(34.6±6.4)％明显低于中剂量锰组(44.6±4.0)％(t=3.813,P=0.019),牛磺酸+高剂量锰组(28.9±13.2)％明显低于高剂量锰组(57.7±6.2)％(t=3.709,P=0.021);电镜下观察,锰组神经元呈凋亡和坏死的形态学改变,牛磺酸+锰组与其比较有所改善.结论 锰在体外可剂量依赖性引起海马神经元死亡,牛磺酸可在一定程度上拮抗锰的神经毒性.     

污灌玉米有机提取物致小鼠肝肾氧化损伤作用

目的 研究某污灌区玉米中有机污染物对小鼠肝肾组织的氧化损伤作用.方法 采用超声振荡法提取某污灌区农田生产的玉米中的有机污染物,对小鼠进行灌胃染毒2周;测定肝、肾组织的总超氧化物歧化酶(T-SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-P_x).结果 污灌区低、高剂量组肝组织的T-SOD活性分别为(32.44±7.93),(30.92±9.29)U/(mg·prot);肾组织的GSH-P_x活性分别为(67.28±27.21),(66.52±15.19)U/(mg·prot),与对照组比较均明显降低(P<0.05或P<0.01).结论 该污灌区玉米有机提取物中含有致小鼠肝肾组织氧化损伤的有机污染物;对照区玉米中的有机污染物很可能来源于被污染的大气.     

硫酸镁对小鼠肾缺血再灌注损伤保护作用

目的 观察硫酸镁对小鼠肾缺血再灌注损伤的抗氧化保护作用.方法 雄性小鼠随机分为假手术组、模型组和硫酸镁高、低剂量(120、60 mg/kg)组,无创动脉夹夹闭左肾蒂45 min和再灌注3h制备急性肾缺血再灌注损伤模型,检测肾脏指数、血清尿素氮(BUN)和肌酐含量、肾组织丙二醛(MDA)含量以及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活力,HE染色观察肾组织学变化.结果 硫酸镁高、低剂量组小鼠肾指数分别为(0.72±0.05)和(0.74±0.07)、血清BUN含量为(12.36±2.24)和(15.58±1.92) mmol/L、血清肌酐水平为(98.23±4.37)和(114.63±6.24) μmol/L、肾组织MDA含量为(2.11±0.24)和(2.27±0.21) nmol/(mg·prot),肾组织SOD活力为(4.03±0.68)和(3.51±0.58) U/(mg·prot),硫酸镁高剂量组肾组织GSH-Px活力为(323.90±23.50)U/( mg· prot),与模型组比较,差异均有统计学意义(P＜0.05),且肾组织病理变化较轻.结论 硫酸镁对小鼠急性肾缺血再灌注损伤具有保护作用,其机制可能与抑制脂质过氧化反应有关.     

枳实对糖尿病小鼠肾脏抗氧化能力及胰岛影响

目的 研究枳实提取物对实验性糖尿病小鼠肾脏抗氧化能力及胰岛形态的影响.方法 将枳实提取物分成高、中、低剂量[5.1,3.4,1.7 g/(kg·bw)]治疗糖尿病小鼠4周后,观察其一般状况、肾脏的抗氧化能力及胰岛形态变化.结果 枳实高剂量组小鼠末期血糖为(20.37±5.25)mmol/L,明显低于糖尿病组的(25.74±2.99)mmol/L(P<0.05);枳实高剂量组谷胱甘肽(GSH)含量为[(34.40±8.54)mg/(g·prot)],明显高于糖尿病组的[(21.38±3.91)mg/(g·prot)](P<0.01);枳实高剂量组丙二醛(MDA)和NO含量分别为[(0.89±0.37)nmol/(mg·prot)],[(1.27±0.56)μmol/(g·prot)],明显低于糖尿病组的[(1.46±0.39)nmol/(mg·prot)],[(2.15±0.85)μmol/(g·prot)](P<0.01或P<0.05),光镜下枳实提取物治疗组胰岛细胞损伤程度较糖尿病组轻.结论 枳实提取物能增强肾脏的抗氧化能力;保护胰岛组织细胞并降低胰岛细胞损伤.     

