bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum pharmacokinetics of oxytetracycline in sheep and calves and tissue residues in sheep following a single intramuscular injection of a long‐acting preparation
Authors: CRAIGMILL A. L. , HOLLAND R. E. , ROBINSON D. , WETZLICH S. , ARNDT T.
Published: September 2010

The pharmacokinetics of a long‐acting oxytetracycline (OTC) formulation (Liquamycin® LA‐200®) injected intramuscularly (i.m.) at a dose of 20 mg/kg were determined in four calves and 24 sheep to determine if the approved label dose for cattle provided a similar serum time/concentration profile in sheep. TheAUCfor the calves was 168±14.6 (μg ? h/mL) and was significantly less than theAUCfor sheep (209±43 μg ? h/mL). Using the standard two‐stage approach and a one‐compartment model, the meanCmax for the calves was 5.2±0.8 μg/mL, and for the sheep was 6.1±1.3 μg/mL. The mean terminal phase rate constants were 0.031 and 0.033 h, and theVdss were 3.3 and 3.08 L/kg for the calves and sheep respectively. Analysis of the data using the standard two‐stage approach, the naive pooled‐data approach and a population model gave very similar results for both the cattle and sheep data. Sheep tissue residues of OTC in serum, liver, kidney, fat, muscle and injection site were measured at 1, 2, 3, 5, 7 and 14 days after a single i.m. injection of 20 mg/kg OTC. Half‐lives of OTC residues in the tissues were 38.6, 33.4, 28.6, 25.4, 21.3, and 19.9 h for injection site, kidney, muscle, liver, mesenteric fat and renal fat, respectively. The ratio of tissue to serum concentration was fairly consistent at all slaughter times, except for the fat and injection sites. The mean ratios were 1.72, 4.19, 0.11, 0.061, 0.84 and 827 for the liver, kidney, renal fat, mesenteric fat, muscle and injection sites, respectively. The tissue concentrations of OTC residues were below the established cattle tolerances for OTC in liver (6 p.p.m.), muscle (2 p.p.m.) and kidney (12 p.p.m.) by 48 h, and in injection site muscle by 14 days after the single i.m. injection of 20 mg/kg.
Clenbuterol administration does not enhance the efficacy of furosemide in attenuating the exercise‐induced pulmonary capillary hypertension in Thoroughbred horses
Authors: MANOHAR M. , GOETZ T. E. , ROTHENBAUM P. , HUMPHREY S.
Published: September 2010

The stimulation of pulmonary β2‐adrenergic receptors causes a decrease in vascular resistance. Thus, the present study was carried out to examine whether concomitant administration of clenbuterol—a β2‐adrenergic receptor agonist, to horses premedicated with furosemide would attenuate the exercise‐induced pulmonary capillary hypertension to a greater extent than furosemide alone, and in turn, affect the occurrence of exercise‐induced pulmonary hemorrhage (EIPH). Experiments were carried out on six healthy, sound, exercise‐trained Thoroughbred horses. All horses were studied in the control (no medications), furosemide (250 mg i.v., 4 h pre‐exercise)‐control, and furosemide (250 mg i.v., 4 h pre‐exercise)+clenbuterol (0.8 μg/kg i.v., 11 min pre‐ exercise) experiments. The sequence of these treatments was randomized for every horse, and 7 days were allowed between them. Using catheter‐tip‐transducers whosein‐vivosignals were referenced at the point of the left shoulder, pulmonary vascular pressures were determined at rest, sub‐maximal exercise, and during galloping at 14.2 m/s on a 3.5% uphill grade—a workload that elicited maximal heart rate. In the control study, incremental exercise resulted in progressive significant (P<0.05) increments in heart rate, right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures, and all horses experienced EIPH. Furosemide administration caused a significant (P<0.05) reduction in mean right atrial as well as pulmonary capillary and venous pressures of standing horses. Although exercise in the furosemide‐control experiments also caused right atrial and pulmonary vascular pressures to increase significantly (P<0.05), the increment in mean pulmonary capillary and wedge pressures was significantly (P<0.05) attenuated in comparison with the control study, but all horses experienced EIPH. Clenbuterol administration to standing horses premedicated with furosemide caused tachycardia, but significant changes in right atrial or pulmonary vascular pressures were not discerned at rest. During exercise in the furosemide+clenbuterol experiments, heart rate, mean right atrial as well as pulmonary arterial, capillary and wedge pressures increased significantly (P<0.05), but these data were not different from the furosemide–control experiments, and all horses experienced EIPH as well. Thus, it was concluded that clenbuterol administration is ineffective in modifying the pulmonary hemodynamic effects of furosemide in standing or exercising horses. Because the intravascular force exerted onto the blood–gas barrier of horses premedicated with furosemide remained unaffected by clenbuterol administration, it is believed that concomitant clenbuterol administration is unlikely to offer additional benefit to healthy horses experiencing EIPH.
Effects of single‐dose intravenous phenylbutazone on experimentally induced, reversible lameness in the horse
Authors: FOREMAN J. H. , BARANGE A. , LAWRENCE L. M. , HUNGERFORD L. L.
Published: September 2010

