Total urinary polyphenols and longitudinal changes of bone properties. The InCHIANTI study.

The aim of this study was to evaluate the association of levels of urinary total polyphenols considered as a proxy measure of polyphenol intake, with longitudinal changes of bone properties, in the InCHIANTI study. Dietary intake of polyphenols appears to be associated with future accelerated deterioration of bone health. INTRODUCTION: Polyphenols, micronutrients ingested through plant-based foods, have antioxidant and anti-inflammatory properties and may contribute to osteoporosis prevention. We evaluated associations of high levels of urinary total polyphenols (UTP), a proxy measure of polyphenol intake, with longitudinal changes of bone properties in a representative cohort of free-living participants of the InCHIANTI study. METHODS: The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998 and follow-up visits in 2001 and 2004. Of the 1453 participants enrolled, 956 consented to donate a 24-h urine sample used to assess UTP, had dietary assessment, a physical examination, and underwent a quantitative computerized tomography (pQCT) of the tibia. From pQCT images, we estimated markers of bone mass (BM), diaphyseal design (DD), and material quality (MQ). Mixed models were used to study the relationship between baseline tertiles of UTP with changes of the bone characteristics over the follow-up. RESULTS: At baseline, higher levels of UTP were positively correlated with markers of BM, DD, and MQ. Compared with lower tertile of UTP, participants in the intermediate and highest tertiles had higher cortical bone area, cortical mineral content, and cortical thickness. However, participants in the intermediate and highest UTP tertiles experienced accelerated deterioration of these same parameters over the follow-up compared with those in the lowest UTP tertile. CONCLUSIONS: Dietary intake of polyphenols estimated by UTP and dietary questionnaire was associated with long-term accelerated deterioration of bone health. Our study does not support the recommendation of increasing polyphenol intake for osteoporosis prevention.

Allergooncology: an expanding research area.

The relationship between allergic diseases and cancer is a very controversial topic, widely discussed in the last decades. Many studies have demonstrated inverse association between allergy and cancer, but others have reached neutral conclusions or have indicated a positive role of allergy in the development of cancer. However, either inhibiting or favoring, many cells and molecules relevant in the allergic process play a role in tumorigenesis. On the one hand, activated immune cells, like classically activated macrophages "M1", activated dendritic cells, IL-33 and amphiregulin stimulated Innate Lymphoid Cells (ILC2), Th1, IFN-γ producing T CD8+ and B lymphocytes have inhibitory effects on tumorigenesis and tumor progression. On the other hand, tolerogenic immune cells, like alternatively activated macrophages "M2" (M2a, M2b and M2c), tolerogenic dendritic cells, ILC3, T regulatory and B regulatory lymphocytes, while inhibiting allergic sensitization and response, appear to favour carcinogenesis. Furthermore, M2 subtypes macrophages (M2a, M2b), IL-25 stimulated ILC2 and Th2 lymphocytes have a role both in inducing allergic reactions and in favouring cancer progression. In addition, mast cells, pivotal cells in allergy, have a different effect of tumorigenesis based on their location - they can promote cancer progression or inhibit it. Finally, eosinophils have shown a prevalent tumoricidal function mediated by α-defensins, TNF-α, granzymes A and IL-18. Better understanding the role of various cells on carcinogenesis can help in developing new strategies (diagnostic, therapeutic and of follow up) against tumor.

Exploratory study on immune phenotypes in Alzheimer's disease and vascular dementia.

