bluuebunny/crossref_metadata_2025 huggingface dataset:
Penises as Variable‐Volume Hydrostatic Skeletons
Authors: KELLY DIANE A.
Published: April 2007

Abstract:  Penises are inflatable intromittent organs that transfer sperm to a female during copulation. Most of the time, males store their penises in a flexible detumesced state, but they can rapidly inflate them with blood when an opportunity for reproductive behavior arises. In mammals, the primary erectile tissue is called the corpus cavernosum; its anatomy is a close match to a model hydroskeleton reinforced by an axial orthogonal fiber array. The wall of the corpus cavernosum contains layers of highly organized collagen fibers arranged at 0° and 90° to the penile long axis. Flaccid wall tissue is folded. Collagen fiber straightening during erection expands the tunica albuginea and increases both its stiffness and its second moment of area. These changes make the entire penis larger and harder to bend. Axial orthogonal fiber reinforcement affects the mechanical behavior of the erect corpus cavernosum, making it resistant to tensile, compressive, and bending forces.
Interstitial Cajal‐Like Cells in Human Uterus and Fallopian Tube
Authors: POPESCU LAURENTIU M. , CIONTEA SANDA M. , CRETOIU DRAGOS
Published: April 2007

Abstract:  Recently, parallels have been drawn between enteric interstitial cells of Cajal (ICC) and similar cells outside the gut—interstitial Cajal‐like cells (ICLC). This article reviews our laboratory findings on ICLC in the female reproductive tract. Since the morphology and function of ICLC are still a subject of debate, our purpose was to investigate whether ICLC are present in the fallopian tube and/or uterus, and if they share ultrastructural and immunohistochemical (IHC) features and/or functional roles. We studied ICLC presence in the human fallopian tube and myometrium primarily by light microscopy, and then by transmission electron microscopy (TEM), in tissue samples and at a single cell level. Taking advantage of our ICLC studies of several organs (pancreas, mammary gland, myocardium), we assembled a set of criteria, derived from ultrastructural features of ICLC, called “platinum standard.” Besides the putative pacemaker function, ICLC might have other physiological roles, depending on tissue type (e.g., intercellular signaling, immune surveillance, steroid sensors). Consequently, there is a great urge for a conceptual framework that could allow a better understanding, from a functional point of view, and more so, as the ICLC processes are the longest cellular prolongations (except neurons).
Modeling Myometrial Smooth Muscle Contraction
Authors: BURSZTYN LIMOR , EYTAN OSNAT , JAFFA ARIEL J. , ELAD DAVID
Published: April 2007

Abstract:  Existing models of uterine contractions assumed a top‐down approach in which the function at the organ or tissue level was explained by the behavior of smaller basic units. A new model of the excitation–contraction process in a single myometrial myocyte was recently developed. This model may be used in a bottom‐up approach for the description of the contribution of cellular phenomena to the overall performance of the tissue or organ. In this review, we briefly survey current knowledge of uterine electrophysiology and contractility as well as current modeling techniques, which were successfully used to study the function of various types of muscle cells. In the physiological part of the review, we relate to mechanisms of intracellular Ca2+ control, Ca2+ oscillations, and Ca2+ waves and to the various membranal transport mechanisms regulating ion exchange between the intracellular and extracellular spaces. In addition, we describe the process leading from excitation to contraction. In the modeling part of the review, we present the Hodgkin–Huxley (HH) model of excitation in the squid axon as well as models of Ca2+ control and the latch‐bridge model of Hai and Murphy describing the kinetics of smooth muscle cell (SMC) contraction. We also present integrative models describing more than one of these phenomena. Finally, we suggest how these modeling techniques can be applied to modeling myometrial contraction and thus may significantly contribute to current efforts of research of uterine function.
Bioengineering Studies of the Embryo Transfer Procedure
Authors: EYTAN OSNAT , ELAD DAVID , JAFFA ARIEL J.
Published: April 2007

Abstract:  Embryo transfer (ET) is the final manual intervention in extracorporeal fertilization in which an embryo is transferred into the uterus by a transcervical catheter. The low rates of embryo implantation within the uterus are attributed, among other factors, to the ET technique, which depends on a multitude of anatomical, physiological, and mechanical aspects. We developed computational and experimental models to simulate ET to examine the contribution of mechanical features to the success of this procedure. The experimental model allowed laboratory simulations of the dispersion of the catheter load as a result of different injection speeds into a tilted uterine model. The mathematical model analyzed potential trajectories of the transferred embryos resulting from the interaction between the injection velocity and the intrauterine flows caused by uterine peristalsis. The simulations revealed the important contribution of mechanical parameters, such as the position of the uterus and the presence of air in the catheter load. The latter was found to increase the potential for the embryo to be near the fundal area during the time limit for implantation. Based on the results of our simulations, we recommended performing ET in a patient‐specific position in which the fundus will be the highest point above the horizon and that the load be delivered slowly, that is, not less than 10 s. We also recommended placing the tip of the catheter at the mid cavity to avoid ectopic pregnancy.
Hedgehog Signaling
Authors: NAGASE TAKASHI , NAGASE MIKI , MACHIDA MASAFUMI , YAMAGISHI MASAAKI
Published: April 2007

Abstract:  Although embryonic development is inevitably affected by biophysical or biomechanical processes, it has yet to be elucidated to what extent molecular mechanisms of development are modulated by such physical factors. The hedgehog family, including Sonic hedgehog (Shh), is the most well‐known morphogens involved in the developmental pattern formation of various organs, such as the nervous system, face, limbs, and skin appendages. There are several unique features in hedgehog signaling including long‐range diffusion or positive and negative feedback loops, suggesting the possible modification of hedgehog signaling by biophysical or biomechanical factors. Especially, the period of embryonic day 8–10 is characterized by various biomechanically regulated processes in mouse development, such as axial rotation and vasculoangiogenesis. We executed a series of experiments using a mouse whole embryo culture system to investigate the biomechanical roles of hedgehog signaling during this period. In this review, we examine various examples in which biophysical and biomechanical aspects of hedgehog signaling in development are revealed, including our own data using the mouse whole embryo culture system.
Control of Uterine Ca2+ by Membrane Voltage
Authors: SHMYGOL ANATOLY , BLANKS ANDREW M. , BRU‐MERCIER GILLES , GULLAM JOANNA E. , THORNTON STEVEN
Published: April 2007

Abstract:  Myometrial contractility is a complex and dynamic physiological process that changes substantially during pregnancy and culminates in childbirth. Uterine contractions are initiated by transient rises in cytoplasmic Ca2+ concentration ([Ca2+]i), which in turn are triggered and controlled by myometrial action potentials. The sequence of events between the action potential generation and the contraction initiation is referred to as excitation–contraction coupling. Hormones and other physiologically active substances affect myometrial contractility by modulating different steps in the excitation–contraction coupling process. It is therefore imperative that we understand that process to understand the regulation of myometrial contractility. The complex action potentials generated by human myometrium result from the activity of many ion channels, transporters, and pumps. Two types of myometrial action potential waveform have been described in the literature: a plateau type and a spike type. Parameters of the myometrial [Ca2+]i transients and contractions differ depending on the type of action potential that triggers them. Some aspects of the excitation–contraction coupling are unique to human myometrium and cannot be found in animal models; some others are common between many species. This article reviews the current state and discusses future directions of physiological research on human myometrial excitation–contraction coupling.
A Contextual Model of Pelvic Floor Muscle Defects in Female Stress Urinary Incontinence
Authors: MADILL STÉPHANIE J. , McLEAN LINDA
Published: April 2007

Abstract:  On the basis of the current literature, we describe a model of structural defects in stress urinary incontinence (SUI) and how physiotherapy for SUI can affect each component of the model with reference to the relevant anatomy and pathophysiology. This model of SUI involves four primary structural defects: (1) increased tonic stress on the pelvic fascia due to pelvic floor muscle (PFM) tears; (2) fascial tearing due to PFM denervation; (3) fascial weakness resulting from tears; and (4) inefficient PFM contraction due to altered motor control. These four components interact to collectively weaken urethral closure and allow urine leakage under conditions of increased intra‐abdominal pressure. Physiotherapy can strengthen the PFM and may improve the efficiency and/or timing of PFM contractions to reduce or eliminate SUI. It is worthwhile for motivated women with SUI to try PFM exercise therapy as a first approach to treatment. Women need to be individually instructed to ensure that they correctly perform PFM contractions and that they can monitor their own performance. Long‐term, high‐intensity exercise, including home exercise, is necessary to achieve maximum effect. Under these conditions the improvement in urinary continence with PFM exercise can be complete and enduring.
Fetal Blood Flow in Branching Models of the Chorionic Arterial Vasculature
Authors: GORDON ZOYA , EYTAN OSNAT , JAFFA ARIEL J. , ELAD DAVID
Published: April 2007

Abstract:  Fetal development depends on adequate exchange of materials between the fetus and maternal circulatory systems, which requires optimal distribution of blood vessels over the chorionic plate to ensure perfusion of the whole placental volume. Based on a previous investigation of the architecture of the chorionic vessels in the human placenta, we developed in this study typical models for the dichotomous and monopodial segments of the chorionic arteries of a mature placenta. Each model also included some intraplacental (IP) vessels that branch off into the cotyledons perpendicular to the chorionic arteries. Computational analysis of steady blood flow through these models was performed to explore the distribution of fetal blood over the chorionic plate. The results demonstrated that energy losses are small in the monopodial model, which explains their efficient delivery of fetal blood over the chorionic plate in cases of a marginal cord insertion. On the other hand, the dichotomous model is efficient in distributing a relatively large volume of blood over large areas near the bifurcation. Accordingly, the combination of dichotomous and monopodial bifurcation in a normal chorionic plate ensures a uniform blood perfusion of the placenta. Simulations with narrow daughter and IP vessels did not result in significant changes in the main mother tubes, supporting clinical observations in which umbilical blood flow remains normal although some peripheral vessels may be occluded.
Myocytes, Myometrium, and Uterine Contractions
Authors: YOUNG ROGER C.
Published: April 2007

