Health Status Of Animals Research Articles

Fattening rabbits in mobile arks: effect of housing system on in vivo oxidative status and meat quality

<p>The aim of this trial was to study the effect of an alternative housing system on the oxidative status and meat quality of fattening rabbits. From May to June 2014, 60 rabbits of 35 d of age were reared in Mobile Arks (MA) placed on alfalfa grass and frequently moved for 40 d. To assess the health status of animals, blood samples were collected at slaughter in MA and in conventional cages (C). Meat quality parameters were also evaluated. Concerning the <em>in vivo </em>oxidative status, ark-reared rabbits showed higher thiobarbituric reactive substances values than C ones, probably for the higher motor activity due to the larger living area. The lipid percentage of <em>Longissimus lumborum </em>muscle was lower (1.22 <em>vs. </em>1.48%) in the ark group. There were no significant differences in the muscle pH, colour, water holding capacity and cooking loss. Given the higher intake of grass, rich in vitamins, carotenes, polyphenols and polyunsaturated fatty acids, the antioxidant content of meat was higher in ark-reared rabbits (7.42 <em>vs. </em>6.82 µg/g of retinol, 719.2 <em>vs. </em>683.3 ng/g of α-tocopherol, respectively). Even the fatty acid profile of MA rabbits reflected the higher intake of essential fatty acids from grass and the n-3 long chain polyunsaturated fatty acids (arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid) were almost doubled. Our study suggested that the fattening of rabbits in ark system could be a possible alternative system to improve the meat quality of rabbits.</p><p><strong><br /></strong></p>

Effect of feeding Acacia nilotica pod meal on hematobiochemical profile and fecal egg count in goats.

Aim:This study was conducted to observe the effect of feeding Acacia nilotica pod meal on hematobiochemical profile and gastrointestinal parasitic load in growing goats.Materials and Methods:To experiment was conducted for a period of 3-month on 24 male goats (3½ month old, average body weight [BW] 6.50±1.50 kg), distributed into four groups of six animals each. The experimental animals were fed graded level of A. nilotica pod meal (0%, 10%, 20% and 30%) mixed in concentrate mixture equivalent to tannin concentration of 0%, 1.91%, 3.82% and 5.73% in the total mixed ration I, II, III and IV, respectively, but ad libitum measured quantity of green sorghum fodder (Sorghum bicolor) feeding. The blood samples were collected from experimental goats during the feeding experiment for the examination of different hematological indices and serum biochemical profile to know the overall health status of animals and standard method was followed to analyze the samples. Fecal sample was collected directly from the anus of goats by inserting middle finger and kept the samples in labeled polythene bag. Further fresh sample was processed and examined by McMaster Technique for eggs per gram and oocysts per gram. It gives accurate information regarding severity of infection.Results:The feeding of babul pod meal did not address significant changes about the hematological parameters among various treatment groups. The lymphocyte count was significantly higher (p=0.07) in T3 group as compared to control and increase with increase in level of babul pod meal in the diet. Blood urea nitrogen (BUN) level was 4.86 and 6.59% lower in T1 and T2 group as compared to control and inversely proportional with level of supplement in ration. The decrease in BUN reflected good dietary protein metabolism happened in animals supplemented with babul pod meal. Serum creatinine level was significantly lower (p<0.01) in T2 group as compared to control. The creatinine level was 20.17% lower in T2 group as compared to control. Haemonchus and Coccidian egg count was significantly reduced (p<0.01) in T2 and T3 group followed with T1 as compared to control group.Conclusion:The metabolic status of the animal was not affected with the supplementation of babul pod meal, however, lower serum creatinine level and remarkable reduction in nematode, as well as protozoan egg count in the treatment group, showed good health impact of babul pod.

Immuno Affinity SELEX for Simple, Rapid, and Cost-Effective Aptamer Enrichment and Identification against Aflatoxin B1.

