Egg production, egg quality, organ weight, bone ash, and plasma metabolites in 30-week-old Lohmann LSL lite hens fed corn and soybean meal-based diets supplemented with enzymatically treated yeast.

Highly prolific modern hens are susceptible to metabolic disorders that could be modulated by functional feedstuffs such as enzymatically treated yeast (ETY). Therefore, we assessed the dose-response of ETY on hen-day egg production (HDEP), egg quality attributes, organ weight, bone ash, and plasma metabolites in laying hens. A total of 160 thirty-week-old Lohmann LSL lite hens were placed in 40 enriched cages (4 birds/cage) based on body weight (BW) and allocated to 5 diets in a completely randomized design for a 12-wk trial. The diets were isocaloric and isonitrogenous corn and soybean meal based supplemented with 0.0, 0.025, 0.05, 0.1, or 0.2% ETY. Feed and water were provided ad libitum; HDEP and feed intake (FI) were monitored weekly, whereas egg components, eggshell breaking strength (ESBS), and thickness (EST) were monitored biweekly, and albumen IgA concentration was measured on wk 12. At the end of the trial, 2 birds/cage were bled for plasma and necropsied for liver, spleen, and bursa weight, ceca digesta for short chain fatty acids (SCFA) and tibia and femur for ash content. Supplemental ETY reduced HDEP quadratically (P = 0.03); the HDEP was 98, 98, 96, 95, and 94% for 0.0, 0.025, 0.05, 0.1, and 0.2% ETY, respectively. However, ETY linearly and quadratically (P = 0.01) increased egg weight (EW) and egg mass (EM). Specifically, EM was 57.9, 60.9, 59.9, 58.9, and 59.2 g/b for 0.0, 0.025, 0.05, 0.1, and 0.2% ETY, respectively. Egg albumen increased linearly (P = 0.01), and egg yolk decreased linearly (P = 0.03) in response to ETY. In response to ETY, the ESBS and plasma Ca increased linearly and quadratically (P ≤ 0.03). Plasma concentration of total protein and albumin increased quadratically (P ≤ 0.05) with ETY. Diets had no (P > 0.05) effects on FI, FCR, bone ash, SCFA, and IgA. In conclusion, 0.1% or higher ETY reduced egg production rate; however, linear improvement in EW and shell quality linked to larger albumen and higher plasma protein and Ca suggested modulation in protein and calcium metabolism.

Enzymatically treated yeast bolstered growth performance of broiler chicks from young broiler breeders linked to improved indices of intestinal function, integrity, and immunity.

Older breeder chicks (OBC) are heavier and robust at hatch than younger breeder chicks (YBC). However, the implications of broiler breeder age on chick intestinal function and the role of functional feedstuffs are unexplored. We evaluated the effects of broiler breeder age and the impact of feeding YBC enzymatically treated yeast on growth, nutrient utilization, and indices of intestinal function. Fertile Ross 708 eggs: 2,250 (56.5 ± 3.4g) from 30-wk-old (YBC) and 550 (64.2 ± 4.2 g) from 47-wk-old (OBC) were hatched and placed in 48 pens (44 chicks/pen) containing equal males and females for growth and intestinal function evaluation and 36 cages (5 chicks/cage) for metabolizable energy (AME). Five corn and soybean meal-based diets were formulated to contain 0, 0.05, 0.10, 0.20, and 0.40% HY40 for a 3-phase feeding program (starter: days 0-10, grower: days 11-24, and finisher; days 25-42). Grower phase diets also contained a 0.3% TiO2 indigestible marker. The diets were allocated within YBC in a completely randomized block design (n = 8 for pens; n = 6 for cages). The OBC were fed a 0% yeast diet. Feed and water were provided freely; BW and feed intake were monitored, and excreta samples were collected on days 17 to 21 for apparent retention (AR). Birds were necropsied for plasma, jejunal tissues, organs weight, and ceca digesta. The OBC were heavier (P < 0.01) than YBC at hatch. Final BW of OBC and YBC fed, ≥0.10% yeast, was similar (P > 0.05). The OBC had similar FCR (P > 0.05) to YBC fed 0 to 0.10% yeast but higher (P = 0.003) than for YBC fed ≥0.20% yeast. Jejunal villi height to crypt depth ratio (VCR) and IgA were higher in OBC than 0% yeast (P = 0.01). Yeast increased VCR, bursa weight, jejunal, and plasma IgA (P = 0.01). The YBC fed ≥0.10% yeast had higher (P < 0.05) AR of crude protein, and gross energy than OBC and YBC fed 0 or 0.05% yeast. In conclusion, yeast improved YBC performance to the level of OBC linked to improved intestinal function, integrity, and immunity.

Dead or alive: sediment DNA archives as tools for tracking aquatic evolution and adaptation.

DNA can be preserved in marine and freshwater sediments both in bulk sediment and in intact, viable resting stages. Here, we assess the potential for combined use of ancient, environmental, DNA and timeseries of resurrected long-term dormant organisms, to reconstruct trophic interactions and evolutionary adaptation to changing environments. These new methods, coupled with independent evidence of biotic and abiotic forcing factors, can provide a holistic view of past ecosystems beyond that offered by standard palaeoecology, help us assess implications of ecological and molecular change for contemporary ecosystem functioning and services, and improve our ability to predict adaptation to environmental stress.

Marine resource abundance drove pre-agricultural population increase in Stone Age Scandinavia.

How climate and ecology affect key cultural transformations remains debated in the context of long-term socio-cultural development because of spatially and temporally disjunct climate and archaeological records. The introduction of agriculture triggered a major population increase across Europe. However, in Southern Scandinavia it was preceded by ~500 years of sustained population growth. Here we show that this growth was driven by long-term enhanced marine production conditioned by the Holocene Thermal Maximum, a time of elevated temperature, sea level and salinity across coastal waters. We identify two periods of increased marine production across trophic levels (P1 7600-7100 and P2 6400-5900 cal. yr BP) that coincide with markedly increased mollusc collection and accumulation of shell middens, indicating greater marine resource availability. Between ~7600-5900 BP, intense exploitation of a warmer, more productive marine environment by Mesolithic hunter-gatherers drove cultural development, including maritime technological innovation, and from ca. 6400-5900 BP, underpinned a ~four-fold human population growth.

Lake eutrophication and its implications for organic carbon sequestration in Europe.

The eutrophication of lowland lakes in Europe by excess nitrogen (N) and phosphorus (P) is severe because of the long history of land-cover change and agricultural intensification. The ecological and socio-economic effects of eutrophication are well understood but its effect on organic carbon (OC) sequestration by lakes and its change overtime has not been determined. Here, we compile data from ~90 culturally impacted European lakes [~60% are eutrophic, Total P (TP) >30 µg P l(-1) ] and determine the extent to which OC burial rates have increased over the past 100-150 years. The average focussing corrected, OC accumulation rate (C ARFC ) for the period 1950-1990 was ~60 g C m(-2) yr(-1) , and for lakes with >100 µg TP l(-1) the average was ~100 g C m(-2) yr(-1) . The ratio of post-1950 to 1900-1950 C AR is low (~1.5) indicating that C accumulation rates have been high throughout the 20th century. Compared to background estimates of OC burial (~5-10 g C m(-2) yr(-1) ), contemporary rates have increased by at least four to fivefold. The statistical relationship between C ARFC and TP derived from this study (r(2) = 0.5) can be used to estimate OC burial at sites lacking estimates of sediment C-burial. The implications of eutrophication, diagenesis, lake morphometry and sediment focussing as controls of OC burial rates are considered. A conservative interpretation of the results of the this study suggests that lowland European meso- to eutrophic lakes with >30 µg TP l(-1) had OC burial rates in excess of 50 g C m(-2) yr(-1) over the past century, indicating that previous estimates of regional lake OC burial have seriously underestimated their contribution to European carbon sequestration. Enhanced OC burial by lakes is one positive side-effect of the otherwise negative impact of the anthropogenic disruption of nutrient cycles.

Spectroscopic (multi-energy) CT distinguishes iodine and barium contrast material in MICE.

