A dose response study was carried out with piglets to examine the effects of increasing amounts of Fusarium toxins in the diet on performance, clinical serum characteristics, organ weights and residues of zearalenone (ZON) and deoxynivalenol (DON) and their metabolites in body fluids and tissues. For this purpose, Fusarium toxin contaminated maize (1.2 mg ZON and 8.6 mg DON per kg maize) was incorporated into a maize based diet for piglets at 0, 6, 12.5, 25 and 50% at the expense of control maize. The experimental diets were tested on 100 female piglets allotted to 20 boxes (five animals per box) covering a body weight range of 12.4 +/- 2.2 kg to 32.5 +/- 5.6 kg. Voluntary feed intake and, consequently, body weight gain of the animals receiving the highest proportion of Fusarium toxin contaminated maize were significantly decreased while the feed conversion ratio was not affected by the treatment. The mean weight of the uterus related to the body weight of the animals of the same group was increased by almost 100% as compared to the control. For this group, significantly decreased values of total serum protein were determined, while the serum activity of the liver enzyme glutamate dehydrogenase and the serum concentration of the follicle stimulating hormone were decreased for all treatment groups receiving 6% contaminated maize or more in the diet. Serum concentrations of immuneglobulins were not consistently altered by the treatment. Corresponding to the dietary exposure, increasing concentrations of ZON and alpha-zearalenol were detected in the bile fluid, liver and in pooled urine samples. The metabolite beta-zearalenol was detected only in bile fluid. The total concentration of ZON plus its metabolites in bile fluid correlated well with the diet contamination (r = 0.844). DON was found in serum, bile fluid and pooled urine samples while de-epoxy-DON was detected only in urine. The serum concentration of DON correlated well with the respective toxin intake 3-4 h prior to slaughtering (r = 0.957). For all mentioned analyses of residues it has to be noted that toxin residues were detectable even if negligible concentrations were present in the diet.
In most cases, the endometrioid adenocarcinoma of the endometrium is preceded by hyperplasia with different risk of progression into carcinoma. The original histologic slides from 560 consecutive cases with complex and atypical hyperplasia were re-examined to assess the interobserver-correlation. The hyperplasias were analyzed separately for their likelihood of progression to carcinoma in patients with and without progestogen hormonal therapy. In all cases, a fractional re-curreting was performed to establish the state of the disease. The leading symptom was vaginal bleeding in 65.5% of the cases in the postmenopausal period. Eighty-six percent of the patients presented with obesity (BMI > 30 kg/m(2)), 23% had had an exogeneous use of estrogens. Twenty-two cases were reclassified as simple hyperplasia and excluded from further analysis. The interobserver-correlation was 91% for complex, 92% for atypical hyperplasia, and 89% for endometrioid carcinoma, representing an overall correlation of 90%. Two percent of the cases with complex hyperplasia (8/390) progressed into carcinoma and 10.5% into atypical hyperplasia. Fifty-two percent of the atypical hyperplasias (58/112) progressed into carcinomas. In the case of progestogen treatment (n = 208; P < 0.0001) 61.5% showed remission confirmed by re-curetting, compared with 20.3% of the cases without hormonal treatment (n = 182; P < 0.0001). Endometrial hyperplasia without atypia is likely to respond to hormonal treatment. Especially in postmenopausal situation, atypical hyperplasia should be treated with total hysterectomy.
Imaging of fundus AF in patients with age-related maculopathy allows identification of different patterns of fundus AF. Our preliminary data suggest that a patchy pattern of AF indicates a relatively high risk of progression to age-related macular degeneration with visual loss.