核因子-κBp65在乙醇诱导小鼠急性肝细胞损伤中的表达及意义

目的 观察核因子-κB(NF-κB)p65蛋白在乙醇诱导肝细胞损伤中的表达.方法 36只小鼠随机分成1个对照组和5个乙醇染毒组,每组6只.以0、62.5、125.0、250.0、500.0、1000.0mmol/kg剂量的乙醇给予小鼠一次性灌胃染毒,16 h后检测小鼠血清中天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)的活力;采用免疫组织化学法观察小鼠肝细胞中NF-κB p65蛋白的表达.结果 62.5、125.0、250.0、500.0、1000.0 mmol/kg小鼠血清中的AST活力分别为(165.00±7.07)、(180.50±7.58)、(185.17±8.08)、(197.50±5.32)、(207.17±5.12)U/L,高于对照组[(156.67±5.16)U/L],差异有统计学意义(P<0.05或P<0.01);62.5、125.0、250.0、500.0、1000.0mmol/kg小鼠血清中ALT活力分别为(43.17±2.14)、(46.33±1.37)、(53.33±2.25)、(52.67±2.25)、(56.17±1.33)U/L,高于对照组[(37.33±2.58)U/L,差异有统计学意义(P<0.05或P<0.01);免疫组织化学方法检测出乙醇染毒剂量组小鼠肝细胞胞浆、胞核内NF-κB p65的表达高于对照组.结论 NF-κB p65参与了小鼠酒精性肝细胞损伤的发展过程.     

虾青素对四氯化碳致小鼠急性肝损伤保护作用

目的 研究虾青素对四氯化碳(CCl4)所致小鼠急性化学肝损伤的保护作用.方法 雄性昆明种小鼠60只,随机分为正常对照组、急性化学性肝损伤模型组、联苯双酯(15 mg/kg)阳性对照组以及虾青素10,15,20mg/kg剂量组,共6组.测定各组小鼠肝脏系数、血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性与丙二醛(MDA)含量;测定肝组织中SOD、GSH-Px活性、MDA含量以及组织病理系数.结果 虾青素3个剂量组小鼠血清SOD由低到高依次为(110.18±14.28),(138.09±17.81),(170.19±20.20)U/(mg pro);肝组织SOD由低到高依次为(141.52±28.29),(172.20±29.24),(200.12±33.42)U/(mg pro);与模型组血清(74.52±14.40)U/(mg pro)、肝组织(102.29±34.29)U/(mg pro)比较均明显升高(P<0.01).虾青素3个剂量组小鼠血清GSH-Px活性由低到高次为(63.30±11.01),(72.40±10.77),(90.17±11.29)U/(mg pro);肝组织GSH-Px活性由低到高依次为(112.29±25.41),(142.96±24.13),(170.38±26.34)U/(mg pro);与模型组血清(60.13±10.28)U/(mg pro)、肝组织(110.69±24.26)U/(mg pro)比较均明显升高(P<0.01).虾青素3个剂量组小鼠血清ALT由低到高依次为(99.29±5.27),(83.50±5.12),(68.12±5.12)U/L;血清AST活性由低到高依次为(80.49±4.28),(64.20±4.10),(52.21±4.42)U/L,与模型组血清ALT(108.02±15.06)U/L、血清AST活性(97.28±12.28)U/L比较明显降低;血清与肝组织MDA含量明显降低,差异均有统计学意义(P<0.01),并能不同程度地改善肝脏病理组织损伤.结论 虾青素对CCl4所致急性化学性肝损伤具有预防性保护作用.     

