Skin sensitization in silico protocol.

The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework.

Evaluation of the potential anti-cancer activity of the antidepressant sertraline in human colon cancer cell lines and in colorectal cancer-xenografted mice.

Evidence has been provided of the anti-proliferative activity of certain antidepressants, mainly the selective serotonin reuptake inhibitors (SSRIs). We tested the effect of different antidepressants on cell viability and proliferation of human colorectal carcinoma cell lines HT29 and the multi-drug resistant (MDR) LS1034. The SSRIs, paroxetine and sertraline, induced a dose-dependent inhibition of cell viability and proliferation in the two cell lines (IC50 8-15 micro M).

Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: possible relevance to depression and hyperactive-immune disorders.

Antidepressants have been found to possess antiproliferative effect. In the immune system depression may activate pro-inflammatory cytokines. Therefore, the aim of this study was to assess the immunomodulatory activity of antidepressants in naïve rat.

Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression.

Antidepressants have an antiproliferative effect in some cell lines. Depression may be associated with activation of some pro-inflammatory cytokines. Therefore, we evaluated the ex-vivo immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) in T cells.

Differential attenuation of oxidative/nitrosative injuries in early prostatic neoplastic lesions in TRAMP mice by dietary antioxidants.

Background: Dietary antioxidants with yet unproven efficacies in averting prostate cancer (PCa) are widely used in the United States as preventives. Experimental evidence establishing a causal relationship between oxidative and nitrosative stress (OS/NS) and PCa development and showing its modulation by dietary antioxidants would help justify their usage.

Methods: The TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) mouse model was used to demonstrate the OS/NS-associated damage, as evident by 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE)-protein-adducts and nitrotyrosine (Ntyr), in prostatic premalignant lesions, and to evaluate the antioxidant efficacy of various dietary supplements [natural antioxidant (NAO) from spinach extracts, (-) epigallocatechin-3-gallate (EGCG), or N-acetylcystein (NAC)] during the early PCa development.

Halofuginone inhibits serum-stimulated pericardial tissue retraction in vitro.

We developed an in vitro model of tissue contraction in which living pericardium, in response to serum, contracted and the cells in situ expressed proliferating cell nuclear antigen (PCNA) and synthesized collagen. Here we evaluated the effects of halofuginone on these serum-stimulated pericardial tissue responses. Parietal pericardium was incubated with media containing increasing doses of halofuginone and evaluated for tissue contraction, evident by tissue curling.

Composition, efficacy, and safety of spinach extracts.

Spinach leaves, containing several active components, including flavonoids, exhibit antioxidative, antiproliferative, and antiinflammatory properties in biological systems. Spinach extracts have been demonstrated to exert numerous beneficial effects, such as chemo- and central nervous system protection and anticancer and antiaging functions. In this review article, we present a compilation of data generated in our laboratories and those of other investigators describing the chemical composition of spinach, its beneficial effects, relative safety information, and its recommended inclusion in the human diet.

A natural antioxidant mixture from spinach does not have estrogenic or antiestrogenic activity in immature CD-1 mice.

The use of natural antioxidants and flavonoids in nutritional and pharmaceutical applications is increasing. Because some phytochemicals such as genistein, found in soy products, have estrogenic activity, we investigated the estrogenic potential of a natural antioxidant mixture (NAO) isolated from spinach leaves, using an in vivo uterotrophic bioassay and an in vitro transcriptional activation assay for the estrogen receptor (ER). Outbred female CD-1 mice (17 d old) were given subcutaneous injections of 17beta-estradiol or genistein [500 and 500,000 microg /(kg x d), respectively] as positive controls or NAO [1000 to 1,000,000 microg/(kg x d)] for 3 d.

Forestomach tumor induction by 2,4-hexadienal in F344N rats and B6C3F1 mice.

2,4-Hexadienal (2,4-Hx) was studied for its toxicity and carcinogenicity because of its alpha, beta-unsaturated aldehyde structure and potential link between exposure to lipid peroxidation products in the diet and human malignancies. Male and female F344N rats and B6C3F1 mice received 2,4-Hx in corn oil by gavage for 16 days, 14 weeks, or 2 years. In the 16-day studies 2,4-Hx induced forestomach necrosis and ulceration at 240 mg/kg and forestomach epithelial hyperplasia at 80 mg/kg in rats and mice.

Slowing tumorigenic progression in TRAMP mice and prostatic carcinoma cell lines using natural anti-oxidant from spinach, NAO--a comparative study of three anti-oxidants.

The TRAMP model and human prostatic cancer (PCA) cell lines DU145 and PC3 are useful forchemopreventive studies. We compared the efficacy of 3 anti-oxidants [a water-soluble natural anti-oxidant. NAO (200 mg/kg).