OBJECTIVE: Spectral CT differs from dual-energy CT by using a conventional X-ray tube and a photon-counting detector. We wished to produce 3D spectroscopic images of mice that distinguished calcium, iodine and barium. METHODS: We developed a desktop spectral CT, dubbed MARS, based around the Medipix2 photon-counting energy-discriminating detector. The single conventional X-ray tube operated at constant voltage (75 kVp) and constant current (150 microA). We anaesthetised with ketamine six black mice (C57BL/6). We introduced iodinated contrast material and barium sulphate into the vascular system, alimentary tract and respiratory tract as we euthanised them. The mice were preserved in resin and imaged at four detector energy levels from 12 keV to 42 keV to include the K-edges of iodine (33.0 keV) and barium (37.4 keV). Principal component analysis was applied to reconstructed images to identify components with independent energy response, then displayed in 2D and 3D. RESULTS: Iodinated and barium contrast material was spectrally distinct from soft tissue and bone in all six mice. Calcium, iodine and barium were displayed as separate channels on 3D colour images at <55 microm isotropic voxels. CONCLUSION: Spectral CT distinguishes contrast agents with K-edges only 4 keV apart. Multi-contrast imaging and molecular CT are potential future applications.

Time-dependent effects of imatinib in human leukaemia cells: a kinetic NMR-profiling study.

The goal of this study was to evaluate the time course of metabolic changes in leukaemia cells treated with the Bcr-Abl tyrosine kinase inhibitor imatinib. Human Bcr-Abl(+) K562 cells were incubated with imatinib in a dose-escalating manner (starting at 0.1 microM with a weekly increase of 0.1 microM imatinib) for up to 5 weeks. Nuclear magnetic resonance spectroscopy and liquid-chromatography mass spectrometry were performed to assess a global metabolic profile, including glucose metabolism, energy state, lipid metabolism and drug uptake, after incubation with imatinib. Initially, imatinib treatment completely inhibited the activity of Bcr-Abl tyrosine kinase, followed by the inhibition of cell glycolytic activity and glucose uptake. This was accompanied by the increased mitochondrial activity and energy production. With escalating imatinib doses, the process of cell death rapidly progressed. Phosphocreatine and NAD(+) concentrations began to decrease, and mitochondrial activity, as well as the glycolysis rate, was further reduced. Subsequently, the synthesis of lipids as necessary membrane precursors for apoptotic bodies was accelerated. The concentrations of the Kennedy pathway intermediates, phosphocholine and phosphatidylcholine, were reduced. After 4 weeks of exposure to imatinib, the secondary necrosis associated with decrease in the mitochondrial and glycolytic activity occurred and was followed by a shutdown of energy production and cell death. In conclusion, monitoring of metabolic changes in cells exposed to novel signal transduction modulators supplements molecular findings and provides further mechanistic insights into longitudinal changes of the mitochondrial and glycolytic pathways of oncogenesis.

The 20th century whole-basin trophic history of an inter-drumlin lake in an agricultural catchment.

Eight 1-m sediment cores were extracted from across the basin of Friary Lough, a 5.4-ha eutrophic lake in a wholly grassland agricultural catchment in Co. Tyrone, Northern Ireland. Sedimentary TP, diatom inferred TP, Ca, Na, Fe, Mn, loss-on-ignition (LOI), dry weight and density were determined in the core profiles. Core dating and correlation gave a 210Pb, 137Cs and 241Am chronology from 1906 to 1995 and enabled a whole-basin estimate of chemical and sediment accumulation rate over the 20th Century. The major changes for all parameters occurred after c. 1946. Sediment accumulation rate was most influenced by organic matter accumulations, probably of planktonic origin, and increasing after c. 1946. Inorganic sediment accumulation rate was found to be largely unchanging through the century at 10 t km(-2) yr(-1) when expressed as catchment exports. All chemical accumulation rate changes occurred after c. 1946. Total phosphorus accumulation rate, however, was found to be the only chemical to be increasing throughout the epilimnion and hypolimnion areas of the sedimentary basin at an average of 22.5 mg m(-2) yr(-1) between 1946 and 1995. The other chemical parameters showed increasing accumulation rates after c. 1946 in the epilimnion part of the basin only. Interpreted in terms of whole-basin sedimentation and catchment export processes over time, it is suggested that diffuse TP inputs are independent of sediment inputs. This corresponds to hydrochemical models that suggest soluble P as the primary fraction that is lost from grassland catchments. The increase in sedimentary TP accumulation rate, and DI-TP concentration, are also explained with regard to current models that suggest increases in runoff P concentrations from elevated soil P concentrations. Increases in eplimnion chemical and sediment accumulation rate after c. 1946 may be due to local erosion that has limited impact on lake basin sedimentation.

Herbal remedy poisoning presenting with acute abdomen and raised urine porphyrins.

We describe a case of lead poisoning due to herbal remedies, presenting with an acute abdomen, raised porphyrins and increased liver enzyme activities. We suggest that lead poisoning should be considered in the differential diagnosis of the 'acute abdomen', and that the presence of liver dysfunction points to the possibility of Asian herbal remedies as the source of the lead poisoning.

Modeling diffuse phosphorus loads from land to freshwater using the sedimentary record.

Diffuse phosphorus (P) loads to a small lake, Friary Lough, in a 1 km2 agricultural subcatchment were quantified over 90 years using a palaeolimnological model. The model assumes that lake total phosphorus (TP) is lost to the sediments and to the lake outflow during periods of steady-state or is also stored within the water column during periods of non-steady-state behavior. Reconstructed TP loads during the 1991-1995 time interval of 2.05-2.53 g m-2 yr-1 are verified by hydrochemical monitoring results from the lake inflow during 1997-1998. This provides evidence for the accuracy of the palaeolomnological model and also that TP loads to the lake can be accounted for from external catchment runoff. An analysis of the TP load data in terms of catchment exports shows that there was a linear rate of increase from ca. 1946 to 1995 of 1.20-1.56 kg km-2 yr-1. The rate of increase is similar to river P load data in the larger 1480 km2 catchment taken over 17 years. The rate of TP increase to the lake is interpreted with regard to current soil P models that propose increasing and threshold soil P concentrations as the cause for increasing diffuse P loss in runoff.

Cholesterol biosynthesis regulation and protein changes in rat liver following treatment with fluvastatin.

The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is a key regulator in cholesterol biosynthesis and HMG CoA reductase inhibitors (statins) have become a widely prescribed family of lipid lowering agents. Cholesterol synthesis occurs predominantly in liver which is the target organ of statins. We studied the effects of fluvastatin (Lescol), a member of the statin family, on hepatic protein regulation. Male F344 rats treated with 0.8 mg/kg per day fluvastatin or 24 mg/kg per day fluvastatin for 7 days showed treatment-related changes in 58 liver proteins (P<0.005). Major effects were evident in the cholesterol biosynthesis pathway including the induction of enzymes upstream and downstream of the target enzyme HMG CoA reductase. Treatment also triggered alterations in key enzymes of carbohydrate metabolism and was associated with changes in a heterogeneous set of cellular stress proteins involved in cytoskeletal structure, calcium homeostasis and protease activity. The latter set of protein alterations indicates that hepatotoxicity is associated with high-dose treatment. Based on the results it is suggested that HMG-CoA synthase and isopentenyl-diphosphate delta-isomerase may be explored as alternative drug targets and that the induction levels of these enzymes may serve as a measure of potency of individual statin drugs. It is proposed that efficacy and cellular stress markers discovered in this study may be used in a high throughput screen (HTS) assay format to compare efficiently and accurately the therapeutic windows of different members of the statin family.

Development of a district Cord Blood Bank: a model for cord blood banking in the National Health Service.

The Bristol Cord Blood Bank was established as a pilot project within existing health services to establish cost-effective recruitment, collection and processing suitable for use in the NHS should cord blood become a routine source of haemopoietic stem cells for transplantation in the UK. An important aim of the project was to evaluate the feasibility of establishing a midwifery-based collection network, thus utilising expertise already in place. Collection was performed on the delivery suite immediately after the placenta was delivered. The clinical experience of the midwife collector/counsellors allowed rapid pre-collection assessment of the condition of the cord and placenta. This prevented collection attempts from diseased or otherwise damaged placentas, leading to conservation of resources by preventing collection of most small volume donations. The bank was established within the National Blood Service, Bristol Centre to achieve Good Manufacturing Practice standards and ensure that processing was subject to the same stringency required for other sources of haemopoietic stem cells. Cord blood is an expensive resource. By utilising existing expertise in district Obstetric and National Blood Services, the Bristol Cord Blood Bank may serve as a model for health economic evaluation of cord blood banking of volunteer donations within the NHS.

The effect of divided attention on encoding and retrieval in episodic memory revealed by positron emission tomography.

