Interactive effects of protein and energy intake on nutrient partitioning and growth in Nile tilapia.

Studies of fish growth response to changes in dietary protein and energy content are often conducted with fish fed to apparent satiation or at fixed percentages of their body mass. Such designs result in simultaneous changes in protein and non-protein energy intake, thereby failing to distinguish their separate effects on nutrient partitioning and growth. The present study was designed to address this limitation and test the existence of distinct protein- and non-protein energy-dependent growth phases in Nile tilapia (Oreochromis niloticus). All-male Nile tilapia (63 g, SD = 1.3) were subjected to an 8 × 2 factorial design consisting of eight levels of digestible protein (DP) intake (0.44-1.25 g/day) and two levels of non-protein digestible energy (NPDE) intake (16.0 and 22.4 kJ/day). Fish (n = 960) were housed in 60-litre tanks with two replicates per treatment and hand-fed twice a day for 42 days. Nutrient balances were calculated from changes in body mass, analysed body composition and digestible nutrient intake. Linear regression models were compared to linear-plateau regression models to determine whether protein gain followed distinct protein- and non-protein energy-dependent phases or not. Body mass gain increased linearly with increasing DP intake and was significantly higher (2.6 vs 2.3 g/d, P < 0.05) in fish receiving a high NPDE intake. This increase mainly reflected a higher mean fat gain (0.29 vs 0.20 g/d) rather than a higher protein gain (0.42 vs 0.39 g/d) in fish fed a high vs low level of NPDE intake. The comparison of linear and linear-plateau models did not give clear support for the presence of distinct protein and non-protein energy-dependent phases in protein gain. These results indicate that non-protein energy intake has a modest protein-sparing potential, and that protein gain is simultaneously limited by protein and energy intake in Nile tilapia.

Adcitmer® , a new CD56-targeting monomethyl auristatin E-conjugated antibody, is a potential therapeutic approach in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer, whose tumour cells often express CD56. While immune checkpoint inhibitors constitute a major advance for treating patients with MCC with advanced disease, new therapeutic options are still urgently required. OBJECTIVES: To produce and evaluate the therapeutic performance of a new antibody-drug conjugate (Adcitmer® ) targeting CD56 in preclinical models of MCC. METHODS: CD56 expression was evaluated in a MCC cohort (immunohistochemistry on a tissue microarray of 90 tumour samples) and MCC cell lines. Interaction of an unconjugated CD56-targeting antibody with CD56+ MCC cell lines was investigated by immunohistochemistry and imaging flow cytometry. Adcitmer® product was generated by the bioconjugation of CD56-targeting antibody to a cytotoxic drug (monomethyl auristatin E) using the McSAF Inside® bioconjugation process. The chemical properties and homogeneity of Adcitmer® were characterized by hydrophobic interaction chromatography. Adcitmer® cytotoxicity was evaluated in vitro and in an MCC xenograft mice model. RESULTS: Similar to previous reports, CD56 was expressed by 66% of MCC tumours in our cohort, confirming its relevance as a therapeutic target. Specific binding and internalization of the unconjugated CD56-targeting antibody was validated in MCC cell lines. The high homogeneity of the newly generated Adcitmer® was confirmed by hydrophobic interaction chromatography. The CD56-mediated cytotoxicity of Adcitmer® was demonstrated in vitro in MCC cell lines. Moreover, Adcitmer® significantly reduced tumour growth in a MCC mouse model. CONCLUSIONS: Our study suggests that Adcitmer® should be further assessed as a therapeutic option in patients with MCC, as an alternative therapy or combined with immune checkpoint inhibitors.

Feasibility and outcomes of a goal-directed physical therapy program for patients with metastatic breast cancer.