The objective was to test the hypothesis that phenylbutazone (PBZ) alleviates lameness in an adjustable heart bar shoe model of equine foot pain. Eight Quarter Horse mares underwent 4‐weekly treatments randomly: 0.9% saline placebo (SAL: 1 mL/45 kg body weight i.v.) with no lameness; SAL with lameness; PBZ (4.4 mg/kg body weight i.v.) with no lameness; and PBZ with lameness. Blinded heart rate (HR) and lameness score (LS) were assessed every 20 min for 2 h and then hourly through 9 h. At 1 h SAL or PBZ was administered. Jugular venous samples were obtained at hours 0, 1, 2, 4, 6, and 8 and were evaluated for packed cell volume (PCV), cortisol, and drug concentrations. Repeated measuresanovaandt‐tests were used to identify PBZ effects at a significance level ofP < 0.05. PBZ‐treated LS was lower 2–8 h post‐treatment, and HR was lower from 2 through 6 h post‐treatment (P < 0.05). Phenylbutazone did not change PCV and had minimal effect on cortisol. Mean plasma PBZ and oxyphenbutazone concentrations 7 h after treatment were 7.2–7.5 and 1.6–1.9 μg/mL, respectively. It was concluded that PBZ was efficacious in alleviating lameness in this model. Cortisol and PCV were not discriminating enough to distinguish between PBZ‐treated and SAL‐treated trials.
Pharmacokinetics of ivermectin in pregnant and nonpregnant sheep
Authors: PÉREZ R. , PALMA C. , NÚÑEZ M. J. , COX J. , ARBOIX M.
Published: September 2010

The plasma kinetic profile of ivermectin during the last trimester of pregnancy was studied in ewes after a single subcutaneous administration of 0.2 mg/kg body weight (BW). Sheep were randomly distributed into two groups. Ewes in group 1 (control,n = 6) were left unmated, whereas in group 2 (pregnant,n = 6) ewes were estrus‐synchronized and mated with rams. Both groups were housed under similar conditions of management and feeding. At 120 days of pregnancy, both groups were given a subcutaneous injection of 0.2 mg/kg BW of ivermectin. Blood samples were taken by jugular puncture according to a fixed protocol between 1 h and 40 days post‐treatment. After plasma extraction and derivatization, samples were analyzed by high performance liquid chromatography with fluorescence detection. A computerized pharmacokinetic analysis was performed, and the data were compared by means of the Studentt‐test.

The results showed that plasma concentrations of ivermectin remained longer in the pregnant than in the control group. The mean values of pharmacokinetic parametersCmax,tmax, and area under the concentration–time curve (AUC) were similar for both groups of sheep. The mean residence time (MRT) values for the pregnant group (8.8 ± 1.4 days) were higher (P < 0.05) than those observed in the control group (5.3 ± 1.9 days). It can be concluded that pregnancy increases the residence time of ivermectin in the plasma of pregnant sheep when it is administered subcutaneously.
Pharmacokinetic–pharmacodynamic integration of orbifloxacin in rabbits after intravenous, subcutaneous and intramuscular administration
Authors: MARÍN P. , FERNÁNDEZ‐VARÓN E. , ESCUDERO E. , VANCRAEYNEST D. , CÁRCELES C. M.
Published: September 2010

The single‐dose disposition kinetics of orbifloxacin were determined in clinically normal rabbits (n = 6) after intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) administration of 5 mg/kg bodyweight. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Minimal inhibitory concentrations (MICs) assay of orbifloxacin against 30 strains ofStaphylococcus aureusfrom several European countries was performed in order to compute pharmacodynamic surrogate markers. The concentration–time data were analysed by compartmental and noncompartmental kinetic methods. Steady‐state volume of distribution (Vss) and total body clearance (Cl) of orbifloxacin after i.v. administration were estimated to be 1.71 ± 0.38 L/kg and 0.91 ± 0.20 L/h·kg, respectively. Following s.c. and i.m. administration orbifloxacin achieved maximum plasma concentrations of 2.95 ± 0.82 and 3.24 ± 1.33 mg/L at 0.67 ± 0.20 and 0.65 ± 0.12 h, respectively. The absolute bio‐availabilities after s.c. and i.m. routes were 110.67 ± 11.02% and 109.87 ± 8.36%, respectively. Orbifloxacin showed a favourable pharmacokinetic profile in rabbits. However, on account of the lowAUC/MICandCmax/MICindices obtained, its use by i.m. and s.c. routes against theS. aureusstrains assayed in this study cannot be recommended given the risk of selection of resistant populations.
Reproductive biology and postnatal development in sloths, Bradypus and Choloepus: review with original data from the field (French Guiana) and from captivity
Authors: Taube Erica , Keravec Joël , Vié Jean‐Christophe , Duplantier Jean‐Marc
Published: September 2010

The reproductive biology of sloths remains obscure despite accounts on mating in the wild and in captivity. We present field data collected in French Guiana over a period of 16 months in the framework of an animal rescue carried out during the filling of a hydroelectric dam, and captive data obtained from breeding records from different zoos. According to these data and a review of the literature, we determined the most likely values for different reproductive parameters in sloths. Choloepus didactylus have a 10‐month gestation period with an inter‐birth interval of 16 months or more; young become independent around 12 months. The gestation period is similar in Choloepus hoffmanni, but the inter‐birth interval is 15 months and young become independent around 9 months. In Bradypus tridactylus pregnancy seems to last 6 months, the inter‐birth interval is approximately 12 months, and the age at which young become independent is about 5 months. In Bradypus variegatus the gestation period is 6 months and the inter‐birth interval 10–12 months; young become independent at 6 months. The occurrence of post‐partum oestrus was established in both genera. All species of sloths have only one young per litter; weaning takes place at a few weeks yet offspring continue riding on their mother until independence. Reproduction does not appear seasonal in Choloepus didactylus, it may be slightly seasonal in Choloepus hoffmanni;Bradypus variegatus have a mating season before the rains, and in Bradypus tridactylus reproduction is clearly seasonal. We suggest that these differences in reproductive strategies are basically linked to different diets. Although sloths are not endangered at present, they are threatened by loss of rainforest habitat. Since these species have such a low reproductive rate and Bradypus do not adapt—let alone reproduce—outside their natural environment, it is essential to understand their habitat requirements and population parameters for conservation purposes.
Variations of diet composition of Red Deer (Cervus elaphus L.) in Europe
Authors: Gebert Claudia , Verheyden‐Tixier Hélène
Published: September 2010