Abstract:  The pregnant uterus is unique because of the dramatic functional changes that occur in the peripartum period. To promote the concept that we have a relatively poor understanding of the physiology of parturition, we will posit 10 facts that are so obvious and so clearly accepted as facts that they probably are not even facts at all. (1) The laboring uterus undergoes peristalsis to dilate the cervix, deliver the fetus, and expel the placenta. (2) The human uterus is composed of longitudinal and circular layers of smooth muscle. (3) The functional cells of the uterus are the myocytes, which are a homogeneous cell type responsible for the generation of contraction forces, passage of action potentials, and control of contractility. (4) The phasic contractions of the uterus are typical for visceral smooth muscle. (5) The primary, and perhaps only, role of gap junctions is to allow passage of action potentials through the tissue. (6) Action potential propagation as the mechanism for global communication (over many centimeters throughout the uterus) is sufficient to recruit all regions and all myocytes of the uterus. (7) Slow waves pace the contractions of human myometrium. (8) Calcium‐activated potassium channels are responsible for repolarization of the membrane potential that terminates each contraction. (9) Chloride channels are not important in uterine electrophysiology. (10) With enough computing power, it would be straightforward to build a closed model of human labor, given our current understanding of the components of myometrium. This manuscript discusses each point to stimulate questions for future investigation.
The Apotheosis of Ajacan's Jesuit Missionaries
Authors: Mallios Seth
Published: April 2007

Historical narratives describing the demise of a sixteenth-century Jesuit mission on the Chesapeake grew from direct accounts of indigenous murder to elaborate constructions of the missionaries' divine sacrifice. A seriation of details from the seven contemporary Jesuit sources demonstrates how and when Father Juan Baptista de Segura and his brethren came to be celebrated as martyrs. Once apotheosized, the Ajacan Jesuits' mythic stature grew despite historically established contradictions. Seemingly analogous martyrdoms, the anticipated self-sacrifice of Segura and his cadre, the individual and corporate benefits of divine forfeiture for clerics like the Jesuits, and parallels between biblical narratives and the sequence of events at the short-lived Chesapeake settlement led to an ecclesiastic apotheosis of the Ajacan missionaries.
Improving the Design of Competitive Bidding in Medicare Advantage
Authors: Cawley John H. , Whitford Andrew B.
Published: April 2007

In 2003, Congress passed the Medicare Prescription Drug, Improvement, and Modernization Act, which required that in 2006 the Centers for Medicare and Medicaid Services (CMS) implement a system of competitive bids to set payments for the Medicare Advantage program. Managed care plans now bid for the right to enroll Medicare beneficiaries. Data from the first year of bidding suggest that imperfect competition is limiting the success of the bidding system. This article offers suggestions to improve this system based on findings from auction theory and previous government-run auctions. In particular, CMS can benefit by adjusting its system of competitive bids in four ways: credibly committing to regulations governing bidding; limiting the scope for collusion, entry deterrence, and predatory behavior among bidders; adjusting how benchmark reimbursement rates are set; and accounting for asymmetric information among bidders.
TGFβ3 inhibits E-cadherin gene expression in palate medial-edge epithelial cells through a Smad2-Smad4-LEF1 transcription complex
Authors: Nawshad Ali , Medici Damian , Liu Chang-Chih , Hay Elizabeth D.
Published: April 2007

Dissociation of medial-edge epithelium (MEE) during palate development is essential for mediating correct craniofacial morphogenesis. This phenomenon is initiated by TGFβ3 upon adherence of opposing palatal shelves, because loss of E-cadherin causes the MEE seam to break into small epithelial islands. To investigate the molecular mechanisms that cause this E-cadherin loss, we isolated and cultured murine embryonic primary MEE cells from adhered or non-adhered palates. Here, we provide the first evidence that lymphoid enhancer factor 1 (LEF1), when functionally activated by phosphorylated Smad2 (Smad2-P) and Smad4 (rather than β-catenin), binds with the promoter of the E-cadherin gene to repress its transcription in response to TGFβ3 signaling. Furthermore, we found that TGFβ3 signaling stimulates epithelial-mesenchymal transformation (EMT) and cell migration in these cells. LEF1 and Smad4 were found to be necessary for up-regulation of the mesenchymal markers vimentin and fibronectin, independently of β-catenin. We proved that TGFβ3 signaling induces EMT in MEE cells by forming activated transcription complexes of Smad2-P, Smad4 and LEF1 that directly inhibit E-cadherin gene expression.
Epithelial tight junctions, gene expression and nucleo-junctional interplay
Authors: Matter Karl , Balda Maria Susana
Published: April 2007

Tight junctions are components of the junctional complex linking neighbouring epithelial cells and are important for barrier formation. Recent evidence suggests that tight junctions also participate in signal transduction mechanisms that regulate epithelial cell proliferation, gene expression, differentiation and morphogenesis. One important class of tight-junction-associated signal transduction mechanism is based on dual localisation of certain proteins both at junctions and in the nucleus. These proteins and their partners participate in various steps of gene expression, ranging from regulation of transcription and chromatin structure to mRNA processing and translation. In cancer tissues, their expression is often deregulated in a manner that suggests that tight junctions function as suppressors of proliferation and transformation.
Clearance-excitation force of shrouded turbine rotor accounting for pitching motion
Authors: Yuan Z , Chu F , Hao R , Wang S
Published: April 2007

