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Employing the thematic concerns and theoretical methods of animal studies, this thesis investigates two representative poets of modern Chinese poetry: Shang Qin (1930-2010) and Zang Di (1964-). These two poets harness their poetic imaginations to explore the potential of re-establishing connections between humans and animals. In Shang Qin’s poems, surrealism is not merely a technical device; rather, animals contribute to the ability of the poems to traverse reality and dreams. Zang displays a deeper interest in re-engaging with earth and its inhabitants through the lens of poetic imagination, envisioning the limitless possibilities of life. These animal poems and the poetics of animals present an imagination that recalls animals from silence.

The popularity of quinoa seeds has increased in the last decade due to their high nutritional value and natural gluten-free composition. Consumption of new proteins may pose a risk of introducing new allergies. In the present study the immunogenicity and sensitising capacity of quinoa proteins were assessed in a dose-response experiment in Brown Norway rats in comparison to proteins from spinach and peanut. Cross-reactivity between quinoa proteins and known allergens was evaluated by in silico analyses followed by analyses with 11 selected protein extracts and their anti-sera by means of ELISAs and immunoblotting. Further, an in vitro simulated gastro-duodenal digestion was performed. Quinoa proteins were found to have an inherent medium to high immunogenicity and sensitising capacity, being able to induce specific IgG1 and IgE levels higher than spinach but lower than peanut and elicit reactions of clinical relevance similar to peanut. Quinoa proteins were generally shown to resist digestion and retain capacity to bind quinoa-specific antibodies. Quinoa proteins were shown to be cross-reactive with peanut and tree nut allergens as high sequence homology and antibody cross-binding were demonstrated. Present study suggests that quinoa pose a medium to high level of allergenicity that should be further investigated in human studies.

PURPOSE: We aimed to histologically evaluate the influence of bone materials used during guided bone regeneration (GBR) on subsequent peri-implantitis in an experimental ligature-induced peri-implantitis model in beagle dogs. METHODS: Bilateral mandibular premolars (PM2-4) were extracted from six beagle dogs. After 3 months, standardized bone defects (3 mm [mesio-distal width] × 2 mm [bucco-lingual width] × 3 mm [depth]) were created in the experimental group, with simultaneous dental implant placement at the center of the defects. The defects were randomly filled with either autograft (AG) or deproteinized bovine bone mineral (DBBM) and covered with a collagen membrane. In the control group, implant fixtures were placed without creating an intrabony defect. After 3 months, a healing abutment was placed. Four weeks later, a 3-0 silk thread was ligated around the implants to induce peri-implantitis. After 4 weeks, the specimens were dissected and histologically examined. RESULTS: There were no clinical findings of inflammation until silk thread ligation. Four weeks after the onset of peri-implantitis, gingival redness and swelling were seen with mild resorption of the peri-implant bone on dental radiographs. There were no significant differences between the AG, DBBM, and control groups for the following parameters: bone-to-implant contact, distance from the implant shoulder to the base of the bone defect, area of bone defect, and area of new bone. CONCLUSIONS: Within the limitations of this study, it can be concluded that peri-implant tissues after GBR using AG and DBBM underwent the same degree of bone resorption by peri-implantitis as the no defect group.

Background During severe respiratory failure, hypoxic pulmonary vasoconstriction (HPV) is partly suppressed, but may still play a role in increasing pulmonary vascular resistance (PVR). Experimental studies suggest that the degree of HPV during severe respiratory failure is dependent on pulmonary oxygen tension (PvO(2)). Therefore, it has been suggested that increasing PvO(2) by veno-venous extracorporeal membrane oxygenation (V-V ECMO) would adequately reduce PVR in V-V ECMO patients. Objective Whether increased PvO(2) by V-V ECMO decreases PVR in global alveolar hypoxia. Methods Nine landrace pigs were ventilated with a mixture of oxygen and nitrogen. After 15 minutes of stable ventilation and hemodynamics, the animals were cannulated for V-V ECMO. Starting with alveolar normoxia, the fraction of inspiratory oxygen (FIO2) was stepwise reduced to establish different degrees of alveolar hypoxia. PvO(2) was increased by V-V ECMO. Results V-V ECMO decreased PVR (from 5.5 [4.5-7.1] to 3.4 [2.6-3.9] mm Hg L-1 min, P = .006) (median (interquartile range),) during ventilation with FIO2 of 0.15. At lower FIO2, PVR increased; at FIO2 0.10 to 4.9 [4.2-7.0], P = .036, at FIO2 0.05 to 6.0 [4.3-8.6], P = .002, and at FIO2 0 to 5.4 [3.5 - 7.0] mm Hg L-1 min, P = .05. Conclusions The effect of increased PvO(2) by V-V ECMO on PVR depended highly on the degree of alveolar hypoxia. Our results partly explain why V-V ECMO does not always reduce right ventricular afterload at severe alveolar hypoxia.