To define the food resources of Red Deer (Cervus elaphus L.) in Europe and to detect the principal sources of variations in their diet, we reviewed field studies based on stomach content analysis. The study areas were classified into three main habitat groups (mixed‐coniferous forest, mixed‐deciduous forest, moorland), the food items into 13 plant categories, and we used five seasonal classes (winter, spring, summer, autumn, hunting season) for analysing the data set. For statistical analyses we used correspondence analysis and analysis of variance.

Red Deer eat a varied diet comprising at least 145 plant species. The main sources of diet variation were due to habitat, leading us to identify three habitat types characterized by the consumption of a few key species. Clear seasonal variation was observed only for the seed and fruit items which were used mainly during the hunting season.

Our results confirm that Red Deer can be classified among the intermediate feeders, with a mixed diet of grass & sedges (29%) and concentrate food items (63%). However, they also show Red Deer to be primarily a concentrate feeder (max. 75%) with no significant seasonal variation between the quantities of grass or sedges and concentrate food in the diet.

In the light of these results, we discuss potential competition with other sympatric ungulates (wild and domestic). We suggest that it may be useful to take into account key food resources in modelling population dynamics and in taking management decisions.
British mammal populations: fifty years of change
Authors: YALDEN D. W. , SHORE R. F. , MCDONALD R. A.
Published: September 2010

Agricultural intensification, urbanization, overpopulation by both native and invasive species and diseases have all had marked effects on populations of British mammals over the last 50 years.

Here, accounts are presented of the effects of these processes with a prospective view of what the future holds for the mammals of Britain.
Replication of live‐attenuated vaccine strains of bluetongue virus in orally infected South African Culicoides species
Authors: VENTER G. J. , MELLOR P. S. , WRIGHT I. , PAWESKA J. T.
Published: September 2010

Abstract Field‐collected South African Culicoides (Diptera, Ceratopogonidae) were fed on sheep blood containing 16 live‐attenuated vaccine strains of bluetongue virus (BTV) comprising serotypes ‐1, ‐2, ‐3, ‐4, ‐5, ‐6, ‐7, ‐8, ‐9, ‐10, ‐11, ‐12, ‐13, ‐14, ‐16 and ‐19. After 10 days extrinsic incubation at 23.5 °C, 11 and seven of the 16 BTV serotypes used were recovered from Culicoides (Avaritia) imicola Kieffer and Culicoides (A.) bolitinos Meiswinkel, respectively. One serotype was also recovered from Culicoides (Remmia) enderleini Cornet & Brunhes. Bluetongue virus recovery rates and the mean titres for most serotypes were significantly higher in C. bolitinos than in C. imicola. Significant differences were found in virus recovery rates from Culicoides species fed on blood containing similar or identical virus titres of different BTV serotypes. In addition, we demonstrated that a single passage of live‐attenuated BTV‐1, ‐2, ‐4, ‐9 and ‐16 through the insect vector, followed by passaging in insect cells, did not alter its infectivity for C. imicola and that the oral susceptibility of C. imicola to the attenuated vaccine strains of BTV‐1, ‐4, ‐9 and ‐16 remained similar for at least three consecutive seasons.
Molecular genetic studies ofAnopheles stephensiin Pakistan
Authors: ALI N. , HUME J. C. C. , DADZIE S. K. , DONNELLY M. J.
Published: September 2010

AbstractAnopheles stephensiListons.l.(Diptera: Culicidae) is one of the major vectors of malaria in Pakistan, India, Iran and Afghanistan. In parts of its range this species has shown increases in both relative and absolute abundance in what is hypothesized to be a response to human‐mediated environmental change resulting from extensive irrigation. We attempted to detect the molecular genetic signatures of this population instability based on three samples obtained from two villages (149/6R and 111/6R) within an irrigation zone in Punjab Province and from one village (Azakhel) outside the irrigation scheme in Northwest Frontier Province (NWFP), Pakistan, using seven microsatellite loci and 682 basepairs of the mitochondrial CO1 gene. For microsatellite loci, high levels of genetic diversity were observed within populations (mean alleles per locus 10.71–11.57; mean heterozygosity 0.703–0.733). Deviation from Hardy–Weinberg expectations was observed for only two microsatellite loci in 21 tests. No genetic differentiation was observed between populations and average pairwise FSTvalues did not differ significantly from zero for any population pair or either marker system. Tests of population expansion for both mitochondrial and microsatellite loci were inconclusive.
Comparative scanning electron microscopy of Gasterophilus third instars
Authors: COLWELL D. D. , OTRANTO D. , HORAK I. G.
Published: September 2010