Two feeding experiments with female weaned piglets were carried out applying a complete two by two factorial design to investigate the effects of the dietary inclusion of 500 g/kg Fusarium toxin contaminated maize (8.6 mg/kg deoxynivalenol (DON); 1.2 mg/kg zearalenone (ZON)) and of 4 g/kg aluminosilicate (AS) as a detoxifying agent. The resulting four diets were fed ad libitum to a total of 80 piglets (20 piglets per group, allotted to a total of 20 pens) covering a live weight range of 10.5 +/- 1.3 to 27.5 +/- 4.4 kg in experiment 1, and to a total of 48 piglets (12 piglets per group, allotted to 12 pens) covering a live weight range of 9.7 +/- 1.8 to 21.4 +/- 4.8 kg in experiment 2. The animals of experiment 1 were slaughtered on days 34-36 of feeding the experimental diets. The mycotoxin analyses revealed that the control maize also contained considerable concentrations of Fusarium toxins, but the differences in DON and ZON concentrations between control and contaminated diets were sufficiently high to demonstrate both dose-related toxin effects. Voluntary feed intake and live weight gain of the animals were significantly reduced by the inclusion of Fusarium toxin contaminated maize into the diets in both experiments, while a significantly decreased feed to gain ratio was found in experiment 1. Furthermore, the relative weight of the uterus, stomach and heart of the animals fed the contaminated maize containing diets were significantly increased. Serum albumin concentrations and the activity of GLDH were significantly reduced by the inclusion of the contaminated maize. The addition of AS to the Fusarium toxin contaminated diets did not prevent or alleviate any of the mentioned effects. Moreover, the feed intake tended to be decreased by this supplementation in both experiments, while a significantly decreased feed to gain ratio was indicated for this factor in experiment one as well. The serum concentration of albumin and the activities of ASAT and gammaGT were significantly increased if AS was present in the diets while serum concentration of cholesterol and alpha-tocopherol were decreased significantly or in tendency, respectively. The concentrations of retinol and retinyl esters in liver and serum were not altered by the treatments. The analysed concentrations of zearalenone (ZON) and its metabolites in the bile fluid clearly indicated the differences in dietary ZON concentrations and showed that AS was ineffective in preventing the absorption of the toxin from the gastrointestinal tract. Also, serum concentrations of DON reflected the DON intake prior to sampling. However, there were no differences between groups fed diets with or without AS which also suggests the inefficacy of the tested AS in preventing the DON absorption. The present investigations failed to demonstrate a detoxifying capacity of the tested additive and emphasize the general necessity for a critical verification of detoxifying agents in vivo.
Aim-To investigate eVects of photodynamic therapy (PDT) on human choroidal neovascularisation (CNV).Methods-Two patients with recurrences after PDT with verteporfin underwent surgical extraction of the CNV. Immediately after surgical excision the subfoveal neovascular membranes were divided for light microscopic and for electron microscopic processing. For light microscopy tissues were embedded in paraYn. Sections were stained with haematoxylin and eosin, and the periodic acid SchiV (PAS) reaction was performed to determine histological diagnosis and to ensure tissue quality. For electron microscopy the specimens were fixed in glutaraldehyde and embedded in epoxy resin. Semithin sections were stained with uranyl acetate and lead citrate and examined with a transmission electron microscope. Results-Light microscopy showed thick fibrovascular membranes in both cases. On the outer surface remnants of retinal pigment epithelial cells resting on thickened inner aspect of Bruch's membrane were found. On the retinal side some outer segments were found. The membrane showed areas with irregularly shaped vessels. Electron photomicrographs showed occluded vessels within the CNV containing thrombotic masses and/or ultrastructural damage of the neovascular endothelium. Most of the vessels presented regressive changes with vacuolisation and fragmentation of the neovascular endothelium accompanied by disintegration of the endothelial cell layer. Extravasation of red blood cells was observed. Occasionally, vessels with normal endothelium containing intact red blood cells were observed. Some vessels contained immature endothelial cells. At some locations the retinal pigment epithelium cells (RPE) were metaplastic showing highly vacuolised cytoplasm. Conclusions-These findings suggest that the evidence of fluorescein leakage from the CNV and enlargement of the neovascular complex following PDT could be related to new vessel growth and recanalisation of occluded vessels. Additionally, RPE disturbances were observed in the specimens. This finding may be related to the original pathology or could indicate that PDT treatment may result in RPE atrophy. Age related macular degeneration (AMD) is the leading cause of new blindness in the elderly, and choroidal neovascularisation (CNV) is responsible for 80% of severe visual loss in patients with AMD.
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