Glucose can reverse the effects of acute fasting on mouse ovulation and oocyte maturation

Food deprivation suppresses ovulation. Although nutritional elements are responsible for this suppression, it is not clear whether energy metabolism has any effect on oocyte development under these circumstances. The aim of the present study was to determine which nutritional element is responsible for the effect of acute fasting on mouse ovulation and how oocyte development is affected. The results demonstrate that 64 h food deprivation blocks mouse ovulation. This was reversed by glucose feeding, oil feeding or short-term feeding, all of which elevated serum glucose levels. Furthermore, 48 h food deprivation inhibited follicle-stimulating hormone-induced oocyte maturation in vitro. However, 48 h glucose feeding increased serum glucose levels and restored oocyte maturation. Food deprivation increased serum progesterone levels and decreased serum oestradiol levels. Food deprivation also impaired follicle development, caused the death of oocytes and attenuated glucose consumption by cumulus-oocyte complexes. Taken together, the results indicate that: (1) the suppression of ovulation by acute fasting may be due to the control of oocyte development; and (2) maintaining serum glucose concentrations at a certain level is important for normal ovulation.     

睡眠剥夺对青年人神经内分泌激素的影响

目的探讨24 h完全睡眠剥夺对青年人血清中肾素、血管紧张素Ⅱ、皮质醇、多巴胺、去甲肾上腺素及肾上腺素的影响。方法整群随机抽取某部队陆军230名青年军人进行24 h完全睡眠剥夺,试验前7 d所有受试者要求正常睡眠(睡眠不少于7 h),试验从下午2:00至次日下午2:00,于试验次日晨7:00(睡眠剥夺期)和试验结束后5日晨7:00(对照期)分别抽取受试者静脉血,测定肾素、血管紧张素Ⅱ和皮质醇,并从受试者中随机选取60名同时测定多巴胺、去甲肾上腺素及肾上腺素,对所得数据进行统计分析。结果睡眠剥夺过程中,受试者血清中的肾素、血管紧张素Ⅱ、皮质醇、多巴胺、去甲肾上腺素及肾上腺素含量与睡眠剥夺前比较,均有明显升高(t=2.132~7.198,P0.05)。结论睡眠剥夺作为一种内源性应激,不仅可激活人体下丘脑-垂体-肾上腺皮质轴(HPA轴),使血清中皮质醇含量明显升高;还可激活人体蓝斑-去甲肾上腺素能神经元(LC-NE)-交感-肾上腺髓质轴(SAM轴),使血清中多巴胺、去甲肾上腺素、肾上腺素含量明显升高;而且还可激活人体肾素-血管紧张素系统(RAS),使血清中肾素、血管紧张素Ⅱ含量明显升高。     

脑源性神经营养因子通过PI3K/Akt/mTOR信号途径对胚鼠缺氧神经元的保护作用

目的 探讨脑源性神经生长因子(brain-derived neurotrophic factor,BDNF)对缺氧(oxygen deprivation,OD)神经元的保护作用是否与激活自噬有关,其信号通路是否通过PI3K/Akt/mTOR途径。方法 1)建立胚鼠神经元OD损伤模型;CCK-8法观察不同浓度BDNF对OD神经元细胞活性的影响;2)检测OD神经元1,3,5 h自噬微管相关蛋白轻链3(LC3)的表达,情况观察BDNF对OD神经元的保护作用是否与自噬有关;3)检测p-Akt,p-mTOR,p-p70S6K以及LC3II的表达,对比BDNF与自噬激活剂雷帕霉素(mammalian target of rapamycin,Rapamycin)对Akt/mTOR/p70S6K的影响,以及自噬被3-MA抑制后,BDNF对Akt/mTOR/p70S6K的影响。结果 1)50 μg/L BDNF可对OD神经元起保护作用(P<0.05),100 μg/L BDNF效应次之;2)BDNF和/或Rapamycin在下调p-Akt/p-mTOR/p-p70S6K表达的同时可上调LC3II的表达;当3-MA抑制自噬后,BDNF对LC3II的上调作用被抑制。结论 BDNF通过PI3K/Akt/mTOR/p70S6K信号途径激活自噬,发挥对OD神经元的保护作用。     