Based on the basic mechanism of turbine rotor's clearance-excitation force and the motion patterns of turbine wheel, a new comprehensive leakage flow mechanism for shrouded turbine rotors is presented by taking into account both the radial and axial clearance variations due to rotor's whirling and pitching motions. According to this mechanism, a comprehensive analytical expression for clearance-excitation force of shrouded turbine rotor is developed. The developed expression reflects both the whirling eccentricity and the pitching angle of turbine rotor, and embodies the mean radial and axial clearances as well. Validations are performed to verify the effectiveness of the present expression. Numerical analyses are conducted to demonstrate the properties of the present clearance-excitation force. It is concluded that the present clearance-excitation force expression not only improves the classical one quantitatively, but also discloses the weak non-linearity of the clearance-excitation force. This is proved to be useful in the analyses of complicated rotordynamic systems where several non-linear factors couple together.
On the eddy characteristics of laminar axisymmetric flows through confined annular geometries with inward expansion
Authors: Nag D , Datta A
Published: April 2007

In this paper, laminar flows through axisymmetric confined annular geometries with sudden expansions have been studied numerically using a third-order accurate upstream biased quadratic scheme to investigate the recirculating eddy characteristics, following the expansion, in terms of recirculation length and eddy intensity. Two variations of annular geometry have been considered. In the first geometry, a smaller annulus abruptly expands inwardly into a larger one, whereas in the second case an abrupt inward expansion of the smaller annulus leads to a coaxial pipe. Fully developed inflow has been observed to separate immediately after the expansion plane forming a recirculating eddy. The variations in the size and intensity of the recirculating eddy are studied at different Reynolds numbers and expansion ratio for both the geometries. The effect of the presence of an inner solid wall after the expansion plane on the behaviour of the eddy is investigated. A secondary wall recirculation has been observed under specific flow situations in both the geometries. The characteristics of the secondary eddy have also been analysed and compared.
Continuous intravenous infusion in athymic (nude) rats: an animal model for evaluating the efficacy of anti-cancer agents
Authors: van Wijk H. , Dick A. , Greenough R. J. , Oshodi R. O. , Robb D.
Published: April 2007

The athymic (nude) rat (rnu/rnu) has been used for a number of years in research into various human tumours involving xenotransplantation. We now report the validation of a continuous intravenous infusion method in nude rats using a tail cuff tether, which enables the study of the efficacy of novel anti-cancer materials in this mutant strain, using intravenous infusion and with no restriction of the animals or of the tumour implantation sites by jackets.

Ten animals each had a cannula surgically implanted into the vena cava via the femoral vein and exteriorized via a tail cuff. Animals were housed singly in conventional cages following surgery. Following a recovery period of 5 days all animals were continuously infused with physiological saline at an infusion rate of 0.5 ml/h for a further 37 days. Body weights and food consumption were recorded weekly. Blood samples were taken approximately 14 days post-surgery and analysed for haematology and clinical chemistry parameters. All animals were successfully cannulated, and no unexpected adverse clinical signs were noted during the recovery period and the 37 days of infusion.

The results demonstrate that it is possible to surgically cannulate the femoral vein of athymic (nude) rats and infuse them in conventional cages for a period of up to 37 days with minimal adverse effects. The minimal restraint required provides benefits both to the animal and to the conduct of studies such as assessment of tumour growth in the absence of a jacket. Recent work has demonstrated that the same techniques can be successfully applied to the nude mouse.
Recommendations for the housing and care of domestic cats in laboratories
Authors: Rochlitz I.
Published: April 2007

In recent years, with increasing interest in applied ethology and animal welfare, research has been carried out on the behaviour and welfare of cats kept in different environments. These include laboratories, animal shelters, quarantine and boarding catteries and the home. This article presents a review of this research, makes recommendations for the housing and care of cats in laboratories, and comments on existing Codes of Practice.
Determination of major and trace elements in the liver of Wistar rats by inductively coupled plasma-atomic emission spectrometry and mass spectrometry
Authors: Takahashi S. , Takahashi I. , Sato H. , Kubota Y. , Yoshida S. , Muramatsu Y.
Published: April 2007

Inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES) were used to determine age-related changes in the concentrations of constituent elements in the livers of Wistar rats of 1 week to 12 months old. At first, sample preparation and analytical conditions were investigated in order to set up a simple routine procedure for measuring multiple elements simultaneously. Seventeen elements in the standard reference samples of bovine and pork livers as well as rat liver samples could be determined with a reasonable precision and reproducibility. They were P, K, Na, Fe, Mg, Ca, Zn, Rb, Cu, Mn, Mo, Al, Co, Sr, Cs, Pb, and Cd in order of the levels of concentration in the adult rat livers. Of these elements, the five major elements (P, K, Na, Fe, Mg, Ca) were determined with ICP-AES and the others with ICP-MS. Although the number of animals was too small to draw a statistically definite conclusion, it seems that age-related changes in the concentrations of these elements could be categorized into three general patterns: (1) remaining essentially constant throughout the animal ages, as observed for P, K, Na, Mg, Ca, Rb, Sr, Cs, and Pb, (2) increasing with age, as observed for Fe, Mn, Mo, Co, and Cd, and (3)decreasing with age, especially in the early stages of growth, as observed for Cu and Zn.
A porcine ex vivo paracorporeal model of lung transplantation
Authors: Wright N. C. , Hopkinson D. N. , Shaw T. E. , Hooper T. L.
Published: April 2007

A technique is described which allows perfusion of an isolated, ventilated pig lung with an extracorporeal veno-venous circuit from a support animal. This model is stable for up to 4 h, and avoids some of the disadvantages of alternative small animal and large animal models of lung transplantation. It may be useful in the investigation of factors affecting lung preservation and reperfusion injury.
Orbital sinus blood sampling in rats: effects upon selected behavioural variables
Authors: van Herck H. , Baumans V. , Boere H. A. G. , Hesp A. P. M. , van Lith H. A. , Beynen A. C.
Published: April 2007

The question addressed was whether the behaviour of rats is changed after orbital sinus blood sampling while they are under diethyl-ether anaesthesia. Twelve rats were subjected to sham anaesthesia, diethyl-ether anaesthesia and anaesthesia plus orbital puncture according to a Latin square. After each treatment, the behaviour of the rats was automatically monitored using the so-called LABORAS method, which discriminates between grooming, locomotion and inactivity. Treatment ended, and behaviour monitoring began, when the light period changed over to the dark period. The various behaviours were quantified as relative duration and frequency. Anaesthesia versus sham anaesthesia reduced the relative duration of grooming during the first 5 h after treatment. Anaesthesia plus orbital puncture versus anaesthesia alone did not significantly influence grooming, but orbital puncture did reduce the relative duration and the frequency of locomotion during the entire 20 h period, which was mainly due to a decrease in the dark period. After orbital puncture, the animals were also less frequently inactive. It is concluded that orbital puncture has an effect on behaviour superimposed on that of diethyl-ether anaesthesia. This observation may contribute new arguments to the debate on the acceptability of the orbital puncture technique.
Midazolam-fentanyl-isoflurane anaesthesia is suitable for haemodynamic and fluid balance studies in pigs
Authors: Husby P. , Heltne J. K. , Koller M.-E. , Birkeland S. , Westby J. , Fosse R. , Lund T.
Published: April 2007

The domestic pig is a useful model in certain areas of biomedical research. Effective use of this species is often encumbered by lack of reference values in conscious as well as anaesthetized animals. Anaesthesia itself influences physiological and biological variables; the anaesthetic technique often affects experimental results. The relationship between anaesthesia and haemodynamics is well characterized in man, but less established in pigs.

We studied the effect of midazolam-fentanyl-isoflurane anaesthesia in six immature, male, domestic pigs (Norwegian landrace). Haemodynamic variables (heart rate, arterial systolic, mean, diastolic pressures, pulmonary systolic, mean, diastolic pressures, pulmonary capillary wedge pressure), tissue perfusion, lymph flow (thoracic duct) were recorded for 3 h in animals with open chest through midline sternotomy.

Variables relevant to fluid balance, e.g. interstitial hydrostatic pressure (Pi), serum-colloid osmotic pressure (s-COP) and serum-albumin (s-albumin) and -protein (s-protein) concentrations were measured.

With the chosen anaesthetic technique haemodynamic variables, including lymph flow, and laboratory variables remained constant during the study period. Most variables were similar to conditions in humans. In contrast to adult humans exposed to the same anaesthetic technique, these pigs had lower haemoglobin-, s-albumin- and s-protein concentrations. A finding which may reflect immaturity. Liver and lung perfusion decreased significantly during the study period whereas perfusion of the other organs studied remained constant. Lack of responses to defined noxious stimuli during the study period suggest adequate analgesia.

We conclude that midazolam, fentanyl and isoflurane provide cardiovascular stability including normal microvascular fluid exchange, which are essential elements for securing the quality of results obtained during cardiovascular research in anaesthetized pigs.
Thoracic electrical bioimpedance: a non-invasive measure of cardiac output for porcine research
Authors: Broomhead C. J. , Wright S. J. , Kiff K. M. , Withington P. S.
Published: April 2007

A comparison of two techniques for measuring cardiac output, thermodilution (TD) and thoracic electrical bioimpedance (TEB), was undertaken in a porcine model. Eight anaesthetized large white pigs were studied. A total of 436 paired measurements were performed over a range of cardiac outputs from 1.7 to 15.11/min as measured by thermodilution. The Pearson product moment correlation coefficient was r=0.963 with P < 0.001. Analysis by Bland and Altman statistics revealed a mean difference (bias) of -0.021/min and the limits of ±1.6l/min, similar to figures found in human comparative studies. These results confirm that thoracic electrical bioimpedance is a valid method of measuring cardiac output in pigs. It has significant advantages compared to thermodilution, in particular it is cheap, simple to use, non-invasive and provides continuous data.
59Fe labelling of rabbit erythrocytes as a continuous source for iron metabolism studies
Authors: Moura E. , Verheul A. F. M. , Marx J. J. M.
Published: April 2007

