Trophic interactions of fish communities at midwater depths enhance long-term carbon storage and benthic production on continental slopes.

Biological transfer of nutrients and materials between linked ecosystems influences global carbon budgets and ecosystem structure and function. Identifying the organisms or functional groups that are responsible for nutrient transfer, and quantifying their influence on ecosystem structure and carbon capture is an essential step for informed management of ecosystems in physically distant, but ecologically linked areas. Here, we combine natural abundance stable isotope tracers and survey data to show that mid-water and bentho-pelagic-feeding demersal fishes play an important role in the ocean carbon cycle, bypassing the detrital particle flux and transferring carbon to deep long-term storage. Global peaks in biomass and diversity of fishes at mid-slope depths are explained by competitive release of the demersal fish predators of mid-water organisms, which in turn support benthic fish production. Over 50% of the biomass of the demersal fish community at depths between 500 and 1800 m is supported by biological rather than detrital nutrient flux processes, and we estimate that bentho-pelagic fishes from the UK-Irish continental slope capture and store a volume of carbon equivalent to over 1 million tonnes of CO2 every year.

Identifying migrations in marine fishes through stable-isotope analysis.

The isotopic composition of many elements varies across both land and ocean surfaces in a predictable fashion. These stable-isotope ratios are transferred into animal tissues, potentially providing a powerful natural geospatial tag. To date, most studies using stable isotopes as geolocators in marine settings have focussed on mammals and seabirds conducting large ocean-basin scale migrations. An increasing understanding of isotopic variation in the marine environment, and improved sampling and analytical techniques, however, means that stable isotopes now hold genuine promise as a natural geolocation tag in marine fishes. Here, the theoretical background underpinning the use of stable isotopes of C, N and O in otolith, scale and muscle tissues as geolocation tools in the marine environment is reviewed, and examples of their applications are provided.

Philosophical and ethical issues in human organ transplantation.

Organ transplantation has moved over 30 years from being experimental and heroic to being the treatment of choice in many terminal diseases of vital organs, such as biliary atresis, which would require a liver transplant, or pulmonary fibrosis, which would require a heart/lung transplant. There are now many more older and chronically sick people than ever before (Hudak et al, 1998). Transplantation offers hope for an improved quality of life. All patients have a right to care, although there remains a dichotomy between the holistic model of care and the medical model. The UKCC's (1992) Code of Professional Conduct informs practice, and clauses 1 and 5 are of particular importance in relation to this client group. This article looks at some of the problems patients may develop pre- and post-transplant and the support required to overcome or minimize these problems. Implications for healthcare staff are considered.

A single measurement of CD38CD8 cells in HIV+, long-term surviving injecting drug users distinguishes those who will progress to AIDS from those who will remain stable.

This study compares the predictive power of a single measurement of CD8+CD38+, CD8+CD45RO+ or CD8+CD38+CD45RO+ subpopulations in predicting progression to AIDS in a cohort of HIV+ long-term surviving injecting drug users. The results showed that both the total CD8+ percentage, and the CD8+CD38+ and CD8+CD38+CD45RO+ subpopulations of cells all individually predicted progression to AIDS. In combination with CD4, only the CD8+CD38+ subpopulation enhanced the predictive power of the CD4 percentage alone. The CD8+ percentage correlated negatively with the CD4 percentage and the CD8+CD45RO+ subpopulation did not predict disease progression. The proportion of CD8+CD38+ cells identified which patients with a moderate CD4 level were more likely to progress to AIDS, and conversely, which patients with a low CD4 count were likely to remain clinically stable. The results were consistent irrespective of whether time was measured from the date of seroconversion, or from the date of the test. This study is the first to measure these markers in HIV-infected injecting drug users, and in long-term survivors. The results demonstrate the considerable added value of the CD8+CD38+ cell percentage over the CD4 count alone, in predicting HIV clinical progression.

Breast reduction outcome study.

