血液灌流联合血液滤过对高脂血症胰腺炎患者生命体征的恢复效果评价

目的 探索血液灌流联合血液滤过法对高脂血症胰腺炎的治疗效果.方法 收集2010年2月至2015年2月宝鸡市中医医院普外科诊断并收治为高脂血症性急性重症胰腺炎患者共90例,所有血三酰甘油(TG)≥11骀.3 mmol/L,血清呈乳糜样改变所有患者按血液净化方式不同,分为血液灌流联合血液滤过治疗组(HP/CVVH组)以及血液滤过治疗组(CVVH组).其中HP/CVVH组45例,CVVH组45例.记录患者治疗后72 h体温、呼吸、心率并进行APACHEⅡ评分,采用酶联免疫吸附法(ELISA)进行肿瘤坏死因子(TNF-α)、白介素6(IL-6)、白介素(IL-8)、TG、淀粉酶(AMY)、脂肪酶(LIPA)的检测.结果 治疗后HP/CVVH组的体温、呼吸、心率以及APACHEⅡ评分均出现下降(P<0.05),而CVVH组APACHEⅡ评分并未出现好转,治疗前后差异无统计学意义(P>0.05).治疗后HP/CVVH组和CVVH组TNF-α、IL-6以及IL-8、AMY、TG以及LIPA均出现下降,差异有统计学意义(P<0.05).将两种血液净化方式治疗后的生命体征进行比较,发现联合血液滤过法能更为有效的降低患者的呼吸频率(t=5.59,P=0.00),TNF-α,IL-6以及IL-8(t=9.18,9.62,6.05;P=0.00,0.00,0.00)和TG、AMY、LIPA的释放(t=16.82,7.83,8.08;P=0.00,0.00,0.00),而对体温、心率和APACHEⅡ评分无明显改善作用(P>0.05).结论 CVVH前行HP治疗可有效清除血液中的TG,防止高血脂症对胰腺功能的损伤,通过抑制性因子的释放促进患者各种生命体征的恢复,从而为机体恢复提供有力的条件.     

血液透析联合血液灌流治疗对慢性肾衰竭患者临床疗效、肾功能及炎性因子的影响研究

目的 浅析血液透析联合血液灌流治疗对慢性肾衰竭(CRF)患者临床疗效、肾功能及炎性因子的影响。方法 选取我院收治的50例慢性肾衰竭患者,随机分为A组(血液透析HD联合血液灌流HP治疗)与B组(血液透析HD治疗),各25例,评价两组疗效。结果 治疗前,两组IL-1、IL-6、hs-CRP、TNF-α、β2-MG、BUN、Scr水平比较无统计学意义(P>0.05);治疗后,A组IL-1、IL-6、hs-CRP、TNF-α、β2-MG、BUN、Scr水平低于B组(P<0.05)。结论 CRF疾病患者给予HD+HP治疗效果乐观,可有效清除毒素,降低炎性因子水平。     

重复血液灌流对重度有机磷农药中毒患者的炎症因子的影响

目的探讨血液灌流治疗急性重度有机磷农药中毒的应用价值。方法选取急性重度有机磷农药中毒患者60例,分为灌流组(HP组)和非灌流组(非HP组),非HP组按常规予积极洗胃、导泻、催吐,并予阿托品及解磷定治疗。HP组在上述治疗基础上进行血液灌流治疗。观察全部病例的阿托品用量、病死率、胆碱酯酶活力恢复时间、住院时间、中间综合征发生率、昏迷时间及肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-10、IL-1β、高敏C反应蛋白(hs-CRP)水平的变化。结果HP组阿托品用量、胆碱酯酶活力恢复时间、住院时间、中间综合征发生率、昏迷时间、病死率低于非HP组(P<0.05或P<0.01)。HP组TNF-α、IL-6、IL-10、IL-1β、hs-CRP水平较对照组降低(P<0.05)。结论血液灌流可以清除重度有机磷农药中毒的部分炎症因子,对重度有机磷农药脏器损害有保护作用。     