BACKGROUND AND PURPOSE: The differentiation of Alzheimer's disease (AD) dementia from vascular dementia (VaD) and mixed-type dementia (mixed dementia) requires stepwise analysis and usually occurs late in the disease process. Early diagnosis and therapy monitoring would benefit greatly from the identification of biomarkers of neurodegeneration, especially blood biomarkers. To this end, the aim of the present pilot study was to investigate differences in the distribution of peripheral T-cell populations in patients with AD compared to VaD and mixed dementia. METHODS: Flow cytometry was performed on blood samples from 11 patients with AD, six with VaD and six with mixed dementia, as well as 17 healthy control subjects (HCs). CD4+ and CD8+ T cells were typed for expression of CD45, CD27, CD28, CD25, FoxP3, CCR4 and CCR6; the other leukocytes were also assessed. Functionally, immune cell uptake of the ß-amyloid (Aß) toxic fragment (Aß1-42 ) was also evaluated. RESULTS: A higher proportion of CD4+CD28- memory T cells and a reciprocal reduction of CD4+CD28+CD27+ naïve T lymphocytes was detected in all patient groups relative to controls. Significantly fewer CD4+CD25+FoxP3 regulatory T cells were present in patients with VaD, and significantly more CCR6+ and CCR4+ CD4+ T cells in those with AD. Higher CCR6+ T-cell frequencies were also present in patients with mixed dementia, potentially due to the inflammation and immune cell chemoattraction triggered by Aß. CONCLUSIONS: The present study was a comprehensive investigation comparing different kinds of dementia, revealing differentially expressed peripheral markers that are potentially useful for early AD, VaD and mixed dementia diagnoses, and that would assist in proper treatments for these disparate diseases. Validation is now required.

Kounis Syndrome as First Manifestation of Allergic Sensitization.

Mast cells are abundant in the heart, among myocardial fibers, around coronary arteries, within arterial intima and intramural vessels, and in atherosclerotic plaques. Their mediators can be released during anaphylaxis and be responsible for acute coronary syndrome. This condition has been described as Kounis syndrome (KS). We report three cases of acute myocardial ischemia, which fulfill the definition for KS. In Cases 1 and 2, the association of intense chest pain with acute urticaria after an allergenic contact (wasp sting and betalactam antibiotic administration, respectively) was suspected to be an attack of angina related to an allergic reaction. No signs of an allergic reaction were observed in Case 3, but only the history of a wasp sting suggested its relationship to loss of consciousness and heart ischemia when hypersensitivity to venom was ascertained. These cases strongly recommend measurement of anaphylactic biomarkers, such as tryptase, during acute coronary syndromes to detect the possible involvement of an allergic reaction. Conversely, measurement of cardiac biomarkers during anaphylaxis, even without obvious signs of myocardial ischemia, might identify patients at risk of myocardial injury.

Occupational allergy: is there a role for nanoparticles?

All fields of industry are applying nanotechnologies for the development of advanced materials, there¬fore at present the number of workers exposed to nanosized materials are significantly increasing. Unfortunately, protective equipment for nanoparticles (NPs) is of uncertain efficacy so the risk of noxious effects, in particular allergic sensitization, on workers gives many concerns. At the same time, studies of allergic physiopathology demonstrated that the lack of prevention and treatment could result in invalidating dis¬eases that, in case of professional etiology, might imply removal from the job and compensation. Therefore, a deeper knowledge of the role of NPs in inducing allergic diseases is mandatory to implement the risk assessment and preventive measures for nanosafety in the workplace. The possibility that NPs favor, ex¬acerbate or directly induce allergy is being suggested by recent experimental investigations in cellular and animal models. Unfortunately, studies are heterogeneous and few data have received experimental confir¬mation, lacking reproducibility. What comes to attention is the uncertainty about the real plausibility of the observed experimental effects, as there are only a few reported cases of allergy onset or exacerbation for workers exposed to NPs. However, the potential for NPs to induce, favor or exacerbate allergies seems possible even though not completely demonstrated. This should be a greater incentive to carry out appro¬priate epidemiological studies that are lacking and really needed.

Role of Anti-Inflammatory Cytokines on Muscle Mass and Performance Changes in Elderly Men and Women.

OBJECTIVES: Investigate the presence of a correlation between systemic inflammatory profile of community-dwelling individuals and the loss of muscular mass and performance in old age over a 4.5y follow-up, focusing on the role of anti-inflammatory cytokines in muscular changes in elderly. DESIGN: Longitudinal clinical study. SETTING: Subjects were randomly selected from lists of 11 general practitioners in the city of Verona, Italy. PARTICIPANTS: The study included 120 subjects, 92 women and 28 men aged 72.27±2.06 years and with BMI of 26.52±4.07 kg/m2 at baseline. MEASUREMENTS: Six minutes walking test (6MWT), appendicular and leg fat free mass (FFM) as measured with Dual Energy X-ray absorptiometry, were obtained at baseline and after 4.5 years (4.5y) of mean follow-up. Height, weight, body mass index (BMI), and circulating levels of TNFα, IL-4, IL-10, and IL-13 were evaluated at baseline. RESULTS: A significant reduction of appendicular FFM, leg FFM and 6MWT performance (all p<0.001) was observed after 4.5 y follow-up. In a stepwise regression model, considering appendicular FFM decline as dependent variable, lnIL-4, BMI, baseline appendicular FFM, lnTNFα and lnIL-13 were significant predictors of appendicular FFM decline explaining 30.8% of the variance. While building a stepwise multiple regression considering leg FFM as a dependent variable, lnIL-4, BMI and leg FFM were significant predictors of leg FFM decline and explained 27.4% of variance. When considering 6MWT decline as a dependent variable, baseline 6MWT, lnIL-13 and lnTNFα were significant predictors of 6MWT decline to explain 22.9% of variance. CONCLUSIONS: Our study suggest that higher serum levels of anti-inflammatory markers, and in particular IL-4 and IL-13, may play a protective role on FFM and performance maintenance in elderly subjects.

Lipid transfer protein sensitization: reactivity profiles and clinical risk assessment in an Italian cohort.

BACKGROUND: Nonspecific lipid transfer proteins (nsLTPs) represent a major cause of systemic food allergic reactions in the Mediterranean area. This study investigate hierarchical patterns and cluster relationships of IgE sensitization to different nsLTPs, and the relationship to clinical allergy in a large Italian cohort. METHODS: A total of 568 nsLTP-positive subjects after IgE ImmunoCAP-ISAC microarray analysis with Ara h 9, Art v 3, Cor a 8, Jug r 3, Pla a 3, Pru p 3 and Tri a 14 allergens were studied. IgE inhibition experiments were carried out with mugwort and plane tree pollen extracts. RESULTS: Eighty-two per cent of nsLTP-positive participants (94% if <6 years old) were Pru p 3(pos) , and 71% were Jug r 3(pos) . Participants who reacted to >5 nsLTPs reported a higher incidence of food-induced systemic reactions. Only Art v 3 and Pla a 3 (mugwort and plane tree nsLTPs, respectively) were associated with respiratory symptoms, and a correlation was observed between sensitization to pollen and plant food nsLTPs, particularly between Pla a 3 and tree nut/peanut nsLTPs. Co-sensitization to Par j 2 and PR-10 or profilin pan-allergens was associated with a lower prior prevalence of severe food-induced reactions. In inhibition assays, plane and mugwort pollen extracts inhibited 50-100% of IgE binding to food nsLTPs in microarrays. CONCLUSIONS: Testing IgE reactivity to a panel of nsLTP allergens unveils important associations between nsLTP sensitization profiles and clinical presentation and allows the identification of novel cluster patterns indicating likely cross-reactivities and highlighting potential allergens for nsLTP immunotherapy.

Serum sFas/sFasL ratio in systemic lupus erythematosus (SLE) is a function of age.

Fas and Fas ligand (FasL), members of the tumor necrosis factor (TNF) and TNF-receptor (TNFR) families of molecules, are involved in apoptosis. They are expressed in membrane-associated as well as soluble forms (sFas, and sFasL). Apoptotic defects underlie some models of autoimmune diseases, and they have been proposed in the pathogenesis of systemic lupus erythematosus (SLE) a prototypic autoimmune disorder. We measured the serum levels of sFas and sFasL in a series of well characterized SLE patients and devised an index of the two forms which resulted to be associated with age, indicating that apoptosis resistance is modulated during aging, thus explaining the conflicting observations made in previous studies.

The "You Are Not Alone" care program for liver transplantation.

Current clinical practice is based on the principles of efficacy, appropriateness, efficiency, quality, and safety. Compliance with these tenets requires experienced medical and nursing staff, and active participation of patients and their families in the planned therapeutic program. To match patients' expectations on quality and safety of care and spur active participation in the transplant care process, we set up an integrated, multiphase, multidisciplinary care program devoted to liver transplantation (LT) candidates, engrafted patients, and their families: the "Non Sei Solo" care program (You Are Not Alone). The basic principle of the care program was that, to provide efficient and effective education to their patients, health care professionals need to learn how to teach and what to teach, acquire successful communication skills, and monitor the process of education. The methodology encompassed 5 distinct phases: phase 1, exploration of patients' needs, by means of a questionnaire devoted to waitlisted and engrafted patients and their care givers; and phase 2, creation of 16 patient-oriented educational brochures directed to patients and their families. Once created, the educational brochures were presented, discussed, and amended during a consensus meeting involving all transplantation nurses and physicians (phase 3). To acquire the necessary skills and ease communication with patients, the transplantation nurses, physicians, surgeons, and anesthesiologists attended a 6-month counseling course under the tutorial of an expert counselor (phase 4). Finally, in June 2007 the program started officially with monthly meetings with patients and their families, guided hospital tours on patient request, and activation of a toll-free phone number to provide support to patients and answer their questions.

Apoptosis in the homeostasis of the immune system and in human immune mediated diseases.

The immune system has evolved sophisticated mechanisms controlling the development of responses to dangerous antigens while avoiding unnecessary attacks to innocuous, commensal or self antigens. The risk of autoimmunity is continuously checked and balanced against the risk of succumbing to exogenous infectious agents. It is therefore of paramount importance to understand the molecular events linking the breakdown of tolerance and the development of immunodeficiency. Apoptotic mechanisms are used to regulate the development of thymocytes, the shaping of T cell repertoire, its selection and the coordinate events leading to immune responses in the periphery. Moreover, they are at the heart of the homeostatic controls restoring T cell numbers and establishing T cell memory. T lymphocytes shift continuously from survival to death signals to ensure immune responsiveness without incurring in autoimmune damage. In this review we shall consider some key facts on the relationship of lymphopenia to autoreactivity, the mechanisms controlling positive and negative selection in the thymus, the role of apoptosis in selected primary immunodeficiency states and in systemic and organ-specific autoimmunity, with examples from human diseases and their animal models.

An IL-15 dependent CD8 T cell response to selected HIV epitopes is related to viral control in early-treated HIV-infected subjects.

In some early-treated HIV-positive patients, Structured Treatment Interruption (STI) is associated to spontaneous control of viral rebound. Thus, in this clinical setting, we analyzed the immunological parameters associated to viral control. Two groups of early treated patients who underwent STI were retrospectively defined, according to the ability to spontaneously control HIV replication (Controller and Non-controller). Plasma cytokine levels were analyzed by multiplex analysis. CD8 T cell differentiation was determined by polychromatic flow cytometry. Antigen-specific IFN-gamma production was analyzed by ELISpot and intracellular staining after stimulation with HIV-peptides. Long-term Elispot assays were performed in the presence or absence of IL-15. Plasma IL-15 was found decreased over a period of time in Non-Controller patients, whereas a restricted response to Gag (aa.167-202 and 265-279) and Nef (aa.86-100 and 111-138) immunodominant epitopes was more frequently observed in Controller patients. Interestingly, in two Non-Controller patients the CD8-mediated T cells response to immunodominant epitopes could be restored in vitro by IL-15, suggesting a major role of cytokine homeostasis on the generation of protective immunity. In early-treated HIV+ patients undergoing STI, HIV replication control was associated to CD8 T cell maturation and sustained IL-15 levels, leading to HIV-specific CD8 T cell responses against selected Gag and Nef epitopes.

Frailty in the elderly: the physical dimension.