Alzheimer’s disease (AD) and cerebrovascular disease (CVD) are the two most prevalent causes of dementia. However, the molecular basis of AD and Vascular dementia (VaD) remains incompletely understood, and effective treatments are still not available. In the last three decades, the interaction(s) between CVD and AD have attracted considerable interest. Mixed AD/CVD pathology is commonly seen in patients with clinically diagnosed AD dementia. Combined vascular and AD pathology is the leading cause of dementia in the very old, and there is a debate on whether this is due to an additive effect of both pathologies on cognitive impairment, and whether it represents an interaction between the two pathologies. This thesis explored the association and interaction between cerebrovascular disease and AD pathology/dementia from the perspectives of plasma lipid profiles, imaging biomarkers, post-mortem pathology, and animal models. In addition, studies on plasma biomarkers of AD and VaD and their independent contribution to dementia and cognitive decline were interpreted. In chapter 2, a systematic review and meta-analyses of several cerebral small vessel disease (CSVD) imaging biomarkers and AD found that CSVDs alone were not able to predict AD incidence but were associated with AD dementia and AD pathology. The strength of relationship increased with the presence of Apolipoprotein E (APOE ε4) genotype. Periventricular and parietal white matter hyperintensities (WMHs) and cortical microbleeds (CMBs) had stronger association with AD than CSVDs in other regions. Microinfarcts were less well studied in related imaging studies. We also further explored CSVDs and other cerebral vascular injuries in the aspect of neuropathology. In chapter 3, a cross-sectional study of autopsy brain pathology from National Alzheimer’s Coordinating Center (NACC) showed that CVD pathology had an additive effect with AD pathology in the development and progression of Alzheimer’s dementia.The relationsh

Background: Fracture fixation has advanced significantly with the introduction of locked plating and minimally invasive surgical techniques. However, healing complications occur in up to 10% of cases, of which a significant portion may be attributed to unfavorable mechanical conditions at the fracture. Moreover, state-of-the-art plates are prone to failure from excessive loading or fatigue. A novel biphasic plating concept has been developed to create reliable mechanical conditions for timely bone healing and simultaneously improve implant strength. This paper introduces the novel fixation concept and presents preclinical results from a large animal study. Methods: Twenty-four sheep underwent a mid-diaphyseal osteotomy stabilized with either the novel biphasic plate fixator or a control locking plate. Different fracture patterns regarding orientation and localization were investigated. Animals were free to fully bear weight during the post-operative period. After 12 weeks, the healing fractures were evaluated for bone formation using micro-computer tomography and strength and stiffness using biomechanical testing. Additionally, histological evaluation of soft tissue samples with respect to metal wear debris was performed. Results: No plate deformation or failures were observed under full weight bearing with the biphasic plate. Defects stabilized with the biphasic plate demonstrated robust callus formation compared to control group. Torsion tests after plate removal revealed no statistical difference in peak torsion to failure and stiffness for the different fracture patterns stabilized with the biphasic plate. However, the biphasic plate group specimens were 45% stronger (p=0.002) and 48% stiffer (p=0.007) than the controls. No histological signs of metal wear due to the biphasic feature could be found. Conclusions: The biphasic plate concept is aimed at improving the biomechanics of locked plating.

This paper is the accumulation of library and laboratory research regarding perivascular adipose tissue as it relates to cardiovascular disease and obesity. The study investigated the impact of isoproterenol, a drug known to imitate epinephrine and other stimuli of the sympathetic nervous system, on the expansion rate of fatty tissue in rats. This work may potentially lead to future human clinical trials to reduce obesity and cardiovascular disease prevalence in our population. Without the aid of dozens of scholarly resources, this project would not have been able to come to fruition.