降钙素原、超敏C反应蛋白、白介素-6、肿瘤坏死因子-α在尿源性脓毒症中的诊断价值

目的 探究降钙素原（PCT）、超敏C反应蛋白（hs-CRP）、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)在尿源性脓毒症中的诊断价值。方法 选取九江市柴桑区人民医院2017年5月至2019年5月140例诊断尿源性脓毒血症患者为尿源性脓毒血症组（C组）,选取同期120例经皮肾镜组或经输尿管镜手术后非尿源性脓毒症患者作为非尿源性脓毒症组（B组）,选取同期120例在九江市柴桑区人民医院行健康体检的健康志愿者作为健康对照组（A组）。检测三组研究对象PCT、hs-CRP、IL-6、TNF-α水平。结果 C组、B组患者PCT、hs-CRP、IL-6、TNF-α水平均高于A组,差异有统计学意义（P<0.05）;C组患者PCT、hs-CRP、IL-6、TNF-α水平均高于B组,差异有统计学意义（P<0.05）。PCT、hs-CRP、IL-6、TNF-α四项联合检测灵敏度高于PCT、hs-CRP、IL-6、TNF-α单项检测（P<0.005）。结论 尿源性脓毒症患者PCT、hs-CRP、IL-6、TNF-α水平升高,四项联合检测诊断价值较高,对临床上尿源性脓毒症的诊治具有重要...     

脓毒血症儿童血清降钙素原与炎症因子的相关性

目的:研究脓毒血症儿童血清降钙素原与炎症因子的相关性,以指导临床治疗。方法:选择细菌感染导致的脓毒血症患儿为脓毒症组,以同期体检的正常健康儿童为对照组,检测两组儿童血常规(WBC、RBC、Neu、PLT和Lym)、血清降钙素原(PCT)和炎症因子(hs-CRP、TNF-α、IL-1、IL-6、IL-8和IL-10)并比较其差异,采用Spearman秩相关分析PCT与hs-CRP、TNF-α、IL-1、IL-6、IL-8和IL-10的相关性。结果:脓毒症组儿童WBC、Neu、PCT、hs-CRP、TNF-α、IL-1β、IL-6和IL-8均高于对照组(P均<0.01),而IL-10低于对照组(P<0.01),在RBC、PLT和Lym方面两组比较差异无统计学意义(P均>0.05)。相关性分析表明血清PCT与hs-CRP、TNF-α、IL-1β、IL-6和IL-8呈正相关(P均<0.05),与IL-10呈负相关(P均<0.05)。结论:细菌致脓毒血症儿童血清PCT高于正常健康儿童,其水平与hs-CRP、TNF-α、IL-1β、IL-6和IL-8呈正相关,与IL-10呈负相关。     

床旁血液灌流联合血液滤过在重症高脂血症胰腺炎中的临床应用

目的:研究床旁血液灌流(HP)联合血液滤过(CVVH)在治疗重症高脂血症胰腺炎中的临床疗效。方法:选择2012年8月—2014年8月就诊的54例重症高脂血症胰腺炎患者,随机分为两组,每组27例。实验组在常规治疗基础上行HP+CVVH治疗,对照组在常规治疗基础上行CVVH治疗。治疗3 d后观察疗效和血肌酐(Cr)、尿素氮(BUN)、三酰甘油(TG)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)等生理生化指标。结果:治疗3 d后,实验组总有效率96.30%,对照组总有效率66.67%,两组疗效比较差异有统计学意义(P<0.05)。两组患者Cr,BUN,TG,IL-6,TNF-α较治疗前明显降低(P<0.05),治疗后实验组与对照组比较差异有统计学意义(P<0.05)。结论:HP联合CVVH治疗重症高脂血症胰腺炎效果明显优于单纯CVVH治疗,HP+CVVH治疗能更有效改善重症高脂血症胰腺炎生理生化指标,保护肾功能,临床疗效更为显著。     