Aflatoxins are naturally occurring mycotoxins that contaminate food and agro commodities, leading to acute and chronic health conditions in human and animals. In the present work, an attempt was made to generate high-affinity single stranded DNA aptamers that specifically bind to Aflatoxin B1 (AFB1) by a modified Systemic Evolution of Ligands by Exponential Enrichment (SELEX) procedure with the aid of Immunoaffinity columns. Ten rounds of SELEX and alternating three counter SELEX rounds with a cocktail of related and other mycotoxins were performed to enhance the specificity. Resultant 105 aptamers were clustered into 12 groups according to their primary sequence homology. Candidates with lowest Gibbs free energy (dG value) and unique stem loop structures were selected for further characterization. Aptamers, AFLA5, AFLA53, and AFLA71 exhibiting lower Kd values (50.45 ± 11.06, 48.29 ± 9.45, and 85.02 ± 25.74 nM) were chosen for development of ELONA and determination of purification ability of toxin. The detection limit (LOD) of AFLA5 and AFLA71 was 20 and 40 ng/ml, respectively. HPLC analysis implied that selected aptamers were able to recover and quantify 82.2 to 96.21% (LOQ – 53.74 ng) and 78.3 to 94.22% (LOQ – 66.75 ng) of AFB1 from spiked corn samples, respectively. These findings indicate, immunoaffinity based SELEX can pave an alternative approach to screen aptamers against mycotoxin detection and purification.

Short-chain fatty acids as feed supplements for sustainable aquaculture: an updated view

Restriction or ban on antibiotic administration in aquaculture encourages the development of environment-friendly feed additives as immunostimulants. Short-chain fatty acids (SCFAs) and their salts are ‘Generally Regarded as Safe’ and are often used as antimicrobials in the livestock feed industry. Formate, acetate, propionate, butyrate and their salts are among the most studied SCFAs in aquaculture. These SCFAs affect the host performance as well as physiological response upon three ways: either through effects of the feeds that are being administered, through effects on the gastrointestinal tract of the animal or through direct effects on metabolism. To date, most of the available data are focused on the effects of SCFAs on growth performance and feed utilization. Despite extensive research studies on the effects of the different type of SCFAs and their salts on growth performance and feed utilization, the effects of these feed additives on the health of aquatic organisms have only been receiving attention recently. The results of the studies demonstrated beneficial effects of SCFAs as promising feed additives in aquaculture. The present review article summarizes and discusses the topic of dietary administration of SCFAs and their salts in aquaculture with a closer look at the recent findings regarding the effects of SCFAs on growth performance and health status of fish and shellfish. Furthermore, this review identifies the gaps of existing knowledge regarding the roles of SCFAs in the growth and health status of aquatic animals and suggests research areas that merit further investigations.

African and classical swine fever situation in Ivory-Coast and neighboring countries, 2008–2013

This study was conducted from 2008 to 2013 to determine the animal health status of Ivory Coast and neighboring countries (Burkina Faso, Ghana, Togo and Benin) for African swine fever (ASF) and classical swine fever (CSF), and to assess the risk factors for ASF introduction in Ivory Coast. Ivory Coast had probably been free from ASF from 1998 to 2014 when it was re-introduced in this country. However, the ASF virus was found in all neighboring countries. In contrast, no evidence of CSF infection was found so far in Ivory Coast and neighboring countries. To assess the risk of ASF reintroduction in Ivory Coast, we surveyed 59 modern pig farms, and 169 pig owners in 19 villages and in two towns. For the village livestock, the major risk factor was the high frequency of pig exchanges with Burkinabe villages. In the commercial sector, many inadequate management practices were observed with respect to ASF. Their identification should enable farmers and other stakeholders to implement a training and prevention program to reduce the introduction risk of ASF in their farms.

Seasonal variations in the blood concentration of selected heavy metals in sheep and their effects on the biochemical and hematological parameters