PURPOSE: To evaluate the feasibility and outcomes of a tailored, goal-directed, and exercise-based physical therapy program for patients with metastatic breast cancer (MBC). METHODS: This was an observational, uncontrolled feasibility study. The physical therapy intervention was highly tailored to the individual patient's goals, abilities, and preferences and could include functional, strength, aerobic, and relaxation exercises. Feasibility outcomes were participation rate (expected: 25%), safety, and adherence (percentage of attended sessions relative to scheduled sessions). Additional outcomes were goal attainment, self-reported physical functioning, fatigue, health-related quality of life, and patient and physical therapist satisfaction with the program. RESULTS: Fifty-five patients (estimated participation rate: 34%) were enrolled. Three patients did not start the intervention due to early disease progression. An additional 22 patients discontinued the program prematurely, mainly due to disease progression. Median intervention adherence was 90% and no major intervention-related adverse events occurred. A goal attainment score was available for 42 patients (of whom 29 had completed the program and 13 had prematurely dropped out). Twenty-two (52%) of these patients achieved their main goal fully or largely and an additional 15 patients (36%) partially. Eighty-five percent would "definitely recommend" the program to other patients with MBC. We observed a modest improvement in patient satisfaction with physical activities (Cohen's dz 0.33). CONCLUSION: The tailored intervention program was feasible in terms of uptake, safety, and outcomes and was highly valued by patients and physical therapists. However, disease progression interfered with the program, leading to substantial dropout. TRIAL REGISTRATION: NTR register: NTR6475.

Operating room ventilation and the risk of revision due to infection after total hip arthroplasty: assessment of validated data in the Norwegian Arthroplasty Register.

BACKGROUND: The air in the operating room is considered a risk factor for surgical site infection (SSI) due to airborne bacteria shed from the surgical staff or from patients themselves. AIM: To assess the influence of validated operating room (OR) ventilation data on the risk of revision surgery due to deep infection after primary total hip arthroplasty (THA) reported to the Norwegian Arthroplasty Register (NAR). METHODS: Forty orthopaedic units reporting THAs to the NAR during the period 2005-2015 were included. The true type of OR ventilation in all hospitals at the time of primary THA was confirmed in a previous study. Unidirectional airflow (UDF) systems were subdivided into: small, low-volume, unidirectional vertical flow (lvUDVF) systems; large, high-volume, unidirectional vertical flow (hvUDVF) systems; and unidirectional horizontal flow (UDHF) systems. These three ventilation groups were compared with conventional, turbulent, mixing ventilation (CV). The association between the end-point, time to revision due to infection, and OR ventilation was estimated by calculating relative risks (RRs) in a multivariate Cox regression model, with adjustments for several patient- and surgery-related covariates. FINDINGS: A total of 51,292 primary THAs were eligible for assessment. Of these, 575 had been revised due to infection. A similar risk of revision due to infection after THA performed was found in ORs with lvUDVF and UDHF compared to CV. THAs performed in ORs with hvUDVF had lower risk of revision due to infection compared to CV (RR = 0.8; 95% CI: 0.6-0.9; P = 0.01). CONCLUSION: THAs performed in ORs with hvUDVF systems had lower risk of revision due to infection compared to THAs performed in ORs with CV systems. The perception that all UDF systems are similar and possibly harmful seems erroneous.

Granulomatous enteritis in rainbow trout (Oncorhynchus mykiss) associated with soya bean meal regardless of water dissolved oxygen level.

This study investigated morphological changes associated with soya bean meal-induced enteritis (SBMIE) in distal intestine (DI) of rainbow trout (Oncorhynchus mykiss) fed a soya bean meal (SBM)-based diet and exposed to normoxia or hypoxia created by optimal and low water flow rates, respectively. A 28-day adaption period was followed by a 42-day challenge period where 600 fish were subjected to dietary challenge and/or hypoxia. Twelve tanks each containing 50 juvenile trout were assigned randomly in triplicate to each treatment. Histopathological and immunohistochemical evaluation revealed pathological features that have not previously been described in association with SBMIE. Vacuolar degeneration of epithelial cells mainly at the base of mucosal folds, epithelial cysts, epithelial dysplasia, necrosis, shedding of necrotic cells, and granulomatous inflammation including infiltration of enlarged, sometimes finely vacuolated or "foamy" macrophages, multinucleated giant cells and increased proliferation of fibroblasts were observed. Acid-fast bacteria were not detected in enlarged macrophages; however, these cells contained AB-PAS- and sometimes cytokeratin-positive material, which was interpreted to be of epithelial/goblet cell origin. Hypoxia did not affect the morphological changes in DI. These results suggest that SBM was associated with a granulomatous form of enteritis in DI of rainbow trout regardless of water oxygen level.