The outcome of 75 consecutive bilateral breast reduction procedures on 73 patients (65 inferior pedicle and 9 superior pedicle with inverted-T closure, and 1 ultrasonic-assisted lipoplasty) is evaluated. Fifty-six surveys at an average follow-up of 35 months, 36 standardized examinations at an average follow-up of 31 months, 52 paired preoperative/postoperative photographs, and 73 chart reviews comprise the data. Mean age at surgery was 32 years. Of the patients surveyed, there were 51 whites, 18 blacks, and 4 other races. The majority of survey respondents reported improvement in breast appearance (93%), self-esteem (85%), posture (84%), and activity level (77%). The percentage of patients free of back pain rose from 9% preoperatively to 59% postoperatively. Some decrease in nipple sensitivity was noted by survey in 34 nipple-areolar complexes (31%), and clinical examination detected decreased sensitivity in 16% of nipples. Thirty-one percent of patients reported improvement in their intimate relationship postoperatively and 65% reported no change. Ninety-five percent felt they had made the right decision in having breast reduction surgery. Physical examination revealed excellent maintenance of shape and impressive fading of surgical scars over the years in the majority of patients. The postoperative aesthetic result depends on several important preoperative factors, including skin tone, breast shape, and degree of ptosis. Adverse sequelae included infection (1.3%), nipple cyanosis (1.3%) but no nipple-areolar necrosis, and wound dehiscence (4.0%) but no skin flap necrosis. Late complications included underresection requiring reoperation (4.0%), fat necrosis (2.7%), hypertrophic scars (6.7%), and pseudoptosis (12.0%). Breast reduction surgery results in a good outcome for most patients, with high patient satisfaction. Patients are accepting of the large T-pattern scar that fades surprisingly well with time in exchange for symptomatic relief and substantial improvement in breast size and shape.

Sucrose acetate isobutyrate (SAIB): three-generation reproduction study in the rat and teratology studies in the rat and rabbit.

A three-generation reproduction study of sucrose acetate isobutyrate (SAIB) in Fischer 344 rats and teratology studies in Fischer 344 rats and New Zealand white rabbits were performed. Dietary SAIB concentrations to provide dose levels of 0, 0.5, 1.0 and 2.0 g/kg body weight were used for the rat studies, and 0, 0.5, 0.85 and 1.2 g/kg body weight doses of SAIB in corn oil were administered by gavage in the rabbit studies. F0 generation male rats were fed SAIB for 10 wk, and female rats were fed SAIB for 2 wk prior to mating. F1 generation rats were raised on the test diets to maturity, mated to produce F2a litters, and remated to produce the F2b litters that were examined for teratology. F2a rats were mated to study fertility indices for the F3 pregnancy. A decrease in female fertility compared with controls was noted at the highest dose of SAIB during breeding of the F1 generation to produce the F2a litters. No difference in fertility rate between controls and treated animals was noted in the results of the other three matings that were performed, and it was concluded that the reduction in female fertility was not related to SAIB treatment. No morphological abnormalities of soft tissue or skeleton were observed in the rat or rabbit teratology studies. The highest dose levels administered, 2.0 g SAIB/kg body weight in the rat and 1.2 g SAIB/kg body weight in the rabbit, were considered to be no-observed-adverse effect levels (NOAEL).

Oral toxicity and carcinogenicity studies of sucrose acetate isobutyrate (SAIB) in the Fischer 344 rat and B6C3F1 mouse.

Sucrose acetate isobutyrate (SAIB), a food additive used as a flavour emulsion stabilizer in citrus-based soft drinks, was evaluated for chronic toxicity in B6C3F1 mice and Fischer 344 rats. SAIB dissolved in acetone was blended into NIH07 rodent diet at concentrations that were adjusted weekly during the first 12 to 18 months of the studies so that ingested dose levels per kg body weight were constant. Groups of 20 rats per sex were given dose levels of 0.0, 0.0, 0.5, 1.0 and 2.0 g SAIB/kg body weight for 1 yr, and groups of 50 rats per sex were given dose levels of 0.0, 0.0, 0.5, 1.0 and 2.0 g SAIB/kg body weight for 2 yr. Mice were fed dose levels of 0.0, 0.0, 1.25, 2.5 and 5.0 g SAIB/kg body weight for 2 yr. The highest doses fed, equivalent to dietary concentrations of approximately 5%, were considered to be the maximum concentrations that could be fed without risk of nutritional deficiencies. Depressions in body weight gain were noted, particularly in female rats during the first 12 to 18 months of the studies. Recovery during the last quarter of the 2-yr study suggests that the reduced body weight gain was nutritional rather than SAIB-related. There were no differences in survival between SAIB-treated rats or mice and controls. Decreased body weight gains, primarily in females, but less consistent than those in the rat, were noted in the 2-yr mouse study. No signs of toxicity were observed in clinical chemistry, haematology, organ weights, gross necropsy findings or light microscopy studies in the 1- or 2-yr rat studies. Electron microscopic examinations of liver sections from high dose level rats from the 1-yr study also revealed no effects of SAIB treatment. There were no significant increases in benign or malignant tumours in the long-term rat or mouse carcinogenicity studies. The lowest no-observed-adverse-effect level (NOAEL) was 2 g SAIB/kg body weight derived from the 1- and 2-yr chronic toxicity studies in the rat.

