Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity.

Understanding mechanisms of aging and determinants of life span will help to reduce age-related morbidity and facilitate healthy aging. Average lifespan has increased over the last centuries, as a consequence of medical and environmental factors, but maximal life span remains unchanged. Extension of maximal life span is currently possible in animal models with measures such as genetic manipulations and caloric restriction (CR).

Equation reliability of soil ingestion estimates in mass-balance soil ingestion studies.

Exposure to chemicals from ingestion of contaminated soil may be an important pathway with potential health consequences for children. A key parameter used in assessing this exposure is the quantity of soil ingested, with estimates based on four short longitudinal mass-balance soil ingestion studies among children. The estimates use trace elements in the soil with low bioavailability that are minimally present in food.

Toxicology rewrites its history and rethinks its future: giving equal focus to both harmful and beneficial effects.

This paper assesses how medicine adopted the threshold dose-response to evaluate health effects of drugs and chemicals throughout the 20th century to the present. Homeopathy first adopted the biphasic dose-response, making it an explanatory principle. Medicine used its influence to discredit the biphasic dose-response model to harm homeopathy and to promote its alternative, the threshold dose-response.

Meta-analysis of mass-balance studies of soil ingestion in children.

Ingestion of soil by young children may be an important source of exposure to environmental contaminants. Estimates of soil ingestion have been made by several studies using trace elements in a mass-balance approach, but differ substantially between studies and trace elements. We conduct a meta-analysis of four major mass-balance soil ingestion studies conducted on children between one and seven in the summer/fall in the northern United States.

Key studies used to support cancer risk assessment questioned.

This paper reassessed studies conducted under the leadership of Drosophila geneticist Curt Stern which played a pivotal role in the acceptance of the linear dose-response model by the U.S. National Academy of Sciences Biological Effects of Atomic Radiation (BEAR) I Committee and the subsequent generalization of their recommendations on the linearity dose-response paradigm for ionizing radiation and chemically induced cancer.

The effects of iridium on the renal function of female Wistar rats.

Despite the widespread use of iridium (Ir) in catalytic converters for improved capacity for reducing carbon monoxide (CO), hydrocarbon (HC) and nitrogen oxide (NO(x)) emissions, there is a lack of studies that have assessed possible toxicological hazards of exposure to Ir. The present investigation indicates that female Wistar rats exposed to Ir in the drinking water for 90 days displayed renal toxicity based on the elevated urinary retinol binding protein (RBP) and albumin. The RBP was more sensitive to albumin, showing significant increases at 0.

Muller's Nobel lecture on dose-response for ionizing radiation: ideology or science?

In his Nobel Prize Lecture of December 12, 1946, Hermann J. Muller argued that the dose-response for radiation-induced germ cell mutations was linear and that there was "no escape from the conclusion that there is no threshold". However, assessment of correspondence between Muller and Curt Stern 1 month prior to his Nobel Prize Lecture reveals that Muller knew the results and implications of a recently completed study at the University of Rochester under the direction of Stern, which directly contradicted his Nobel Prize Lecture.

The hormesis database: the occurrence of hormetic dose responses in the toxicological literature.

In 2005 we published an assessment of dose responses that satisfied a priori evaluative criteria for inclusion within the relational retrieval hormesis database (Calabrese and Blain, 2005). The database included information on study characteristics (e.g.

Stem cell mobilization in patients with newly diagnosed multiple myeloma after lenalidomide induction therapy.

Lenalidomide has raised concerns regarding its potential impact on the ability to collect stem cells for autologous stem cell transplantation, especially after prolonged exposure. The use of cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells may overcome this concern. In newly diagnosed multiple myeloma (MM) patients, we investigated the influence of lenalidomide on stem cell collection.

Evidence for hormesis in mutagenicity dose-response relationships.

This study assessed the occurrence of hormetic dose responses from three previously published data sets [1-3] with 825 chemicals in three Ames assay tester strains (i.e., TA97, TA98, TA100) with and without the S9 fraction, using a five dose protocol and semi-log dose spacing.

A potential role for the PD1/PD-L1 pathway in the neuroinflammation of Alzheimer's disease.

The interaction between PD1 on T lymphocytes and PD-L1 on antigen presenting cells (APC) modulates the balance between inflammation and tolerance by inducing IL-10 production and apoptosis of antigen-specific cells. We analyzed the PD1/PD-L1 pathway, annexin V (AV)-expression, and proliferation in amyloid-beta (Aβ)-stimulated PBMC of patients with Alzheimer's disease (AD) (N = 35) or mild cognitive impairment (MCI) (N = 30) and of age-matched healthy controls (HC; N = 30). Results showed that PD1-expressing CD4(+) T cells, density of PD-L1 on CD14(+) APC, IL-10 production, and PD-L1-expressing/IL-10-producing CD14(+) APC were significantly reduced in AD and MCI patients compared to HC.

Hormesis provides a generalized quantitative estimate of biological plasticity.

Phenotypic plasticity represents an environmentally-based change in an organism's observable properties. Since biological plasticity is a fundamental adaptive feature, it has been extensively assessed with respect to its quantitative features and genetic foundations, especially within an ecological evolutionary framework. Toxicological investigations on the dose-response continuum (i.