The effects of divided attention (DA) on episodic memory encoding and retrieval were investigated in 12 normal young subjects by positron emission tomography (PET). Cerebral blood flow was measured while subjects were concurrently performing a memory task (encoding and retrieval of visually presented word pairs) and an auditory tone-discrimination task. The PET data were analyzed using multivariate Partial Least Squares (PLS), and the results revealed three sets of neural correlates related to specific task contrasts. Brain activity, relatively greater under conditions of full attention (FA) than DA, was identified in the occipital-temporal, medial, and ventral-frontal areas, whereas areas showing relatively more activity under DA than FA were found in the cerebellum, temporo-parietal, left anterior-cingulate gyrus, and bilateral dorsolateral-prefrontal areas. Regions more active during encoding than during retrieval were located in the hippocampus, temporal and the prefrontal cortex of the left hemisphere, and regions more active during retrieval than during encoding included areas in the medial and right-prefrontal cortex, basal ganglia, thalamus, and cuneus. DA at encoding was associated with specific decreases in rCBF in the left-prefrontal areas, whereas DA at retrieval was associated with decreased rCBF in a relatively small region in the right-prefrontal cortex. These different patterns of activity are related to the behavioral results, which showed a substantial decrease in memory performance when the DA task was performed at encoding, but no change in memory levels when the DA task was performed at retrieval.

Comparison of preservative-free bupivacaine vs. lidocaine for intracameral anesthesia: a randomized clinical trial and in vitro analysis.

PURPOSE: To determine whether intracameral bupivacaine hydrochloride 0.5% is as effective as lidocaine hydrochloride 1.0% in controlling discomfort of patients during phacoemulsification and posterior chamber intraocular lens implantation. In rabbits, corneal endothelial cell function, ultrastructure, and viability were evaluated after in vitro perfusion of bupivacaine 0.5%. METHODS: In a double-masked, controlled trial, 48 eyes of 48 patients with uncomplicated age-related cataract were randomly assigned to receive bupivacaine 0.5% or lidocaine 1.0% intracamerally before phacoemulsification with a posterior chamber intraocular lens. Outcome measures such as pain, visual acuity, amount of sedation, length of surgery, pupil size, intraocular pressure, corneal clarity, and anterior chamber reaction were compared. In laboratory studies, paired rabbit corneas were evaluated by endothelial cell perfusion with either bupivacaine 0.5%, bupivacaine 0.5% and glutathione bicarbonate Ringer solution in a 1:1 ratio or bupivacaine 0.5% buffered to a pH of 7.0. The paired control corneas were perfused with glutathione bicarbonate Ringer solution and rates of corneal swelling were determined. Cell ultrastructure and viability were also evaluated. RESULTS: In the randomized trial, there was no significant difference in the pain patients had during surgery or in the early or late postoperative period. No statistically significant difference was seen between the two groups in terms of pupil size, intraocular pressure, corneal edema, anterior chamber reaction, or visual acuity immediately after the operation or on postoperative day 1. Paired rabbit corneas perfused with bupivacaine 0.5% and bupivacaine 0.5% buffered to a pH of 7.0 swelled significantly (P<.001, P = .009, respectively), and had corneal endothelial cell damage. Dilution of the bupivacaine 1:1 with glutathione bicarbonate Ringer solution prevented corneal edema and damage to the corneal endothelium. Endothelial cell viability was also decreased after perfusion of bupivacaine 0.5% (P<.001). CONCLUSIONS: Clinically, bupivacaine 0.5% is as effective as lidocaine 1.0% for anesthesia during phacoemulsification and posterior chamber intraocular lens implantation. However, in vitro perfusion of bupivacaine 0.5% damaged the corneal endothelium of rabbits except when the drug was diluted 1:1 with glutathione bicarbonate Ringer solution. Surgeons who use 0.2 to 0.5 ml of intracameral bupivacaine 0.5% should be aware of its potential to cause endothelial cell damage because of its lipid solubility. The bupivacaine 0.5% should be diluted at least 1:1 with balanced salt solution before intracameral injection, followed immediately by phacoemulsification. The surgeon should ensure that the bupivacaine 0.5% is nonpreserved and packaged in single-use vials or flip-top containers.

Intracameral anesthesia: in vitro iris and corneal uptake and washout of 1% lidocaine hydrochloride.