Abstract Comparison of cuticular features, including spine distribution and shape, structure of the maxillae and mandibles, the cephalic sensillae and the terminal abdominal segments of third instar Gasterophilus haemorrhoidalis, Gasterophilus inermis, Gasterophilus intestinalis, Gasterophilus meridionalis, Gasterophilus nasalis and Gasterophilus pecorum was conducted using scanning electron microscopy. One or more features distinguished among the species, with the exception of G. haemorrhoidalis and G. intestinalis, which shared all morphological characteristics. The features presented in this study complement and extend those presented in Zumpt’s compendium. The function of some features described by Zumpt (e.g. the ‘warts’ on the rim of the respiratory chamber) is clarified and the presence of previously described sensory structures in the grooves on the maxillae of G. intestinalis is called into question.
Body size‐associated survival and dispersal rates of Aedes aegypti in Rio de Janeiro
Authors: MACIEL‐DE‐FREITAS R. , CODEÇO C. T. , LOURENÇO‐DE‐OLIVEIRA R.
Published: September 2010

Abstract The daily survival rate of Aedes aegypti (L) (Diptera: Culicidae) is one of the most important parameters in mathematical models of dengue transmission. In this report, we evaluate the effect of adult body size on the survival and dispersal rates of male and female Ae. aegypti, the primary dengue vector in Brazil. Independent of larval diet (i.e. size), the daily survival rate of females recaptured in the field was greater than that of males (smaller: t = 5.617; d.f. = 15; P < 0.05; larger: t = 4.241; d.f. = 16; P < 0.05). Larger males lived longer than smaller males (t = 2.2893; d.f. = 7; P < 0.05), but no size effect was observed for females (t =– 0.086; d.f. = 19; P= 0.932). The daily survival rate of smaller females was similar to that of larger females (0.712 and 0.730, respectively, as calculated by an exponential model, and 0.743 and 0.779, respectively, calculated by a non‐linear model), and they dispersed further than larger females (mean distances travelled were 78.8 m and 40.9 m, respectively; t =− 10.22; d.f. = 323; P < 0.05). Adult body size did not influence male dispersal distances (t = 0.904; d.f. = 206; P= 0.367). Given our evidence that smaller females appear to have similar lifespans and evidence from other studies that they bite more frequently during a single gonotrophic cycle than larger females, our results suggest that smaller females have a higher vectorial capacity.
Genetic structure of Mediterranean populations of the sandfly Phlebotomus papatasi by mitochondrial cytochrome b haplotype analysis
Authors: HAMARSHEH O. , PRESBER W. , ABDEEN Z. , SAWALHA S. , AL‐LAHEM A. , SCHÖNIAN G.
Published: September 2010

Abstract Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae) is the main vector of Leishmania major Yakimoff & Schokhor; which is the cause of self‐limiting cutaneous leishmaniasis in the Old World. This sandfly is found in houses, animal shelters, caves and rodent burrows. It has a large geographical range, which includes the Middle East and the Mediterranean regions. A population analysis of colony and field specimens of P. papatasi was conducted on 25 populations originating from 10 countries. The distribution of haplotypes of the maternally inherited mitochondrial cytochrome b gene were analysed to assess the population differentiation of P. papatasi. Alignment of a 442‐basepair region at the 3′ end of the gene identified 21 haplotypes and 33 segregating sites from 131 sandflies. The pattern of sequence variations did not support the existence of a species complex. The median‐joining network method was used to describe both the origin of the haplotypes and the population structure; haplotypes tended to cluster by geographical location, suggesting some level of genetic differentiation between populations. Our findings indicate the presence of significant population differentiation for populations derived from Syria, Turkey, Palestine, Israel, Jordan and Egypt. Knowledge of population differentiation among P. papatasi populations is important for understanding patterns of dispersal in this species and for planning appropriate control measures.
Effects of horsefly (Tabanidae) salivary gland extracts on isolated perfused rat heart
Authors: RAJSKÁ P. , KNEZL V. , KAZIMÍROVÁ M. , TAKÁČ P. , ROLLER L. , VIDLIČKA L. , ČIAMPOR F. , LABUDA M. , WESTON‐DAVIES W. , NUTTALL P. A.
Published: September 2010

AbstractThe speed with which horseflies (Diptera: Tabanidae) obtain a bloodmeal suggests they have potent vasodilators. We used isolated perfused rat heart to examine the vasoactivity of salivary gland extracts (SGEs) of three horsefly species,Hybomitra bimaculataMacquart,Tabanus bromiusLinnaeus andTabanus glaucopisMeigen. Administration of horsefly SGEs to the heart produced biphasic coronary responses: a decrease and subsequent increase in coronary flow (CF), characterized by initial vasoconstriction followed by prolonged vasodilation of coronary vessels. However, although SGEs ofH. bimaculatainduced a significant decrease in left ventricular pressure (LVP), the effect on changes in CF was not significant except at the highest dose tested. The ability to reduce LVP without significantly lowering CF, or affecting heart rate and rhythm, represents a unique set of properties that have considerable therapeutic potential if they can be reproduced by a single molecule.
Mitochondrial DNA analysis reveals cryptic large‐scale invasion of non‐native genotypes of common carp (Cyprinus carpio) in Japan
Authors: MABUCHI K. , SENOU H. , NISHIDA M.
Published: September 2010

