The effect of omega-3 polyunsaturated fatty acids on the inflammatory response of the amnion.

OBJECTIVE: To investigate the effect of omega-3 PUFAs, eicosapentanoic acid (EPA) and docosohexanoic acid (DHA) on inflammatory cytokine production in the amnion. STUDY DESIGN: Amnion explants were obtained at elective caesarean sections and cultured in vitro with EPA and DHA. IL-8 and IL-6 secretion was determined by ELISA, the role of PPARγ was investigated using specific agonists and antagonists and activity of MMP assessed by gelatin zymography. RESULTS: A combination of EPA and DHA significantly reduced the concentration of IL-8 and IL-6 released into the supernatant compared to untreated controls (p<0.001). Stimulation of PPARγ with troglitazone reduced IL-8 production, and the PPARγ antagonist GW9662 partially reversed this effect. The activity of MMP-9 was also significantly reduced by treatment with EPA and DHA in combination compared to untreated control (p<0.05). CONCLUSION: The omega-3 PUFAs EPA and DHA decrease the inflammatory response of the amnion, and this may be partially mediated through PPARγ.

Clinically relevant fatigue in men with hormone-sensitive prostate cancer on long-term androgen deprivation therapy.

BACKGROUND: The purpose of the study was to determine the prevalence and associations of clinically relevant fatigue (CRF) in men with biochemically controlled prostate cancer on long-term androgen deprivation therapy (ADT). PATIENTS AND METHODS: One hundred and ninety-eight men were surveyed and the prevalence of CRF (Brief Fatigue Inventory score >3) determined. Associations with other measures (Hospital Anxiety and Depression Scale; International Prostate Symptom Score; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; Brief Pain Inventory worst pain; clinical and demographic information) were explored in univariate and multivariate analyses. RESULTS: Eight-one per cent (160 of 198) of questionnaires were analysable. CRF prevalence was 43% (68 of 160). CRF associations included moderate/severe urinary symptoms, anxiety and medical co-morbidities; the strongest associations were depression [odds ratio (OR) 9.8, 95% confidence interval (CI) 4.3-22.8] and pain (OR 9.2, 95% CI 4.0-21.5). After controlling for other factors, the independent associations were depression (OR 4.7, 95% CI 1.6-14.0) and pain (OR 3.1, 95% CI 1.0-8.9). There was no association with age, disease burden or treatment duration. CONCLUSIONS: Two-fifths of men with biochemically controlled prostate cancer on long-term ADT report CRF that interferes with function. Management aimed at improving CRF should address depression and pain.

Synergy between vitamin D precursor 25-hydroxyvitamin D and short chain ceramides on keratinocyte proliferation and differentiation.

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25D), and its analogs induce normal human keratinocyte differentiation and are used for the treatment of psoriasis. Long-term topical use of 1,25D, however, causes hypercalcemia. The precursor of 1,25D, 25-hydroxyvitamin D3 (25D) is converted to 1,25D in the keratinocyte in a regulated manner. The action of 1,25D is reported to be mediated, at least in part, by cellular ceramides in the leukemia cell line, HL-60 cells. Therefore, in this study we evaluated the synergy between 25D and short chain cell permeable ceramides (SCC) or synthetic analogs of ceramides on keratinocyte growth and differentiation in vitro. C2 ceramide (acetyl sphingosine) synergistically enhanced the growth inhibitory effect of 25D and 1,25D in a concentration-dependent manner. Short chain analogs of ceramide-like compounds, neoceramides and pseudoceramides, also inhibited keratinocyte proliferation and acted in synergy with 25D and 1,25D. SCC alone increased transglutaminase and cornified envelope levels. 25D potentiated this prodifferentiating effect of SCC. Twenty-four-hour preincubation with SCC did not alter 25D or 1,25D uptake into keratinocytes. These studies demonstrate a synergy between vitamin D metabolites and ceramides in human keratinocytes and indicate the potential of using 25D as an effective and safer alternative to deliver 1,25D benefits to the epidermis.

Late ultrastructural changes in the retina of the rat following low-dose X-irradiation.

This study describes ultrastructural changes in the pigmented hooded Lister rat retina, 3-12 months following X-irradiation with single doses of between 200 and 2000 cGy. The extreme radiosensitivity of the photoreceptor cells was underlined by the continued manifestation of fine structural changes and cell death up to 6 months post-radiation in animals receiving doses above 500 cGy. The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy. One year after irradiation with 1500 cGy the retinal vasculature showed capillary occlusion with some evidence of recanalisation. Telangiectasia was observed in the large retinal veins. Although the inner retinal neurones and glial cells showed no evidence of direct radiation damage, the nerve fibre layer adjacent to occluded retinal vessels demonstrated ultrastructural evidence of ischaemic neuropathy and retinal oedema. At doses above 1500 cGy the choriocapillaris showed platelet aggregation and capillary loss.

In vitro viability of choroidal melanomata following pre-enucleation irradiation.

In a group of eighteen patients with uveal melanomas, seven underwent low-dose pre-enucleation irradiation of approximately 2000 cGy. All the tumours were propagated in tissue culture and the growth characteristics of tumour cells from irradiated eyes were compared with tumour cells from non-irradiated eyes. Cultures were observed with phase-contrast microscopy, and radioactive thymidine labelling was used to study cell turnover. Although tissue samples from peripheral areas of irradiated tumours produced a mixture of viable and non-viable cells, with reduced ability to attach to substrate, central regions of irradiated tumours contained viable cells which propagated freely in tissue culture.

Early ultrastructural changes after low-dose X-irradiation in the retina of the rat.

In this study Lister rats were given doses of X-rays ranging from 200-2,000 Rads to the retina of one eye, sacrificed at various time intervals between one hour and one month later and the irradiated eye processed for electron microscopy. The rod photoreceptor cells were by far the most radiosensitive cells in the retina, their outer segments showing distinctive membrane damage at one hour after 200 Rads of X-rays. Photoreceptor cell death was not seen at doses less than 1,000 Rads in the time period of the experiment. The retinal pigment epithelial (RPE) cells showed damage in the form of mitochondrial swelling but only in doses over 500 Rads. Retinal pigment epithelial cell loss did not occur under 2,000 Rads. The inner retinal neurones, glial elements and the retinal vasculature did not show any ill effects in the time period of this study.