Frailty may be considered as a vulnerable status, which can precede the onset of overt disability. Operational definitions of frailty vary widely according to the conceptual framework: some authors consider frailty in a broad sense, which encompasses the physical, social, cognitive, psychological dimensions and comorbidity, whereas others define the syndrome more restrictively, mainly on the basis of performance parameters, such as gait speed, grip strength and physical activity. All these definitions are provided of a high predictive value for adverse outcomes, such as disability, hospitalization and mortality. Sarcopenia (i.e. the reduction of muscular mass and function) plays a predominant role in the pathogenesis of frailty. Among the factors responsible for sarcopenia (such as proinflammatory cytokines, low growth hormone and testosterone levels, increased production of oxygen free radicals, malnutrition and reduced neurological drive), immobility and lack of exercise have a preponderant role. Therefore, the diagnosis of frailty is mandatory for the early identification of a subset of elderly subjects at high risk, which can receive benefit from rehabilitation. A self-report and objective evaluation of physical performance are the best indicators of frailty in elderly subjects, a poor performance suggesting the need of an early and proper intervention. Structured exercise programs are effective in contrasting the progression of frailty, but an healthy and active lifestyle may be sufficient for delaying the onset of disability. In conclusion, there is clear evidence for prescription of exercise within the mainstream of the medical practice, rather than as an optional adjunct to standard care of the oldest old, given the public health implication of frailty, whose prevalence is going to increase in western populations.

Sarcopenia: age-related skeletal muscle changes from determinants to physical disability.

Human aging is characterized by skeletal muscle wasting, a debilitating condition which sets the susceptibility for diseases that directly affect the quality of life and often limit life span. Sarcopenia, i.e. the reduction of muscle mass and/or function, is the consequence of a reduction of protein synthesis and an increase in muscle protein degradation. In addition, the capacity for muscle regeneration is severely impaired in aging and this can lead to disability, particularly in patients with other concomitant diseases or organ impairment. Immobility and lack of exercise, increased levels of proinflammatory cytokines, increased production of oxygen free radicals or impaired detoxification, low anabolic hormone output, malnutrition and reduced neurological drive have been advocated as being responsible for sarcopenia. It is intriguing to notice that multiple pathways converge on skeletal muscle dysfunction, but the factors involved sometimes diverge to different pathways, thus intersecting at critical points. It is reasonable to argue that the activity of these nodes results from the net balance of regulating mechanisms, as in the case of the GH/IGF-1 axis, the testosterone and cortisol functions, the pro- and anti-inflammatory cytokines and receptors. Both genetic and epigenetic mechanisms operate in regulating the final phenotype, the extent of muscle atrophy and reduction in strength and force generation. It is widely accepted that intervention on lifestyle habits represents an affordable and practical way to modify on a large scale some detrimental outcomes of aging, and particularly sarcopenia. The identification of the molecular chain able to reverse sarcopenia is a major goal of studies on human aging.

Frailty of older age: the role of the endocrine--immune interaction.

The so-called demographic transition has changed the age structure of the population worldwide, with profound effects on societal organization. The growing number and percentage of old and very old people has compelled the scientific community to focus on age related diseases and peculiar consequences of aging itself such as disability and frailty. Understanding the pathophysiology of frailty, a syndrome characterized by a reduced functional reserve and impaired adaptive capacity that results from cumulative declines of multiple subsystems, and causes increased vulnerability to adverse outcomes, is a major topic in aging research. Aging processes induce multiple changes in the hormones network (menopause, andropause, somatopause and adrenopause), in the immune system, and can modulate their efficiency and effectiveness in determining a response to stressors. These triggering events can unmask frailty in older people. Starting from these assumptions, we analyzed the relationship of the endocrine and immune networks in aging and in the different domains that are characteristically associated with the frailty syndrome, such as disability and sarcopenia, as well as in diseases related to aging such as Alzheimer's dementia and Congestive Heart Failure.

Alpha4beta1 and alpha4beta7 CD4 T cell numbers increase and CLA CD4 T cell numbers decrease in systemic sclerosis.

