胃癌和结肠癌小肠细菌过度生长情况分析

目的探讨胃癌、结肠癌小肠细菌过度生长(SIBO)的情况,及应用益生菌治疗SIBO后能否改善肿瘤患者的临床症状。方法 86例消化道恶性肿瘤患者分为胃癌组和结肠癌组,两组患者均通过葡萄糖氢呼气试验(GHBT)检测其SIBO发生率,并与对照组进行组间比较分析。对于消化道恶性肿瘤中检测SIBO阳性者,分为益生菌治疗组和安慰剂组,比较其治疗前后SIBO阳性率及患者临床症状评分的变化。结果 (1)86例消化道肿瘤患者中,54例(62.8%)GHBT阳性;30例对照组中3例(10.0%)GHBT阳性,两者比较差异有统计学意义(P0.01);(2)给予双歧三联活菌胶囊治疗后,益生菌组22例(81.5%)SIBO转阴;安慰剂组6例(22.2%)SIBO转阴,且两组患者给药后的临床症状评分对比差异有统计学意义(P0.05);(3)益生菌组治疗前后症状评分比较差异有统计学意义(t=3.681,P0.05),而安慰剂组治疗前后症状评分比较差异无统计学意义(P0.05)。结论消化道肿瘤恶性患者容易发生SIBO,益生菌治疗可通过抑制SIBO改善肿瘤患者的临床症状。     

质子泵抑制剂相关小肠细菌过生长与血清炎症因子的研究

目的观察长期应用质子泵抑制剂(PPI)患者,在强效抑酸状态下小肠细菌过生长(SIBO)的发生情况;及观察发生SIBO的患者中血清TNF-α变化。方法用葡萄糖呼气H2试验(GBT)检测176例服用PPI制剂患者,35名慢性胃炎志愿者作为对照;同时,对71例服用PPI SIBO患病者(PPI+SIBO阳性组)检测血清TNF-α,32例服用PPI未发生SIBO者(PPI+SIBO阴性组)作为对照组。结果 PPI组GBT阳性111例(63.1%),阴性65例(36.9%);对照组中GBT阳性6例(17.1%),阴性29例(82.9%)。PPI组SIBO发病率显著高于对照组(P0.001),应用趋势卡方、逐步Logistic回归分析得知PPI使用时间、年龄与SIBO患病率存在正相关性(P0.001、P0.05)。PPI+SIBO阳性组71例检测TNF-α,其中38例TNF-α8.1pg/mL(53.5%);对照组(PPI+SIBO阴性组)32例中TNF-α8.1pg/mL 3例(9.4%),两组之间差异有统计学意义(P0.001)。结论长期服用PPI制剂的患者可并发SIBO,且SIBO的患病率与PPI制剂使用时间、年龄呈正相关。然而,SIBO者更易出现血清慢性亚临床炎症状态。这也提示长期服用PPI可发生慢性亚临床炎症状态。     

应用质子泵抑制剂导致小肠细菌过度生长发生的可能性

目的观察应用质子泵抑制剂(PPI)患者,在强效抑酸状态下小肠细菌过生长(SIBO)的发生情况。方法用葡萄糖呼气H2试验,检测57例服用PPI制剂患者,30名健康志愿者作为对照。结果 PPI制剂组中呼气H2检测SIBO阳性28例,阴性29例;健康对照组中SIBO阳性3例,阴性27例。PPI组与健康对照组比较差异有统计学意义(P0.01),PPI制剂使用时间与SIBO阳性率存在正相关性。结论长期服用PPI制剂的患者可并发SIBO,且SIBO的发病率与PPI制剂使用时间呈正相关。     

细菌性脑膜炎大鼠模型的尿液蛋白质组学变化

与脑脊液和血液不同,尿液不受到稳态机制的调节,更倾向于积累和反应机体生理和病理状态下的变化。生物标志物的本质特征是变化,因此尿液是寻找疾病早期标志物的更好来源。在世界范围内,细菌性脑膜炎依然是引起新生儿和儿童疾病的主要原因。为了降低死亡率和致残率,需要用无创的方法寻找细菌性脑膜炎的相关线索。本研究中,使用大鼠脑室内注射大肠杆菌模型模拟细菌性脑膜炎,在第1天和第3天的大鼠尿液中寻找尿液蛋白谱的差异变化,为进一步寻找大肠杆菌性脑膜炎的早期生物标记物研究进行初步的探索。通过膜上酶切和胶内酶切将尿蛋白切成肽段并通过液相色谱串联质谱技术(LC-MS/MS)分析肽段信息。第1天的尿液通过胶内酶切方法鉴定到17个差异蛋白,通过膜上酶切鉴定到20个差异蛋白;第3天的尿液通过膜上酶切方法鉴定到5个差异蛋白。这些差异蛋白为寻找细菌性脑膜炎早期生物标志物的初步探索奠定了基础。     

Preliminary observations on enteritis associated with a coronavirus-like agent in rabbits

An outbreak of fatal enteritis in 3-8-week old rabbits in a barrier-maintained breeding colony is described. The laboratory findings and treatments attempted suggest that a viral agent was the primary pathogen.     