Background: Mean arterial blood pressure (MAP) and/or pump flow during normothermic cardiopulmonary bypass (CPB) are the most important factors of cerebral perfusion. The aim of this study was to explore the influence of CPB blood flow on cerebral blood flow (CBF) measured by dynamic positron emission tomography (PET) using O-15-labelled water with no pharmacological interventions to maintain the MAP. Methods: Eight pigs (69-71 kg) were connected to normothermic CPB. After 60 minutes (min) with a CPB pump flow of 60 mL/kg/min, the pigs were changed to either 35 mL/kg/min or 47.5 mL/kg/min for 60 min and, thereafter, all the pigs returned to 60 mL/kg/min for another 60 min. The MAP was measured continuously and the CBF was measured by positron emission tomography (PET) during spontaneous circulation and at each CPB pump flow after 30 min of steady state. Results: Two pigs were excluded due to complications. CBF increased from spontaneous circulation to a CPB pump flow of 60 mL/kg/min. A reduction in CPB pump flow to 47.5 mL/kg/min (n=3) resulted in only minor changes in CBF while a reduction to 35 mL/kg/min (n=3) caused a pronounced change (correlation coefficient (R-2) 0.56). A return of CPB pump flow to 60 mL/kg/min was followed by an increase in CBF, except in the one pig with the lowest CBF during low flow (R-2=0.44). CBF and MAP were not correlated (R-2=0.20). Conclusion: In this experimental porcine study, a relationship was observed between pump flow and CBF under normothermic low-flow CPB. The effect of low pump flow on MAP showed substantial variations, with no correlation between CBF and MAP.

Background: Muscle tissue saturation (StO(2)) measured with near-infrared spectroscopy has generally been considered a measurement of the tissue microcirculatory condition. However, we hypothesized that StO2 could be more regarded as a fast and reliable measure of global than of regional circulatory adequacy and tested this with muscle, intestinal and brain metabolomics at normal and two levels of low cardiopulmonary bypass blood flow rates in a porcine model. Methods: Twelve 80 kg pigs were connected to normothermic cardiopulmonary bypass with a blood flow of 60 mL/kg/min for one hour, reduced randomly to 47.5 mL/kg/min (Group I) or 35 mL/kg/min (Group II) for one hour followed by one hour of 60 mL/kg/min in both groups. Regional StO(2) was measured continuously above the musculus gracilis (non-cannulated leg). Metabolomics were obtained by brain tissue oxygen monitoring system (Licox) measurements of the brain and microdialysis perfusate from the muscle, intestinal mucosa and brain. A non-parametric statistical method was used. Results: The systemic parameters showed profound systemic ischaemia during low CPB blood flow. StO(2) did not change markedly in Group I, but in Group II, StO(2) decreased immediately when blood flow was reduced and, furthermore, was not restored despite blood flow being normalized. Changes in the metabolomics from the muscle, colon and brain followed the changes in StO(2). Conclusion: We found, in this experimental cardiopulmonary bypass model, that StO(2) reacted rapidly when the systemic circulation became inadequate and, furthermore, reliably indicate insufficient global tissue perfusion even when the systemic circulation was restored after a period of systemic hypoperfusion.

OBJECTIVE: To investigate whether changes in muscle tissue perfusion measured with positron emission tomography would be reflected by parallel changes in muscle tissue oxygen saturation (StO2) measured using near-infrared spectroscopy during high and low blood flow levels achieved using cardiopulmonary bypass (CPB) in an animal model. DESIGN: A prospective, randomized study. SETTING: Research laboratory, single institution. PARTICIPANTS: Eight pigs (69-71 kg). INTERVENTIONS: In anesthetized pigs, normothermic CPB was established with a blood flow of 60 mL/kg/min for 1 hour. Thereafter, a low blood flow of either 47.5 or 35 mL/kg/min was applied for 1 hour followed by a blood flow of 60 mL/kg/min for an additional hour. Regional StO2 was measured continuously by placing a near-infrared spectroscopy electrode on the skin above the gracilis muscle of the noncannulated back leg. Muscle tissue perfusion was measured using positron emission tomography with (15)O-labeled water during spontaneous circulation and the different CPB blood flows. Systemic oxygen consumption was estimated by measurement of venous saturation and lactate levels. MEASUREMENTS AND MAIN RESULTS: The results showed profound systemic ischemia during low CPB blood flow. StO2 remained high until muscle tissue perfusion decreased to about 50%, after which StO2 paralleled the linear decrease in muscle tissue perfusion. CONCLUSION: In an experimental CPB animal model, StO2 was stable until muscle tissue perfusion was reduced by about 50%, and at lower blood flow levels, there was almost a linear relationship between StO2 and muscle tissue perfusion.