持续低效血液透析联合血液灌流治疗多脏器功能障碍综合征患者的疗效观察

目的观察持续低效血液透析(SLED)联合血液灌流(HP)对多脏器功能障碍综合征(MODS)患者的炎症水平及预后的影响,评价其疗效。方法72例MODS患者,根据所采用的血液净化方法不同分为SLED组(给予SLED治疗)、SLED+HP组(给予SLED+HP治疗)、持续静脉-静脉血液滤过(CRRT)组(给予CRRT治疗)、CRRT+HP组(给予CRRT+HP治疗),各18例。比较四组患者治疗前和治疗后的急性生理学及慢性健康状况评分系统Ⅱ(APACHEⅡ)评分、血清肌酐(Scr)、超敏C反应蛋白(hs-CRP)、白介素(IL)-6、IL-10、肿瘤坏死因子-α(TNF-α)水平,治疗后28 d存活率。结果治疗后,四组患者的APACHEⅡ评分、Scr、hs-CRP、IL-6、IL-10、TNF-α水平均显著降低,差异有统计学意义(P<0.05)。SLED+HP组的APACHEⅡ评分、Scr、hs-CRP、IL-6、IL-10、TNF-α水平降低大于SLED组,CRRT+HP组的APACHEⅡ评分、Scr、hs-CRP、IL-6、IL-10、TNF-α水平降低大于CRRT组,差异均有统计学意义(P<0.05)。SLED+HP组和CRRT+HP组、SLED组和CRRT组比较差异无统计学意义(P>0.05)。SLED+HP组的28 d存活率为88.9%,CRRT+HP组的28 d存活率为83.3%,均高于SLED组的55.6%与CRRT组的50.0%,差异有统计学意义(P<0.05)。SLED+HP组与CRRT+HP组、SLED组和CRRT组患者的28 d存活率比较,差异无统计学意义(P>0.05)。结论四种血液净化治疗方案均能有效降低MODS患者的血清Scr、hs-CRP、IL-6、IL-10、TNF-α水平,改善患者临床症状和体征。SLED联合HP具有更强的清除炎症因子能力和肾功能保护作用,能改善患者的预后,其治疗效果与CRRT联合HP相当。     

血液灌流联合血液滤过治疗高脂血症性胰腺炎的疗效观察

目的:探讨不同血液净化方式对高脂血症性胰腺炎的治疗作用。方法:选择2016年1月-2017年6月28例高脂血症性胰腺炎患者,其中15例行血液灌流联合血液滤过治疗(HP/CVVH组),13例行血液滤过治疗(CVVH组)。比较2组患者治疗前后生命体征、APACHEⅡ评分、血浆炎性介质(TNF-α、IL-6、IL-8)及血清甘油三酯变化。结果:两组患者治疗后临床症状缓解,APACHEⅡ评分、血浆炎性介质及血清甘油三酯均下降(P0.05);但HP/CVVH治疗组患者APACHEⅡ评分、炎性介质及甘油三酯水平在相同时间点明显低于CVVH组(P0.05)。结论:HP/CVVH比CVVH能更有效地清除甘油三酯及炎性介质,提高生存率,有望成为SAP重要的辅助治疗措施。     

血液灌流对尿毒症透析患者IL-6、IL-8、TNF-α的影响

目的:探讨血液灌流(HP)串联血液透析(HD)对透析患者血清IL-6、IL-8、TNF-α的影响。方法:选30例维持性HD患者,采用自身对照法,行HD串联HP治疗设为(HD HP)组,行常规血透设为HD组。分别测定两组治疗前后的IL-6、IL-8、TNF-α水平。结果:(1)(HD HP)组治疗后TNF-a显著下降(P<0.05),IL-6、IL-8稍有下降,但无统计学意义(P>0.05)。(2)HD组治疗后TNF-α、IL-6、IL-8均略微上升,但差异无显著性。结论:常规血透治疗后患者血清IL-6、IL-8、TNF-α无下降,HP串联HD治疗后IL-6、IL-8略微下降,血清TNF-α明显下降,有利于改善尿毒症患者的细胞免疫功能。     