Neuromuscular disorders associated with static lumbar flexion: a feline model.

Static flexion of the lumbar spine with constant load applied to the viscoelastic structures for 20 minutes and for 50 minutes resulted in development of spasms and inhibition in the multifidus muscles (e.g., deep erector spinae) and in creep of the supraspinous ligament in the feline model. The development of spasms and inhibition was not dependent on load magnitude. It is suggested that occupational and sports activities which require prolonged static lumbar flexion within the physiological range can cause a "sprain"-like injury to the ligaments, which in turn reflexively induce spasms and inhibition in some erector spinae muscles. Such disorder may take a long time to recover, in the order of days to weeks, depending on the level of creep developed in the tissues.     

Modular and functionally-different descending recto-anal motor pathways in a rat model

We evaluated the motor responses in recto-anal preparations obtained from rats, in terms of the excitation displayed by modules of nerve networks and descending distally directed pathways, when subjected to the mechanographic on-line technique, a partitioned organ bath, electrical stimulation (EFS, 0.8 ms, 5 Hz) and distension. EFS elicited modular contractions, which increased in amplitude distally, in circular muscle rings isolated from the proximal, middle or distal rectum. The modular responses of the internal anal sphincter or anal canal were relaxation or contraction, respectively. The application of EFS to the distal rectum induced a descending contractile response in the anal canal (5.24±0.34 mN), while distension by balloon evoked a descending response consisting of contraction (1.72±0.20 mN) followed by relaxation (3.42±0.24 mN). The responses were sensitive to tetrodotoxin. Atropine considerably depressed the contractions in all preparations. Whether or not atropine was present, L-NNA increased the excitatory responses, while L-arginine decreased the contractions and extended the relaxation of internal anal sphincter and anal canal. The results suggest that excitatory neurotransmission(s) expressed in the distal rectum dominate modular nerve networks. Functionally-different descending pathways are involved in the motor activity of the anal canal. Stimulatory cholinergic pathways are dependent on the electrically-induced excitation, and inhibitory nitrergic pathways are sensitive to distension of rectal wall.     

Neutral genetic differentiation in an island model with cyclical parthenogenesis

Unusually high levels of genetic differentiation are often observed between populations of Daphnia (Crustacea: Cladocera) and other cladocerans. Selection and departure from migration–mutation–drift equilibrium have been invoked to explain this fact. However, the null model of neutral genes at equilibrium has not been explicitly stated. Using a simple island model that takes into account the main characteristics of the cyclical parthenogenetic life‐cycle, we show that a high level of differentiation can be obtained for neutral genes at equilibrium if the migration rate during the asexual phase is low and the effective size over the season is reduced, or if mating within clones is common. Recurrent population bottlenecks have a large effect on differentiation and the time to reach equilibrium. Such fluctuating clonal dynamics could be brought about by limitations in the number of clones that hatch and establish themselves each season, or by random associations between neutral and selected genes, as previously suggested in the literature.     

Bacteria-lectin interactions in phytohemagglutinin-induced bacterial overgrowth of the small intestine

The mechanism of phytohemagglutinin-induced bacterial overgrowth of the small bowel in the rat was studied. Interaction of the lectin with bacterial isolates selected at random from those that comprised the major population of the overgrowth was determined. In both bacterial agglutination assays and glycocalyx stabilization, no specific association between lectin and bacteria was seen. In three independent binding assays phytohemagglutinin was not found to increase bacterial adherence to washed intestinal mucosa. Phytohemagglutinin would not appear to act, therefore, as a direct ligand to mediate bacterial adherence or to modify the mucosal surface to increase bacterial adherence.     

Specific mucosal immunity in the pathophysiology of bacterial prostatitis in a rat model

Mucosal immunity was established in the rat prostate by stimulating the common mucosal system through serosal exposure of formalin-killed Escherichia coli. Immunized but not sham-immunized rats developed bacterial specific IgG and IgA in prostatic fluid, and IgA in urine. Immunized (n = 21) and sham-immunized control rats (n = 30) were challenged by transurethral injection of E. coli into the prostate ducts. Mortality, gross and microscopic pathology, tissue bacterial counts, bacterial associated immunoglobulins, and antibody titers in serum and urine were assessed at 7 days following the challenge. Increased E. coli specific immunoglobulin titers were seen in immunized rats, and E. coli, but not Proteus, found in the prostates of immunized animals were coated with IgG and IgA. Immunization protected against toxaemia and septicemia, seen as a rare complication of acute prostatitis, but did not protect against acute prostatitis, nor alter the degree of tissue damage seen in the rat model.     

