[Vibration as a risk of mastitis during milking]. / Vibration als Mastitis-Risiko beim Melken.

INTRODUCTION: Mastitis is one of the most important factor diseases in dairy cattle worldwide. Milking technique represents one of the factors involved in the development of mastitis. The purpose of this study was to investigate the influence of vibrations during milking on the rate of clinical and subclinical mastitis. For this purpose, milking measurements, tank milk analyses and survey forms (general farm data, assessment of milking work and milking hygiene, teat condition, feeding, farm problems, animal behavior) were assessed in 8 Swiss dairy farms. The results show a correlation between present vibrations at the output of the milk meter and increasing bulk milk somatic cell count. Further, a tendency was shown for vibrations at the input of the milk meter to influence bulk milk somatic cell count. Also, a tendency regarding vibrations at the outlet of the milk meter and acute phase protein milk amyloid A was evident. In conclusion, the results suggest that vibration during milking might have a negative effect on udder health. However, further research with a larger number of dairies is needed to make a more generally valid statement.

INTRODUCTION: La mammite est l'une des maladies les plus importantes chez les vaches laitières dans le monde entier. La technique de traite représente l'un des facteurs impliqués dans le développement de la mammite. L'objectif de cette étude était d'étudier l'influence des vibrations pendant la traite sur le taux de mammites cliniques et subcliniques. Pour ce faire, des mesures de traite, des analyses de lait de tank et des formulaires d'enquête (données générales de l'exploitation, évaluation du travail de traite et de l'hygiène de la traite, état des trayons, alimentation, problèmes de l'exploitation, comportement des animaux) ont été évalués dans 8 exploitations laitières suisses. Les résultats montrent une corrélation entre les vibrations présentes à la sortie du compteur à lait et l'augmentation du nombre de cellules somatiques du lait en vrac. En outre, les vibrations à l'entrée du compteur à lait ont tendance à influencer le nombre de cellules somatiques du lait en vrac. De même, une tendance concernant les vibrations à la sortie du compteur à lait et la protéine amyloïde A du lait de phase aiguë a été mise en évidence. En conclusion, les résultats suggèrent que les vibrations pendant la traite pourraient avoir un effet négatif sur la santé de la mamelle. Cependant, des recherches supplémentaires avec un plus grand nombre de laiteries sont nécessaires pour faire une déclaration plus généralement valable.

3D micro-scale deformations of wood in bending: synchrotron radiation muCT data analyzed with digital volume correlation.

A micro-scale three-point-bending experiment with a wood specimen was carried out and monitored by synchrotron radiation micro-computed tomography. The full three-dimensional wood structure of the 1.57x3.42x0.75mm(3) specimen was reconstructed at cellular level in different loading states. Furthermore, the full three-dimensional deformation field of the loaded wood specimen was determined by digital volume correlation, applied to the reconstructed data at successive loading states. Results from two selected regions within the wood specimen are presented as continuous displacement and strain fields in both 2D and 3D. The applied combination of synchrotron radiation micro-computed tomography and digital volume correlation for the deformation analysis of wood under bending stress is a novel application in wood material science. The method offers the potential for the simultaneous observation of structural changes and quantified deformations during in situ micro-mechanical experiments. Moreover, the high spatial resolution allows studying the influence of anatomical features on the fracture behaviour of wood. Possible applications of this method range from bio-mechanical observations in fresh plant tissue to fracture mechanics aspects in structural timber.

The spatial distribution of perseverations in neglect patients during a nonverbal fluency task depends on the integrity of the right putamen.

Deficient inhibitory control leading to perseverative behaviour is often observed in neglect patients. Previous studies investigating the relationship between response inhibition and visual attention have reported contradictory results: some studies found a linear relationship between neglect severity and perseverative behaviour whereas others could not replicate this result. The aim of the present study was to shed further light on the interplay between visual attention and response inhibition in neglect, and to investigate the neural underpinnings of this interplay. We propose the use of the Five-Point Test, a test commonly used to asses nonverbal fluency, as a novel approach in the context of neglect. In the Five-Point Test, participants are required to generate as many different designs as possible, by connecting dots within forty rectangles. We hypothesised that, because of its clear definition of perseverative errors, the Five-Point Test would accurately assess both visual attention as well as perseverative behaviour. We assessed 46 neglect patients with right-hemispheric stroke, and performed voxel-based lesion-symptom mapping (VLSM) to identify neural substrates of perseverative behaviour as well as the spatial distribution of perseverations. Our results showed that the Five-Point Test can reliably measure neglect and perseverative behaviour. We did not find any significant relationship between neglect severity and the frequency of perseverations. However, within the subgroup of neglect patients who displayed perseverative behaviour, the spatial distribution of perseverations significantly depended on the integrity of the right putamen. We discuss the putative role of the putamen as a potential subcortical hub to modulate the complex integration between visual attention and response inhibition processes.

Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor.

The new neuropeptide Y (NPY) Y5 receptor antagonist CGP 71683A displayed high affinity for the cloned rat NPY Y5 subtype, but > 1, 000-fold lower affinity for the cloned rat NPY Y1, Y2, and Y4 subtypes. In LMTK cells transfected with the human NPY Y5 receptor, CGP 71683A was without intrinsic activity and antagonized NPY-induced Ca2+ transients. CGP 71683A was given intraperitoneally (dose range 1-100 mg/kg) to a series of animal models of high hypothalamic NPY levels. In lean satiated rats CGP 71683A significantly antagonized the increase in food intake induced by intracerebroventricular injection of NPY. In 24-h fasted and streptozotocin diabetic rats CGP 71683A dose-dependently inhibited food intake. During the dark phase, CGP 71683A dose-dependently inhibited food intake in free-feeding lean rats without affecting the normal pattern of food intake or inducing taste aversion. In free-feeding lean rats, intraperitoneal administration of CGP 71683A for 28 d inhibited food intake dose-dependently with a maximum reduction observed on days 3 and 4. Despite the return of food intake to control levels, body weight and the peripheral fat mass remained significantly reduced. The data demonstrate that the NPY Y5 receptor subtype plays a role in NPY-induced food intake, but also suggest that, with chronic blockade, counterregulatory mechanisms are induced to restore appetite.

Interrelation of peri-operative morbidity and ASA class assignment in patients undergoing gynaecological surgery.

OBJECTIVE: The aim of this study was to estimate intra- and post-operative risk using the American Society of Anaesthesiologists (ASA) classification which is an important predictor of an intervention and of the entire operating programme. STUDY DESIGN: In this retrospective study, 4435 consecutive patients undergoing elective and emergency surgery at the Gynaecological Clinic of the University Hospital of Zurich were included. The ASA classification for pre-operative risk assessment was determined by an anaesthesiologist after a thorough physical examination. We observed several pre-, intra- and post-operative parameters, such as age, body-mass-index, duration of anaesthesia, duration of surgery, blood loss, duration of post-operative stay, complicated post-operative course, morbidity and mortality. The investigation of different risk factors was achieved by a multiple linear regression model for log-transformed duration of hospitalisation. RESULTS: Age and obesity were responsible for a higher ASA classification. ASA grade correlates with the duration of anaesthesia and the duration of the surgery itself. There was a significant difference in blood loss between ASA grades I (113+/-195 ml) and III (222+/-470 ml) and between classes II (176+/-432 ml) and III. The duration of post-operative hospitalisation could also be correlated with ASA class. ASA class I=1.7+/-3.0 days, ASA class II=3.6+/-4.3 days, ASA class III=6.8+/-8.2 days, and ASA class IV=6.2+/-3.9 days. The mean post-operative in-hospital stay was 2.5+/-4.0 days without complications, and 8.7+/-6.7 days with post-operative complications. Multiple linear regression model showed that not only the ASA classification contained an important information for the duration of hospitalisation. Parameters such as age, class of diagnosis, post-operative complications, etc. also have an influence on the duration of hospitalisation. CONCLUSION: This study shows that the ASA classification can be used as a good and early available predictor for the planning of an intervention in gynaecological surgery. The ASA classification helps the surgeon to assess the peri-operative risk profile of which important information can be derived for the planning of the operation programme.

[Tick-borne encephalitis in the North part of the canton de Vaud]. / Méningo-encéphalite verno-estivate dans le Nord vaudois.

Tick-borne encephalitis (TBE) is described in Switzerland since 1969. More than 200 cases are reported every year to the Federal office of public health (FOPH) and new sites of endemic disease have been documented recently, in particular in the North part of the canton de Vaud. The aim of this article is to review the clinical pictures of 11 patients hospitalised in Yverdon-les-Bains with a diagnosis of TBE between 2003 and August 2007. The occurrence of 5 new cases exposed in the North part of the canton de Vaud over these last 18 months confirms the presence of endemic foci in this area and should prompt the vaccination against the MEVE which is recommended by the FOPH in endemic zones. The sequels of MEVE being observed mainly in the elderly, vaccination should be afforded also to this group of patients.

Time-lapsed investigation of three-dimensional failure and damage accumulation in trabecular bone using synchrotron light.