OBJECTIVES: To characterize the uptake, washout, and metabolism of lidocaine hydrochloride in the iris/ciliary body and cornea. METHODS: Iris/ciliary body uptake of lidocaine hydrochloride was measured by incubating human and rabbit irides in radiolabeled carbon 14-1% lidocaine hydrochloride for 2 to 60 minutes. Washout was determined by incubating the iris in 14C-1% lidocaine hydrochloride for 5 minutes and transferring the iris to a series of wells. The wells contained a common intraocular irrigating solution of essential ions, glucose, and glutathione buffered with bicarbonate (an enriched balanced salt solution [BSS PLUS]), which is similar to aqueous humor. Corneal uptake was measured by exposing the endothelial surface to 14C-1% lidocaine hydrochloride for 5 or 15 minutes. Corneal washout was performed after 5-minute exposure to 14C-1% lidocaine hydrochloride using a 2-chambered diffusion apparatus. Samples of the iris, cornea, and BSS PLUS washout solution were analyzed by high-performance liquid chromatography and liquid scintillation spectrometry. RESULTS: In vitro iris/ciliary body uptake of 14C-1% lidocaine hydrochloride follows a logarithmic curve, with 50% to 60% of maximum lidocaine hydrochloride uptake present at 5 minutes. There was no difference in uptake between human, albino rabbit, and pigmented rabbit irides. Washout of lidocaine from the iris occurs with a halflife of 8 to 9 minutes. Corneal uptake of lidocaine was greater after incubation for 15 vs. 5 minutes. The washout of lidocaine from the cornea had a half-life of 5 minutes. Results of high-performance liquid chromatography confirmed that there were no metabolites or breakdown products in the iris, cornea, or washout solution. CONCLUSIONS: Lidocaine is taken up quickly by the iris/ ciliary body and cornea and rapidly removed from these tissues after BSS PLUS washout. Irrigation during phacoemulsification seems to limit lidocaine exposure to the ocular tissues, resulting in a short duration of anesthesia. Lidocaine is not metabolized or broken down by the iris or cornea during this short period.

Automated histometry in quantitative prostate pathology.

OBJECTIVE: To review progress on the development of machine vision and image understanding in prostate tissue histology and to discuss the problems and opportunities afforded to pathology through the use of these techniques. STUDY DESIGN: A variety of concepts in machine vision are explored, and methodologies are described that have been developed to deal with the complexities of histologic imagery. The theory of human vision and its impact on machine vision are discussed. Software has been specifically developed for the analysis of prostate histology, allowing accurate gland segmentation, basal cell identification and measurement of vascularization within lesions. RESULTS: Image interpretation can be achieved using knowledge-based image analysis and the application of local object-oriented processing. This successfully allows an automated quantitative analysis of histologic morphology in the diagnosis of prostate intraepithelial neoplasia and invasive prostatic cancer. The use of low-power image scanning, based on textural or n-gram mapping, permits the development of fully automated devices for the rapid detection of tissue abnormalities. High-power, knowledge-guided scene segmentation can be carried out for the quantitative analysis of cellular features and the objective grading of the lesion. CONCLUSION: Automated tissue section scanning and image interpretation is now possible and holds much promise in prostate pathology and other diagnostically demanding areas. Issues of standardization still need to be addressed, but the development of such systems will undoubtedly enhance our diagnostic capabilities through the automation of time-consuming procedures and the quantitative evaluation of disease processes.

Effect of supplemental L-arginine in a chemical-induced model of colorectal cancer.

L-Arginine inhibits the development of spontaneous, transplantable solid tumors and chemically induced mammary tumors. The aim of the present study was to investigate the effect of l-arginine on chemically induced colorectal cancer in male Wistar rats. Colorectal cancer was induced in all animals by weekly subcutaneous injections of the colonic procarcinogen 1,2-dimethylhydrazine (DMH) at a dosage of 20 mg/kg body weight. Arginine was given in a 1% solution of drinking water. Group I was the DMH control; group II, arginine for 22 weeks; group III, arginine for the first 10 weeks only. Lymphocyte function was evaluated by measuring the thymic lymphocyte proliferative response to the T cell mitogen phytohemagglutinin. The results show that tumor incidence and tumor burden (tumors/rat and tumors/tumor-bearing rat) were significantly reduced in both groups of animals receiving arginine compared to DMH controls (p < 0.05). The tumor areas and volumes were also reduced in both arginine groups (p < 0.05). Thymic lymphocyte stimulation indices were significantly increased by arginine supplementation (p < 0.05). These results would be in keeping with the reduction in colorectal tumor production due to a "nonspecific" stimulation of the host immune system by L-arginine.