Comparison of endogenous loss and maintenance need for minerals in rainbow trout (Oncorhynchus mykiss) fed fishmeal or plant ingredient-based diets.

Mineral needs as affected by changes in dietary protein and oil sources were studied in rainbow trout. Duplicate groups (n = 30 fish per replicate) of rainbow trout (initial BW: 37 g) were fed either a fish meal/fish oil-based (M) or a complete plant ingredient (V)-based diet at four graded ration (R) levels [apparent satiation (AS), R75, R50 and R25 % of AS]; one treatment group was maintained under starvation. The feeding trial lasted 12 weeks at a water temperature of 17 °C. Dietary intake, apparent digestibility and initial and final whole-body composition data were used to calculate mineral gain which was regressed against digestible mineral intake (both expressed as mg or µg kg(-0.8) day(-1)). Starvation loss (SL), endogenous loss of fed fish (ELF, y-intercept at x = 0) and point of intake for zero balance (PZB, x-intercept at y = 0) were used as estimates of maintenance requirements. SL provided the lowest estimate, ELF provided the net requirement of a mineral for maintenance and PZB provided the digestible dietary intake required to meet maintenance (SL < ELF < PZB). Dietary ingredient composition did not significantly affect the digestible mineral supply required for maintenance (PZB) for any of the minerals (P, Mg, K, Cu and Zn) studied. However, ELF of micro-minerals such as Cu and Zn were significantly affected. The ELF of Cu was significantly lower and that of Zn was significantly higher in V group compared with M-fed fish. Further studies on the effects of such changes in dietary formulations on micro-mineral metabolism are warranted.

Baseline comprehensive geriatric assessment is associated with toxicity and survival in elderly metastatic breast cancer patients receiving single-agent chemotherapy: results from the OMEGA study of the Dutch breast cancer trialists' group.

AIM: To evaluate the association between baseline comprehensive geriatric assessment (CGA) or the Groningen Frailty Indicator (GFI) and toxicity in elderly metastatic breast cancer (MBC) patients treated with first-line palliative chemotherapy. PATIENTS AND METHODS: MBC patients (≥65 years) were randomized between pegylated liposomal doxorubicine or capecitabine. CGA included instrumental activities of daily living (IADL), cognition using the mini-mental state examination (MMSE), mood using the geriatric depression scale (GDS), comorbidity using the Charlson index, polypharmacy and nutritional status using the body mass index. Frailty on CGA was defined as one or more of the following: IADL ≤ 13, MMSE ≤ 23, GDS ≥ 5, BMI ≤ 20, ≥5 medications or Charlson ≥2. The cut-off for frailty on the GFI was ≥4. RESULTS: Of the randomized 78 patients (median age 75.5 years, range 65.8-86.8 years), 73 were evaluable for CGA; 52 (71%) had one or more geriatric conditions. Grade 3-4 chemotherapy-related toxicity was experienced by 19% of patients without geriatric conditions compared to 56% of patients with two geriatric conditions and 80% of those with three or more (p = 0.002). Polypharmacy was the only individual factor significantly associated with toxicity (p = 0.001). GFI had a sensitivity of 69% and a specificity of 76% for frailty on CGA, and was not significantly associated with survival or toxicity. CONCLUSION: In this study of elderly patients with MBC, the number of geriatric conditions correlated with grade 3-4 chemotherapy-related toxicity. Therefore, in elderly patients for whom chemotherapy is being considered, a CGA could be a useful addition to the decision-making process.

Dietary electrolyte balance affects the nutrient digestibility and maintenance energy expenditure of Nile tilapia.

