Elicitation of immune responsiveness against antigenic challenge in age-related diseases: effects of red wine polyphenols

Polyphenols contained in red wine possess a broad array of properties which seem to be beneficial to human and animal health. We have investigated the ability of red wine polyphenols to promote the in vitro release of both proinflammatory and antiinflammatory cytokines from human healthy mononuclear cells, as well as of immunoglobulins from B cells. Following red wine (Negroamaro) pretreatment of lymphomonocytes, results will show a production of regulatory [Interleukin(IL)-12], proinflammatory (IL-1 beta and IL-6), and anti-inflammatory (IL-10) cytokines, as well as of IgA and IgG. The fine balance between inflammation and antiinflammation, as well as the role of humoral immune response either systemic or mucosal will be discussed as a consequence of red wine intake. Finally, since ageing is characterized by a decline of many immune functions, our results suggest that moderate use of red wine may be beneficial in age-related disorders where the host immune response is very often not effective against a variety of antigens.     

绝经期妇女红细胞免疫功能测定的临床意义

目的检测绝经期妇女红细胞免疫水平,探讨其变化在绝经期妇女的临床意义。方法分别采用郭峰法及AP-APP桥联免疫检测法检测57例绝经期无冠心病妇女、49例绝经期有冠心病妇女及50例月经正常健康妇女红细胞C3b受体花环率(RBC-C3bR)、红细胞免疫复合物花环率(RBC-ICR)水平及CD4/CD8比值。结果绝经期无冠心病妇女和绝经期有冠心病妇女RBC-C3bR、CD4/CD8比值均明显低于月经正常的健康妇女,而RBC-ICR却明显高于月经正常健康妇女对照组,且3组间差异显著(P<0.01,P<0.05)。结论绝经期妇女机体红细胞免疫功能低下,其变化可作为某些疾病的预测指标。     

Nonalcoholic compounds of wine: the phytoestrogen resveratrol and moderate red wine consumption during menopause.

The literature on the natural sources of resveratrol, a phytochemical substance found in grapes and wine, is reviewed herein. Its structure is similar to that of diethylstilbestrol and, like other authors, we consider that resveratrol might be a phytoestrogen. We analyzed the populations who ingest this substance, as well as the known biological effects of phytoestrogens in humans. The literature on the effects of resveratrol on female reproduction, osteoporosis and cancer was assessed using relevant case reports and cohort studies, as well as randomized trials and review articles. We conclude that phytoestrogens exhibit physiological effects in humans and that these estrogenic actions increase the biological reactions produced by moderate red wine consumption with meals.     

Hepatitis C virus infection: immune responsiveness and interferon-alpha treatment

Hepatitis C virus (HCV) is responsible for most cases of posttransfusion hepatitis and sporadic or community-acquired non-A, non-B hepatitis. Different generations of enzyme-linked immunosorbent assay have been generated for detecting antibodies to HCV epitopes. HCV-RNA quantitative analysis has been developed by means of polymerase chain reaction technique. This approach is the only reliable method for HCV-RNA tissue localization, being helpful in early diagnosis. HCV infected liver is characterized by an inflammatory infiltrate including CD4+, CD8+, and B lymphocytes. Evidence has been provided that in HCV patients CD8+ cell response is associated with low level of viraemia and higher level of disease activity. CD4+ T cells exhibit specificity for the core antigen, also correlating with disease activity and viraemia. Costimulatory molecules, cytokines, oxygen radicals, the complex Fas/Fas-ligand and soluble class I HLA structures are discussed as putative cofactors involved in disease evolution. Various forms of interferon (IFN)-alpha have been evaluated for the treatment of patients with HCV infection. Initial enthusiasm has been attenuated by the evidence of a low sustained virological response rate and the constant side effects of IFN-alpha therapy in patients with chronic HCV disease. Among possible markers for predicting therapeutic outcome in HCV-positive individuals, anti-core antibodies correlate positively with response to IFN-alpha administration, as well as reduction of interleukin-2 serum levels has been detected in patients with a good therapeutic response. Association between HCV infection and autoimmune phenomena, also in relation to IFN-alpha therapy has been reported. Finally, results of the combined treatment with IFN-alpha/ribavirin are illustrated.     

Cardioprotection of red wine: role of polyphenolic antioxidants.