Topical glutamine therapy in experimental inflammatory bowel disease.

This study investigated the effects of glutamine and steroid enemas on disease activity in an animal model of colitis. Colitis was induced in male Wistar rats by intracolonic instillation of 30 mg trinitrobenzenesulphonic acid in 50% ethanol (TNBS/E). Controls were given an isovolumetric bolus of normal saline. After 24 h, animals were randomised to receive enemas (1 mL twice daily) of prednisolone (200 mg/L), or L-glutamine (500 g/L) or the suspending agent (placebo). On day 8, the colon was weighed and the degree of inflammation assessed using a colon macroscopic score (CMS). Thymic weight, splenic weight, percentage gain in body weight (%GBW), food intake, plasma interleukin-6 (IL6) and plasma alpha(2)-macroglobulin (alpha(2)M) were also determined. There was a significant increase in CMS, colon weight, splenic weight, IL6 and alpha(2)M in TNBS/E animals compared to controls (P< 0.01). There was also a significant decrease in %GBW, food intake and thymic weight in TNBS/E animals (P< 0.01). The therapeutic enema of prednisolone reduced colonic inflammation (CMS, colon weight), improved thymic weight, %GBW and food intake, and reduced plasma IL6 concentrations (P< 0.05). In contrast administration of glutamine enemas was associated with an exaggerated acute phase protein (alpha(2)M) response (P< 0.05) and failed to improve the colonic and systemic inflammatory response in this experimental model of colitis.

Manipulation of the L-arginine-nitric oxide pathway in experimental colitis.

The role of the L-arginine-nitric oxide pathway in the pathogenesis of colonic inflammation was assessed using L-arginine and its competitive analogue N omega-nitro-L-arginine methyl ester (L-NAME) in a rat model of colitis. In the first study oral L-arginine 2 per cent (control: 3.4 per cent L-glycine) was administered with and without L-NAME 100 mg/l. Orally administered L-arginine increased colonic inflammation (P = 0.004) and decreased thymic weight (P = 0.0007). Addition of L-NAME reduced the colonic inflammation and prevented loss of body-weight (P < 0.04). In the second study L-NAME was administered orally in concentrations of 100, 200 and 500 mg/l (control: no L-NAME). L-NAME 500 mg/l reduced colonic inflammation and increased thymic weight and body-weight (P < 0.01). Thymic weight and body-weight correlated positively with the concentration of L-NAME administered orally (rs > or = 0.3, P = 0.04). L-NAME l g/l was administered topically as an enema (control: suspension agent). Topical L-NAME reduced colonic inflammation and increased thymic weight (P < 0.05). These results suggest that the L-arginine-nitric oxide pathway mediates colonic inflammation in this model.

Leukocyte functions of young dairy calves fed milk replacers supplemented with vitamins A and E.

Holstein calves (n = 44) were fed milk replacers from d 3 to 45 with low or high concentrations of vitamin A (7000 or 87,000 IU/kg) and vitamin E (11.2 or 57 IU/kg) to examine the influence of vitamin concentrations on vitamin bioavailability and leukocyte functions. Concentrations of alpha-tocopherol in plasma reflected increased vitamin E but were unaffected by increased vitamin A. Plasma retinol concentrations were greatest with high supplementation of vitamins A and E at wk 3; however, at wk 6, plasma of calves fed high vitamin A and low vitamin E contained the most retinol. Increased supplementation of vitamin A improved fecal consistency compared with that for calves fed the low vitamin A diet at wk 3 and 4. At wk 3, calves that received increased supplementation of vitamins E and A had enhanced neutrophil bactericidal activity compared with that of calves with increased individual vitamins. Lymphocyte DNA synthesis and chemotactic index were unaffected by dietary treatments. Results indicate that increased vitamin A in milk replacer did not affect plasma vitamin E concentrations, benefited fecal scores regardless of vitamin E concentrations, but was only beneficial to bactericidal activity of neutrophils in conjunction with increased vitamin E.