The study of iron metabolism in human phagocytes requires a continuous source of 59Fe-labelled erythrocytes with high specific activity. Previously, rats and mice have been used for this purpose, but only limited amounts of blood can be obtained and the animals are (often) sacrificed during the experiment. This paper describes the development of a rabbit model for use as a continuous source of highly labelled erythrocytes as an alternative to mice and rats. A chinchilla rabbit was serially injected with 59Fe citrate to maintain a level of labelling of 12 × 105 cpm/ml of blood. During the 42-month use of the chinchilla rabbit, a total of 190 MBq was injected and a total of 277 ml blood was withdrawn. During the whole period, the health of the animal was not affected and no important changes were found in any of the haematological parameters studied. The protocol was successfully applied with a second rabbit with the same results. Our model provides a simple continuous source of highly labelled erythrocytes, minimizing the number of animals otherwise needed for this type of experiment.
The effect of different fibre components on growth rate, nutrient digestibility, rate of digesta passage and hindgut fermentation in domesticated rabbits
Authors: Chiou Peter Wen-Shyg , Yu Bi , Lin Chang
Published: April 2007

Trials were conducted to study the effect of dietary fibre on performance and nutrient digestibility in growing rabbits. The basal diet was supplemented with 12% cellulose, pectin, lignin, or alfalfa, in four different treatments. Twenty-four 4-week-old Californian male rabbits were randomly allocated into four groups and placed in individual cages. The lignin supplement severely affected both feed intake and performance, pectin second, with dietary cellulose having the least effect. Dietary lignin significantly decreased the digestibility of crude protein, gross energy and dry matter content ( P < 0.05). Rabbits on the pectin supplemented diet digested dry matter, crude fibre and neutral detergent fibre (NDF) better ( P < 0.05) than other treatment groups. On the other hand, rabbits in the lignin group digested crude fibre, acid detergent fibre (ADF) and NDF significantly less well than rabbits in other groups ( P < 0.05). Dietary lignin also significantly decreased the caecal concentration of volatile fatty acids (VFA, P < 0.05) but did not significantly affect the molar ratios of the VFAs among treatment groups. The turnover rate of the marker, chromic oxide, in the gastrointestinal (GI) tract of rabbits was 64.94, 51.81, 44.05 and 29.59 h in the pectin, alfalfa, lignin and cellulose treatment groups, respectively. The rate of turnover in the digestive tract significantly influenced digestibility of fibre components but did not significantly influence caecal fermentation.
A microchip implant system as a method to determine body temperature of terminally ill rats and mice
Authors: Kort W. J. , Hekking-Weijma J. M. , Tenkate M. T. , Sorm V. , VanStrik R.
Published: April 2007

In a series of experiments, Klebsiella pneumoniae was inoculated intratracheally into rats and mice, and the temperature of the animals was recorded twice daily using microchip transponders. Transponders are interrogated by radio frequencies and were implanted either subcutaneously or intraperitoneally. The microchip temperatures were compared with rectal temperatures taken at the same time. The purpose of the experiments was (a) to investigate the practicability and reliability of the ELAMSTM for temperature recording; (b) to compare values given by subcutaneously or intraperitoneally implanted transponders with rectal temperatures; and (c) to determine a 'temperature-cut-off point' as an alternative for 'death of the animal' as an end point for the experiment. The results showed that the ELAMSTM was easy to operate and no important drawbacks in the use of the system were observed. The temperatures generated by the transponders implanted subcutaneously and intraperitoneally did not differ significantly from rectal temperatures. In two out of three experiments on rats, it was shown that when the temperatures reached values below 36°C, the median survival time of the animals was 24 h. In the one experiment on mice the same median survival time was observed at 36°C. In one experiment using rats, however, the disease was so acute that death occurred before any temperature drop was seen. The results show that when a 36°C cut-off point is used instead of the time of death in this particular animal model, the statistical analysis was not altered, but that it would spare animals further suffering for approximately 24 h. The argument that measuring body temperature is a laborious job and stressful to the animals is overcome when the ELAMSTM system is used.
Injection technique and scanning electron microscopic study of the arterial pattern of the 20 gestation days (G20) rat fetus
Authors: Navarro M. , Carretero A. , Canut L. , Perez-Aparicio F. J. , Cristofol C. , Manesse M. , Sautet J. , Arboix M. , Ruberte J.
Published: April 2007

A technique to obtain microvascular corrosion casts of the G20 rat fetus and the normal pattern of the main arteries of the G20 rat fetus are described. The casts were studied by means of scanning electron microscopy (SEM). The arterial pattern is similar to that described in the adult; however, several variations have been found. It is concluded that the use of vascular corrosion casts studied by SEM may be particularly helpful to observe the extremely small arteries of rat fetuses. Moreover, we suggest that this technique may be useful in practical teratological studies.
Observations on the use of medetomidine/ketamine and its reversal with atipamezole for chemical restraint in the mouse
Authors: Cruz J. I. , Loste J. M. , Burzaco O. H.
Published: April 2007

