Electronic properties of a-CNx thin films: An x-ray-absorption and photoemission spectroscopy study

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Tamoxifen and the Rafoxifene analog LY117018: their effects on arachidonic acid release from cells in culture and on prostaglandin I(2 )production by rat liver cells

BACKGROUND: Tamoxifen is being used successfully to treat breast cancer. However, tamoxifen also increases the risk of developing endometrial cancer in postmenopausal women. Raloxifene also decreases breast cancer in women at high risk and may have a lower risk at developing cancer of the uterus. Tamoxifen has been shown to stimulate arachidonic acid release from rat liver cells. I have postulated that arachidonic acid release from cells may be associated with cancer chemoprevention. METHODS: Rat liver, rat glial, human colon carcinoma and human breast carcinoma cells were labelled with [(3)H] arachidonic acid. The release of the radiolabel from these cells during incubation with tamoxifen and the raloxifene analog LY117018 was measured. The prostaglandin I(2 )produced during incubation of the rat liver cells with μM concentrations of tamoxifen and the raloxifene analog was quantitatively estimated. RESULTS: Tamoxifen is about 5 times more effective than LY117018 at releasing arachidonic acid from all the cells tested. In rat liver cells only tamoxifen stimulates basal prostaglandin I(2 )production and that induced by lactacystin and 12-O-tetradecanoyl-phorbol-13-acetate. LY117018, however, blocks the tamoxifen stimulated prostaglandin production. The stimulated prostaglandin I(2 )production is rapid and not affected either by preincubation of the cells with actinomycin or by incubation with the estrogen antagonist ICI-182,780. CONCLUSIONS: Tamoxifen and the raloxifene analog, LY117018, may prevent estrogen-independent as well as estrogen-dependent breast cancer by stimulating phospholipase activity and initiating arachidonic acid release. The release of arachidonic acid and/or molecular reactions that accompany that release may initiate pathways that prevent tumor growth. Oxygenation of the intracellularly released arachidonic acid and its metabolic products may mediate some of the pharmacological actions of tamoxifen and raloxifene

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Orally available Mn porphyrins with superoxide dismutase and catalase activities

Superoxide dismutase/catalase mimetics, such as salen Mn complexes and certain metalloporphyrins, catalytically neutralize reactive oxygen and nitrogen species, which have been implicated in the pathogenesis of many serious diseases. Both classes of mimetic are protective in animal models of oxidative stress. However, only AEOL11207 and EUK-418, two uncharged Mn porphyrins, have been shown to be orally bioavailable. In this study, EUK-418 and several new analogs (the EUK-400 series) were synthesized and shown to exhibit superoxide dismutase, catalase, and peroxidase activities in vitro. Some also protected PC12 cells against staurosporine-induced cell death. All EUK-400 compounds were stable in simulated gastric fluid, and most were substantially more lipophilic than the salen Mn complexes EUK-189 and EUK-207, which lack oral activity. Pharmacokinetics studies demonstrate the presence of all EUK-400 series compounds in the plasma of rats after oral administration. These EUK-400 series compounds are potential oral therapeutic agents for cellular damage caused by oxidative stress

Bear bile: dilemma of traditional medicinal use and animal protection

Bear bile has been used in Traditional Chinese Medicine (TCM) for thousands of years. Modern investigations showed that it has a wide range of pharmacological actions with little toxicological side effect and the pure compounds have been used for curing hepatic and biliary disorders for decades. However, extensive consumption of bear bile made bears endangered species. In the 1980's, bear farming was established in China to extract bear bile from living bears with "Free-dripping Fistula Technique". Bear farming is extremely inhumane and many bears died of illness such as chronic infections and liver cancer. Efforts are now given by non-governmental organizations, mass media and Chinese government to end bear farming ultimately. At the same time, systematic research has to be done to find an alternative for bear bile. In this review, we focused on the literature, laboratory and clinical results related to bear bile and its substitutes or alternative in English and Chinese databases. We examined the substitutes or alternative of bear bile from three aspects: pure compounds derived from bear bile, biles from other animals and herbs from TCM. We then discussed the strategy for stopping the trading of bear bile and issues of bear bile related to potential alternative candidates, existing problems in alternative research and work to be done in the future

Promoting optimal parenting and children’s mental health : a preliminary evaluation of the How-to Parenting Program

Parenting quality is widely accepted as a primary predictor of children’s mental health. The present study examined the effectiveness of a parenting program in fostering optimal parenting and child mental health. The selected program was How to talk so kids will listen & listen so kids will talk (How-to Parenting Program). This program was selected because its content corresponds closely to what the parenting style literature suggests is optimal parenting (i.e., includes structure, affiliation and autonomy support). Eleven groups of six to twelve parents were conducted in 7 local grade schools. The program, offered by two trained leaders, consisted of eight weekly sessions and taught a total of 30 skills. A total of 82 parents completed questionnaires both prior to and after the program. Participants’ children between eight and 12 years old (N = 44) completed questionnaires at school, at both assessment points. Repeated measures ANOVAs using parent reports indicated that structure, affiliation and autonomy support were increased after the program, compared to baseline. The level of child internalizing and externalizing problems also decreased significantly. Importantly, children reports confirmed that parental autonomy support increased from pre to post-test and child-reported well-being improved as well. The preliminary evidence from this pre-test versus post-test repeated measures design suggests that the How-to Parenting Program is effective in improving parenting style and in promoting children’s mental health and that future evaluation research examining the potential of this program is warranted

Preconditioning-induced ischemic tolerance: a window into endogenous gearing for cerebroprotection

Ischemic tolerance defines transient resistance to lethal ischemia gained by a prior sublethal noxious stimulus (i.e., preconditioning). This adaptive response is thought to be an evolutionarily conserved defense mechanism, observed in a wide variety of species. Preconditioning confers ischemic tolerance if not in all, in most organ systems, including the heart, kidney, liver, and small intestine. Since the first landmark experimental demonstration of ischemic tolerance in the gerbil brain in early 1990's, basic scientific knowledge on the mechanisms of cerebral ischemic tolerance increased substantially. Various noxious stimuli can precondition the brain, presumably through a common mechanism, genomic reprogramming. Ischemic tolerance occurs in two temporally distinct windows. Early tolerance can be achieved within minutes, but wanes also rapidly, within hours. Delayed tolerance develops in hours and lasts for days. The main mechanism involved in early tolerance is adaptation of membrane receptors, whereas gene activation with subsequent de novo protein synthesis dominates delayed tolerance. Ischemic preconditioning is associated with robust cerebroprotection in animals. In humans, transient ischemic attacks may be the clinical correlate of preconditioning leading to ischemic tolerance. Mimicking the mechanisms of this unique endogenous protection process is therefore a potential strategy for stroke prevention. Perhaps new remedies for stroke are very close, right in our cells

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference