Pancreatic secretory responses to intravenous hyperalimentation and intraduodenal elemental and full liquid diets

Intravenous hyperalimentation and enteral elemental diets have both been advocated for the nutritional support of patients with acute pancreatitis, pancreatic fistula, and proximal small bowel fistula. The exocrine pancreatic responses to these nutrients compared to one another and to full liquid diet have been inadequately studied. Therefore, pancreatic protein, volume, and bicarbonate responses to graded doses of (1) intravenous hyperalimentation, (2) intraduodenal elemental diet, and (3) intraduodenal full liquid diet were compared in duplicate experiments in five dogs with chronic pancreatic fistulas. Both intraduodenal elemental and full liquid diets caused comparable and significant dose-related increases in pancreatic protein, volume, and bicarbonate outputs over basal levels (p less than 0.05). In contrast, there was no stimulation of pancreatic secretion by intravenous hyperalimentation. It therefore appears that of the methods studied, only intravenous hyperalimentation can provide full nutritional support while maintaining the pancreas at rest.     

Boosters of a therapeutic HIV-1 vaccine induce divergent T cell responses related to regulatory mechanisms

Therapeutic human immunodeficiency virus (HIV) vaccines aim to reduce disease progression by inducing HIV-specific T cells. Vacc-4x are peptides derived from conserved domains within HIV-1 p24 Gag. Previously, Vacc-4x induced T cell responses in 90% of patients which were associated with reduced viral loads. Here we evaluate the effects of Vacc-4x boosters on T cell immunity and immune regulation seven years after primary immunization. Twenty-five patients on effective antiretroviral therapy received two Vacc-4x doses four weeks apart and were followed for 16 weeks. Vacc-4x T cell responses were measured by proliferation (CFSE), INF-γ, CD107a, Granzyme B, Delayed-Type Hypersensitivity test (DTH) and cytokines and chemokines (Luminex). Functional regulation of Vacc-4x-specific T cell proliferation was estimated in vitro using anti-IL-10 and anti-TGF-ß monoclonal antibodies.     

关于GLP实验室建设的软硬件要求

通过对GLP的产生背景和我国的现状以及今后GLP发展趋势的分析 ,阐明了建立GLP实验室的重要性和具体实施中的软硬件要求。软件建设中人员素质是关键 ,标准操作规程 (SOP)的制定对实施GLP至关重要 ,管理监督是实施GLP的有力保证。硬件建设中完整配套的实验设施和自动化仪器设备是毒性评价工作顺利进行和高质量完成的重要保障。实施GLP可以提高药品非临床安全性评价研究的质量 ,减少人为误差 ,得到可信性高的实验数据 ,以保障人民用药安全。     

Dose related acute irritant symptom responses to occupational exposure to sodium borate dusts.

A repeated measurement design was employed in the study of acute symptoms of eye and respiratory tract irritation resulting from occupational exposure to sodium borate dusts. The symptom assessment of the 79 exposed and 27 unexposed subjects comprised interviews before the shift began and then at regular hourly intervals for the next six hours of the shift, four days in a row. Exposures were monitored concurrently with a personal real time aerosol monitor. Two different exposure profiles, a daily average and short term (15 minute) average, were used in the analysis. Exposure-response relations were evaluated by linking incidence rates for each symptom with categories of exposure. Acute incidence rates for nasal, eye, and throat irritation, and coughing and breathlessness were found to be associated with increased exposure levels of both exposure indices. Steeper exposure-response slopes were seen when short term exposure concentrations were used. Results from multivariate logistic regression analysis suggest that current smokers tended to be less sensitive to the exposure to airborne sodium borate dust. There was no indication that anhydrous sodium borate was more potent than the other sodium borates in this work environment.     

Dose related acute irritant symptom responses to occupational exposure to sodium borate dusts.

A repeated measurement design was employed in the study of acute symptoms of eye and respiratory tract irritation resulting from occupational exposure to sodium borate dusts. The symptom assessment of the 79 exposed and 27 unexposed subjects comprised interviews before the shift began and then at regular hourly intervals for the next six hours of the shift, four days in a row. Exposures were monitored concurrently with a personal real time aerosol monitor. Two different exposure profiles, a daily average and short term (15 minute) average, were used in the analysis. Exposure-response relations were evaluated by linking incidence rates for each symptom with categories of exposure. Acute incidence rates for nasal, eye, and throat irritation, and coughing and breathlessness were found to be associated with increased exposure levels of both exposure indices. Steeper exposure-response slopes were seen when short term exposure concentrations were used. Results from multivariate logistic regression analysis suggest that current smokers tended to be less sensitive to the exposure to airborne sodium borate dust. There was no indication that anhydrous sodium borate was more potent than the other sodium borates in this work environment.     