The main objective of this study was to assess the concentration of various heavy metals (Cd, Pb, Zn, Cu, Hg) in the blood of sheep, followed by biochemical and hematological analysis in order to reveal possible associations. Blood was collected in two different seasons: winter (fed by fodder) and spring (grazing animals). The higher concentrations of Pb (p < 0.01), Cu (p < 0.05) and Hg, but lower of Cd and Zn were found in spring. Evaluation of the biochemical and hematological parameters during different seasons showed a possible environmental effect on the health of animals. A statistically significant increase of Ca (p < 0.001), Mg (p < 0.05), urea (p < 0.001), TP (p < 0.05), glucose (p < 0.01), AST (p < 0.001), ALT (p < 0.001), ALP (p < 0.01), cholesterol (p < 0.001), bilirubin (p < 0.05), triglycerides (p < 0.001) and a decrease of P (p < 0.05), HGB (p < 0.05), MCHC (p < 0.05) and RDWc (p < 0.05) in spring was detected. The results of this study showed statistically significant correlations between Pb and ALP (r = 0.53) level in winter and between Pb and Ca (r = −0.73) in the spring. The hematological analysis revealed a significant correlation between Zn and RBC (r = 0.61), MCV (r = −0.74), MCH (r = −0.71) and between Pb and MCH (r = −0.55), PCT (r = −0.66), PDWC (r = −0.55) in the winter. A high positive significant correlations were found between Cd and RDWC (r = 0.77) and Cu and RDWC (r = 0.75). The significance of this work is the use the data in the preventive diagnosis of metabolic and production diseases. The collected data may serve as a control indicator to detect toxic hazards related to the heavy metal occurrence on animal health status.

Fatlening and meat qualities of swine during feding up with probiotic additives «PROPYGplv» as a part of the ration

Nowadays main part of pork is produced at the farms of different ownership forms mainly at the feeds of own production. A lot of problems arise and their solving influence quantity, quality and value of production. With the help of scientific investigations it was proved that intensification of swine breeding depends upon fodder basis at any farm. Besides, swine need to be fed with feeds from well balanced rations in accordance with detailed portions. Their usage will increase the productivity of swine up to 10% in comparison with such rations balanced according to limited quantity of indices. That is why while organizing rational nutrition one should remember that gastrointestinal tract in swine doesn’t have enzymec ability to the hydrolysis of cellular tissue and they are rather weak to withstand diseases connected with disturbances in digestion. That is why special attention should be paid to the usage of probiotic fodder additives in the system of prophylactic. It is especially important when different kinds of fads are used which can enrich rations, or positively influence the processes of productions formation. The main task of the investigation was to optimize rationed feeding of feeding up young swine using biologically active additive «PROPIGplv» as a part of a ration. It was stated that feeding up animals with food bioadditive when full rationed mixed fodder at dynamics 2–6 gr head per day served as a background to determine the optimum doze and using of such bioadditive doesn’t influence negatively the functional health condition of animals. Positive results concerning the intensity of animals growth, quality of production were obtained thanks to stimulating effect of bioadditive and it is economically advantageously to use bioadditives at the rations of fattening young swine.

Nutrigenomic activity of plant derived compounds in health and disease: Results of a dietary intervention study in dog

The study was conducted to investigate the effects of dietary administrations of four nutraceuticals in dogs. Seventy four dogs were enrolled in the trials, 24 healthy dogs were fed with a control diet (CT) and the experimental groups received for 60days the same diet supplemented with nutraceuticals, namely Echinacea angustifolia (EA, 0.10mg/kg live weight as echinacoside; 14 dogs), Vaccinium myrtillus (VM, 0.20mg/kg live weight as anthocyanidin, 13 dogs), Curcuma longa (CL, 6.60mg/kg live weight as curcumin, 18 dogs with arthrosis), and Sylibum marianum (SM, 1.5mg/kg live weight as sylibin, 8 dogs with hepatopathy). Dogs were weighted at the beginning of study and blood samples were collected at the beginning (T0) and at the end (T60) of the study. VM significantly down regulated TNF, CXCL8, NFKB1 and PTGS2 and decreased plasma ceruloplasmin (CuCp). The activity of EA was evidenced by the significant decrease of TNF and NFKB1 expression and CuCp levels and by the increase of plasma Zn. Administration of CL caused a significant decrease of CuCp and increase of Zn and a down regulation of TNF, CXCL8, NFKB1 and PTGS2, corroborating the anti-inflammatory action of curcuminoids. After 60days of treatment with SM, plasma ALT/GPT activity was reduced and paraoxonase was increased, supporting the antioxidant activity of silymarin, also confirmed by the significant up regulation of SOD2. Results indicated that nutraceutical administrations in dogs can be an interesting approach to modulate immune response in order to improve health condition of animals.