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Iron (Fe) nanoparticles have been synthesized by simple co-precipitation method. The x-ray diffraction studies indicated the formation of Fe nanoparticles with cubic phase. Surface morphology of Fe and has been studied using scanning electron microscopy (SEM). Transmission electron microscopy (TEM) images reveal that Fe nanoparticle have size ranging from 25-41 nm. Also we have reported about the changes in the growth of piglets such as its body weight (kg), its haemoglobin (g %) level, its hematocrit (%) level and its erythrocyte count, when it was supplemented with different compositions of iron nanoparticles since iron is an integral component of hemoglobin which plays major role in supply of oxygen for normal functioning of body cells. Besides that iron is necessary for activity of several enzymes and catalytic pathways at cellular level. &nbsp

Iron (Fe) nanoparticles have been synthesized by simple co-precipitation method. The x-ray diffraction studies indicated the formation of Fe nanoparticles with cubic phase. Surface morphology of Fe and has been studied using scanning electron microscopy (SEM). Transmission electron microscopy (TEM) images reveal that Fe nanoparticle have size ranging from 25-41 nm. Also we have reported about the changes in the growth of piglets such as its body weight (kg), its haemoglobin (g %) level, its hematocrit (%) level and its erythrocyte count, when it was supplemented with different compositions of iron nanoparticles since iron is an integral component of hemoglobin which plays major role in supply of oxygen for normal functioning of body cells. Besides that iron is necessary for activity of several enzymes and catalytic pathways at cellular level. &nbsp

Background: Open-vent jet nebulizers are frequently used to promote drug deposition in the lung, but their clinical efficacy and indications are not clear. Our study compared lung deposition of amikacin using two different configurations of a jet nebulizer (Sidestream(®)): one vented (N1) and one unvented with a corrugated piece of tubing (N2). Methods: In vitro nebulizer performance was assessed by laser diffraction and filtering. Lung delivery was evaluated by scintigraphy in baboons as a child model, and by amikacin urinary drug concentration in seven healthy spontaneously breathing volunteers. Subjects were randomly assigned to the two nebulizer systems (N1 and N2). Results and conclusions: In vitro results showed a higher efficiency of N2 than N1 in terms of lung deposition prediction (95±3 mg vs. 70±0 mg; p<0.0001). Radioactivity deposition in the baboons' lungs was lower with N1 than with N2 (1.8% vs. 4.7% of nebulizer charge; p<0.05). The total daily amount of amikacin urinary excretion was lower with N1 than with N2 (29.5 mg vs. 40.1 mg; p<0.01). Conversely, in vivo drug output rate was higher with N1 than with N2 (3.1 mg/min vs. 2.2 mg/min; p<0.05). Using a corrugated piece of tubing with standard jet nebulizers delivers higher doses to the lungs than open-vent jet nebulizers. The open-vent jet nebulizer might be recommended for rapid administration of a lower dose to the lungs and the standard jet nebulizer with corrugated piece of tubing for a higher dose in the lungs.

Vertebral cement augmentation is reported to be a safe and effective technique for providing stabilization and pain relief. However, adjacent intervertebral discs may be at risk of accelerated degeneration as a result of aggravated nutritional constraints. Therefore, we investigated the effects of injecting polymethylmethacrylate (PMMA) into three adjacent lumbar vertebrae on intervertebral disc and vertebral bone tissue in 12 skeletally mature sheep. After 6 and 12 months of augmentation, the sheep were euthanized and their spines were processes for histological evaluation. Semiquantitative histomorphological analysis of discs and endplates was conducted using published criteria. Histomorphological changes in the augmented bone were assessed qualitatively. Free to read Approximately 80% of the length of the endplates was in contact with PMMA. However, there was no significant difference between the histopathological score of the discs adjacent to augmented vertebrae and the score of the control discs. Bone tissue reaction to PMMA was characterized by a thin fibrous tissue layer and occasional foreign-body reactions. New bone formation was present in all augmented vertebrae. Concerns about aggravation of disc degeneration as a result of vertebral cement augmentation seem to be unsubstantiated. Furthermore, adverse effects of PMMA cement on bone biology do not seem to be a relevant issue. © 2011 Wiley Periodicals