Acid-base disturbances caused by environmental factors and physiological events including feeding have been well documented in several fish species, but little is known about the impact of dietary electrolyte balance (dEB). In the present study, we investigated the effect of feeding diets differing in dEB (-100, 200, 500 or 800 mEq/kg diet) on the growth, nutrient digestibility and energy balance of Nile tilapia. After 5 weeks on the test diet, the growth of the fish was linearly affected by the dEB levels (P< 0·001), with the lowest growth being observed in the fish fed the 800 dEB diet. The apparent digestibility coefficient (ADC) of fat was unaffected by dEB, whereas the ADC of DM and protein were curvilinearly related to the dEB levels, being lowest and highest in the 200 and 800 dEB diets, respectively. Stomach chyme pH at 3 h after feeding was linearly related to the dEB levels (P< 0·05). At the same time, blood pH of the heart (P< 0·05) and caudal vein (P< 0·01) was curvilinearly related to the dEB levels, suggesting the influence of dEB on postprandial metabolic alkalosis. Consequently, maintenance energy expenditure (MEm) was curvilinearly related to the dEB levels (P< 0·001), being 54 % higher in the 800 dEB group (88 kJ/kg(0·8) per d) than in the 200 dEB group (57 kJ/kg(0·8) per d). These results suggest that varying dEB levels in a diet have both positive and negative effects on fish. On the one hand, they improve nutrient digestibility; on the other hand, they challenge the acid-base homeostasis (pH) of fish, causing an increase in MEm, and thereby reduce the energy required for growth.

Control of voluntary feed intake in fish: a role for dietary oxygen demand in Nile tilapia (Oreochromis niloticus) fed diets with different macronutrient profiles.

It has been hypothesised that, at non-limiting water oxygen conditions, voluntary feed intake (FI) in fish is limited by the maximal physiological capacity of oxygen use (i.e. an 'oxystatic control of FI in fish'). This implies that fish will adjust FI when fed diets differing in oxygen demand, resulting in identical oxygen consumption. Therefore, FI, digestible energy (DE) intake, energy balance and oxygen consumption were monitored at non-limiting water oxygen conditions in Nile tilapia fed diets with contrasting macronutrient composition. Diets were formulated in a 2 × 2 factorial design in order to create contrasts in oxygen demand: two ratios of digestible protein (DP):DE ('high' v. 'low'); and a contrast in the type of non-protein energy source ('starch' v. 'fat'). Triplicate groups of tilapia were fed each diet twice daily to satiation for 48 d. FI (g DM/kg(0·8) per d) was significantly lower (9·5%) in tilapia fed the starch diets relative to the fat diets. The DP:DE ratio affected DE intakes (P < 0·05), being 11% lower with 'high' than with 'low' DP:DE ratio diets, which was in line with the 11·9% higher oxygen demand of these diets. Indeed, DE intakes of fish showed an inverse linear relationship with dietary oxygen demand (DOD; R 2 0·81, P < 0·001). As hypothesised ('oxystatic' theory), oxygen consumption of fish was identical among three out of the four diets. Altogether, these results demonstrate the involvement of metabolic oxygen use and DOD in the control of FI in tilapia.

Dietary nutrient composition affects digestible energy utilisation for growth: a study on Nile tilapia (Oreochromis niloticus) and a literature comparison across fish species.

The effect of the type of non-protein energy (NPE) on energy utilisation in Nile tilapia was studied, focusing on digestible energy utilisation for growth (k(gDE)). Furthermore, literature data on k(gDE) across fish species were analysed in order to evaluate the effect of dietary macronutrient composition. A total of twelve groups of fish were assigned in a 2 × 2 factorial design: two diets ('fat' v. 'starch') and two feeding levels ('low' v. 'high'). In the 'fat'-diet, 125 g fish oil and in the 'starch'-diet 300 g maize starch were added to 875 g of an identical basal mixture. Fish were fed restrictively one of two ration levels ('low' or 'high') for estimating k(gDE). Nutrient digestibility, N and energy balances were measured. For estimating k(gDE), data of the present study were combined with previous data of Nile tilapia fed similar diets to satiation. The type of NPE affected k(gDE) (0.561 and 0.663 with the 'starch' and 'fat'-diets, respectively; P < 0.001). Across fish species, literature values of k(gDE) range from 0.31 to 0.82. Variability in k(gDE) was related to dietary macronutrient composition, the trophic level of the fish species and the composition of growth (fat:protein gain ratio). The across-species comparison suggested that the relationships of k(gDE) with trophic level and with growth composition were predominantly induced by dietary macronutrient composition. Reported k(gDE) values increased linearly with increasing dietary fat content and decreasing dietary carbohydrate content. In contrast, k(gDE) related curvilinearly to dietary crude protein content. In conclusion, energy utilisation for growth is influenced by dietary macronutrient composition.