Amoxicillin-clavulanic acid and ciprofloxacin-treated SPF mice as gnotobiotic model

The experiment was carried out on 24 SPF BALB/c female mice and lasted for 15days with a 5-day antibiotic (ATB) treatment and then 10days without ATB treatment. The aim of our study was to acquire an animal model with reduced and controlled microflora and, at the same time, to ensure that the good health of these animals is maintained. Per oral administration of amoxicillin and clavulanate potassium in Amoksiklav (Sandoz, Slovenia) at a dose of 387.11mg/kg body weight (0.2ml of dilution per mouse) and subcutaneous administration of ciprofloxacin in Ciloxan (Alcon, Spain) at a dose of 18.87mg/kg body weight (0.1ml of dilution per mouse) were performed every 12h during first 5days of experiment. Five-day treatment with ATB led to a reduced survivability of microorganisms in faeces (28.33±0.43% on day 2) and caecum content (28.10±1.56%), where no cultivable microorganisms in faeces were present. Ten-day convalescence of decontaminated animals under gnotobiotic conditions prevented recovery of species diversity in mice gut microflora. This was reduced to two detectable cultivable species, namely Escherichia coli (GenBank KX086704) and Enterococcus sp. (GenBank KX086705) which were capable to restore its metabolic (CRL 2012) and morphological potential (Baratta et al. Histochem Cell Biol 131:713-726, 2009) within physiological range. Animals obtained under this procedure can be used in further studies. As a result, we created a mouse gnoto model with reduced and controlled microflora without alteration of the overall health status of the respective animals.

Cardiorespiratory dose-response relationship of isoflurane in Cinereous vulture (Aegypius monachus) during spontaneous ventilation.

Anesthesia is an inevitably important component of diagnosis and treatments examining the health condition of wild animals. Not only does anesthesia become an essential tool in minimizing stress of the patients and providing an opportunity to deliver accurate and safe procedures, but it also ensures the safety of the medical crew members. This study was conducted to investigate the dose-response cardiorespiratory effects of isoflurane during spontaneous ventilation in ten cinereous vultures. Each bird was administered isoflurane at initial concentration of 1.0, 1.5, 2.0, 2.5 and 3.0 and then an end-tidal isoflurane concentrations (ETiso) of 1.0% for an equilibration period of 15 min in the given order. At the end of the equilibration period, the direct blood pressure (BP), heart rate (HR), respiratory rate (RR) and end tidal CO2 partial pressure (PETCO2) were recorded, and blood gas analysis was performed. Increasing isoflurane concentrations during spontaneous ventilation led to dose-dependent increases in HR and PETCO2, with minimal changes in RR, decreased arterial BP and respiratory acidosis. Overall, isoflurane for anesthesia of spontaneously breathing cinereous vultures is a suitable choice for diagnostic or surgical procedures.

Flowering Calendar of the Macrophytes of Keibul Lamjao National Park, Loktak Lake, Manipur, India

&lt;div&gt;&lt;p&gt;&lt;em&gt;Flowering calendar of a particular area will give the information of the period and duration of flowering among plants. The purpose of the study is to investigate the presence of the habitat of some dominant macrophytes in Keibul Lamjao National Park (a Ramsar site) which have ethnobotanical relationships with human beings (the lake dwellers in particular and tourist in general) and wild animals. Flowering calendar of six study sites viz., Keibul, Nongmaikhong, Kumbi, Khordak, Sargam and Toyaching were studied and monthly flowering calendars were taken for two year period (2010 to 2011). Flowering calendars of the macrophytes were surveyed by following standard methodologies and comparison of the stages of flowering period of 6 study sites was incorporated. Maximum number of flowering plants (44) was recorded in Sargam, Khordak (32), Kumbi (30), Nongmaikhong (29) during the period September to November. Whereas, Toyaching reached 35, Keibul recorded lowest plant numbers (14) during the period June to August. Four plant species viz., Ageratum conyzoides, Alternanthera philoxeroides, Leersia hexandra and Hedychium coronarium were found throughout the year in all the 6 sites. From the findings, it can be concluded that flowering calendar will give the information of plants which are used as fodder for the wild animals like Sangai (Rucervus eldii eldii McClelland), an endangered deer species in this globe and ethnobotanically important plants of the lake dwellers as food, medicinal plants and allergens, thereby maintaining health status of man and animals. Conservation is required by controlling the human anthropogenic harassments, thereby maintaining the luxuriant growth of the seasonal and perennial, macrophytes observed during the study of flowering calendar, so as to maintain and conserve the natural flora and fauna of the park.&lt;/em&gt;&lt;/p&gt;&lt;/div&gt;

Impacts of self- and cross-sucking on cattle health and performance.