Toxicity studies of Caramel Colour III and 2-acetyl-4(5)-tetrahydroxybutylimidazole in F344 rats.

Caramel Colour III is used as a colour additive in beers and a variety of foods. Beer is the most important single source of Caramel Colour III in the diet although consumption of dark beers has been decreasing in recent years. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has established an acceptable daily intake of 200 mg/kg/day for Caramel Colour III. The safety of Caramel Colour III has been questioned during recent years following feeding studies in the rat that were associated with reduced white cell and lymphocyte counts. These effects have been attributed to the presence of 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI) in this class of caramel colour. Short-term oral toxicity studies were conducted on low-THI and high-THI samples of Caramel Colour III (13 wk) and on a sample of THI (28 days). In both studies, the test materials were mixed with demineralized water and the solutions were given to the animals ad lib. in the drinking fluid. In the 13-wk subchronic toxicity study of Caramel Colour III, groups of 20 rats/sex were given concentrations of caramel colour equivalent to intakes of 0, 10, 15 or 20 g low-THI caramel colour/kg body weight/day or 20 g/kg of a high-THI caramel colour. In the 4-wk toxicity study with THI, groups of 20 rats/sex were given 0, 8 or 64 ppm THI (equivalent to approx. 0, 0.9 or 7.2 mg/kg/day) and 10 rats/sex were given 1, 2, 4, 16 or 32 ppm THI (equivalent to approx. 0.1, 0.2, 0.5, 1.9 or 3.7 mg/kg/day) for 4 wk followed by a 2-wk recovery phase for 10 rats/sex in the 0, 8 and 64 ppm groups. Rats given Caramel Colour III had soft faeces; there were no other treatment-related clinical observations and no treatment-related deaths occurred. All treated groups given Caramel Colour III had lower food and fluid consumption than controls. Males given 15 or 20 g low-THI caramel colour/kg or 20 g high-THI caramel colour/kg and females given 20 g/kg of either type had lower body weights than controls. In the 4-wk toxicity study with THI, there were no treatment-related ante-mortem observations, and no effects on body weights or food consumption. Fluid consumption by males and females treated with 64 ppm THI was lower than that of controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Toxicity and carcinogenicity studies of Caramel Colour IV in F344 rats and B6C3F1 mice.

Caramel Colour IV, a type of caramel colour used in the manufacture of cola soft drinks, was evaluated for subchronic and chronic toxicity in rats, and carcinogenicity in Fischer-344 (F344) rats and B6C3F1 mice. In each of the studies, Caramel Colour IV was mixed with demineralized water and the solutions given to the animals ad lib. in the drinking fluid. The concentrations of Caramel Colour IV in the drinking fluid were adjusted periodically to achieve the desired caramel colour intake per kg body weight. In the range-finding studies, groups of 30 rats/sex were given Caramel Colour IV at levels of 0, 15, 20, 25 or 30 g/kg for 13 wk, and groups of 10 male rats were given levels of 0, 2.5, 5, 10 or 15 g/kg for 6 wk followed, for some dose groups, by a 2-wk withdrawal period, and then re-initiation of dosing for another 2 wk. In the rat chronic toxicity study, levels of Caramel Colour IV of 0, 2.5, 5, 7.5 or 10 g/kg were given to groups of 25 rats/sex for 12 months. The test groups in the rat and mouse carcinogenicity studies were composed of 50 animals/sex and each species was given the caramel colour at levels of 0, 0, 2.5, 5 or 10 g/kg for 24 months. In each of the studies, treated animals tended to have dose-related lower water consumption than controls. This was attributed to poor palatability of the drinking fluid, and was generally associated with decreased food consumption and body weights. Rats given caramel colour often had soft or liquid malodorous faeces although there were no treatment-related ante-mortem observations in mice. Blood biochemical changes in the rat (i.e. reduced blood urea nitrogen, alkaline phosphatase and total serum protein) appeared to be related to dietary influences and were not considered toxicologically significant. There were no treatment-related alterations in haematological variables or treatment-related differences in survival or in the incidence of benign or malignant tumours among treated and control groups and no toxicologically important pathological findings. On the basis of these studies, Caramel Colour IV was not toxic or carcinogenic in F344 rats or B6C3F1 mice. The highest dose level tested in the long-term studies (10 g/kg) was considered to be the no-observed-adverse-effect level (NOAEL).