Epidemiological studies suggest that the consumption of wine, particularly of red wine, reduces the incidence of mortality and morbidity from coronary heart disease. This has given rise to what is now popularly termed the "French paradox". The cardioprotective effect has been attributed to antioxidants present in the polyphenol fraction of red wine. Grapes contain a variety of antioxidants, including resveratrol, catechin, epicatechin and proanthocyanidins. Of these, resveratrol is present mainly in grape skin while proanthocyanidin is present in the seeds. In this report, we provide evidence that red wine extract as well as resveratrol and proanthocyanidins are equally effective in reducing myocardial ischemic reperfusion injury, which suggests that these red wine polyphenolic antioxidants play a crucial role in cardioprotection.     

Potential application of dietary polyphenols from red wine to attaining healthy ageing

Polyphenols are ubiquitous compounds present in the vegetal kingdom and endowed with an array of beneficial activities to human health. In this review, the effects of dietary polyphenols on the prevention and/or mitigation of cancer, neurodegenerative diseases, obesity, metabolic syndrome and atherosclerosis will be illustrated. Moreover, emphasis will be placed on our own data concerning the in vitro effects performed by polyphenols from an Italian red wine "Negroamaro" on human healthy peripheral blood mononuclear cells. Particularly, production of nitric oxide and maintenance of the inflammatory/anti-inflammatory cytokine network will be discussed also in relation to potential application to human age-related diseases. In conclusion, polyphenols in virtue of the plethora of protective effects manifested in various experimental models and clinical trials seem to be appropriate as dietary supplements for preventing the functional decline of organs with age.     

儿童肾病综合征患者免疫球蛋白的检测及其临床意义

目的探讨儿童肾病综合征患者血清中免疫球蛋白的变化及临床意义。方法采用散射比浊法检测50例肾病综合征患儿血清中IgG、IgA、IgM、IgE的含量,并以20例正常儿童作比较。结果肾病综合征的患儿血清的IgG明显低于正常儿童（P〈0.01）。IgM、IgE显著高于正常儿童（P〈0.01）,IgA与正常儿童无差异。结论测定肾病综合征患儿血清中IgG、IgA、IgM、IgE的水平,可为进一步探讨其发病机理提供重要的参考依据,同时对指导临床治疗具有一定的意义。     

Basic and clinical aspects of non-neuronal acetylcholine: biological and clinical significance of non-canonical ligands of epithelial nicotinic acetylcholine receptors

Mucocutaneous keratinocytes and bronchial epithelial cells express nicotinic acetylcholine receptors (nAChRs). Emerging evidence indicates that nAChRs can be stimulated also by the tobacco-derived nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) that can induce tumors in laboratory animals. Nitrosamines may disturb the delicate balance between cell proliferation, growth arrest, and apoptosis. A novel paradigm of cell regulation via nAChR has been discovered in studies of SLURP (secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein)-1 and -2. Experimental results suggest that SLURP-1 and -2 regulate keratinocyte proliferation, apoptosis, and differentiation. Most importantly, SLURPs and professional nicotinic antagonists can abolish, in part, the abilities of NNK and NNN to cause tumorigenic transformation of immortalized keratinocytes. Learning the pharmacology of the nitrosamine vs. SLURP action on epithelial cells may help develop an effective anti-cancer treatment and prevention programs wherein hazardous effects of tobacco products are anticipated, or even abolished, by a pharmacologic ligand of the specific nicotinic receptor acting as an antidote.     

上皮内瘤变和肿瘤生物学行为的临床意义及新近展

上皮内瘤病变（IN）是一种形态学上以细胞学和结构学异常、遗传学上以基因克隆性改变、生物学行为上以易进展为具有侵袭和转移能力的浸润性癌为特征的癌前病变。     

Basic and clinical aspects of non-neuronal acetylcholine: overview of non-neuronal cholinergic systems and their biological significance

Acetylcholine (ACh) is a phylogenetically ancient molecule involved in cell-to-cell signaling in almost all life-forms on earth. Cholinergic components, including ACh, choline acetyltransferase, acetylcholinesterase, and muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively) have been identified in numerous non-neuronal cells and tissues, including keratinocytes, cancer cells, immune cells, urinary bladder, airway epithelial cells, vascular endothelial cells, and reproductive organs, among many others. Stimulation of the mAChRs and nAChRs elicits cell-specific functional and biochemical effects. These findings support the notion that non-neuronal cholinergic systems are expressed in certain cells and tissues and are involved in the regulation of their function and that cholinergic dysfunction is related to the pathophysiology of certain diseases. They also provide clues for development of drugs with novel mechanisms of action.     