Bacterial findings in infected hip joint replacements in patients with rheumatoid arthritis and osteoarthritis: a study of 318 revisions for infection reported to the norwegian arthroplasty register.

High rates of Staphylococcus aureus are reported in prosthetic joint infection (PJI) in rheumatoid arthritis (RA). RA patients are considered to have a high risk of infection with bacteria of potentially oral or dental origin. One thousand four hundred forty-three revisions for infection were reported to the Norwegian Arthroplasty Register (NAR) from 1987 to 2007. For this study 269 infection episodes in 255 OA patients served as control group. In the NAR we identified 49 infection episodes in 37 RA patients from 1987 to 2009. The RA patients were, on average, 10 years younger than the OA patients and there were more females (70% versus 54%). We found no differences in the bacterial findings in RA and OA. A tendency towards a higher frequency of Staphylococcus aureus (18% versus 11%) causing PJI was found in the RA patients compared to OA. There were no bacteria of potential odontogenic origin found in the RA patients, while we found 4% in OA. The bacteria identified in revisions for infection in THRs in patients with RA did not significantly differ from those in OA. Bacteria of oral or dental origin were not found in infected hip joint replacements in RA.

An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients.

BACKGROUND: Breast cancer cells deficient for BRCA1 are hypersensitive to agents inducing DNA double-strand breaks (DSB), such as bifunctional alkylators and platinum agents. Earlier, we had developed a comparative genomic hybridisation (CGH) classifier based on BRCA1-mutated breast cancers. We hypothesised that this BRCA1-like(CGH) classifier could also detect loss of function of BRCA1 due to other causes besides mutations and, consequently, might predict sensitivity to DSB-inducing agents. PATIENTS AND METHODS: We evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss through mutation or promoter methylation and immunohistochemical basal-like status in the triple-negative subgroup (TN subgroup). RESULTS: We observed greater benefit from HD-PB chemotherapy versus conventional chemotherapy among patients with BRCA1-like(CGH) tumours [41/230 = 18%, multivariate hazard ratio (HR) = 0.12, 95% confidence interval (CI) 0.04-0.43] compared with patients with non-BRCA1-like(CGH) tumours (189/230 = 82%, HR = 0.78, 95% CI 0.50-1.20), with a significant difference (test for interaction P = 0.006). Similar results were obtained for overall survival (P interaction = 0.04) and when analyses were restricted to the TN subgroup. Sixty-three percent (20/32) of assessable BRCA1-like(CGH) tumours harboured either a BRCA1 mutation (n = 8) or BRCA1 methylation (n = 12). CONCLUSION: BRCA1 loss as assessed by CGH analysis can identify patients with substantially improved outcome after adjuvant DSB-inducing chemotherapy when compared with standard anthracycline-based chemotherapy in our series.

Coping strategies in farmed African catfish Clarias gariepinus. Does it affect their welfare?

The objective of this study was to assess whether and how coping strategies affect the welfare of African catfish Clarias gariepinus housed at low and high densities. Group composition influenced feed intake; re-active groups (comprised of 100% re-active fish) had a lower specific growth rate (G) and feed intake and a higher feed conversion ratio (R(FC)) than pro-active groups. Furthermore, re-active groups had a lower energy retention than pro-active groups. The latter was fully due to differences in feed intake, since energy partitioning (on % total gross energy intake basis) was similar among the group composition treatments. Fish held at high stocking density showed a higher R(FC) and feeding speed and a lower energy retention and agonistic behaviour. None of the measured variables was influenced by the interaction effect. In mixed groups, G and number of skin lesions seemed to be affected by different behavioural phenotypes at low stocking density, but not at high density. These results indicate that both stocking density and group composition affect physical and behavioural responses of C. gariepinus. Furthermore, physical and behavioural data of individual fish housed in mixed groups suggest that coping strategy affects the fitness of different behavioural phenotypes at low, but not at high, stocking density.