Subchronic toxicity study of Caramel Colour II in F344 rats.

Caramel Colour II is a distinct type of colourant with a pronounced reddish hue. It is made with sulphite reactants but without ammonia. The red colour and a high alcohol solubility provide functional characteristics that are important in foods or beverages containing natural flavour extractives. Caramel Colour II is widely used in ice creams and liqueurs; however, it represents less than 1% of total caramel colour manufacture. The toxicity of Caramel Colour II was evaluated in a 13-wk study in Fischer-344 (F344) rats. The test material was mixed with demineralized water and the solutions were given to the animals ad lib. in the drinking fluid. The concentrations of caramel colour in the drinking fluid were adjusted periodically to achieve the desired caramel colour intake/kg body weight/day. Groups of 20 rats/sex were given Caramel Colour II at levels of 0, 4, 8, 12 or 16 g/kg for at least 13 wk. There were no deaths in any of the groups fed Caramel Colour II. All rats fed caramel colour had soft faeces. All treated groups also had lower fluid consumption that was attributed to poor palatability of the high concentrations of caramel colour that were fed. A number of changes observed (reduced food consumption in all treatment groups except males given 4 g/kg; significantly lower body weights for males given 12 g/kg or more and for females given 8 g/kg or more; lower urine volume and higher specific gravity) were attributed to the reduced water intake and not considered to be toxicologically significant. There were no consistent treatment-related alterations in haematology or blood chemistry variables, and random changes noted were not associated with macroscopic or microscopic pathological alterations. There were no toxicologically important pathological findings. Based on this study, Caramel Colour II was not toxic in F344 rats treated for 13 wk. The highest dose level tested in this study (16 g/kg) was considered to be the no-observed-adverse-effect level.

Subchronic toxicity studies in dogs and in utero rats fed diets containing Bacillus stearothermophilus alpha-amylase from a natural or recombinant DNA host.

Beagle dogs and Fischer 344 rats were fed diets containing 0, 36 or 72 units Bacillus stearothermophilus alpha-amylase (Bsa)/g food or of Bacillus subtilis alpha-amylase (cBsa)/g food. The dogs (four/sex/group) received treated diets for 13 wk. For the rat studies, the parental (F0) generation (12 males and 24 females/group for the Bsa study, and 26 rats/sex/group for the cBsa study) received treated diets for 13 or 4 wk, respectively, before breeding and through weaning of the F1 pups; 20 F1 rats/sex/group received treated diets for at least 13 wk (from weaning until necropsy). There were no treatment-related antemortem observations, reproductive effects or ophthalmic, haematological, macroscopic or microscopic findings in treated dogs or rats, and no differences were noted in body weights for dogs or parental rats. Mean body weights of F1 pups from F0 rats exposed to 72 units cBsa/g were significantly lower than those of the control animals on lactation day 28. This effect may have been related to the slight reduction in body weights and significant reduction in food consumption (gestation days 14-20) of the F0 dams. However, this did not continue into the growth phase for the F1 generation. In the Bsa studies, there were no treatment-related effects in clinical pathology values, and organ-weight data did not correlate with macroscopic or microscopic findings. Male dogs given cBsa had significantly lower albumin (36 units/g), calcium (36 and 72 units/g) and inorganic phosphorus (72 units/g) values compared with those of the control males; there were no treatment-related changes in blood chemistry values in rats. Based on the results of these studies, the no-observable-effect level for alpha-amylase fed to dogs or rats is 36 units/g food.

Subchronic toxicity studies in dogs and in utero-exposed rats fed diets containing Bacillus megaterium amylase derived from a recombinant DNA organism.