Nutrients, essential fatty acids and prostaglandins interact to augment immune responses and prevent genetic damage and cancer

Micronutrients, vitamins A, C, and E, beta-carotene, and selenium can decrease the incidence of cancer, possibly due to their antioxidant action(s). These nutrients prevent lipid peroxidation, especially that of gamma-linolenic, dihomo-gamma-linolenic and arachidonic acids, the precursors of prostaglandins. Gammma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA), prostaglandin E1 (PGE1) and prostacyclin can prevent genetic damage in vitro and in vivo. They augment immune responses and tumoricidal actions of macrophages. Prostacyclin also has anti-metastatic properties. Zinc, magnesium, calcium and pyridoxine are cofactors in the formation of GLA, DGLA, PGE1 and PGI2. Hence, in situations where there is a reduced intake of trace elements and vitamins, there may be a decrease in the synthesis of GLA, DGLA, PGE1 and PGI2, leading to immune suppression and genetic damage that cannot be reversed or prevented. In the presence of adequate amounts of selenium, beta-carotene and Vitamin A and E, peroxidation of GLA/DGLA/AA would not occur, so that they are available for the synthesis of PGE1 and PGI2. This interaction between nutrients, essential fatty acids and prostaglandins can be exploited to develop new preventive and therapeutic strategies in cancer.     

功能性消化不良患者血清GLP-1水平变化及意义

目的探讨空腹血清GLP-1水平变化与功能性消化不良不同临床亚型及消化不良症状积分严重程度的关系。方法将50例FD患者按罗马Ⅲ标准分为上腹不适综合征、上腹痛综合征两组;按消化不良症状积分分为轻、中、重三组。采用ELISA法测定所用受试者血清GLP-1的含量,判断血清GLP-1水平变化与FD发病、不同临床亚型及疾病严重程度的关系。结果 FD患者空腹血清GLP-1水平明显低于正常对照组(P<0.01);PDS组及EPS组患者空腹血清GLP-1水平差异无统计学意义(P>0.05);消化不良症状积分轻、中、重三组两两比较患者空腹血清GLP-1水平差异均无统计学意义(P>0.05)。结论 FD患者空腹血浆GLP-1水平降低,空腹血清GLP-1可能参与FD的发病,但与FD不同临床亚型及症状严重程度无关。     

300例儿童分泌性中耳炎的相关因素分析

目的探讨儿童分泌性中耳炎的相关因素。方法选择该院2010年1月—2014年1月收治的300例分泌性中耳炎患儿,对其临床资料与相关因素进行回顾性分析。结果入选患儿中111例（37.0%）存在腺样体肥大,75例（25.0%）合并鼻窦炎,63例（21.0%）变应原检测呈阳性,51例（17.0%）合并衣原体或支原体、病毒、细菌感染。根据其症状有针对性的进行治疗,可采取置管或鼓膜切开治疗,300例（586耳）患儿中无效17耳,好转76耳,治愈493耳,总有效率达到97.6%。结论儿童患分泌性中耳炎的相关因素包括衣原体或支原体、病毒、细菌感染以及变态反应疾病、鼻窦炎和腺样体肥大等,在临床上医生需要对这些症状加以重视,积极采取相应方式进行治疗。     

HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime

HSV-1 amplicon vectors elicit strong T-cell responses to encoded antigens but the qualitative nature of these responses is poorly understood. Antigen-specific CD4(+) and CD8(+) T-cell responses to amplicon and adenovirus (rAd5) vectors encoding HIV-1 gp120 were assessed following immunization of mice, by performing intracellular cytokine staining for IFNgamma, IL2 and TNFalpha, following stimulation of splenocytes with a HIV-1 Env peptide pool. The quality of the primary T-cell response to amplicon and rAd5 vectors was strikingly similar, but there were qualitative differences in responses to amplicon vectors that incorporated different promoters upstream of gp120 - suggesting that promoters can significantly influence immune response quality. When prime-boost combinations were studied, a rAd5 prime and amplicon boost elicited the highest T-cell response. Furthermore, protocols that incorporated a rAd5 prime consistently elicited a greater proportion of polyfunctional CD4(+) T-cells-regardless of boost. This suggests that initial priming can shape immune response quality after a boost. Overall, these findings provide insight into effective vector combinations for HIV-1 vaccine development.     