放疗对肿瘤患者免疫功能的影响及临床意义

目的 研究放射治疗对肿瘤患者免疫功能的影响.方法 选取本院120例恶性肿瘤患者为研究对象,采取流式细胞仪检测患者放疗前后免疫功能指标CD3、CD4、CD8、CD56、CD4/CD8,比较放疗对免疫功能的影响,同时根据不同靶体积、放疗剂量及是否出现骨髓抑制进行分组,比较组间免疫功能的差异,以分析不同放疗信息患者之间免疫功能的具体差异.结果 120例患者放疗前后CD3比较无统计学意义(P＞0.05),放疗后CD4、CD56及CD4/CD8分别为(26.88±1.76)％、(10.26±0.97)％、(0.74±0.02),与放疗前[(34.66±2.02)％、(19.25±2.01)％、(1.24±0.05)]比较显著降低(P＜0.05),CD8放疗后为(34.02±1.98)％,与放疗前[(28.55±1.96)％]比较显著升高(P＜ 0.05);＜60Gy放射剂量患者CD56低于≥60 Gy者(P＜0.05),而CD4/CD8高于≥60 Gy者(P＜0.05),靶体积＜397cm3者CD4、CD56、CD4/CD8高于靶体积≥397 cm3者(P＜0.05),CD8低于靶体积≥397 cm3者(P＜ 0.05);120例患者中,共47例在放疗中或放疗后出现骨髓抑制,与无骨髓抑制患者比较,骨髓抑制患者CD4显著较低(P＜0.05),其他免疫指标比较差异无统计学意义(P＞0.05).结论 放疗可导致恶性肿瘤患者免疫功能降低,放疗剂量及靶体积对免疫功能均有不同程度影响,其中以靶体积影响更为显著,放疗剂量越高、靶体积范围越大,则免疫抑制越明显,而有关骨髓抑制与免疫抑制的相关性仍需要更大样本的研究.     

幼年类风湿关节炎免疫指标检测及临床意义

目的 探讨幼年类风湿关节炎(JRA)息儿T细胞亚群、免疫球蛋白(Ig)和红细胞沉降率(ESR)、C反应蛋白(CRP)联合检测的临床价值.方法 对40例确诊JRA患儿采用流式细胞术测定外周血T淋巴细胞亚群(CD3+、CD4+、CD16+、CD16+CD56+),采用速率散射比浊法检测Ig、CRP,ESR采用魏氏法,设正常对照组40例.结果 T细胞亚群CD3+、CD8+、CD16+CD56+与对照组比较明显降低,CD4+与对照组比较明显升高(均P<0.05),IgG、IgA、IgM、ESR和CRP均高于正常对照组(均P<0.05).结论 JRA患儿存在炎性反应,疾病活动时伴有细胞免疫、体液免疫两种免疫功能紊乱.     

Influencing mucosal homeostasis and immune responsiveness: the impact of nutrition and pharmaceuticals

Both nutrition and orally ingested drugs pass the gastrointestinal mucosa and may affect the balance between the mucosal immune system and microbial community herein, i.e. affecting composition of the microbial community as well as the status of local immune system that controls microbial composition and maintains mucosal integrity. Numerous ways are known by which the microbial community stimulates mammalian host's immune system and vice versa. The communication between microbiota and immune system is principally mediated by interaction of bacterial components with pattern recognition receptors expressed by intestinal epithelium and various local antigen-presenting cells, resulting in activation or modulation of both innate and adaptive immune responses. Current review describes some of the factors influencing development and maintenance of a proper mucosal/immune balance, with special attention to Toll like receptor signaling and regulatory T cell development. It further describes examples (antibiotic use, HIV and asthma will be discussed) showing that disruption of the balance can be linked to immune function failure. The therapeutic potential of nutritional pharmacology herein is the main focus of discussion.     

Comparison of antioxidant potentials of red wine, white wine, grape juice and alcohol

Antioxidant potential (AOP) and non-enzymatic superoxide radical scavenger activity (NSSA) values of red wine, white wine, grape juice and ethyl alcohol were assessed and values were compared. The effects of these beverages on serum AOP and NSSA values were also measured in vitro. Red wine, white wine and grape juice exert strong antioxidant activity in similar degrees and all produce significant effects on serum AOP and NSSA values. However, ethyl alcohol does not have either AOP or NSSA, nor does it have an effect on serum AOP or NSSA values. AOP values (nmol/ml h) of red wine, white wine and grape juice were 20.8 +/- 4.2, 23.2 +/- 4.0 and 24.6 +/- 4.8, respectively. NSSA values (U/ml) of red wine, white wine and grape juice were 30.4 +/- 6.8, 26.8 +/- 5.6 and 32.6 +/- 5.8, respectively. There were no statistically meaningful differences between AOP and NSSA values of the groups (p > 0.05 for all). Results suggest that red wine, white wine and grape juice all have high antioxidant potential to protect cellular structures against peroxidation reaction owing to their rich phenolic contents.     