Subchronic toxicity studies were performed using a food-grade enzyme product from a recombinant Bacillus subtilis containing the B. megaterium amylase gene. Beagle dogs (four/sex/group) and Fischer 344 rats (25/sex/group) were fed diets containing 0, 20, 60 or 100 units amylase/g food. The dogs received treated diets for 13 wk. The parental (F0) rats received treated diets for 4 wk before breeding and through weaning of the F1 pups; 25 F1 rats/sex/group received treated diets for at least 13 wk (from weaning until necropsy). All animals appeared healthy throughout the studies. Treated animals had sporadic significant differences in body weight and food consumption values when compared with those of controls, but they were not considered toxicologically meaningful. There were no treatment-related effects on reproduction indices, growth variables or litter data in rats. There were no changes in clinical pathology values, organ weights or macroscopic and microscopic observations that were related to treatment. Based on the results of this study, the no-observable-effect level for this amylase fed to dogs or rats is no less than 100 units/g food. This is 6000-12,700 times the predicted human use level.

Evaluation of 60 chemicals in a preliminary developmental toxicity test.

The number of chemicals in commerce which have not been evaluated for potential developmental toxicity is large. Because of the time and expense required by conventional developmental toxicity tests, an abbreviated assay is needed that will preliminarily evaluate otherwise untested chemicals to help prioritize them for conventional testing. A proposed short-term in vivo assay has been used in a series of studies in which a total of 60 chemicals were tested. Some were independently tested two or four times each. In this preliminary test, pregnant mice were dosed during mid-pregnancy and were then allowed to deliver litters. Litter size, birth weight, and neonatal growth and survival to postnatal day 3 were recorded as indices of potential developmental toxicity. Results in this assay and conventional mouse teratology tests were generally concordant. Conventional data were available for 14 chemicals (ten teratogens, one fetotoxin, three nonteratogens), of which 11 (nine teratogens, one fetotoxin, one nonteratogen) produced evidence of developmental toxicity. This included conventional data for three chemicals (ethylene glycol, diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether) that were untested before the present study. As high priority candidates for conventional testing on the basis of results here, all were subsequently studied in a standard teratology assay and were confirmed to be teratogenic in mice. Additionally, one of them (ethylene glycol) plus a fourth high priority candidate for conventional study (diethylene glycol monomethyl ether) were subsequently tested in rats and were found to be teratogenic in that species.

Three-generation reproduction study of rats ingesting up to 10% sorbitol in the diet--and a brief review of the toxicological status of sorbitol.

Groups of 12 male and 24 female 5-wk-old Charles River CD (SD) BR rats (F0) were fed a sucrose-containing ground cereal-based diet in which 0, 2.5, 5.0 and 10.0% (w/w) sorbitol was included at the expense of sucrose. The rats were first mated after 14 wk on the diet. F1a litters were born 19 wk after the start of the study and F1b litters at wk 30. Groups of 12 male and 24 female F1b rats were first mated when 18 wk old. They gave rise to F2a litters after 3 wk and to F2b litters 10 wk later. Likewise, groups of 12 male and 24 female F2b rats were first mated when 18 wk old, producing F3a and F3b litters 3 wk and 10 wk later, respectively. F0 rats were killed 33 wk after the start of the study, F1a in wk 22, F1b in wk 68, F2a in wk 57, F2b in wk 92 and F3a in wk 96. Apart from slight reductions in food consumption in sorbitol-fed F1b males and in body-weight gain in sorbitol-fed F0, F1b and F2b rats of both sexes, treatment was associated with no clinically observed effects. There were no deaths attributable to treatment and no adverse effects on mating performance or pregnancy rates in the parent animals of any generation. Treatment was associated with no consistent adverse effect on any measure of reproductive performance or behaviour during gestation or lactation. No abnormal pups were observed in any generation. Not unexpectedly, caecal enlargement was consistently observed at necropsy of sorbitol-treated rats of all generations and significant rises in serum calcium were observed in F0 males and females exposed to 10% sorbitol and in F1b males exposed to either 5 or 10% sorbitol. Differences between treated and control F3a rats in respect of T3 and TSH levels were probably spurious as they followed no consistent pattern. Similarly, between-group variations in gonadal weight were considered to have no toxicological significance because they lacked consistency and were not accompanied by any histologically-evident changes. Microscopic examination of lesions from F1a and F2a animals, of gonads from F1b and F2b and of selected tissues from the F3a generation revealed no changes of toxicological significance.(ABSTRACT TRUNCATED AT 400 WORDS)