Campylobacter enteritis associated with consumption of unpasteurised milk.

In October and November 1978 two outbreaks of enteritis occurred in the north of England. Symptoms lasted two to over eight days but in no case necessitated admission to hospital. Faecal specimens from most of the patients were found to contain thermophilic Campylobacter sp. Inquiry disclosed that all patients had consumed unpasteurised milk from local farms. Examination of rectal swabs from the cattle concerned and milk socks yielded strains of Campylobacter sp indistinguishable from those isolated from the patients. It was therefore concluded that, since campylobacters are not known to be excreted in milk, faecal contamination of the milk had probably occurred and had led to these outbreaks. Evidence suggests that thermophilic Campylobacter sp is an occasional contaminant of milk. So long as unpasteurised milk continues to be distributed further outbreaks will probably occur.     

An animal model of eating disorders associated with stressful experience in early life

Experience of childhood abuse is prevalent among patients with eating disorders, and dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is implicated in its pathophysiology. Neonatal maternal separation is considered as an animal model of stressful experience early in life. Many of studies have demonstrated its impact both on the activity of HPA axis and the development of psycho-emotional disorders later in life. In this paper, a series of our researches on developing an animal model of eating disorders is reviewed. An animal model of neonatal maternal separation was used; Sprague-Dawley pups were separated from dam daily for 180 min during the first 2 weeks of life (MS) or undisturbed. Anxiety-/depression-like behaviors were observed in MS rats at the age of two months with decreased serotonergic activity in the hippocampus and the raphe. Post-weaning social isolation promoted food intake and weight gain of adolescent MS pups, with impacts on anxiety-like behaviors. Sustained hyperphagia was observed in the MS pups subjected to a fasting/refeeding cycle repeatedly during adolescence, with increased plasma corticosterone levels. Anhedonia, major symptom of depression, to palatable food was observed in adolescent MS pups with blunted response of the mesolimbic dopaminergic activity to stress. Results suggest that neonatal maternal separation lead to the development of eating disorders when it is challenged with social or metabolic stressors later in life, in which dysfunctions in the HPA axis and the brain monoaminergic systems may play important roles.     

Aortic banding in rat as a model to investigate malnutrition associated with heart failure

Heart failure is a severe pathology, which has displayed a dramatic increase in the occurrence of patients with chronic heart disease in developed countries, as a result of increases in the population's average age and in survival time. This pathology is associated with severe malnutrition, which worsens the prognosis. Although the cachexia associated with chronic heart failure is a well-known complication, there is no reference animal model of malnutrition related to heart failure. This study was designed to evaluate the nutritional status of rats in a model of loss of cardiac function obtained by ascending aortic banding. Cardiac overload led to the development of cardiac hypertrophy, which decompensates to heart failure, with increased brain natriuretic peptide levels. The rats displayed hepatic dysfunction and an associated renal hypotrophy and renal failure, evidenced by the alteration in renal function markers such as citrullinemia, creatininemia, and uremia. Malnutrition has been evidenced by the alteration of protein and amino acid metabolism. A muscular atrophy with decreased protein content and increased amino acid concentrations in both plasma and muscle was observed. These rats with heart failure displayed a multiorgan failure and malnutrition, which reflected the clinical situation of human chronic heart failure.     

Autophagy activation is associated with neuroprotection in a rat model of focal cerebral ischemic preconditioning

Several recent studies have showed that autophagy is involved in ischemic brain damage, but it may also play a pro-survival role in ischemic preconditioning. This study was taken to determine the role of autophagy in an animal model of cerebral ischemic preconditioning (IPC). Focal cerebral IPC was produced in rats by a brief ischemic insult followed by permanent focal ischemia (PFI) 24 h later using the suture occlusion technique. The rats were pretreated with intracerebral ventricle infusion of the autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (Baf A1) or the autophagy inducer rapamycin to evaluate the contribution of autophagy to IPC-induced neuroprotection. The results from electron microscopic examinations and immunofluorescence showed that both IPC and PFI induced autophagy activation, but the extent and persistence of autophagy activation were varied. IPC treatment significantly reduced infarct volume, brain edema and motor deficits after subsequent PFI, whereas 3-MA and Baf A1 suppressed the neuroprotection induced by IPC. 3-MA pretreatment also significantly attenuated upregulation of LC3-II, beclin 1 and HSP70 and downregulation of p62. To further determine if autophagy induction is responsible for IPC-induced neuroprotection, rats were treated with rapamycin 24 h before the onset of PFI. The results showed that rapamycin reduced infarct volume, brain edema and motor deficits induced by PFI. Rapamycin pretreatment also increased the protein levels of LC3-II and beclin 1. These results demonstrate that autophagy activation during IPC offers a remarkable tolerance to a subsequent fatal ischemic insult, and IPC's neuroprotective effects can be mimicked by autophagy inducers.     