Antibody responses to influenza A(H1N1)pdm infection

We investigated humoral immune response to influenza A(H1N1)pdm infection and found 32 (22%) of the infected individuals identified by PCR failed to produce a ≥ 4-fold hemagglutinin inhibition assay (HAI) response; a subset of 18 (56%) produced an alternate antibody response (against full-length HA, HA stalk, or neuraminidase). These individuals had lower pre-existing HAI antibody titers and showed a pattern of milder illness. An additional subset of 14 (44%) did not produce an alternate antibody response, had higher pre-existing antibody titers against full-length & stalk HA, and were less sick. These findings demonstrate that some individuals mount an alternate antibody response to influenza infection. In order to design more broadly protective influenza vaccines it may be useful to target these alternate sites. These findings support that there are influenza cases currently being missed by solely implementing HAI assays, resulting in an underestimation of the global burden of influenza infection.     

人体必需营养素及其功能(一)

人类为了维持生存、繁衍和进行生产劳动 ,必须每天从膳食中获取各种各样的营养物质。不同的个体由于其年龄、性别和生理状况不同 ,对各种营养素的需要也不相同。人体是一个复杂而精密的系统 ,其每一项生理活动或生命过程的完成都需要多种营养物质的共同参与。生命中所需要的这些营养素都需要从每天的饮食中获得 ,饮食是健康的基础 ,均衡饮食的意义不但在于各类食物的多样化 ,还包括营养素充足和合理比例 ,这些基础概念和学说是健康教育的根据。食物和人体必需营养素食物是生物为了生存和繁衍所必须摄入的物质 ,人类经过多年的筛选认识并留传…     

S1PR1 expression correlates with inflammatory responses to Newcastle disease virus infection

Newcastle disease virus (NDV) is the causative agent of Newcastle disease, which is characterized by inflammatory pathological changes in the organs of chickens. The inflammatory response to this disease has not been well characterized. Previous reports showed that the sphingosine-1-phosphate-1 receptor (S1PR1), a G protein-coupled receptor, is important to the activation of inflammatory responses. To understand better the viral pathogenesis and host inflammatory response, we analyzed S1PR1 expression during NDV infection. We observed a direct correlation between chicken embryo fibroblast (CEF) cellular inflammatory responses and S1PR1 expression. Virulent NDV-infected CEF cells also had elevated levels of pro-inflammatory cytokines (IL-1β, IL-6 and IL-18). When S1PR1 was inhibited by using the specific antagonist W146, pro-inflammatory cytokine production declined. Overexpression of S1PR1 resulted in increased virus-induced IL-1β production. S1PR1 expression levels did not impact significantly NDV replication. These findings highlight the important role of S1PR1 in inflammatory responses in NDV infection.     

Everyday behaviour and everyday risk: An approach to study people's responses to frequently encountered food related health risks

Food consumption constitutes behaviour that is carried out on a daily basis. The risks and benefits associated with such behaviours are often small, and the time and effort people are, consequently, willing to invest in behavioural decisions are limited. Instead, experience, in the form of an integrated evaluation of past behaviours, may serve as a predictor for future behaviour, allowing reasonable choices to be made with limited effort. This paper discusses the characteristics of daily occurring risks and suggests a model of how prior experience can accumulate and play a role in acting while exposed to daily risk. The core of the approach is a feedback loop that adjusts the current situation until a preset situation is reached. This is based on integrated past experiences and is, thus, continually updated by new experiences. To establish such a feedback mechanism, emotions are argued to play a vital role as an integrator for different types of information, such as perceptual, cognitive and physiological information. This approach may help in understanding how consumers deal with risks in daily (food-handling) practices.     