胚胎中期胚胎脑室管膜下区缺氧缺血性损伤及神经保护

【目的】观察缺氧缺血(hypoxic-ischemia,HI)对人类妊娠中期胚胎脑室管膜下区(subventricular,SVZ)的影响及脑活素、神经生长因子(nerve growth factor,NGF)的神经保护作用。【方法】将5例17~22孕周人胚胎脑SVZ快速解离,行即刻培养,以氧糖缺失法建立HI损伤模型,采用析因分析,将HI组和对照组SVZ细胞按NGF、脑活素两因素,用药、不用药两个水平,交叉分成4组即刻培养。通过台盼蓝染色法观测的细胞存活率,并采用神经元特异性抗体MAP2标记神经元。【结果】SVZ神经细胞成活率在HI组为(63.41±0.06)%明显低于对照组(98.9±0.01)%(P0.001)。HI组MAP2(+)神经元占(14.7±0.02)%明显低于对照组(48.81±0.03)%(P0.001)。析因分析结果:HI组NGF、脑活素的主效应、交互作用均具有统计学意义(P0.01),两药交互作用不具有统计学意义(P0.05);而对照组两药的主效应、交互作用亦均无统计学意义(P0.05)。【结论】妊娠中期人类胚胎脑SVZ神经细胞对HI损伤敏感。NGF和脑活素对正常神经细胞无明显影响,但可提高HI后存活的神经元数量;两药联合应用对HI损伤神经元的保护作用增强。     

Insulin levels, physical activity, and urinary catecholamine excretion of obese and non-obese rhesus monkeys

The hypothesis that spontaneous obesity in rhesus monkeys is associated with abnormalities in energy expenditure was tested. Obese (n=7) and non-obese (n=5) monkeys were described in terms of body size and composition, food intake, and physical activity. Additionally, the relationships among fasting and stimulated insulin levels in serum, C-peptide levels in serum and urine, and urinary catecholamines were examined. Obese animals had primarily abdominal deposition of excess body fat, as indicated by markedly elevated abdominal circumferences and skin-fold thicknesses. Food intake did not differ between groups. Physical activity was much lower in the obese group. Obese monkeys had markedly higher serum insulin and C-peptide levels in the fasted state and in response to an intravenous glucose challenge. Urinary excretion of C-peptide and catecholamines was measured during successive 2-day periods of ad libitum feeding, food deprivation, and refeeding in order to examine potential differences between groups in sympathoadrenal activity and their relationship to insulin secretion. C-peptide excretion was greater for obese and decreased for both groups during food deprivation. Urinary dopamine (DA), norepinephrine (NE), and epinephrine (E) levels were significantly greater for obese animals in all conditions. DA excretion was lowest during deprivation and E excretion was lowest during refeeding, whereas NE excretion was relatively unaffected by feeding condition. The overall patterns of C-peptide and catecholamine excretion were qualitatively similar for both groups, and there were no reliable differences between obese and non-obese in their responses to the feeding manipulation. The results suggest that hyperinsulinemia associated with obesity in rhesus monkeys is linked to increased catecholamine secretion and a resistance to catecholaminergic action.     