Small bowel capsule endoscopy vs conventional techniques in patients with symptoms highly compatible with Crohn's disease.

Background & Aims: The diagnostic role of Small Bowel Capsule Endoscopy (SBCE) in Crohn's Disease (CD) is under investigation. In a prospective study we investigated the diagnostic role of SBCE in patients with symptoms highly compatible with CD and undefined diagnosis after conventional techniques.

Methods: From September 2005 to May 2009, all patients with clinically suspected CD and not conclusive diagnosis after Ileocolonoscopy (IC), Small Bowel Follow Through (SBFT) and Small Intestine Contrast Ultrasonography (SICUS) were enrolled.

Assessment of non-cirrhotic portal hypertension associated with thiopurine therapy in inflammatory bowel disease.

Thiopurines represent an effective and widely used immunosuppressant in the therapeutic armamentarium of inflammatory bowel disease. However up to 25% of patients may be unable to continue the drug due to side effects. The incidence of hepatotoxicity associated with thiopurine use is reported between 0% and 32%.

Immunocompetent cell functions in Ph+ acute lymphoblastic leukemia patients on prolonged Imatinib maintenance treatment.

Imatinib mesylate (Imatinib) is a potent inhibitor of defined tyrosine kinases and is effectively used for the treatment of malignancies characterized by the constitutive activation of these tyrosine kinases, such as Philadelphia chromosome-positive (Ph(+)) leukemias and gastrointestinal stromal tumors. Suppressive as well as stimulating effects of this drug on T lymphocytes or dendritic cells (DC), which play a major role in immune tumor surveillance, have been reported. For this reason, we questioned whether Imatinib could also affect the phenotypic and functional properties of these subpopulations in Ph(+) acute lymphoblastic leukemia (ALL) patients on prolonged Imatinib maintenance treatment.

Exposure to nanoparticles and hormesis.

Nanoparticles are particles with lengths that range from 1 to 100 nm. They are increasingly being manufactured and used for commercial purpose because of their novel and unique physicochemical properties. Although nanotechnology-based products are generally thought to be at a pre-competitive stage, an increasing number of products and materials are becoming commercially available.

Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer's disease.

Inflammatory mediators are responsible for the neuroinflammation observed in Alzheimer's disease (AD), a phenomenon that might be the culprit of disease or, possibly, a reaction to pathology. To better investigate inflammation in AD we performed an extensive immunophenotypic and functional analysis of amyloid-beta (Aβ) stimulated T lymphocytes in patients with a diagnosis of AD comparing data to those obtained in individuals with mild cognitive impairment (MCI) or aged-matched healthy individuals (HC). Results showed that IL-21- and IL-9-producing Aβ stimulated CD4(+) T cells, as well as IL-23- and IL-6-producing monocytes and CD4(+) T cells expressing the RORγ and NFATc1 transcriptional factors (TF), were significantly increased, whereas IL-10-producing monocytes were decreased in AD.

Endoscopic vs ultrasonographic findings related to Crohn's disease recurrence: a prospective longitudinal study at 3 years.

Background And Aims: Ileocolonoscopy (IC) is the gold standard for assessing Crohn's Disease (CD) recurrence after ileo-colonic resection. In a prospective longitudinal study we compared findings related to CD recurrence when using techniques visualizing either the luminal or the extraluminal surface (IC and small bowel follow through, SBFT vs Small Intestine Contrast Ultrasonography, SICUS).

Methods: From 2003 to 2008, 25 CD patients undergoing ileo-colonic resection were enrolled.

Dose response biology: the case of resveratrol.

Resveratrol often displays hormesis-like biphasic dose responses. This occurs in a broad range of biological models and for numerous endpoints of biomedical interest and public health concern. Recognition of the widespread occurrence of the hormetic nature of many of the responses of resveratrol is important on multiple levels.

Resveratrol commonly displays hormesis: occurrence and biomedical significance.

Resveratrol induces hormetic dose responses in a wide range of biological models, affecting numerous endpoints of biomedical and therapeutic significance. These responses were reported for numerous human tumor cell lines affecting breast, prostate, colon, lung, uterine and leukemia. In such cases, low concentrations of resveratrol enhanced tumor cell proliferation whereas higher concentrations were inhibitory.

Cellular stress responses, mitostress and carnitine insufficiencies as critical determinants in aging and neurodegenerative disorders: role of hormesis and vitagenes.

The widely accepted oxidative stress theory of aging postulates that aging results from accumulation of oxidative damage. A prediction of this theory is that, among species, differential rates of aging may be apparent on the basis of intrinsic differences in oxidative damage accrual. Although widely accepted, there is a growing number of exceptions to this theory, most contingently related to genetic model organism investigations.

Predicting low dose effects for chemicals in high through-put studies.

High through-put studies commonly use automated systems with 96-well plates in which multiple chemicals are tested at multiple doses using log-2 dose increments after a suitable incubation period. There are typically multiple (ranging from five to eleven) doses on each chemical, and occasionally plate replications of the dose-response studies. The target endpoint for such studies is typically the LC50, but for some chemicals, there may be multiple doses below a benchmark dose where there is no apparent adverse response relative to control response.