Background:Improvement of dairy farms economics requires intensification, automatic milking, and artificial rearing methods. The ability to express normal behavior is one of the five freedoms to achieve animal welfare, whereas the display of abnormal behaviors is considered as an indicator of poor welfare. Cross-sucking is defined as sucking any body parts of pen-mate calves, whereas inter-sucking in cows is defined as sucking the udder or udder area. Previous studies showed that self- and cross-sucking during the calf-hood period could be a causal factor of milk sucking in adulthood.Aim:To investigate the effects of cross-sucking among calves and inter-sucking in cows on animal health status and performance.Materials and Methods:Gathering information from customized questionnaires, the study of the breeding records, recording of self- and cross-sucking behaviors, and health status of calves till weaning, and dairy cows before milking were performed in two governmental farms under the same managemental conditions in Sohag and Qena governorates.Results:Cross-sucking appeared in calves at the 2nd week of age followed by abscesses at ears and navels that were observed within cross-sucker calves. Milk sucking was higher in primiparous than multiparous cows during the second lactation period, as primiparous cows start to suck mostly around the 4th month of milking. Mastitis and elongation of the front teats were observed in sucker cows. Suffered animals had body condition scoring 3.5 or less. Interestingly, most of the cows displaying self-sucking were sucking another cow and were experienced self- or cross-sucking in their calf-hood. The use of pronged nose-rings was ineffective in preventing milk sucking and all cows were ultimately culled at the end of the season.Conclusion:The results of this study demonstrate the health problems of abnormal oral behaviors in terms of developed ears and navels abscesses in cross-sucker calves, and mastitis and teat deformities in milk-sucker cows. Furthermore, indexes that lead to oral satisfaction should be taken in priorities of farm managers to effectively reduce or prevent cross-sucking in calves. Culling of cows and heifers suffering from sucking would be the ultimate uneconomic alternative in case of persistent suckers.

The 2016 Gilruth Prize.

The 2016 Gilruth Prize.

Use of Bayesian Belief Network techniques to explore the interaction of biosecurity practices on the probability of porcine disease occurrence in Canada

Identification and quantification of pathogen threats need to be a priority for the Canadian swine industry so that resources can be focused where they will be most effective. Here we create a tool based on a Bayesian Belief Network (BBN) to model the interaction between biosecurity practices and the probability of occurrence of four different diseases on Canadian swine farms. The benefits of using this novel approach, in comparison to other methods, is that it enables us to explore both the complex interaction and the relative importance of biosecurity practices on the probability of disease occurrence.In order to build the BBN we used two datasets. The first dataset detailed biosecurity practices employed on 218 commercial swine farms across Canada in 2010. The second dataset detailed animal health status and disease occurrence on 90 of those farms between 2010 and 2012. We used expert judgement to identify 15 biosecurity practices that were considered the most important in mitigating disease occurrence on farms. These included: proximity to other livestock holdings, the health status of purchased stock, manure disposal methods, as well as the procedures for admitting vehicles and staff. Four diseases were included in the BBN: Porcine reproductive and respiratory syndrome (PRRS), (a prevalent endemic aerosol pathogen), Swine influenza (SI) (a viral respiratory aerosol pathogen), Mycoplasma pneumonia (MP) (an endemic respiratory disease spread by close contact and aerosol) and Swine dysentery (SD) (an enteric disease which is re-emerging in North America).This model indicated that the probability of disease occurrence was influenced by a number of manageable biosecurity practices. Increased probability of PRRS and of MP were associated with spilt feed (feed that did not fall directly in a feeding trough), not being disposed of immediately and with manure being brought onto the farm premises and spread on land adjacent to the pigs. Increased probabilities of SI and SD were associated with the farm allowing access to visiting vehicles without cleaning or disinfection. SD was also more likely to occur when the health status of purchased stock was not known. Finally, we discuss how such a model can be used by the Canadian swine industry to quantify disease risks and to determine practices that may reduce the probability of disease occurrence.