Ketamine and medetomidine produced chemical restraint for minor procedures in mice. Male mice required 50 mg/kg ketamine, 10 mg/kg medetomidine intraperitoneally (i.p.), and females a higher dose of ketamine (75 mg/kg i.p.). The onset of restraint effects, judged by loss of righting reflex, was more rapid in males than females. The effects were reversed using atipamezole (1–2.5 mg/kg). Recovery following administration of atipamezole was more rapid in males than females. We conclude that ketamine/medetomidine, followed by reversal with atipamezole, is an effective technique for chemical restraint in the mouse.
Detection of endogenous retrovirus antigens in NOD mouse pancreatic β-cells
Authors: Tsumura H. , Miyazawa M. , Ogawa S. , Wang J. Z. , Ito Y. , Shimura K.
Published: April 2007

We characterized C-type retroviruses expressed in the pancreatic β-cells of non-obese diabetic (NOD) mice by immunohistochemical techniques and by inhibiting the production of viral particles using antisense oligonucleotides. Some cells in the pancreatic islets from both NOD and diabetes-resistant NOD-related mice (NON) reacted with a monoclonal antibody directed against the envelope protein(s) of polytropic viruses. On the other hand, NOD islet cells also showed strong immunoreactivity with an anti- gag protein monoclonal antibody and another anti-envelope protein(s) monoclonal antibody that is specific for xenotropic viruses. In antisense oligodeoxynucleotide inhibition assays, a xenotropic virus-specific phosphorothionate antisense oligodeoxynucleotide significantly inhibited the occurrence of C-type virus particles in NOD mouse islet β-cells. Therefore, C-type retrovirus-like particles expressed in NOD mouse pancreatic β-cells were considered to be endogenous xenotropic virus. The expression of the xenotropic viral genome may be involved in the pathogenesis of the diabetic syndrome in NOD mice.
A rapid and non-surgical procedure for jugular catheterization of pigs
Authors: Matte J. J.
Published: April 2007

A rapid and non-surgical method for jugular catheterization in pigs was set up in 30 piglets of 6.2 kg, 23 pigs of 46 kg and 84 kg and two lactating multiparous sows. The animal was restrained on a V-shaped table (piglets) or with a rope around the mandible (slaughter pigs and sows). The vein was located with the Vacutainer® system and a wire guide was inserted into the Vacutainer® needle up to the vein lumen. When the needle was removed, the catheter was inserted over the wire guide and advanced until it penetrated the skin and thereafter, the vein wall. The catheter was fixed outside by a large tape and coiled inside a patch just behind the ears. The technique utilizes readily available material and is no more risky for the animal than a single blood sampling. Moreover, it can be performed within 15 to 20 min (including animal restraint) within pens. This new approach might have important implications not only for research purposes by facilitating repeated blood samplings but also for projects which require a rapid and easy method for testing of any kind of pharmaceutical or other type of products under husbandry conditions.
Monitoring of piglets' open field activity and choice behaviour during the replay of maternal vocalization: a comparison between Observer and PID technique
Authors: Puppe B. , Schön P. C. , Wendland K.
Published: April 2007

The paper presents a new system for the automatic monitoring of open field activity and choice behaviour of medium-sized animals. Passive infrared motion detectors (PID) were linked on-line via a digital I/O interface to a personal computer provided with self-developed analysis software based on LabVIEW (PID technique). The set up was used for testing 18 one-week-old piglets ( Sus scrofa) for their approach to their mother's nursing vocalization replayed through loudspeakers. The results were validated by comparison with a conventional Observer technique, a computer-aided direct observation.

In most of the cases, no differences were seen between the Observer and PID technique regarding the percentage of stay in previously defined open field segments, the locomotor open field activity, and the choice behaviour. The results revealed that piglets are clearly attracted by their mother's nursing vocalization. The monitoring system presented in this study is thus suitable for detailed behavioural investigations of individual acoustic recognition. In general, the PID technique is a useful tool for research into the behaviour of individual animals in a restricted open field which does not rely on subjective analysis by a human observer.
Haematology and serum chemistry parameters of the pregnant rat
Authors: LaBorde J. B. , Wall K. S. , Bolon B. , Kumpe T. S. , Patton R. , Zheng Q. , Kodell R. , Young J. F.
Published: April 2007