We studied the expression of adhesion molecules affecting recirculation and homing on peripheral blood CD4(+) T cells of patients with systemic sclerosis (SSc), in order to evaluate whether the distribution of tissue targeted subsets could reflect the participation of internal organs or the extent of cutaneous involvement [i.e. limited cutaneous (lc) and diffuse cutaneous (dc)]. Peripheral blood mononuclear cells (PBMC) from 51 patients with SSc and 19 sex- and age-matched controls were investigated by cytofluorimetric analysis for lymphocyte subpopulations carrying the following surface molecules: CD3, CD4, CLA, alpha4beta7 and alpha4beta1. Standard routine biochemistry and clinical examinations were also performed in all patients. We found that both alpha4beta1(+) and alpha4beta7(+) cells within the CD4(+) T cell population were significantly increased, while CLA(+) CD4(+) T cells were significantly reduced in SSc, compared to healthy donors. Significantly lower absolute numbers of alpha4beta7(+) cells were found in lc- compared to dc-SSc. Patients with oesophageal involvement had high numbers of alpha4beta7(+) cells, while those with nephritis also showed low levels of CLA(+) cells. Lung involvement was related directly to alpha4beta1(+) cell numbers and inversely to alpha4beta7(+) CD4 cell numbers. Taken together, our findings demonstrate that distinct CD4(+) T cell populations with selective homing properties show changes from normal distribution in SSc, and such changes are related to clinical expression and organ involvement in the course of the disease.

Cytokine and chemokine levels in systemic sclerosis: relationship with cutaneous and internal organ involvement.

Systemic sclerosis (SSc) is a connective tissue disorder characterized by excessive collagen deposition in the skin and internal organs. Several cytokines and chemokines have been implicated in the induction of fibrosis, but a definitive relationship between specific cytokines and organ involvement has not been established yet. Serum samples, PBMC and T cell lines (TCL) obtained from 54 patients affected by SSc and 20 healthy donors (HD) were examined by ELISA for Interferon-gamma (IFN-gamma ), interleukin (IL)-4, IL-6, IL-10, IL-18, Transforming growth factor (TGF)-beta1, Tumour necrosis factor (TNF)-alpha, sCD30, Macrophage derived chemokine (MDC), Monocyte chemoattractant protein (MCP)-1, Macrophage inflammatory protein (MIP)-1alpha and Regulated on activation normal T-cell expressed and secreted (RANTES). In all the SSc serum samples, we found significantly increased levels of IL6, TNFalpha and MCP-1 but reduced amounts of gamma-IFN and MDC. IL6, IL10, IL18, MIP-1alpha and TNFalpha measured in supernatants from PHA-stimulated PBMC and IL6, MCP-1 and RANTES in supernatants from stimulated TCL were also increased in patients. MDC was decreased in all the biological SSc sources studied. TGF-beta1, IL10, and sCD30 were produced at a significantly lower level by SSc TCL. Serum IL6 and sCD30 levels were significantly increased in dc-SSc patients compared to lc-SSc as were levels of MCP-1 produced by PBMC and IL10 from TCL. We observed a strict relationship between pulmonary fibrosis and IL10, MCP-1 (both from TCL) and serum IL6. Kidney involvement was related to serum MCP-1 levels and IL18 production from PBMC. Oesophageal involvement correlated with MDC production from PBMC and IL10 synthesis by TCL. We showed that IL-6, IL-10, MDC and MCP-1 are variably associated with internal organ involvement and allow the discrimination between limited and diffuse forms of the disease.

Study of immune alterations in patients with chronic fatigue syndrome with different etiologies.

The Chronic Fatigue Syndrome (CFS) is characterized by symptoms lasting for at least six months and accompanied by disabling fatigue. The etiology of CFS is still unclear. At the National Center for Study of the Infectious Diseases Department of the Chieti University some immune investigations were performed with the purpose of detecting markers of the disease. CD4+, CD8+, NK CD56+ and B CD19+ lymphocytes were studied in 92 male and 47 female patients and in 36 control subjects. CFS patients were divided in three groups with a post-infectious onset (PI-CFS), an non post-infectious onset (NPI-CFS) and a non post-infectious onset with associated infections (NPI-CFS + AI). Both CD4+ and CD8+ lymphocytes were reduced in the CFS patients. However, the CD4+/CD8+ ratio was increased in the CFS patients without difference between males and females. CD56+ cells of CFS patients were also reduced. In particular, blood CD56+ cells counts were significantly higher in PI-CFS patients than in the NPI-CFS subjects. These data confirm our preliminary results suggesting a key-role of a dysfunction of the immune system as a precipitating and-or perpetuating factor of the syndrome.