Wild common carp (Cyprinus carpio) are probably suffering from biological invasions of conspecific domesticated strains. However, such invasions may be largely camouflaged by morphological similarities between introduced and native strains. We conducted a large survey of mitochondrial DNA sequences (complete D‐loop region) from 11 localities in Japan. From a total of 166 individuals, 28 haplotypes were determined to fit into six divergent clades. One of the six clades included 19 closely related haplotypes with moderate nucleotide differences; however, the remaining five clades each included either a single haplotype or two almost identical haplotypes. Phylogenetic analysis together with the previously published Eurasian haplotypes further demonstrated that the ‘monotypic’ clades were sisters to various Eurasian lineages, whereas the 19 related haplotypes formed a monophyletic group apart from the whole Eurasian clade. Given their monophyly and genetic diversity, the 19 related haplotypes were thought to originate from the Japanese native strain. Conversely, their phylogenetic affinities to Eurasian lineages and unnaturally low genetic diversities caused the haplotypes of the five monotypic clades to be considered as domesticated strains introduced from Eurasia. These hypotheses were supported by further evidences; i.e. the probable non‐native haplotypes were frequently found from Japanese domesticated strains, and the probable native population structure was rescued when the probable non‐native haplotypes were excluded from the analyses. This study revealed that almost half or more of the haplotypes in all of the locations studied originated from domesticated strains introduced from Eurasia.
Gastric emptying and the organization of antro‐duodenal pressures in the critically ill
Authors: Chapman M. J. , Fraser R. J. , Bryant L. K. , Vozzo R. , Nguyen N. Q. , Tam W. , Zacharakis B. , Davidson G. , Butler R. , Horowitz M.
Published: September 2010

Abstract  The motor dysfunctions underlying delayed gastric emptying (GE) in critical illness are poorly defined. Our aim was to characterize the relationship between antro‐duodenal (AD) motility and GE in critically ill patients. AD pressures were recorded in 15 mechanically ventilated patients and 10 healthy volunteers for 2 h (i) during fasting, (ii) following an intragastric nutrient bolus with concurrent assessment of GE using the 13C‐octanoate breath test and (iii) during duodenal nutrient infusion. Propagated waves were characterized by length and direction of migration. Critical illness was associated with: (i) slower GE (GEC: 3.47 ± 0.1 vs 2.99 ± 0.2; P = 0.046), (ii) fewer antegrade (duodenal: 44%vs 83%, AD: 16%vs 83%; P < 0.001) and more retrograde (duodenal: 46%vs 12%, AD: 38%vs 4%; P < 0.001) waves, (iii) shorter wave propagation (duodenal: 4.7 ± 0.3 vs 6.0 ± 0.4 cm; AD: 7.7 ± 0.6 vs 10.9 ± 0.9 cm; P = 0.004) and (iv) a close correlation between GE with the percentage of propagated phase 3 waves that were antegrade (r = 0.914, P = 0.03) and retrograde (r = −0.95, P = 0.014). In critical illness, the organization of AD pressure waves is abnormal and associated with slow GE.
Different behaviour of implanted stem cells in intact and lesioned forebrain cortices
Authors: Ágoston V. A. , Zádori A. , Demeter K. , Nagy Z. , Madarász E.
Published: September 2010

Cell‐replacement therapy promises a useful tool to regenerate compromised brain tissue, but the interaction between grafted cells and host tissues is not well understood. In these studies, the fates of neuroectodermal stem cells were compared in ‘healthy’ or damaged mouse forebrains. One‐cell derived, fluorescent GFP‐4C neural stem cells were implanted into normal and cold‐lesioned mouse cortices. The fates of implanted cells were followed by histological and immunocytochemical assays for a 55‐day postimplantation period. Cells were recultivated from lesioned cortices and characterized by cell cycle parameters, chromosome numbers, immunocytochemical markers and in vitro inducibility. Their intracerebral fates were checked upon re‐implanting into ‘healthy’ mouse brain cortices. GFP‐4C cells, giving rise to neurones and astrocytes upon in vitro induction, failed to differentiate in either normal or lesioned cortical tissues. The rate of proliferation and the length of the survival, however, depended on the host environment, markedly. In intact cortices, implanted cells formed compact, isolated aggregates and their survival did not exceed 4 weeks. In compromised cortices, GFP‐4C cells survived longer than 8 weeks and repopulated the decayed region. The morphology, viability, immunocytochemical properties, in vitro inducibility and chromosome number of cells recultivated from lesioned cortices were identical to those of the master cells. Long‐term survival and repopulating capability were due to signals present in the lesioned, but missing from the intact cortical environment. The results underline the importance of host environment in the fate determination of grafted cells and emphasize the need to understand the ‘roles’ of recipient tissues for potential cell‐replacement methodologies.
Morphopathological features in tissues of α‐mannosidosis guinea pigs at different gestational ages
Authors: Auclair D. , Hopwood J. J.
Published: September 2010

Alpha‐mannosidosis is an inherited metabolic disorder characterized by a reduction in α‐D‐mannosidase and intralysosomal accumulation of undegraded mannose‐containing oligosaccharides. The α‐mannosidosis guinea pig exhibits pathological similarities to its human counterpart, which make it a valuable animal model. To trace the progression of α‐mannosidosis during foetal development, brain and visceral organs from affected and unaffected guinea pigs at 30, 36, 38, 51 and 65 days of gestation (dg) were examined by light and electron microscopy (term: approximately 68 dg). In the affected brain, distended lysosomes (vacuoles) were scarce up to 38 dg and were seen in few differentiating neuronal cells but mostly in macrophages, pericytes and endothelial cells. At 51 and 65 dg, several vacuoles were observed in some neurones, in many Purkinje cells, pericytes, endothelial and microglial cells, and in few cerebellar internal granule cells. Myelination had started by 51 dg. Non‐myelinated axonal spheroids were detected in the brainstem at 65 dg. In the kidney cortex and liver, an increase in vacuolation was noticed between 36 and 65 dg. Some vacuolated cells were also noticed in the lungs and spleen at 51 and 65 dg. Altogether, these histological observations suggest that α‐mannosidosis is unlikely to affect ontogenesis before the second half of gestation in guinea pigs; however, the morphopathological features recorded during the last quarter of gestation (which may roughly correspond to the period covering near term to 1–2 years of age in human) were clearly noticeable and may have had some impact.
Vascular endothelial growth factor counteracts the loss of phospho‐Akt preceding motor neurone degeneration in amyotrophic lateral sclerosis
Authors: Dewil M. , Lambrechts D. , Sciot R. , Shaw P. J. , Ince P. G. , Robberecht W. , Van Den Bosch L.
Published: September 2010