This study describes the baseline haematology and serum chemistry values found in non-pregnant, pregnant (gestational days [GD] 2-21) and lactating (postnatal days 1-9) Sprague Dawley rats ( n = 3-10/day) from the NCTR breeding colony of Cr1:COBS CD(SD)BR strain. Maternal body weights on GD0 ranged from 250 to 300 g. Multiple analytes were measured in both whole blood and serum of dams. Amniotic fluid, fetal serum, and postnatal pup serum analyte values were also acquired. Maternal blood was collected from the heart under sub-terminal carbon dioxide (CO2) anaesthesia. Most pregnant dam blood values were not appreciably different from values for non-pregnant dams until near term; near-term values for some analytes (red blood cells, haemoglobin, haematocrit, mean corpuscular haemoglobin concentration, alkaline phosphatase, albumin, total protein, glucose, total bilirubin, sodium, and chloride) decreased but returned to near-normal values soon after delivery. The most dramatic change was a three-fold elevation of serum triglyceride levels near term with a subsequent decrease at birth. Most serum chemistry analytes measured in progeny increased after birth except for alkaline phosphatase, calcium and potassium levels which decreased.
The influence of pre-anaesthetic administration of buprenorphine on the anaesthetic effects of ketamine/medetomidine and pentobarbitone in rats and the consequences of repeated anaesthesia
Authors: Roughan J. V. , Ojeda O. Burzaco , Flecknell P. A.
Published: April 2007

Rats received pentobarbitone (60, 48 and 36 mg/kg i.p.) or ketamine/medetomidine (75/100, 60/80 and 45/60 mg/μg/kg i.p.) alone, or one hour following buprenorphine (0.5 mg/kg s.c.). Animals were anaesthetized once per week for 6 weeks with one of three anaesthetic doses according to a randomized block design. In the pentobarbitone group, animals which received buprenorphine had longer sleep times (236 ± 22 cf. 204 ± 21 min) and longer durations of surgical anaesthesia (83 ± 14 cf. 27 ± 8 min) ( P <0.01), these effects being potentiated with increasing anaesthetic doses ( P <0.01). A greater degree of respiratory depression was found in animals that received buprenorphine ( P <0.01) although this was judged clinically acceptable in all cases. Unexpectedly high mortality and a high incidence of anaesthetic complications (nine of 16 animals) in the ketamine/medetomidine group made statistical analysis of these data impossible. We conclude that for pentobarbitone, pre-anaesthetic administration of buprenorphine reduces the dose of anaesthetic required to produce surgical anaesthesia, in addition to the presumed benefits of pre-emptive analgesia. In view of the high mortality encountered, we advise caution when considering pre-anaesthetic use of opioids in combination with ketamine/medetomidine in rats.
Comparison of the effects of four anaesthetic agents on somatosensory evoked potentials in the rat
Authors: Hayton S. M. , Kriss A. , Muller D. P. R.
Published: April 2007

Electrophysiological techniques provide an objective and non-invasive measure of neurological function. In order to undertake detailed evoked potential studies in rats on repeated occasions, it is necessary to find an appropriate anaesthetic agent which has minimal and reproducible effects on the parameters to be studied and also has a minimal effect on the general welfare of the animals. In this study we compared the effects of four common anaesthetic agents (ketamine-xylazine, medetomidine, isoflurane and fentanyl/fluanisone-midazolam) on somatosensory evoked potentials (SEPs) in rats following electrical stimulation of the fore- and hind-paw. Fentanyl/fluanisone-midazolam was found to be well tolerated by the animals and to have, in general, the least deleterious effect on SEPs. For example, the response recorded at the level of the somatosensory cortex (P1), following forelimb stimulation, appeared on average 1.80 ms earlier with fentanyl/fluanisone-midazolam than with the other agents and the peak-to-peak amplitude (CI to CII) of the response recorded at the cervical (C3) level was on average 5.86 μV greater with fentanyl/fluanisone-midazolam. Fentanyl/fluanisone-midazolam is, therefore, recommended as the anaesthetic of choice for longitudinal studies of SEPs in the rat.
Housing conditions affect susceptibility to mercury in the golden hamster
Authors: Korz V. , Gattermann R.
Published: April 2007

Individually-housed and group-housed golden hamsters ( Mesocricetus auratus), aged 8 weeks, were studied with regard to their susceptibility to a single gavage of mercuric chloride (10 mg/kg body weight). Body weight and food consumption were measured for 10 days (day-9 to day 0) in a pre-application period and for 13 days (day 1 to day 13) in a post-application period. Mercuric chloride administration significantly reduced body weight gain in both isolated and grouped hamsters at day 1 compared to vehicle controls. While the individually-housed treated hamsters recovered during the post-application period, the group-housed treated hamsters showed a reduced body weight gain over the whole post-application period. Results are discussed in relation to elevated susceptibility to intoxication in group-housed hamsters triggered by high social stress. This study highlights the need to carefully consider the housing conditions which can influence the results of teratological experiments.
The ethical acceptability of animal experiments: a proposal for a system to support decision-making
Authors: Stafleu F. R. , Tramper R. , Vorstenbosch J. , Joles J. A.
Published: April 2007

We describe a system to support decision-making on the ethical acceptability of animal experiments for scientific researchers and others responsible for ethical decision-making in animal experiments. The system consists of eight steps. Each step contains a number of substantive questions or a computational rule, leading to a well-articulated moral judgment on specific animal experiments. The system comprises a number of moral assumptions and pre-emptive norms, but leaves enough room for moral discretion and personal responsibility. The general ethical ideas behind the moral choices and assumptions are sketched and potential objections to the overall approach are discussed.