Fatty acids isolated from royal jelly modulate dendritic cell-mediated immune response in vitro

Royal jelly (RJ), especially its protein components, has been shown to possess immunomodulatory activity. However, almost nothing is known about the influence of RJ fatty acids on the immune system. In this work we studied the effect of 10-hydroxy-2-decanoic acid (10-HDA) and 3,10-dihydroxy-decanoic acid (3,10-DDA), isolated from RJ, on the immune response using a model of rat dendritic cell (DC)-T-cell cocultures. Both fatty acids, at higher concentrations, inhibited the proliferation of allogeneic T cells. The effect of 10-HDA was stronger and was followed by a decrease in interleukin-2 (IL-2) production and down-regulation of IL-2 receptor expression. Spleen DC, cultivated with 10 microg/ml of fatty acids down-regulated the expression of CD86 and the production of IL-12, but up-regulated the production of IL-10. In contrast, DC, pretreated with 100 microg/ml of 3,10-DDA, up-regulated the expression of CD86 and augmented the proliferation of allogeneic T cells. The highest dose (200 microg/ml) of both fatty acids which was non-apoptotic for both T cells and DC, down-regulated the expression of MHC class II and CD86, decreased the production of IL-12 and made these DC less allostimulatory. The immunosuppressive activity of 3,10-DDA was also confirmed in vivo, using a model of Keyhole lymphet hemocyanine immunization of rats. In conclusion, our results showed the immunomodulatory activity of RJ fatty acids and suggest that DC are a significant target of their action.     

滤泡辅助性T细胞亚群在慢性特发性血小板减少性紫癜患儿发病机制中的作用分析

目的探索滤泡辅助性T细胞(Tfh)在慢性特发性血小板减少性紫癜(ITP)患儿中的作用机制。方法用流式细胞术检测38名健康儿童、35例ITP患儿外周血CXCR5+CD4+T细胞占CD4+T细胞的比例。采用酶联免疫吸附试验检测健康儿童、ITP患儿血浆白细胞介素-21(IL-21)浓度。结果与健康对照组相比,ITP患儿外周血CXCR5+CD4+T细胞占CD4+T细胞的比例显著增高[(13.86±7.53)%,(7.65±5.36)%,P<0.05]。经过激素治疗后,ITP患儿外周血中CXCR5+CD4+T细胞占CD4+T细胞比例有所下降[(13.8±0.41)%,(8.23±6.12)%,P<0.05]。初发ITP患儿外周血血浆IL-21浓度显著高于健康对照组[(80.47±25.79)μg/mL,(32.41±17.53)μg/mL,P<0.05]。经过激素治疗后,ITP患儿外周血血浆IL-21浓度有所下降,但两者差异无统计学意义[(80.47±25.79)μg/mL,(60.35±19.54)μg/mL,P>0.05]。结论慢性ITP患儿与健康对照组相比,存在Tfh细胞数量及功能异常,可能与慢性ITP的发病相关。     

Encapsulation of biological active phenolic compounds extracted from wine wastes in alginate-chitosan microbeads

Grapes (Vitis vinifera) are produced in large amounts worldwide and mostly are used for winemaking. Their untreated wastes are rich in valuable secondary metabolites, such as phenolics. Thus, in this study, white and red wine wastes (Malagouzia and Syrah variety) were investigated for their added value phenolics, which were analysed by high performance liquid chromatography (HPLC) and electrospray ionisation-mass spectrometry (ESI/MS) and subsequently encapsulated in several polymers. Extracts from all wastes gave high amounts of total phenolics (13?±?2.72–22?±?2.69?mg?g^?1) and possessed high antioxidant activity (67–97%). In addition to their significant antibacterial activity against gram-negative and gram-positive bacteria, interesting results were also obtained from their anti-inflammatory and antiplatelet activity, in vitro. Encapsulation of the extracts was selective, leaving out most of sugars and other organic compounds when alginate-chitosan was used. Encapsulation efficiency recorded for all extracts ranged from 55% to 79%. Release studies were also performed in several solutions aiming in their commercial use in food and pharmaceutical industries.