调整肠道菌群对肝硬化患者血浆内毒素及肝功能的影响

目的 观察肝硬化患者口服益生菌制剂前后肠道菌群、血浆内毒素及肝功能指标的变化.方法 选择肠道菌群中具有代表性的细菌共5种进行培养和计数.56例肝硬化失代偿期患者随机分成2组,益生菌组(治疗组)28例,对照组28例,对照组给予常规治疗,治疗组在常规治疗的基础上给予益生菌治疗,疗程14 d.测定治疗前后肠道菌群菌落计数、血浆内毒素水平及肝功能指标.另选择30例正常人为正常对照组.结果与正常对照组相比,肝硬化组患者存在不同程度的肠道菌群失调, 主要表现为双歧杆菌减少(10.19±0.72 vs 9.13±1.01,P<0.05),治疗后治疗组双歧杆菌、乳杆菌、肠球菌[(12.28±1.02)lg CFU/g、(11.17±1.18)lg CFU/g、(11.56±1.27)lg CFU/g]较治疗前 [(9.39±1.23)lg CFU/g、(9.26±1.13)lg CFU/g、(8.57±1.45)lg CFU/g]明显增加(P＜0.05),血浆内毒素则明显低于对照组[(0.082±0.031) EU/mL vs (0.145±0.047) EU/mL,P<0.05],肝功能指标明显好于对照组(P<0.05).结论 肝硬化患者存在肠道菌群失调.益生菌制剂可有效改善肝硬化患者肠道菌群失调,并降低血浆内毒素水平,改善患者的肝功能,可作为肝硬化患者的辅助用药.     

肝硬化患者肠道菌群的研究

目的　观察肝硬化患者口服三联活菌和二联活菌前后肠道菌群、粪便pH、粪氨、血氨及血浆内毒素的变化。方法　选择肠道菌群中具有代表性的细菌共 7种进行培养和计数。 5 0例肝硬化患者随机分成 2组 ,分别予三联活菌及二联活菌治疗 14d。测定治疗前后肠道菌群菌落计数、粪便 pH值 ,粪氨、血氨 (干片法 ) ,血浆内毒素 (改良鲎试验法 )。结果　与正常对照组相比 ,肝硬化组患者存在不同程度的肠道菌群失调 ,主要表现为双歧杆菌减少 (10 .0 4± 0 .78比 9.4 8± 1.13,P <0 .0 5 )。治疗后 ,三联活菌组双歧杆菌由 9.4 6± 1.0 9增至 10 .30± 1.11;二联活菌组由 9.81± 0 .6 2增至 10 .4 4± 1.0 8,差异均有显著性 (P值均 <0 .0 5 )。且血氨、粪氨和粪便 pH值降低 (P <0 .0 5 )。二联活菌可降低合并内毒素血症的肝硬化患者血浆内毒素水平 [(0 .0 876± 0 .0 117Eu/ml比 (0 .0 6 85± 0 .0 2 4 6 )Eu/ml,P <0 .0 5 ]。结论　肝硬化患者存在肠道菌群失调。益生菌制剂可有效改善肝硬化患者肠道菌群失调 ,并降低血氨、粪氨和粪便 pH值。     

肝硬化患者肠道菌群的研究

目的:研究肝硬化患者肠道菌群的变化、并分析血内毒素水平与肠道细菌的关系。方法:对37例肝硬化患者和18例健康者粪便中8种常见的厌氧菌及需氧菌进行定量研究,以偶氮基质显色法测外周血内毒素。结果:(1)肝硬化患者双歧杆菌、拟杆菌、真杆菌量明显低于正常组,而大肠杆菌、产气荚膜梭菌量高于正常组(P<0.05);(2)肝硬化患者肠菌失调程度与肝功能Child-Pugh分级有关;(3)肝硬化患者血内毒素水平与大肠杆菌量存在相关性。结论:肝硬化患者存在肠道菌群失调,具有代表性的厌氧菌减少,需氧菌增多。需氧革兰阴性杆菌大量繁殖可能是引起肝硬化肠源性内毒素血症的一个重要因素。     