Factors Affecting the Hematological Parameters in Different Goat Breeds from Italy

Abstract Hematological parameters in healthy goats show several variations in relation to breed, age, reproductive status, environmental factors and management conditions. Therefore, there is the need to investigate these factors and how they affect the animal’s hematology. The aims of this study were to establish hematological reference values of five Italian goat breeds at different age classes (1–2, 3–4 and over 5 years) considered in autumn and to evaluate the effects of some factors (breed, age and environmental conditions). Ninety-six dried female Aspromontana goats, 102 Girgentana goats, 99 Messinese goats, 96 Maltese goats and 108 Argentata dell’Etna goats, clinically healthy, were used. Blood samples were collected from each animal and analyzed for Red Blood Cell (RBC), White Blood Cell (WBC), Hemoglobin concentration (Hb), Hematocrit (Hct), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC) and Platelets (PLT). Statistical analysis showed the effect of breed (P&lt;0.05) on all studied parameters and the effect of age (P&lt;0.05) on: RBC and Hb in Messinese goats; Hct in Girgentana, Maltese and Argentata dell’Etna goats; MCV and MCHC in Argentata dell’Etna goats; WBC in Aspromontana goats; and PLT in Girgentana and Messinese goats. The findings of the present study may serve as reference values for hematology of Italian goat breeds studied in autumn which could help veterinarians to interpret laboratory data appropriately and to monitor animal health status in order to improve the management and conservation of these breeds.

Farm characteristics and perceptions regarding costs contribute to the adoption of biosecurity in Finnish pig and cattle farms

The goal of this study was to estimate how the perceived costs of biosecurity measures and the characteristics of the farm and the producer influence the adoption of four biosecurity measures: (1) the use of protective clothing when entering an animal shelter and (2) the use of protective shoes when entering an animal shelter, (3) the verification of the health status of animals coming to the farm, and (4) the use of a carcass container to temporarily store dead animals at the farm. Questionnaire data from 852 Finnish livestock farms were analysed by a logistic regression model. The higher the producers perceived the cost of the biosecurity measure the less likely they were to adopt that measure. However, this response was inelastic. The results suggest that the use of biosecurity could be promoted by providing producers with economic incentives to follow stricter biosecurity policy. University education and the producer’s activity to maintain his/her professional knowledge had a positive effect on the adoption of biosecurity measures. Also factors such as the producer’s gender, farm size and production type contributed significantly to the adoption of biosecurity measures. The ongoing structural change in the livestock sector likely increases the use of biosecurity measures as larger farms were more likely to adopt biosecurity measures.

Recognition of culling reasons in Polish dairy cows using data mining methods

Cow longevity and reasons for culling are one of the most important research problems in the contemporary cattle breeding. Therefore, the analysis of the relationship between cow performance and involuntary disposal contributes to taking more informed decisions in herd management. The aim of the present study was to compare the efficiency of artificial neural networks (ANN) and boosted classification trees (BT) with that of linear discriminant analysis (LDA) and classification functions (CF) in recognizing culling reasons of dairy cows in Poland, based on the lifetime performance data, routinely monitored in a herd. The analyses carried out in the present study showed that the accurate recognition of different culling reasons based on predictors included in the above-mentioned models is, in general, impossible. Only BT had limited discrimination abilities, but the results obtained using this method were not much improved compared with ANN and LDA with CF. In order to predict precisely various culling reasons, more specific data are required. They could be obtained from the increasingly popular, technologically advanced, systems of real-time monitoring of animal health status (physical activity, rumination rate, etc.), dependent also on environmental conditions (e.g. temperature–humidity index).

Acute and subacute toxicity studies of CMICE-013, a novel iodinated rotenone-based myocardial perfusion tracer, in Sprague Dawley rats and Gottingen minipigs

PurposeExtensive acute and subacute toxicities studies are required to evaluate the toxicological profile of the novel cardiac perfusion imaging tracer 123I-CMICE-013 to support applications for clinical trials. MethodsSprague-Dawley rats and Gottingen minipigs received injections of non-radioactive 127I-CMICE-013 at two dosage levels of 1 and 5 μg/kg, and vehicle buffer as control. In the acute toxicity studies, each animal was injected on two occasions 24 h apart and then underwent a 14-day recovery period; in the subacute study, animals received daily injections for 14 days continuously. The health status and mortality of test animals were monitored daily and body weight, food consumption, physiological and biochemical parameters were measured at various time points during the study. Animals were euthanized at the end of the studies and dissected for pathologic examination of organs and tissues. ResultsThe acute and subacute administrations of injections of the non-radioactive CMICE-013 in rats and minipigs were well tolerated. Little to no dosing-related adverse effects were observed in animal body and organ weights, hematology, coagulation, clinical chemistry, urinalysis, ophthalmoscopy, electrocardiograms, heart rates, blood pressure, macroscopic and microscopic examination of the preserved animal tissues including the brain. ConclusionThe lack of adverse effects from acute and subacute dosing suggest that the CMICE-013 injection solution has a reasonable safety margin within the designed concentration range to be utilized in imaging applications. The dosage level of 5 μg/kg was considered the no adverse effect level for both rats and minipigs based on our acute and subacute studies.