PURPOSE: Large infusion of crystalloids may induce acid-base alterations according to their strong ion difference ([SID]). We wanted to prove in vivo, at constant PCO(2), that if the [SID] of the infused crystalloid is equal to baseline plasma bicarbonate, the arterial pH remains unchanged, if lower it decreases, and if higher it increases. METHODS: In 12 pigs, anesthetized and mechanically ventilated at PCO(2) ≈40 mmHg, 2.2 l of crystalloids with a [SID] similar to (lactated Ringer's 28.3 mEq/l), lower than (normal saline 0 mEq/l), and greater than (rehydrating III 55 mEq/l) baseline bicarbonate (29.22 ± 2.72 mEq/l) were infused for 120 min in randomized sequence. Four hours of wash-out were allowed between the infusions. Every 30 min up to minute 120 we measured blood gases, plasma electrolytes, urinary volume, pH, and electrolytes. Albumin, hemoglobin, and phosphates were measured at time 0 and 120 min. RESULTS: Lactated Ringer's maintained arterial pH unchanged (from 7.47 ± 0.06 to 7.47 ± 0.03) despite a plasma dilution around 12%. Normal saline caused a reduction in pH (from 7.49 ± 0.03 to 7.42 ± 0.04) and rehydrating III induced an increase in pH (from 7.46 ± 0.05 to 7.49 ± 0.04). The kidney reacted to the infusion, minimizing the acid-base alterations, by increasing/decreasing the urinary anion gap, primarily by changing sodium and chloride concentrations. Lower urine volume after normal saline infusion was possibly due to its greater osmolarity and chloride concentration as compared to the other solutions. CONCLUSIONS: Results support the hypothesis that at constant PCO(2), pH changes are predictable from the difference between the [SID] of the infused solution and baseline plasma bicarbonate concentration

The study of the in-vivo regeneration of a nerve, made by purely histological methods, requires a high number of animals: this poses serious problems of technique, ethics and funding. A cheaper analysis, performed on the same animal along the duration of a study, is seeked with favour and Authors wanted to evaluate gait recovery after sciatic nerve transection as a non-invasive method to evaluate the performance of an artificial nerve-guide in rats. Male Wistar rats (n=16) were divided into three groups: in group A (n=5) the experimental gap produced was bridged by a custom-made guide; in group B (n=7) animals were “sham-operated”; in group C (n=4) a PMMA cap sealed the proximal nerve stump. In group A a regenerated nerve was retrieved after 8 weeks, in all animals. In group B it was possible to retrieve mostly bulbous neuromatous stumps. In group C all the animals presented a voluminous neuroma. Signs of auto-mutilation had the following distribution: 1/5 in group A; 4/7 in group B; 3/4 in group C. A clear difference in gait recovery exists only between group C (no recovery) and the two other groups (early recovery in both). The present study highlights that in the male Wistar rat sciatic model a spontaneous recovery in gait pattern occurs very early (within the first or second week); with this animal model, a recovery in gait is likely to ensue irrespective of the kind of device eventually tested since it may happen even without a device.

The biocompatibility of titanium implants in bone depends on the response shown by cells in contact with the implant surface. Several developments have been targeted at achieving successful implant treatment. The aim of this study was to develop a novel preparation procedure to evaluate the bone cell response produced at the bone–implant interface using the technique scanning electron microscopy with backscattered electron imaging (SEM-BSE). Dental prostheses with an SLA-modified or TOP-modified surface were implanted in a toothless part of the mandibula in female pigs. The animals were sacrificed 12 weeks after surgery, at which time block specimens containing the implants were obtained. These specimens were then processed for SEM-BSE by optimizing a protocol involving chemical fixation and heavy metal staining. In addition, element distribution maps for the implant–bone tissue interface were obtained using a microanalytical system based on energy-dispersive X-ray spectrometry (EDS). This novel visualisation approach enabled a comprehensive study of the extracellular matrix and cell components of the host tissues neoformed around the implant. SEM-BSE images also provided ultrastructural details of the bone cells. This technique appears to be an effective and very promising tool for detailed studies on the implant–bone tissue interface and the host response to the bone incorporation process

The 90-day animal study is the core study for the safety assessment of genetically modified foods in the SAFOTEST project. The model compound tested in the 90-day study was a rice variety expressing the kidney bean Phaseolus vulgaris lectin agglutinin E-form (PHA-E lectin). Female Wistar rats were given a nutritionally balanced purified diet with 60% parental rice, 60% PHA-E rice or 60% PHA-E rice spiked with 0.1% recombinant PHA-E lectin for 90 days. This corresponded to a mean daily PHA-E lectin intake of approximately 0, 30 and 100 mg/kg body weight for each group, respectively. The spiking was used to increase the specificity and to demonstrate the sensitivity of the study. A range of biological, biochemical, microbiological and pathological parameters were examined and significant differences in weight of small intestine, stomach and pancreas and plasma biochemistry were seen between groups. Included in this paper are also data from the molecular characterisation and chemical analysis of the PHA-E rice, from the construction and production of the PHA-E lectin, and from the preceding 28-day in vivo study where the toxicity of the pure PHA-E lectin was determined. In conclusion, the combined use of information from the compositional analysis, the 28-day study and the characterisation of the PHA-E rice and the PHA-E lectin has improved the design of the 90-day study. The spiking procedure has facilitated the interpretation of the results of the study and transferred it into a valuable tool for the future safety testing of genetically modified foods.