Uterine motor alterations and estrous cycle disturbances associated with colonic inflammation in the rat

The impact of colitis on uterine contractility and estrous cycle was investigated after intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. Colitis severity was assessed by macroscopic damage scoring (MDS) 4 days after TNBS, and myeloperoxidase (MPO) activity was measured in both colon and uterus of control and colitic rats. Estrous cycle stages were determined by vaginal smears and histology, and uterine contractility was assessed in vitro on longitudinal and circular strips. In control rats, uterine MPO activity varied markedly during the cycle and peaked around estrus. In rats with moderate colitis [MDS < 5, 3.1 +/- 0.2 (mean +/- SE)], uterine MPO decreased by 61% compared with estrus control, without disruption of the cycle. Frequency of spontaneous contractions was reduced by 32% in circular muscle. Contractile responses to KCl and carbachol were not affected, whereas maximal response to oxytocin decreased by 47% in the longitudinal muscle. In rats with severe colitis (MDS > 5, 6.0 +/- 0.2), uterine MPO was reduced by 96% and estrous cycle was disrupted. Spontaneous contractility was impaired in circular strips, and a 39% decrease in the contraction frequency occurred in the longitudinal strips. Circular strips did not contract to KCl or carbachol; however, longitudinal strips had maximal responses to KCl, carbachol, and oxytocin reduced by 36%, 27%, and 46%, respectively. Estrogen replacement protected the uterine responses to carbachol in colitic rats, whereas oxytocin responses remained depressed. These data indicate that colonic inflammation can influence both spontaneous and evoked uterine contractility, in relation to estrous cycle disturbances, impaired estradiol production, and functional alterations of myometrial cells.     

2型糖尿病兼抑郁症大鼠模型的建立与评价

目的：用体重检测、空腹血糖检测、宏观表征、旷场实验行为学评价糖尿病兼抑郁症的大鼠模型。方法采用高脂饲料喂养加腹腔注射小剂量链脲佐菌素（ STZ）的方法制备2型糖尿病模型,在其基础上再用21 d慢性束缚的方法建立糖尿病兼抑郁症大鼠模型。将32只Wistar大鼠随机分为3组（ n ＝8）：正常组（N组）,2型糖尿病组（T组）,2型糖尿病兼抑郁症组（T＋D组）。2型糖尿病模型建立后,在慢性束缚的第0、7、14、21天检测大鼠的空腹血糖和体重,并对大鼠的宏观表征、饮食量、粪便、小便、精神状态进行观察,在第21天利用行为学设备分析软件,对大鼠旷场实验进行分析,检测大鼠的抑郁程度,验证评价2型糖尿病兼抑郁症大鼠模型是否成功。结果给予高脂饲料及腹腔注射STZ制备2型糖尿病模型后,T＋D组大鼠的毛发散乱,无光泽,活动迟缓,进食量、饮水量增加,粪便尿量增加,精神萎靡。第0、7、14、21天T组和T＋D组组大鼠体重均下降,与N组比较差异有显著性（P＜0.05;P＜0.01）,21d慢性束缚刺激后,T＋D组体重比T组大鼠体重增加较慢,差异有显著性（P＜0.05）;第0、7、14、21天,T组和T＋D组大鼠血糖均升高,与N组比较差异有显著性（ P＜0.01）,21 d慢性束缚刺激后,第21天T＋D组大鼠血糖比T组较高,差异有显著性（P＜0.01）,大鼠5 min内总移动距离有变化,与N组相比,T组差异没有显著性（P＞0.05）,T＋D组差异有显著性（P＜0.05）;与N组相比,T组大鼠5 min内移动速度减慢,差异有显著性（P＜0.05）,T＋D组差异有显著性（ P＜0.01）。结论利用高脂饲料喂养加腹腔注射小剂量STZ及21天慢性束缚的方法,可以成功复制2型糖尿病兼抑郁症大鼠模型,适用于后续研究。     

Changes of traits in a bacterial population associated with protozoal predation

In an attempt to understand the significance of predation in the evolution of prey species, the ecological and morphological characteristics of bacterial species under predation by a ciliated protozoa,Cyclidium sp., were investigated. Serial transfer at 7 day intervals was applied to the bacterial populations in the presence or absence ofCyclidium. Although cells of the parental bacterial strain are typically short rods up to 1.5 μm long, cells of much greater length, up to 20 μm long (type L) were found in populations exposed to predation fromCyclidium. However, the wildtype, shorter length bacteria persisted even after the appearance of type L. Type L was not observed in the singl bacterial culture throughout the serial transfers. Type L appeared to improve the ability to escape predation by elongating cell size, but growth rate and saturation density were decreased.