Time-related changes of the intestinal morphology of Atlantic salmon, Salmo salar L., at two different soybean meal inclusion levels.

Abstract Soybean meal (SBM) induces enteritis in the distal intestine of Atlantic salmon. The present study assesses the effects of SBM concentrations on the kinetics of the enteritis process. Fish of 300 g, kept at 12 degrees C, were fed diets with different SBM inclusions: 0%, 10% and 20% SBM for 57 days. Samples of the distal intestine of five fish per treatment were taken for histological and electron microscopical analysis. A semi-quantitative scoring system was used to assess the degree of the morphological changes induced by SBM feeding in the distal intestinal epithelium. The first signs of enteritis appeared earlier in the salmon fed the 20SBM diet than in those fed the 10SBM diet. Thereafter, the condition increased steadily, displaying no signs of recovery. Furthermore, at the lower concentration, the process marking the onset of enteritis began more gradually than at the higher concentration and it displayed a tendency to stabilize after 13-20 days of continuous feeding. Electron microscopy indicated that the endocytosis process was hampered at day 3 of 20SBM and at 7 days of 10SBM. Furthermore, a strong reduction of microvilli was already evident after 7 days of 20SBM feeding, thus indicating a decreased uptake capacity of the distal enterocytes. In addition, transformation and migration of eosinophilic granulocytes was observed, which, in combination with the lysozyme C immunoreactivity supports their protective role during the inflammatory process in the distal gut of Atlantic salmon. It can be concluded that the severity of enteritis and its kinetics are concentration-dependent, showing no signs of recovery during feeding with diets containing SBM.

Kinetics of Lactobacillus plantarum 44a in the faeces of tilapia (Oreochromis niloticus) after its intake in feed.

AIMS: To study the kinetic passage of Lactobacillus plantarum 44a from feed to faeces of tilapia in order to calculate the number of Lactobacillus excreted. METHODS AND RESULTS: In a single-dose experiment, duplicate lots of 26 fish devoid of intestinal lactobacilli were fed with diets containing c. 4.5 x 10(11), 6.3 x 10(8), 6.0 x 10(5) and 0 CFU of Lact. plantarum 44a per single feed ration. In the multiple-dose experiment, duplicate lots of 30 fish each were supplied with a diet containing 1 x l0(11) CFU of Lact. plantarum 44a as follows: 14 times in 14 days, five times in 14 days, once in 14 days and zero times in 14 days. Faeces were periodically collected and analysed for their lactobacilli content by using a selective media. The kinetics of Lactobacillus in the faeces was described as a pulse signal defined by three parameters: theta, A(o) and the time. theta, was identified as the time to reach the peak (x axis) and A(o) was a constant. A(o) divided by e, was identified as the height of the peak (y axis). The area below the curve A(o)theta allowed the calculation of the total number of lactobacilli excreted. The ability of the mathematical model to describe the actual values was tested by a linear regression analysis. In most of the cases, the equations showed an intercept close to zero (P > 0.05) and angular coefficients near one. CONCLUSIONS: Lactobacillus plantarum 44a was excreted in short pulse signals described by a mathematical model which allowed calculating the area below the curve and consequently the survival rate. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a quantitative method to study the kinetics of excretion of a probiotic bacterium in the faeces.

Soybean meal induces intestinal inflammation in common carp (Cyprinus carpio L.).