肠道菌群失衡与肝硬化分级及预后的关系

目的运用两种方法测定肝硬化患者肠道菌群变化,探讨其与肝硬化病情的关系。方法纳入160名肝硬化患者及84名正常人,通过细菌培养及实时定量PCR检测粪便菌群变化,分析肠道菌群改变与肝硬化分级和预后的关系。结果细菌培养结果显示,与正常对照组比较,肝硬化患者肠杆菌、葡萄球菌、肠球菌、酵母菌数量显著增加(P分别为0.004、0.043、0.001、0.025),拟杆菌、乳酸杆菌、梭菌数量显著降低(P分别为0.028、0.045、0.043)。定量PCR结果显示,肝硬化组肠杆菌、肠球菌数量显著增高(P均0.01),细菌总量、乳酸杆菌、双歧杆菌、拟杆菌及梭菌数量显著降低(P均0.01)。肠杆菌与肝功能CTP评分、MELD预后评分及CRP均呈正相关(P分别为0.003、0.001、0.002)。乳酸杆菌、梭菌分别与上述三个指标呈负相关(P分别0.005、0.003、0.004,0.004、0.011、0.004)。结论传统细菌培养与荧光定量PCR的结果具有一致性。肝硬化患者肠道中肠杆菌增多、乳酸杆菌及梭菌减少的程度与肝硬化严重程度及不良预后相关。肠道菌群失调与全身炎症反应相关,可能促进肝硬化患者病情进展。     

加味胃苓汤对肝硬化腹水患者肠道菌群的影响

目的:观察加味胃苓汤对肝硬化腹水患者肠道菌群的影响。方法:70例肝硬化腹水患者随机分为治疗组与对照组,每组35例,另取35例健康医护人员作为健康组。对照组患者给予常规西药综合治疗,治疗组患者在常规西药综合治疗基础上,加服中药加味胃苓汤,疗程均为4周。观察两组患者治疗前后粪便细菌培养中常见细菌(肠杆菌、肠球菌、葡萄球菌、酵母菌、拟杆菌、双歧杆菌、梭菌、乳酸杆菌)的变化。结果:(1)与健康人比,肝硬化腹水患者肠道菌群肠杆菌、肠球菌、葡萄球菌、酵母菌数量显著增加(P 0. 01),拟杆菌、双歧杆菌、梭菌、乳酸杆菌数量显著下降(P 0.05)。(2)治疗组患者经加味胃苓汤治疗后肠道菌群肠杆菌、肠球菌、葡萄球菌数量显著下降(P 0. 05),拟杆菌、乳酸杆菌数量显著增加(P 0.05);4周治疗后,两组患者比较,治疗组肠道肠杆菌、肠球菌、葡萄球菌数量较对照组低,拟杆菌、乳酸杆菌数量较对照组高(P 0.05)。结论:肝硬化腹水患者存在肠道菌群失衡,表现为肠道肠杆菌、肠球菌、葡萄球菌、酵母菌数量增加,拟杆菌、双歧杆菌、梭菌、乳酸杆菌数量下降。加味胃苓汤可有效改善肝硬化腹水患者的肠道菌群失调情况。     

益生菌干预对慢性乙肝患者肠道菌群、炎症因子及肝功能等的影响

目的探讨益生菌干预对慢性乙型肝炎(乙肝)患者肠道菌群、炎症因子、内毒素及肝功能的影响。方法将2010年3月至2015年12月在我院诊治的乙肝患者380例按照随机数表法分为观察组和对照组,每组190例。对照组患者给予常规治疗,观察组在常规治疗基础上联合益生菌干预治疗,比较两组患者治疗前后肠道菌群变化、血清内毒素水平、炎症因子水平和肝功能的变化。结果观察组患者治疗后肠球菌、双歧杆菌和乳酸杆菌均显著增加(P0.05),肠杆菌和梭菌无显著变化(P0.05);对照组患者治疗前后肠道菌群无显著变化(P0.05)。两组患者治疗后内毒素、肝功能、炎症因子水平均显著降低(P0.05);观察组患者内毒素、ALT、AST、TBIL、IL-6、TNF-α水平均显著低于对照组(P0.01)。结论在常规治疗的基础上联合益生菌干预治疗慢性乙肝患者,能有效改善肠道菌群失调,降低炎症反应,改善肝功能,可作为乙肝患者的辅助治疗。     

化疗药物对胃癌患者肠道菌群谱的影响及益生菌干预作用的临床研究

目的通过对胃癌患者在化疗前后肠道中菌群的变化进行定量分析,探讨胃癌患者肠道菌群的变化情况及微生态调节剂对胃癌患者肠道菌群的干预作用。方法选取商丘市第一人民医院及郑州大学第一附属医院80例符合标准的中晚期胃癌作为治疗组。另选取商丘市第一人民医院体检中心20例健康人作为健康对照组。80例胃癌患者被随机分成观察组(40例)和干预组(40例)。观察组采用奥沙利铂+卡培他滨联合化疗方案,干预组采用奥沙利铂+卡培他滨+金双歧联合治疗方案。使用粪便细菌及真菌培养法培养粪便中的大肠杆菌、双歧杆菌、肠球菌、乳酸杆菌、类杆菌、酵母菌、葡萄球菌、消化链球菌。结果治疗组胃癌患者肠道双歧杆菌、乳酸杆菌数量及杆/球比均低于健康对照组(P0.01);治疗后观察组患者肠道双歧杆菌、乳酸杆菌数量及杆/球比,均低于治疗前观察组(P0.01);治疗后干预组患者肠道双歧杆菌、乳酸杆菌数量及杆/球比均高于治疗前干预组(P0.01);治疗后干预组患者肠道双歧杆菌、乳酸杆菌数量及杆/球比例均高于治疗后观察组(P0.01);干预组患者腹泻、恶心呕吐、食欲下降、白细胞减少、血红蛋白减少和血小板减少、肝功能损害均低于观察组(P0.01)。结论胃癌患者肠道菌群处于一种失平衡状态;化疗药物可抑制肠道正常菌群生长,可导致肠道菌群失调进一步加重;双歧杆菌乳杆菌三联活菌片可扶植正常菌群生长,调整肠道菌群失调,对胃癌患者化疗导致的肠道菌群失调有预防作用,可明显降低化疗的不良反应,提高患者对化疗的耐受性。     