An animal model for safety assessment of genetically modified foods was tested as part of the SAFOTEST project. In a 90-day feeding study on Wistar rats, the transgenic KMD1 rice expressing Cry1Ab protein was compared to its non-transgenic parental wild type, Xiushui 11. The KMD1 rice contained 15 mg Bt toxin/kg and based on the average feed consumption the daily intake was 0.54 mg Bt toxin/ kg body weight. No adverse effects on animal behaviour or weight gain were observed during the study. Blood samples collected one week prior to sacrifice were analyzed and compared for standard haematological and biochemical parameters. A few parameters were significantly different, but all within the normal reference intervals for rats of this breed and age and not in relation to any other findings, thus not considered treatment related. Upon sacrifice a large number of organs were weighed, macroscopic and histopathological examinations were performed with only minor changes to report. The aim of the study was to use a known animal model in performance of safety assessment of a GM crop, in this case KMD1 rice. The results show no adverse or toxic effects of KMD1 rice when tested in the design used in this 90-day study. Nevertheless the experiences from this study lead to the overall conclusion that safety assessment for unintended effects of a GM crop cannot be done without additional test group(s).

Genetically modified plants expressing insecticidal traits offer a new strategy for crop protection, but at the same time present a challenge in terms of food safety assessment. The present 90-day feeding study was designed to assess the safety of a rice variety expressing the snowdrop Galanthus nivalis lectin (GNA lectin), and forms part of a EU-funded project where the objective has been to develop and validate sensitive and specific methods to assess the safety of genetically modified foods. Mate and female Wistar rats were given a purified diet containing either 60% genetically modified or parental rice for 90 days. This corresponds to a mean daily GNA lectin intake of approximately 58 and 67 mg/kg body weight for males and females, respectively. Prior to the animal study comprehensive analytical characterization of both rice materials was performed. The chemical analyses showed a number of statistically significant differences, with the majority being within the ranges reported in the literature. In the animal study a range of clinical, biological, immunological, microbiological and pathological parameters were examined. A number of significant differences were seen between groups fed the two diets, but none of them were considered to be adverse. In conclusion, the design of the present animal study did not enable us to conclude on the safety of the GM food. Additional group(s) where the expressed gene products have been spiked to the diet should be included in order to be able to distinguish whether the observed effects were due to the GNA lectin per se or to secondary changes in the GM rice.

The 90-day animal study is the core study for the safety assessment of genetically modified foods in the SAFOTEST project. The model compound tested in the 90-day study was a rice variety expressing the kidney bean Phaseolus vulgaris lectin agglutinin E-form (PHA-E lectin). Female Wistar rats were given a nutritionally balanced purified diet with 60% parental rice, 60% PHA-E rice or 60% PHA-E rice spiked with 0.1% recombinant PHA-E lectin for 90 days. This corresponded to a mean daily PHA-E lectin intake of approximately 0, 30 and 100 mg/kg body weight for each group, respectively. The spiking was used to increase the specificity and to demonstrate the sensitivity of the study. A range of biological, biochemical, microbiological and pathological parameters were examined and significant differences in weight of small intestine, stomach and pancreas and plasma biochemistry were seen between groups. Included in this paper are also data from the molecular characterisation and chemical analysis of the PHA-E rice, from the construction and production of the PHA-E lectin, and from the preceding 28-day in vivo study where the toxicity of the pure PHA-E lectin was determined. In conclusion, the combined use of information from the compositional analysis, the 28-day study and the characterisation of the PHA-E rice and the PHA-E lectin has improved the design of the 90-day study. The spiking procedure has facilitated the interpretation of the results of the study and transferred it into a valuable tool for the future safety testing of genetically modified foods.

Genetically modified plants expressing insecticidal traits offer a new strategy for crop protection, but at the same time present a challenge in terms of food safety assessment. The present 90-day feeding study was designed to assess the safety of a rice variety expressing the snowdrop Galanthus nivalis lectin (GNA lectin), and forms part of a EU-funded project where the objective has been to develop and validate sensitive and specific methods to assess the safety of genetically modified foods. Mate and female Wistar rats were given a purified diet containing either 60% genetically modified or parental rice for 90 days. This corresponds to a mean daily GNA lectin intake of approximately 58 and 67 mg/kg body weight for males and females, respectively. Prior to the animal study comprehensive analytical characterization of both rice materials was performed. The chemical analyses showed a number of statistically significant differences, with the majority being within the ranges reported in the literature. In the animal study a range of clinical, biological, immunological, microbiological and pathological parameters were examined. A number of significant differences were seen between groups fed the two diets, but none of them were considered to be adverse. In conclusion, the design of the present animal study did not enable us to conclude on the safety of the GM food. Additional group(s) where the expressed gene products have been spiked to the diet should be included in order to be able to distinguish whether the observed effects were due to the GNA lectin per se or to secondary changes in the GM rice.