超滤量的血液滤过对全身炎症反应的影响

目的研究高流量血液滤过(HVHF)对全身炎症反应综合征(SIRS)患者炎症介质水平和预后的影响。方法对ICU内31例SIRS患者接收血液滤过治疗,随机分为超滤量60ml·kg-1·h-1的HVHF组(15例)和超滤量35ml·kg-1·h-1的连续性静脉静脉血液滤过(CVVH)组(16例),每次血液滤过治疗时间不少于24h。分别于血液滤过前(T0)、滤过12h(T1)及24h(T2)抽取静脉血检测肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-8,并观察SIRS指标和APACHEⅡ评分。结果 T1时,HVHF组TNF-α、IL-6水平显著下降且低于CVVH组(P<0.05);T2时两组TNF-α、IL-6下降均不明显。两组的IL-8在治疗24h中均缓慢下降。两组治疗后SIRS指标和APACHEⅡ评分均显示明显改善,HVHF组的存活率明显高于CVVH组(P<0.05)。结论 HVHF降低SIRS患者炎症介质的效果较CVVH更为明显。     

Di(isononyl) phthalate (DINP) and di(isodecyl) phthalate (DIDP) are not mutagenic

Recently there have been reports of liver and kidney tumors in rodents following long-term exposure to di(isononyl) phthalate (DINP). Mechanistic studies suggested that the liver tumors were a consequence of peroxisomal proliferation, whereas the kidney tumors (found only in male rats) were associated with induction of alpha(2u)-globulin. Because both peroxisomal proliferation and alpha(2u)-globulin are considered to be non-genotoxic carcinogenic processes, it seemed appropriate to investigate the genotoxic potential of DINP. Additional studies were also conducted on di(isodecyl) phthalate (DIDP), a structurally related substance that also induces peroxisomal proliferation, although it has not been tested in a carcinogenicity bioassay. The DINP was tested in Salmonella, in vitro cytogenetics and mouse micronucleus assays, whereas DIDP was evaluated in a mouse micronucleus test. All of these tests produced negative results, i.e. neither phthalate was mutagenic in any of the test systems. These data are consistent with results of other published and unpublished genotoxicity tests and provide support for the hypothesis that the liver and kidney tumors induced by DINP were the result of non-genotoxic processes.     

Allosteric interaction of zinc with recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) GABA(A) receptors

In a recent study we have provided evidence that inhibition of native GABA(A) receptors by zinc depends primarily on the allosteric modulation of receptor gating. Both the kinetics and the sensitivity of the GABA(A) receptor to zinc depend on subunit composition, especially on the presence of the gamma(2) subunit. To analyze the mechanism of action of zinc its effects have been tested on recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors expressed in HEK 293 cells. The currents produced by ultrafast application of GABA have been measured to assess the impact of zinc ions on GABA(A) receptor gating with resolution corresponding to the time scale of synaptic currents. While, as expected, zinc markedly reduced the peak amplitude of alpha(1)beta(2)-mediated currents, its effect on kinetics was significantly different from that observed for alpha(1)beta(2)gamma(2). In particular, unlike alpha(1)beta(2)gamma(2), zinc did not affect the onset of alpha(1)beta(2)-mediated responses. Moreover, zinc increased the extent of desensitisation of alpha(1)beta(2)gamma(2) receptors and reduced desensitisation of alpha(1)beta(2) ones. Quantitative analysis suggests that zinc exerts an allosteric modulation on both alpha(1)beta(2)gamma(2) and alpha(1)beta(2) receptors. Zinc effects on alpha(1)beta(2)gamma(2) were qualitatively similar to those reported for native receptors.     