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that results in the selective loss of motor neurones. In the present study, the involvement of the antiapoptotic protein, Akt (protein kinase B), was studied. We found that motor neurones of both sporadic and familial ALS patients lack phospho‐Akt, and that motor neurones of mutant SOD1 mice lose activated Akt early in the disease, before the onset of clinical symptoms. In vitro, overexpression of constitutively active Akt protects against mutant SOD1‐dependent cell death. In vivo, levels of phospho‐Akt in the spinal cord increase after intracerebroventricular administration of vascular endothelial growth factor to mutant SOD1 rats, a treatment we previously described to significantly protect motor neurones. From these results, we conclude that the loss of phospho‐Akt could be involved in motor neurone death in ALS, and that therapies upregulating phospho‐Akt thus might be of clinical relevance.
Embryonic stem cells and prospects for their use in regenerative medicine approaches to motor neurone disease
Authors: Christou Y. A. , Moore H. D. , Shaw P. J. , Monk P. N.
Published: September 2010

Human embryonic stem cells are pluripotent cells with the potential to differentiate into any cell type in the presence of appropriate stimulatory factors and environmental cues. Their broad developmental potential has led to valuable insights into the principles of developmental and cell biology and to the proposed use of human embryonic stem cells or their differentiated progeny in regenerative medicine. This review focuses on the prospects for the use of embryonic stem cells in cell‐based therapy for motor neurone disease or amyotrophic lateral sclerosis, a progressive neurodegenerative disease that specifically affects upper and lower motor neurones and leads ultimately to death from respiratory failure. Stem cell‐derived motor neurones could conceivably be used to replace the degenerated cells, to provide authentic substrates for drug development and screening and for furthering our understanding of disease mechanisms. However, to reliably and accurately culture motor neurones, the complex pathways by which differentiation occurs in vivo must be understood and reiterated in vitro by embryonic stem cells. Here we discuss the need for new therapeutic strategies in the treatment of motor neurone disease, the developmental processes that result in motor neurone formation in vivo, a number of experimental approaches to motor neurone production in vitro and recent progress in the application of stem cells to the treatment and understanding of motor neurone disease.
The relevance to protection of three forms of delayed skin‐test response evoked by M. leprae and other mycobacteria in mice. Correlation with the classical work in the guinea‐pig
Authors: ROOK G.A.W. , STANFORD J.L.
Published: September 2010

Summary The controversy surrounding the protective role of ‘delayed hyper‐sensitivity’ in tuberculous guinea‐pigs has never been resolved. This controversy has arisen because the term ‘delayed hypersensitivity’ is used indiscriminately to describe both a type of necrotic skin‐test reactivity which does not appear until 4–6 weeks after infection, and also non‐necrotic reactions which can be elicited within a few days. Responses closely analogous to both have been characterized in mice immunized with mycobacteria. Simple criteria are described which allow these responses to be distinguished from one another, and from the Jones‐Mote phenomenon. The relevance of each type to protection, susceptibility and immunopathology in leprosy, tuberculosis, leishmaniasis and listeriosis is discussed.
Distribution of blood groups and secretor status in schistosomiasis
Authors: TRANGLE K.L. , GOLUSKA M.J. , O'LEARY M.J. , DOUGLAS S. D.
Published: September 2010

Summary Urine and stool specimens from 425 school children in Swaziland were examined for evidence of Schistosoma mansoni or Schistosoma haematobium infection. Concurrently, saliva collections were analysed for ABH secretory ability and blood samples were typed for ABO, Rh and Lewis groups. Among individuals infected with S. mansoni, the frequency of blood group B was significantly increased (P<0.001), and there was a greater prevalence of positive secretor status (P < 0.05). In contrast, the presence and severity of S. haematobium infection did not correlate with any of the variables tested.
Immunosuppression in murine malaria. IV. The secondary response to bovine serum albumin
Authors: STRAMBACHOVÁ‐McBRIDE JANA , MICKLEM H.S.
Published: September 2010

Summary The anamnestic antibody response of CBA mice to bovine serum albumin was characterized by a rapid production of high‐avidity antibody. After 3 weeks both the total amount of antibody and its avidity declined but still remained above those seen in the primary response for at least 6 weeks. The effects of acute Plasmodium berghei and Plasmodium yoelii yoelii infections upon the induction and the expression of this anamnestic response were studied. Mice infected with these malaria parasites responded poorly to primary immunization and the immunological memory generated was quantitatively subnormal. In addition, presence of the infection during a period between approximately the second and third weeks of the primary response prejudiced the development of high‐avidity memory. Optimally primed mice, challenged during a subsequent acute infection, responded well initially, but were unable to maintain the secondary response at a normal level in terms of both quantity and avidity of the antibody. However, if challenge was delayed until after recovery from the infection, a normal secondary response ensued. Antibody concentrations in the sera of primed animals declined rapidly during infection. This was at least partly due to increased catabolism.
Strongyloides stercoralis infection and small intestinal lymphoma
Authors: COHEN J. , SPRY C.J.F.
Published: September 2010

SummaryA West Indian man who was infected with Strongyloides stercoralis developed small intestinal obstruction. Treatment with thiabendazole did not relieve the obstruction which was found at laparotomy to be due to a poorly differentiated small intestinal lymphoma. There was no blood eosinophilia or accumulation of eosinophils in the sites of infection. There was no reaction in the skin to delayed hypersensitivity antigens and the blood T lymphocyte count and serum C3 levels were low.