An animal model for safety assessment of genetically modified foods was tested as part of the SAFOTEST project. In a 90-day feeding study on Wistar rats, the transgenic KMD1 rice expressing Cry1Ab protein was compared to its non-transgenic parental wild type, Xiushui 11. The KMD1 rice contained 15 mg Bt toxin/kg and based on the average feed consumption the daily intake was 0.54 mg Bt toxin/ kg body weight. No adverse effects on animal behaviour or weight gain were observed during the study. Blood samples collected one week prior to sacrifice were analyzed and compared for standard haematological and biochemical parameters. A few parameters were significantly different, but all within the normal reference intervals for rats of this breed and age and not in relation to any other findings, thus not considered treatment related. Upon sacrifice a large number of organs were weighed, macroscopic and histopathological examinations were performed with only minor changes to report. The aim of the study was to use a known animal model in performance of safety assessment of a GM crop, in this case KMD1 rice. The results show no adverse or toxic effects of KMD1 rice when tested in the design used in this 90-day study. Nevertheless the experiences from this study lead to the overall conclusion that safety assessment for unintended effects of a GM crop cannot be done without additional test group(s).

Purpose: To determine whether the contrast agent MnHPTA has potential for detecting differences in myocardial blood flow. Materials and Methods: R1 in the myocardium was calculated from MR signal intensity measurements in 18 pigs after intravenous injection of 5, 15, or 25 mu mol MnHPTA/kg body weight. Measurements were made in each animal after administration at rest and during dobutamine-induced stress. Results: A difference of approximately 0.1 see(-1) in the R1 increase between rest and stress still remained 31 minutes after administration of 25 mu mol MnHPTA/kg body weight. When two consecutive MnHPTA injections were performed, the second injection induced a lower R1 increase than the corresponding first injection. Conclusion: MnHPTA at a dose of 25 mu mol/kg body weight (b.w.) has the potential to detect perfusion differences in myocardium. When two consecutive injections of MnHPTA were administered, the RI change after the second injection was affected by the earlier administration. Therefore, a protocol including more than one administration is not ideal for this contrast agent.

Purpose: To determine whether the contrast agent Mn-HPTA has potential for detecting differences in myocardial blood flow. Materials and Methods: R1 in the myocardium was calculated from MR signal intensity measurements in 18 pigs after intravenous injection of 5, 15, or 25 µmol MnHPTA/kg body weight. Measurements were made in each animal after administration at rest and during dobutamine-induced stress. Results: A difference of approximately 0.1 sec -1 in the R1 increase between rest and stress still remained 31 minutes after administration of 25 µmol MnHPTA/kg body weight. When two consecutive MnHPTA injections were performed, the second injection induced a lower R1 increase than the corresponding first injection. Conclusion: MnHPTA at a dose of 25µmol/kg body weight (b.w.) has the potential to detect perfusion differences in myocardium. When two consecutive injections of MnHPTA were administered, the R1 change after the second injection was affected by the earlier administration. Therefore, a protocol including more than one administration is not ideal for this contrast agent. © 2006 Wiley-Liss, Inc.

type:text, Accumulating evidence indicates that an important event in the tissue response in periodontal disease is the recruitment of polymorphonuclear leukocytes (PMN). This study investigated immunohistochemical expression of CXC-chemokines, including macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant-2 (CINC-2) in rat periodontal tissue at 1 and 3 hours and 1, 2, 3 and 7 days after topical application of lipopolysaccharide (LPS; 5 mg/ml in saline) from E. Coli into the rat molar gingival sulcus. In normal periodontal tissues before LPS application, a small number of MIP-2 and CINC-2 positive cells were seen in junctional epithelium (JE) especially in its coronal half. After topical application of LPS, a prominent increase of MIP-2 and CINC-2 positive JE cells was observed. Almost all JE cells strongly expressed them at day 1 and day 2, and then the number of chemokine-positive cells returned to normal at day 7. Corresponding to these chemokine expressions, LPS application induced a significant increase in number of PMNs in sub-JE area at 1 hour (P <0.01) and 3 hours (P <0.05) and a significant increase in JE area at 1 day(P< 0.05) and 2 days (P <0.01), indicating a dynamic flow of PMNs from the sub-JE area into JE. These findings indicated that JE cells produced MIP-2 and CINC-2 in response to LPS stimulation and suggested that MIP-2 and CINC-2 may be responsible for PMN migration toward the periodontal pathogen and may play an important role in the initiation of inflammation and subsequent periodontal tissue destruction.