肝硬化患者腹水中细菌DNA与相关因素的关系

目的 探讨肝硬化患者腹水中细菌DNA与血浆内毒素、肠通透性、肠道菌群等因素的关系. 方法 选取失代偿期肝硬化伴腹水患者55例,于入院当日或次日抽取腹水行腹水中细菌DNA的提取及PCR扩增,同时行腹水常规、需氧菌及厌氧菌培养检查,于入院次日测定血浆内毒素、肠通透性并进行肠道菌群分析,同时测定血常规、肝肾功能、凝血功能等生物化学指标.30例健康成年人作为正常对照,行除腹水之外的上述检查. 结果 55例肝硬化患者腹水细菌培养均为阴性,其中19例(34.55%)患者腹水中检测到细菌DNA.与细菌DNA阴性组比较,细菌DNA阳性组患者的凝血酶原活动度明显降低(t=-3.184,P=0.002),而肝功能Child-Pugh评分(t=3.224,P=0.002)和腹水白细胞计数(t'=4.088,P=0.001)明显升高.与正常对照组比较,肝硬化患者血浆内毒素水平(t=13.705,P=0.000)、尿中乳果糖/甘露醇(L/M,t'=28.568,P=0.000)和肠道肠杆菌数量(t=2.912,P=0.005)明显升高,而肠道双歧杆菌数量明显减少(t=-3.669,P=0.000).与腹水中细菌DNA相关的指标为肠道肠杆菌数量(P=0.007)和凝血酶原活动度(P=0.011).结论 肝硬化患者发生腹水细菌移位的关键因素是肠腔细菌过度生长,并与肝病的严重程度相关.     

肝硬化腹水患者的临床危险因素分析

目的研究肝硬化腹水患者的临床特征,探讨腹水程度与肝功能、血清钠、钾、肌酐及预后的关系。方法 259例肝硬化腹水患者,根据腹水量程度分成A组(少量腹水组)、B组(中等量腹水组)及C组(大量腹水组)3组,比较3组患者的肝功能Child-Pugh分级,血清钠、钾、肌酐异常的情况以及疗效。结果 3组不同程度腹水量患者的肝功能CTP分级比较,差异有统计学意义(P0.01)。3组不同程度腹水量患者治疗后显效率、死亡率比较,差异有统计学意义(P0.01)。3组不同程度腹水量患者低钠血症发生率比较,差异有统计学意义(P0.05)。3组不同程度腹水量患者低钾血症、血清肌酐升高发生率比较,差异无统计学意义(P0.05)。结论本研究肝硬化腹水患者的肝功能Child-Pugh分级以B级为主,腹水程度与肝硬化患者的肝功能、疗效相关;肝硬化腹水患者低钠血症和血清肌酐异常发生率较高,重度腹水者更易发生低钠血症;腹水程度影响肝硬化患者的预后。     

肝炎肝硬化患者肝脏MRI分数评定及其临床意义

目的探讨肝炎肝硬化患者肝脏MRI分数与Child-Pugh分级之间的关系。方法48例肝炎肝硬化病人均进行肝脏MRI平扫检查,观察测量肝脏长径、腹水厚度、侧枝循环数目等参数,并与Child-Pugh分级进行相关性分析。结果Child-Pugh分级与侧枝循环数目、腹水厚度呈显著正相关(P0.01),与肝脏长径呈显著负相关(P0.05)。肝脏MRI分数与Child-Pugh分级呈显著正相关(r=0.935,P0.01);运用肝脏MRI评分系统区分Child-Pugh A级与其他级别的肝硬化,其准确度、敏感性、特异性分别为93.8%、95.2%及92.6%。结论基于侧枝循环数目、腹水厚度及肝脏长径三项指标的肝脏MRI评分系统,可良好地运用于评估肝硬化的临床严重程度。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.