From these findings and a review of the literature it was concluded that the immune response in man to Strongyloides stercoralis may depend on T lymphocyte mediated reactions including granuloma formation, and mast cell and eosinophil responses in tissues. We suggest that the association of strongyloides hyperinfection and small bowel lymphoma in this patient may not have been fortuitous. The lymphoma may have led to a reduction in cellular immunity, with the subsequent development of strongyloides hyperinfection.
Immunization against malaria with a recombinant protein
Authors: LING I. T. , OGUN S. A. , HOLDER A. A.
Published: September 2010

We have expressed in bacteria the C‐terminal part of Plasmodium yoelii merozoite surface protein‐1 (MSP1) containing the two epidermal growth factor‐like domains. The protein, either alone or fused to glutathione Stransferase, was highly effective as a vaccine and protected mice against challenge infection. Reduction and alkylation abolished the protection obtained with the protein. This shows for the first time the absolute requirement of the disulphide‐bonded conformation for immunogenicity. In a short term experiment, mice were protected against a massive challenge. The immunity was effective at the time of merozoite release/reinvasion. Recombinant protein based on this part of MSP1 may be suitable as a vaccine against malaria.
Modulation of T‐cell responsiveness during Trypanosoma cruzi infection: analysis in different lymphoid compartments
Authors: VANDEKERCKHOVE FILIP , DARJI AYUB , RIVERA MARIA‐TERESA , CARLIER YVES , VRAY BERNARD , BILLIAU ALFONS , BAETSELIER PATRICK DE
Published: September 2010

Spleen and lymph node cells of Trypanosoma cruzi‐infected mice were studied for mitogen‐induced responsiveness in terms of proliferation and lymphokine production (IL‐2, IFN‐gamma). Splenocyte (SP) as well as lymph node cell (LN) proliferation and IL‐2 production were depressed during the acute phase of the infection. Proliferative capacity of LN cells recovered completely and that of SP partially during the chronic phase. In contrast to these suppressive effects, the mitogen‐induced IFN‐gamma response was enhanced. In vitro co‐incubation of normal SP or LN cells with trypomastigotes resulted in a reduced mitogen‐induced cell proliferation and IL‐2 secretion, similar to those seen with cells taken from infected mice. In contrast, trypomastigotes exerted a stimulatory activity on the mitogen‐induced IFN‐gamma response of both SP and LN cells. Addition of lymph node cells from T. cruzi‐infected mice (LN‐I) to lymph node cells of control mice (LN‐C) suppressed strongly the mitogen‐induced responsiveness of such cocultures. A marginal level of suppression was recorded in cocultures of spleen cells from infected mice (SP‐I) and control spleen cells (SP‐C). The potent suppressive cells within LN‐I populations were identified as macrophage‐like and such cells were absent in SP‐C and peritoneal exudate cells from T. cruzi infected animals.
Identification and diagnostic value of a major antibody epitope on the 12 kDa antigen from Echinococcus granulosus (hydatid disease) cyst fluid
Authors: LEGGATT G. R. , McMANUS D. P.
Published: September 2010

An IgG1 monoclonal antibody (MoAb), designated C9E7H8, has been produced against an epitope on the 12 kDa antigen of Echinococcus granulosus cyst fluid, believed to represent the smallest subunit of antigen B. This MoAb, raised against purified 12 kDa antigen eluted from a reducing SDS‐PAGE gel, demonstrated strong binding to native sheep cyst fluid in ELISA and recognition of all three subunits of antigen B (at 12, 16, 23 kDa) by immunoblot under both reducing and non‐reducing conditions. Immunoblot analysis also indicated that the complementary epitope is conserved amongst cyst fluids from different intermediate hosts of E. granulosus, including fluids from cysts of two distinct strains, and is present in cyst fluid from E. multilocularis. The monoclonal displays binding to a cDNA clone, EgPS‐3, which we have previously shown expresses part of the 12 kDa molecule. EgPS‐3, expressed as a glutathione‐S‐transferase fusion protein, was successful in positive detection of 74% of cystic hydatid patients, although cross‐reactions were observed with 25% of sera from alveolar hydatid and 22% of sera from schistosomiasis japonica patients. Three peptides, based on the predicted amino acid sequence of EgPS‐3. showed increased specificity but slightly reduced sensitivity in the detection of antibody from E. granulosus patients. The predominant epitope recognized by human antibody occurs in the Nterminal 27 amino acids (peptide 65) of EgPS‐3 which also correlates with the location of the monoclonal antibody epitope.
Immune interactions between mosquitoes and their hosts
Authors: BILLINGSLEY P. F. , BAIRD J. , MITCHELL J. A. , DRAKELEY C.
Published: September 2010