Accumulating evidence indicates that an important event in the tissue response in periodontal disease is the recruitment of polymorphonuclear leukocytes (PMN). This study investigated immunohistochemical expression of CXC-chemokines, including macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant-2 (CINC-2) in rat periodontal tissue at 1 and 3 hours and 1, 2, 3 and 7 days after topical application of lipopolysaccharide (LPS; 5 mg/ml in saline) from E. Coli into the rat molar gingival sulcus. In normal periodontal tissues before LPS application, a small number of MIP-2 and CINC-2 positive cells were seen in junctional epithelium (JE) especially in its coronal half. After topical application of LPS, a prominent increase of MIP-2 and CINC-2 positive JE cells was observed. Almost all JE cells strongly expressed them at day 1 and day 2, and then the number of chemokine-positive cells returned to normal at day 7. Corresponding to these chemokine expressions, LPS application induced a significant increase in number of PMNs in sub-JE area at 1 hour (P <0.01) and 3 hours (P <0.05) and a significant increase in JE area at 1 day(P< 0.05) and 2 days (P <0.01), indicating a dynamic flow of PMNs from the sub-JE area into JE. These findings indicated that JE cells produced MIP-2 and CINC-2 in response to LPS stimulation and suggested that MIP-2 and CINC-2 may be responsible for PMN migration toward the periodontal pathogen and may play an important role in the initiation of inflammation and subsequent periodontal tissue destruction.

A method for production of carrier-free (114m)In (half-life 49.5 days), which is a potential radionuclide for radionuclide therapy of slowly growing tumors, is presented. A target consisting of five enriched cadmium ((114)Cd) foils, each 50 microm thick, was irradiated by protons (from 12.6-6.5 MeV) giving a target yield of 0. 8 MBq/microAh. A simple and cost-efficient thermal diffusion method was used for the separation. The irradiated target foils were heated for 2 h at 306 degrees C and then etched in 0.05 M HCl. The obtained cadmium/indium solution was purified using a cation ion-exchange resin (AG 1 x 8, Bio-Rad Laboratories, Hercules, CA USA). An overall yield of approximately 60% was obtained, whereas the loss of the target material was <1% per separation cycle. The (114m)In production gave (114m)In with high specific radioactivity and was successfully used to label diethylenetriamine pentaacetic acid (DTPA)-D-Phe-octreotide. Furthermore, no difference in biodistribution between [(114m)In]- and [(111)In]-DTPA-D-Phe(1)-octreotide in tumor-bearing nude mice was seen. The high radionuclide uptake in the tumors indicates a good receptor binding of the labeled octreotide.

Accumulating evidence indicates that an important event in the tissue response in periodontal disease is the recruitment of polymorphonuclear leukocytes (PMN). This study investigated immunohistochemical expression of CXC-chemokines, including macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant-2 (CINC-2) in rat periodontal tissue at 1 and 3 hours and 1, 2, 3 and 7 days after topical application of lipopolysaccharide (LPS; 5 mg/ml in saline) from E. Coli into the rat molar gingival sulcus. In normal periodontal tissues before LPS application, a small number of MIP-2 and CINC-2 positive cells were seen in junctional epithelium (JE) especially in its coronal half. After topical application of LPS, a prominent increase of MIP-2 and CINC-2 positive JE cells was observed. Almost all JE cells strongly expressed them at day 1 and day 2, and then the number of chemokine-positive cells returned to normal at day 7. Corresponding to these chemokine expressions, LPS application induced a significant increase in number of PMNs in sub-JE area at 1 hour (P <0.01) and 3 hours (P <0.05) and a significant increase in JE area at 1 day(P< 0.05) and 2 days (P <0.01), indicating a dynamic flow of PMNs from the sub-JE area into JE. These findings indicated that JE cells produced MIP-2 and CINC-2 in response to LPS stimulation and suggested that MIP-2 and CINC-2 may be responsible for PMN migration toward the periodontal pathogen and may play an important role in the initiation of inflammation and subsequent periodontal tissue destruction.