"In vitro" comparative immune effects of different titanium compounds.

Exposure to Ti compounds is today an occupational and environmental health hazard. Object of this study was to determine "in vitro" effects of different Ti salts on cultured human peripheral blood mononuclear cells (PBMC) proliferation and cytokine release. 10(-4) and 10(-7) M Ti compounds did not modify spontaneous PBMC proliferation. Ti dioxide (a biocompatible material and sunscreen component) did not exert effects on phytoemagglutinin (PHA) stimulated PBMC proliferation and on PHA stimulated IFN-gamma and TNF-alpha release from PBMC. On the other hand, 10(-4) M Ti oxalate (with wide industrial applications) and Ti ascorbate (used mainly in agriculture) inhibited about 70% the PHA stimulate PBMC proliferation; both these Ti compounds at 10(-4) and 10(-7) M concentrations significantly inhibited TNF-alpha release, while only Ti oxalate inhibited that of IFN-gamma. Titanocene (used in chemotherapy) did no exert effects on PBMC proliferation but markedly inhibited IFN-gamma and TNF-alpha release. On the whole, this study demonstrates that Ti dioxide is not immunotoxic; Ti oxalate shows marked immunotoxicity; titanocene exerts selective toxicity on cytokine release but not on PBMC proliferation, while Ti ascorbate affects TNF-alpha release from PBMC but not iFN-gamma release. In conclusion, the data show that immunotoxicity fo Ti depends on speciation.

A further evaluation of the clinical use of specific IgE antibody testing in allergic diseases.

BACKGROUND: The evaluation and interpretation of the results from blood tests measuring specific immunoglobulin E (IgE) antibody concentration is currently made using the dichotomized result from the test despite a quantitative result is obtained. It has been shown that different levels of IgE antibodies, assessed by blood test and skin prick test, may have a relation to presence of symptoms, implying that there is more information in a quantitative result than in the dichotomous--positive or negative. OBJECTIVE: To investigate the clinical utility of quantification of IgE antibodies in the diagnosis of allergic patients and whether such procedure has any advantage to the presently dichotomously used sensitivity and specificity at a fixed cut-off. METHODS: Data from a previously published study (R. Paganelli, I.J. Ansoteugi, J. Sastre, C.-E. Lange, M.H.W.M. Roovers, H. de Groot, N.B. Lindholm, P.W. Ewan, Allergy, 1998; 53) analysing diagnosis of allergic patients in four different clinics were re-evaluated. In the original study consecutive patients with suspected IgE-mediated allergy had been examined and evaluated according to the clinical routine at each clinic, using case history, physical examination, skin tests and laboratory tests, except the test to be evaluated, and given a "doctors' allergen-specific diagnosis" as positive or negative. In the present study the relation between "doctors' allergen-specific diagnosis", expressed as pos/neg, and the quantitative levels of specific IgE antibody concentration was analysed using a logistic regression model. This presentation of results was also compared with the more common characteristics of sensitivity and specificity, and also with Receiver-operator characteristics (ROC) curves. RESULTS: The used logistic model described the relationship between allergen-specific diagnosis in each study and the levels of IgE antibodies. The shape of the curve illustrated the physicians' disposition for a positive diagnose in the study, in relation to the specific IgE antibody level. Differences in the shape of the curve was found both between allergens within clinics and between clinics for the same allergen. No association could be demonstrated between prevalence and shape of the curve. CONCLUSIONS: Conventional sensitivity/specificity figures or ROC concepts only use the qualitative statement of whether IgE is present or not. A risk assessment using the quantitative level of IgE antibody to an allergen increases the utility of the information in clinical context compared with a qualitative statement of whether IgE is present or not. The quantification demonstrated the link between specific IgE antibodies and allergic reactions. The use of objective, well performing quantitative tests should help improve diagnostic accuracy and might provide a way for the patient to understand and manage his or her daily situation and risk for reactions.