The Significance of Anox?mia in Modern Psychiatric Treatment: (Section of Psychiatry)

Blood in its passage through the brain loses oxygen and glucose at relatively high rates, the amount of oxygen disappearing being approximately equivalent to the amount of glucose consumed, calculating on the basis that the sugar is completely oxidized. The respiratory quotient of brain in vivo is unity. These facts point to the dominance of carbohydrate oxidation in brain respiration in vivo and are similar to those found in studies of brain in vitro.Various factors influence glucose oxidation in brain, e.g. changes in the ionic environment of the cells, vitamin B₁, or the presence of narcotics. The latter bring about inhibitions of glucose oxidation in brain tissue which may in most cases be shown to be reversible in vitro. Glucose is not only important for the maintenance of respiration of brain but for enabling certain synthetic processes to occur. One of these is the formation of acetylcholine whose physiological significance is now well known and whose synthesis seems to be confined to the nervous system. This synthesis depends not only on the presence of glucose but on that of oxygen. The influence of glucose has been observed also in investigations on cortical potentials.An important feature of the nerve cell is its vulnerability to the lack of oxygen. Reversibility depends on the degree and duration of the anoxæmia.During insulin shock treatment studies of brain in vivo show lowered oxygen consumption and glucose utilization, these depending on the degree of hypoglycæmia. In cardiazol treatment, in vivo studies show that the oxygen content of the blood may fall to 42%. During the convulsion there is a greatly lowered arterial and venous blood-flow through the brain and cerebral anæmia becomes a marked feature. In narcosis treatment both in vitro and in vivo studies show a diminished ability of the brain to consume oxygen.It is suggested that the most significant facts to be taken into account are (1) the importance of glucose and oxygen for the metabolism and function of the nervous system, (2) the vulnerability and varying sensitivities of nerve cells to lack of oxygen and glucose, (3) the occurrence of varying degrees of cerebral anoxæmia in narcosis, insulin and cardiazol treatments.     

Effects of ethanol drinking on central nervous system functional activity of alcohol-preferring rats.

The [(14)C]-2-deoxyglucose (2-DG) technique was used to assess the rates of local cerebral glucose utilization (LCGU) in key limbic, cerebral cortical, hippocampal, basal ganglionic, and subcortical regions of alcohol-preferring (P) rats following chronic 24-h free-choice ethanol drinking. Adult male P rats were submitted to (1) 8 continuous weeks of two-bottle access to 15% ethanol and water (E-C group); (2) 8 weeks of identical two-bottle access followed by 2 weeks of ethanol deprivation (E-D group); (3) cycles of 2 weeks of two-bottle ethanol access and 2 weeks of deprivation, repeated for four cycles (E-RD group); or (4) water only treatment [ethanol-naive group (E-N group)]. A single pulse of [(14)C]-2-DG (125 microCi/kg) was administered via a venous catheter, and timed arterial blood samples were collected over 45 min and later assayed for plasma glucose and [(14)C]-2-DG concentrations. Quantitative autoradiography was used to determine [(14)C] densities, and LCGU values were calculated. With the exception of a few small differences in the hippocampus, no significant differences were found in any of the central nervous system (CNS) regions examined among the four experimental groups of P rats. Animals in the E-D group had lower LCGU rates in the anterior hippocampal CA1 subregion than animals in the E-N, E-C, and E-RD groups. In the anterior hippocampal CA3 subregion and the anterior hippocampal dentate gyrus, the E-D group had significantly lower LCGU rates than the E-RD group. Overall, the results of this study indicate that 24-h ethanol-drinking experience has little effect on CNS functional neuronal activity in P rats.     

Anti-TNF-alpha antibody normalizes serum leptin in IL-2 deficient mice

OBJECTIVE: A recent study reports that the interleukin-2 deficient (IL-2(-/-)) mouse model of autoimmune and inflammatory bowel disease (IBD) with elevated pro-inflammatory cytokine production has elevated leptin concentrations during food deprivation. The objective of this study was to examine whether increased tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, contributes to the abnormally elevated leptin in IL-2(-/-) mice. METHODS: Eight week old, IL-2(-/-) and wild-type control (IL-2(+/+)), male mice were fed regular laboratory mouse food for two weeks. At the end of the study, blood was collected in the fed state, IL-2(-/-) and IL-2(+/+) mice were injected with either anti-TNF-alpha monoclonal antibody or normal saline, and blood was collected in the starved state. RESULTS: The IL-2(-/-) mice consumed less food and lost weight. Administration of anti-TNF-alpha antibody markedly reduced serum leptin concentrations in IL-2(-/-) and control mice after food deprivation. Serum leptin in the IL-2(-/-) mice not receiving anti-TNF-alpha antibody increased significantly in the starved state. Serum concentrations of TNF-alpha were higher in IL-2(-/-) mice compared to controls in both the fed and starved state. CONCLUSIONS: These results suggest that elevated TNF-alpha may be one mechanism for the sustained elevated leptin observed in IL-2(-/-) mice during food deprivation.     