Use of an integrated biomarker-based strategy to evaluate physiological stress responses induced by environmental concentrations of caffeine in the Mediterranean mussel Mytilus galloprovincialis

The occurrence of caffeine (CF), a biologically active drug, has widely been documented in coastal waters, and whether its environmental concentrations do represent a threat for marine organisms is unclear. The present study aimed at assessing sub-lethal effects induced by a 7-day exposure to environmentally relevant concentrations of CF (5, 50 and 500ng/L) in the Mediterranean mussel, Mytilus galloprovincialis. CF in water and mussel tissues, and a battery of biomarkers, including lysosomal parameters of general stress, oxidative stress responses and endpoints of neurological and genetic damages, were evaluated and tested for significance vs controls (p<0.05). CF exposure triggered a significant decrease of lysosomal membrane stability in both haemocytes and digestive gland (at 50 and 500ng/L CF) and a significant increase of lysosomal content of neutral lipids (at 500ng/L CF), indicating the onset of a stress syndrome. No effects were noted on lipid peroxidation parameters, such as malondialdehyde and lipofuscin content. The activity of the antioxidant enzymes glutathione S-transferase (GST) and catalase was unmodified in gills, while a significant increase of GST activity was observed in digestive gland (at 5 and 500ng/L CF), suggesting the occurrence of GST-mediated phase II detoxifying processes. CF did not induce geno/neurotoxicity, as shown by the lack of effects on primary DNA damages and acetylcholinesterase activity. In line with its high hydrophilicity, CF did not bioaccumulate in mussel tissues. Data were integrated using the Mussel Expert System, which assigned a low stress level to mussels exposed to 500ng/L CF, whereas no alterations of animal health status were highlighted at lower dosages. This study revealed a low profile of toxicity for environmental concentrations of CF, and confirmed the suitability of an integrated biomarker-based approach to provide a comprehensive picture of the degree of stress induced by emerging contaminants in marine invertebrates.

Models of TCRαβ/CD19-depleted hematopoietic stem cell transplantation

Abstract Accelerating the reconstitution of protective immune T cell populations and immune function, while avoiding graft-versus-host disease (GVHD), is crucial for improving clinical outcomes following hematopoietic stem cell (HSC) transplantation. We developed and validated a clinical HSC graft engineering technique that selectively depletes αβ TCR T cells and CD19+ B cells from the graft, thereby minimizing GVHD and lymphoproliferative disease while maintaining HSC and important immunoprotective cell populations in the graft. The enrollment of the first patients in a University of Wisconsin conducted phase I clinical trial using this TCRαβ/CD19-depletion method in haploidentical HSC transplantation is to begin in the current year. In parallel, we developed preclinical models to explore the post-transplant HSC persistence and differentiation, and to evaluate the role of accompanying cell populations in facilitating HSC engraftment and immune recovery. We evaluated the efficiency of both CliniMACS and AutoMACS αβ TCR T cell depletion procedures by flow cytometry. Threshold numbers of contaminating αβ TCR T cells capable of inducing acute GVHD were determined after adoptive cell transfer in immunodeficient NOD.Scid.gamma mice. In vivo post-transplant persistence of αβ TCR and of γδ TCR T cells, NK cells and CD34+ engraftment were determined by flow cytometry at early (1–4 week) and late (5–12 week) time points. In addition to monitoring the post-transplant animal health status as a measure of graft alloreactivity/xenoreactivity, T cell activation markers (CD197, CD45RA) were assessed by flow cytometry. The murine models we developed will be instrumental in determining the effect of drug therapies on T cell reconstitution.