Serotonin(7) receptors (5-HT(7)Rs) and their ligands

Serotonin (5-HT) is involved in various physiological and pathological processes by interaction with 14 distinct receptor subtypes, grouped in seven classes of receptors (5-HT(1-7)) on the basis of amino acid sequence, pharmacology, and signal transduction pathways. The 5-HT(7)R is a G-protein coupled receptor with seven transmembrane domains. It was found by the application of molecular cloning and has been identified in rat, mouse, human, pig, and guinea pig. Although the biological functions of the 5-HT(7)Rs are poorly understood, preliminary evidence suggests that it may be involved in depression, control of circadian rhythms, and relaxation of vascular smooth muscles. For these reasons, the 5-HT(7)R has become a target for the development of novel drugs. This review will give a brief introduction of the pharmacology of 5-HT(7)R (molecular structure, distribution of 5-HT(7)R mRNA, localization of the 5-HT(7)R protein, functional correlates, and therapeutic potential) and a detailed survey of the 5-HT(7)R ligands, which have appeared in the literature in both papers and patents. Structure-activity relationships (SAR) of these ligands will also be described.     

Interactions between depressants (alcohol-type) and stimulants (amphetamine-type)

The rotarod disruption in rats by 1.5 g/kg of ethanol was prolonged by combining the depressant with 2 or 8 mg/kg d-amphetamine, but not after combinations with 4 or 6 mg/kg of the stimulant. The combination with 8 mg/kg d-amphetamine also induced a prolonged coma and lethality. Cocaine or methylphenidate in combination form with ethanol also showed prolonged disruption of rotarod performance, but severe depression and lethality were not observed at any dose combination. d-Amphetamine in combination with pentobarbital or diazepam also increased the duration of rotarod impairment. Amphetamine plus methaqualone did not prolong rotarod disruption, but rather showed a trend toward antagonism. These combinations of 8 mg/kg d-amphetamine with depressants other than alcohol did not cause prolonged coma and lethality. Lower doses of ethanol (0.25 and 0.5 g/kg) plus 8 mg/kg d-amphetamine induced a delayed impairment of rotarod performance in rats as well as a comatose state and lethality. Mice showed a similar trend for these interactions between alcohol and d-amphetamine but the influence was much less predictable. Analysis of alcohol levels in rat serum and brain indicated little effect of d-amphetamine on the rate of elimination of ethanol. On the other hand, 1.5 g/kg of ethanol prolonged the d-amphetamine decay from brain and serum. This latter interaction was not observed in rats treated with 8 mg/kg d-amphetamine plus 0.5 g/kg ethanol. Mice treated with 8 mg/kg d-amphetamine plus 2.25 g/kg alcohol showed little trend for changes in rate of elimination of either drug. The behavioral effects of the combination of d-amphetamine and ethanol cannot be explained adequately on the basis of altered pharmacokinetics of either drug.     

Bioaccumulation and toxicity of 4-nonylphenol (4-NP) and 4-(2-dodecyl)-benzene sulfonate (LAS) in Lumbriculus variegatus (Oligochaeta) and Chironomus riparius (Insecta)