The development of soybean meal (SBM) induced enteritis in the hindgut of the omnivorous common carp (Cyprinus carpio L.). The developed condition was assessed when carp, continuously fed on animal protein, were transferred to a diet in which 20% of the protein was replaced by SBM. After week 1, most of the inflammation parameters were already present, but at week 3, a strong aggravation of the condition was observed which included a shortening of the mucosal folds, the disappearance of the supranuclear vacuoles, an increased number of goblet cells, a thickened lamina propria and sub-epithelial mucosa with increased numbers of basophilic granulocytes as well as a decreased uptake capacity of enterocytes (impaired endocytosis and microvilli). Contrary to previous observations made with respect to Atlantic salmon, common carp start to recover from the fourth to the fifth week after switching to SBM feeding. At this stage, the supranuclear vacuoles refill and most of the parameters revert to basal levels. During the enteritis process, a real-time quantitative PCR analysis was conducted to measure the expression of inflammatory and anti-inflammatory cytokine genes in the isolated intraepithelial lymphocytes (IEL). The pro-inflammatory interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha1 (TNF-alpha1) genes were up-regulated during the inflammation process while the anti-inflammatory interleukin 10 (IL-10) was down-regulated after an initial up-regulation at week 1. Transforming growth factor beta (TGF-beta) expression showed an up-regulation from week 3 onwards despite the high Ct value and the low primer efficiency shown. This study confirms the contribution of IEL (mainly T-like cells) and basophils in the enteritis process. In addition, the results show a clear involvement of up- and down-regulated cytokine genes in both the onset and recovery of the SBM-induced enteritis in the hindgut of carp.

A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity.

BACKGROUND: Targeting the vascular endothelial growth factor or the epidermal growth factor receptor (EGFR) has shown efficacy in advanced colorectal cancer (ACC), but no data are available on the combination of these strategies with chemotherapy in the first-line treatment. The CAIRO2 study evaluates the effect of adding cetuximab, a chimeric mAb against EGFR, to capecitabine, oxaliplatin and bevacizumab in the first-line treatment of ACC. PATIENTS AND METHODS: In all, 755 patients were randomly assigned between treatment with capecitabine, oxaliplatin and bevacizumab with or without cetuximab. The primary end point is progression-free survival. We here present the toxicity results in the first 400 patients that entered the study. RESULTS: The incidence of overall grade 3-4 toxicity was significantly higher in arm B compared with arm A (81% versus 72%, P = 0.03). This difference is fully attributed to cetuximab-related skin toxicity. The addition of cetuximab did not result in an increase of gastrointestinal toxicity or treatment-related mortality. CONCLUSIONS: The addition of cetuximab to capecitabine, oxaliplatin and bevacizumab in the first-line treatment of ACC appears to be safe and feasible. No excessive or unexpected toxicity in the cetuximab-containing treatment arm was observed.

Synchronising the availability of amino acids and glucose increases protein retention in pigs.

Effects of synchronising the availability of amino acids and glucose within a day on protein and energy metabolism were studied in growing pigs. Ten pigs of on average 54 (s.e. 1.0) kg live weight were assigned to each of two dietary treatments (synchronous v. asynchronous nutrient supply) in a change-over design. On the synchronous treatment (SYN), pigs received two balanced meals: one at 0800 h and one at 1600 h. On the asynchronous treatment (ASYN), pigs received virtually all protein at 0800 h and all carbohydrates at 1600 h. The dietary supply of ingredients and nutrients to pigs was similar for both treatments. Pigs were housed individually in respiration chambers. Faecal apparent nutrient digestibility was determined and nitrogen and energy balances were measured. Faecal apparent digestibility of energy, organic matter and non-starch polysaccharides was higher ( P < 0.05) for SYN than for ASYN. The efficiency of utilisation of digestible protein with protein gain was higher ( P = 0.001) for SYN (56.7%) than for ASYN (47.1%). The substantial decrease ( P < 0.05) in respiratory quotient and 13C enrichment of the expired CO2 after the morning meal indicated higher amino acid oxidation for ASYN than for SYN. Heat production and energy retention as fat were not affected by nutrient synchrony. In conclusion, an asynchronous availability of glucose and amino acids within a day increases amino acid oxidation, resulting in a substantial reduction in protein utilisation but with virtually no effect on fat retention.