Neuroendocrine and neurochemical consequences of long-term sleep deprivation in rats: similarities to some features of depression.

The paradigm of long-term sleep deprivation was used as a model of chronic inescapable stress in rats. Several basic metabolic parameters (body weight changes, food and water intake, rectal temperature, serum glucose and creatinine), adrenal and thyroid secretion, norepinephrine and dopamine content and turnover in discrete brain regions, and open field behaviour were examined in the course of the exposure to experimental stress. Sleep deprivation over 7-9 days caused complete physical exhaustion of the animals. It was accompanied by hypothermia and hyperphagia. Adrenal activity was characterized by significant hypercorticism, but also by a relative decrease of the responsiveness to ACTH. A gradual decrease in the thyroid secretion was observed. Sleep deprivation elicited a depletion of norepinephrine in the hypothalamus and decreased its turnover, whereas hippocampal norepinephrine content decreased without considerable turnover alterations. Striatal dopamine content and turnover remained unaffected. Behavioural depression and altered open field activity were also observed in exhausted animals. Long-term sleep deprivation, therefore, seems to reproduce some of the biological correlates of the depressive illness, and may be useful in studying the development of coping failure as a result of chronic stress exposure.     

Dietary magnesium deficiency induces heart rhythm changes, impairs glucose tolerance, and decreases serum cholesterol in post menopausal women

OBJECTIVE: To determine whether or not dietary magnesium restriction to about 33% of the Recommended Dietary Allowance (RDA) causes changes in glucose, cholesterol and electrolyte metabolism that could lead to pathologic consequences. DESIGN: The length of the experiment was 136 days. Subjects were fed a basal Western-type diet that provided 4.16 mmol (101 mg) magnesium per 8.4 MJ (2000 kcal) for 78 days then replenished with magnesium by supplementing the diet with 200 mg magnesium as the gluconate per day for 58 days. If a subject exhibited adverse heart rhythm changes before 78 days of depletion were completed, she entered the repletion period early. SETTING: The metabolic research unit of the Grand Forks Human Nutrition Research Center. SUBJECTS: A total of 14 post menopausal women were recruited by advertisement throughout the United States. Thirteen women (ages 47 to 75 years) completed the study. RESULTS: During magnesium depletion, heart rhythm changes appeared in 5 women and resulted in 4 prematurely entering the magnesium repletion period (42 to 64 days of depletion instead of 78). Three women exhibited atrial fibrillation and flutter that responded quickly to magnesium supplementation. Magnesium deprivation resulted in a non-positive magnesium balance that became highly positive with magnesium repletion. Magnesium deprivation decreased red blood cell membrane magnesium, serum total cholesterol and erythrocyte superoxide dismutase concentrations, increased the urinary excretion of sodium and potassium, and increased serum glucose concentration. CONCLUSIONS: Magnesium balance may be a suitable indicator of magnesium depletion under experimental conditions. Magnesium deficiency resulting from feeding a diet that would not be considered having an atypical menu induces heart arrhythmias, impairs glucose homeostasis, and alters cholesterol and oxidative metabolism in post menopausal women. A dietary intake of about 4.12 mmol (100 mg) Mg/8.4 MJ is inadequate for healthy adults and may result in compromised cardiovascular health and glycemic control in post menopausal women.