The discharge of surfactants, such as 4-nonylphenol (4-NP) and linear alkylbenzene sulfonates (LAS), into water bodies leads to accumulation of the chemicals in the sediments and may thus pose a problem to benthic organisms. To study the bioaccumulation of surfactants, Oligochaeta worm Lumbriculus variegatus was exposed to sediment-spiked, [14C]-labeled 4-NP and 4-(2-dodecyl)-benzene sulfonate (C12-LAS) in three different sediments (S1-S3). The sediments were characterized for organic carbon (OC) content and particle size distribution. The acute toxicity was examined by exposing L. variegatus and three to four instar Chironomus riparius (Insecta) larvae in water-only exposure to 4-NP and LAS at different concentrations. After 48-h exposure, lethal water concentrations (LC50) and lethal body residues (LBR50) were estimated using liquid scintillation counting. Chronic toxicity was evaluated in two different sediments by exposing first instar C. riparius larvae to sediment-spiked chemicals at different concentrations. After 10 days, the sublethal effects of surfactants were observed by measuring wet weight and head capsule length. Finally, another 10-day test was set up in order to measure the LAS body residues associated with sublethal effects in C. riparius in S2 sediment. The bioaccumulation test revealed that the bioaccumulation of both 4-NP and LAS increased as the sediment organic matter content decreased. It is assumed that the chemical binding to organic material decreased chemical bioavailability. The acute toxicity tests showed that L. variegatus was more tolerant of 4-NP, and C. riparius was more tolerant of LAS when based on water exposure concentration. The LBR-estimates revealed, however, that L. variegatus tolerated clearly higher tissue residues of both chemicals compared with C. riparius. Both chemicals had sublethal effects on C. riparius growth in sediment exposure, reducing larvae wet weight and head capsule size. 4-NP, however, showed an irregular dose-response pattern. The characteristics of the exposure media affected the bioaccumulation potential of both chemicals. Thus, exposure concentrations offered no prediction of body residue, and therefore it is proposed that organism body residue offered a more accurate dose-metric for chemical exposure than the chemical concentration of the environment.     

Developmental toxicity of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat

Two phthalate esters, di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), have been assessed for their potential to cause developmental toxicity in the rat. Groups of 22 timed-mated Sprague-Dawley rats were administered 250, 500, or 1000 mg/kg D79P or D911P daily by oral gavage (5 ml/kg) between gestation days (GD) 1 and 19. Control animals received the vehicle (olive oil) alone. On GD20, the animals were sacrificed and the fetuses examined. Treatment resulted in no signs of maternal toxicity, as assessed by adjusted maternal bodyweight gain throughout gestation and clinical examinations, and no effects upon litter size, fetal survival or bodyweight. Pups of the high dose D79P and intermediate and high dose D911P groups showed increased incidences of supernumerary lumbar ribs. There was a significant increase in dilated renal pelves in pups of the low dose D79P and high dose D911P groups, but only for D911P was there a significant trend. Consequently, the no observed adverse effect level (NOAEL) for maternal toxicity for both D79P and D911P is 1000 mg/kg/day. The NOAEL values for developmental toxicity are 500 mg/kg/day D79P and 250 mg/kg/day D911P.     

Two-generation reproduction toxicity studies of di-(C(7)-C(9) alkyl) phthalate and di-(C(9)-C(11) alkyl) phthalate in the rat

Di-(C(7)-C(9) alkyl) phthalate (D79P) and di-(C(9)-C(11) alkyl) phthalate (D911P), based on high-normality linear oxo-alcohols, have been assessed for their impact upon reproductive performance in Sprague-Dawley rats. Rats were continuously exposed to either D79P or D911P at dietary levels of 0%, 0.1%, 0.5%, or 1.0% over two generations. Selected F(0) offspring (F(1) generation) were exposed to the same dietary concentration of D79P or D911P as the respective F(0) animals, and were mated to produce F(1) offspring. Both D79P and D911P markedly reduced body weight gain in F(0) and F(1) adult males at the highest dose, but females were affected to a lesser extent. There was no impairment of fertility, fecundity, or development in either generation, but body weights of offspring in the 1.0% D79P and 1.0% D911P groups were slightly and transiently reduced over the weaning period. Although decreases in the weight of several organs were accounted for by depressed body weight, ovary weights were reduced in both generations exposed to 1.0% D79P, and epididymidal weights were slightly reduced in adults of both generations exposed to 1.0% D911P. However, ovarian function-assessed by the oestrus cycle and mating behaviour-and epididymidal sperm concentration, motility, and morphology were unaffected by either substance. Treatment resulted in liver changes, particularly in males, characterised by increased liver weight in young animals, histopathologic changes and reduced organ weight in mature animals, and an increase in palmitoyl CoA oxidase activity. In conclusion, neither D79P nor D911P impaired reproductive function in rats when administered in the diet at levels that induce systemic toxicity, and the NOAEL for effects on reproduction in the rat is 0.5% for both D79P and D911P.