The intimate contact between mosquitoes and the immune system of their hosts is generally not considered important because of the transient nature of mosquito feeding. However, when hosts are exposed to many feeding mosquitoes, they develop immune responses against a range of salivary antigens. Understanding the importance of these responses will provide new tools for monitoring vector populations and identifying individuals at risk of mosquito‐borne diseases, and allow the development of novel methods for monitoring control and mosquito‐release programmes. Antibodies targeting the mosquito midgut are also important in the development of mosquito vaccines. The feasibility of this approach has been demonstrated and future research opportunities are considered in this review. The potential impact of mosquito vaccines is also discussed. Our understanding of the interplay between mosquitoes and the immune system of their hosts is still in its infancy, but it is clear that there is great potential for exploiting this interplay in the control of mosquito‐borne diseases.
Intranasal immunization with Naegleria fowleri lysates and Cry1Ac induces metaplasia in the olfactory epithelium and increases IgA secretion
Authors: JARILLO‐LUNA A. , MORENO‐FIERROS L. , CAMPOS‐RODRÍGUEZ R. , RODRÍGUEZ‐MONROY M. A. , LARA‐PADILLA E. , ROJAS‐HERNÁNDEZ S.
Published: September 2010

According to previous reports, intranasal administration of the Cry1Ac protein alone or with amoebic lysates increases protection against Naegleria fowleri meningoencephalitis in mice, apparently by eliciting IgA responses in the nasal mucosa. In the current study, we performed an immunohistochemical analysis of IgA in the nasal mucosa of mice immunized intranasally with Cry1Ac, and amoebic lysates or a combination of both. The animals were sacrificed 24 h after the last immunization or after an intranasal lethal challenge with N. fowleri. Our results indicate that all of the intranasal immunizations provoked an increase in areas with metaplasia in the olfactory epithelium, allowing for secretion of IgA. As a result, IgA antibodies were found interacting with trophozoites in the nasal lumen, and there was a marked increase of IgA in the metaplasic epithelium. On the other hand in nonimmunized mice trophozoites were observed invading the nasal mucosa, which was not the case for immunized mice. Our results suggest that intranasal immunization provokes cellular changes in the olfactory epithelium, leading to greater protection against N. fowleri that is probably caused by an increased secretion of IgA. The increased IgA response induced in the nasal mucosa by immunization probably impedes both amoebic adhesion and subsequent invasion of the parasite to the nasal epithelium.
Influence of periparturient nutritional demand on resistance to parasites in livestock
Authors: HOUDIJK J. G. M.
Published: September 2010

Periparturient relaxation of immunity (PPRI) to gastrointestinal nematode parasites may have a nutritional basis, as the increasing nutrient demand at times of nutrient scarcity during late pregnancy and subsequent lactation may result in a penalty on expression of acquired immunity to parasites. This nutritional basis implies that lowering nutritional demand, at constant nutrient supply, should reduce the degree of PPRI. Evidence to support the latter is reviewed through exploration of the effects of reproductive effort on periparturient resistance to parasites. A large body of evidence shows that a lower nutritional demand arising from rearing single rather than multiple lambs and/or kids consistently reduces the degree of PPRI in small ruminants, as manifested by reduced worm burdens and/or nematode egg excretions. Such variation in reproductive effort may also account, at least to some extent, for the often observed between‐breed differences in PPRI, which may arise from differences in production potential, and thus nutritional demand. A reduction in nutrient demand can reduce the degree of PPRI in a matter of days. However, host immune responses associated with this nutritional sensitivity of host resistance remain to be elucidated, which may be achieved through a recently established periparturient rodent model.
The ABA1 gene and carotenoid biosynthesis are required for late skotomorphogenic growth in Arabidopsis thaliana
Authors: BARRERO JOSÉ MARÍA , RODRÍGUEZ PEDRO L. , QUESADA VÍCTOR , ALABADÍ DAVID , BLÁZQUEZ MIGUEL A. , BOUTIN JEAN‐PIERRE , MARION‐POLL ANNIE , PONCE MARÍA ROSA , MICOL JOSÉ LUIS
Published: September 2010

Several plant hormones, including auxin, brassinosteroids and gibberellins, are required for skotomorphogenesis, which is the etiolated growth that seedlings undergo in the absence of light. To examine the growth of abscisic acid (ABA)‐deficient mutants in the dark, we analysed several aba1 loss‐of‐function alleles, which are deficient in zeaxanthin epoxidase. The aba1 mutants displayed a partially de‐etiolated phenotype, including reduced hypocotyl growth, cotyledon expansion and the development of true leaves, during late skotomorphogenic growth. In contrast, only small differences in hypocotyl growth were found between wild‐type seedlings and ABA‐deficient mutants impaired in subsequent steps of the pathway, namely nced3, aba2, aba3 and aao3. Interestingly, phenocopies of the partially de‐etiolated phenotype of the aba1 mutants were obtained when wild‐type seedlings were dark‐grown on medium supplemented with fluridone, an inhibitor of phytoene desaturase, and hence, of carotenoid biosynthesis. ABA supplementation did not restore the normal skotomorphogenic growth of aba1 mutants or fluridone‐treated wild‐type plants, suggesting a direct inhibitory effect of fluridone on carotenoid biosynthesis. In addition, aba1 mutants showed impaired production of the β‐carotene‐derived xanthophylls, neoxanthin, violaxanthin and antheraxanthin. Because fluridone treatment of wild‐type plants phenocopied the phenotype of dark‐grown aba1 mutants, impaired carotenoid biosynthesis in aba1 mutants is probably responsible for the observed skotomorphogenic phenotype. Thus, ABA1 is required for skotomorphogenic growth, and β‐carotene‐derived xanthophylls are putative regulators of skotomorphogenesis.