Genetic polymorphisms related to interleukin-1 beta production and disease risk

PURPOSE: Interleukin (IL)-1A C-889T, IL-1B C-511T, IL-1B C-31T, IL-1B C3954T, and IL-1RN 86-bp VNTR (variable number of tandem repeats) are polymorphisms potentially influencing IL-1 beta production. This review summarizes 1) the biological roles of IL-1 beta, 2) allele frequencies of the polymorphisms, and 3) the reported associations between these polymorphisms and disease risk. METHODS: Papers were obtained from PubMed with keywords "IL-1, polymorphism", as well as from the references in each paper. The most relevant papers were then selected. In this review, a narrative approach was adopted. RESULTS: IL-1 beta is a multifunctional proinflammatory cytokine, whose signal is transduced through IL-1 receptor I (IL-1RI) on the cell surface. Binding levels are influenced by the IL-1 receptor antagonist (IL-1Ra), IL-1RII (decoy receptor with no signal transduction), soluble IL-1RI, and soluble IL-1RII. IL-1B encoding IL-1 beta is located on chromosome 2q14, along with IL-1A encoding IL-1 alpha and IL-1RN encoding IL-1Ra. The minor alleles, IL-1A-889T, IL-1B 3954T, and IL-1RN 2R, are rarer in Japanese than in Caucasians, while IL-1B-511T and IL-1B-31C are more frequent. These polymorphisms have been reported to have potential associations with the risk of diseases, such as stomach cancer, breast cancer, inflammatory bowel, Alzheimer's, and osteoporosis. DISCUSSION: Although there are many inconsistent findings on associations with the polymorphisms, IL-1B C-511T and the tightly linked T-31C may be useful for predicting the risk of diseases with an inflammation basis among Japanese.     

母亲和新生儿GSTM1、GSTT1和细胞色素P_(450)1A1基因多态性与早产易感性关系

目的探讨母亲和新生儿GSTM1、GSTT1基因以及细胞色素P4501A1基因多态性对早产的影响。方法采用病例-对照调查方法,应用多重PCR和限制性内切酶PCR(RFLP-PCR)技术对早产母亲和对照母亲以及早产新生儿和对照新生儿GSTM1、GSTT1基因和CYP1A1基因MSPI位点多态性分别进行检测。结果GSTM1、GSTT1基因和CYP1A1基因MSPI位点多态性在早产母亲和对照母亲组中没有显著性差异(P>0.05);以上基因在早产新生儿和对照新生儿组中也没有显著性差异(P>0.05)。GSTM1与GSTT1联合基因型在母亲和新生儿的病例与对照组中也没有显著性差异(P>0.05);GSTT1缺失型和CYP1A1变异型联合基因在早产母亲组与对照母亲组中有显著性差异(χ2=4.683,P<0.05,OR=2.440)。结论携带GSTT1缺失型基因以及CYP1A1变异型基因的母亲,其发生早产的危险性增大。     

Strong T cell type-1 immune responses to HIV-1 Tat (1-72) protein-coated nanoparticles

A significant emphasis has been placed on the development of adjuvants and/or delivery systems to improve both antibody production and cell-mediated immune responses. We previously reported on a novel anionic nanoparticle, which led to enhanced humoral and T helper type-1 (Th1) biased immune responses in mice when coated with cationized model antigen. Tat (1-72) is a conserved regulatory HIV-1 protein. It was hypothesized that HIV vaccine strategies employing Tat (1-72) may be a promising approach. Although previous reports have suggested that Tat (1-86) may be immunosuppressive, it was demonstrated in this present study that Tat (1-72) was not immunosuppressive when co-administered to mice with ovalbumin (OVA). Tat (1-72) was coated on novel anionic nanoparticles. BALB/c mice were immunized with Tat (5 microg)-coated nanoparticles (15 microg) by subcutaneous injection on days 0 and 14. Antibody and cytokine release were determined on day 28 and compared to Tat (5 microg) adjuvanted with Alum (15 microg) as a Th2 control, Tat (5 microg) adjuvanted with Lipid A (50 microg) as a Th1 control. Immunization of BALB/c mice with Tat-coated nanoparticles resulted in antibody levels (IgG and IgM) comparable to those elicited from Tat and Alum. However, Tat-coated nanoparticles led to a Th1 biased immune response. The IFN-gamma release from splenocytes with Tat-coated nanoparticles was comparable to that from mice immunized with Tat and Lipid A, and 3.3-fold greater than that from mice immunized with Tat and Alum. These studies warrant further investigation of these nanoparticles to enhance both antibody and cellular-based immune responses.