Synchrotron radiation micro-computed tomography (SRmicroCT) is a very useful technique when it comes to three-dimensional (3D) imaging of complex internal and external geometries. Being a fully non-destructive technique, SRmicroCT can be combined with other experiments in situ for functional imaging. We are especially interested in the combination of SRmicroCT with mechanical testing in order to gain new insights in the failure mechanism of trabecular bone. This interest is motivated by the immense costs in health care due to patients suffering from osteoporosis, a systemic skeletal disease resulting in decreased bone stability and increased fracture risk. To better investigate the different failure mechanisms on the microlevel, we have developed a novel in situ mechanical compression device, capable of exerting both static and dynamic displacements on experimental samples. The device was calibrated for mechanical testing using solid aluminum and bovine trabecular bone samples. To study different failure mechanisms in trabecular bone, we compared a fatigued and a non-fatigued bovine bone sample with respect to failure initiation and propagation. The fatigued sample failed in a burst-like fashion in contrast to the non-fatigued sample, which exhibited a distinct localized failure band. Moreover, microscopic cracks - microcracks and microfractures - were uncovered in a 3D fashion illustrating the failure process in great detail. The majority of these cracks were connected to a bone surface. The data also showed that the classification of microcracks and -fractures from 2D section can sometimes be ambiguous, which is also true for the distinction of diffuse and distinct microdamage. Detailed investigation of the failure mechanism in these samples illustrated that trabecular bone often fails in delamination, providing a mechanism for energy dissipation while conserving trabecular bone architecture. In the future, this will allow an even better understanding of bone mechanics related to its hierarchical structural organization.

Tissue distribution of succinylacetone in the rat in vivo: a possible basis for neurotoxicity in hereditary infantile tyrosinemia.

Neurologic dysfunction is a significant component of hereditary infantile tyrosinemia, an autosomal recessive disorder of man. The specific enzyme defect leads to endogenous production of the biochemical marker compound, succinylacetone (SA). Earlier study of the role which SA plays in generation of the renal Fanconi syndrome, also associated with this disorder, led to speculation that SA might also have neurotoxic effects. Thus, we have studied the distribution and impact on heme metabolism of SA in brain, liver and kidney from rats treated in vivo. Our results show far greater retention of SA in brain and kidney than in liver, by a ratio of approx. 3:1. Delta-aminolevulinate dehydratase (ALAD) was reduced to less than 10% of control activity in all three tissues after three daily injections; after a 7-day recovery, activity was regained at different rates in the three tissues. Total heme content of each tissue showed a steady decline beyond the treatment period, the most marked reduction being found in kidney. Porphyrin intermediates, heme oxygenase activity and cytochrome P-450 content evidenced varying responses to SA exposure which differed from tissue to tissue. Our results show that brain tissue sequesters SA and that heme biosynthesis in brain, as distinct from liver and kidney, is adversely affected. Such effects could result in impaired oxidative metabolism in brain, producing the CNS manifestations of tyrosinemia.

Renal heme metabolism in hereditary tyrosinemia: use of succinylacetone in rat renal tubules.

Succinylacetone (SA), a metabolic end-product found in urine from individuals with hereditary tyrosinemia and associated renal Fanconi syndrome and a known inhibitor of hepatic 5-aminolevulinic acid dehydratase (ALAD), has been used to study heme metabolism in isolated rat renal tubules. Heme biosynthetic porphyrin precursors are increased selectively in the presence of 4 mmol/1 SA. Total porphyrin content of the tubules are increased approximately 2-fold, while both ferrochelatase and heme oxygenase activities remain unaffected by SA. Nonetheless, total heme content is reduced, as was incorporation of radioactive label from amino[14C]levulinic acid. Cytochrome P-450 content remained unaffected. Impairment of iron uptake and/or transport within the cell or enhancement of heme catabolism via a non-heme oxygenase-dependent pathway could explain the observations.

Comparison of microfocus- and synchrotron X-ray tomography for the analysis of osteointegration around Ti6Al4V implants.

Micro-computed tomography (microCT) provides quantitative three-dimensional information of bone around titanium implants similar to classical histology. The study, based on an animal model, containing cuboid-shaped biofunctionalised Ti6Al4V implants with surrounding bone after 4 weeks, is performed using 3 microCT-systems with X-ray tubes, one synchrotron-radiation-based microCT-system (SRmicroCT), and classical histology. Although the spatial resolution of the microCT-systems is comparable, only the results of SRmicroCT agree with results of classical histology. The X-ray tube sources give rise to huge artefacts in the tomograms (interface scattering, beam hardening), which impaired the quantitative analysis of bone up to about 200microm from the implant surface. Due to the non-destructive character of microCT the specimens can be subsequently examined by classical histology without restriction. The quantitative comparison of bone formation uncovers the strong dependence of the newly formed bone from the selected slice. This implies the necessity of 3D analysis. SRmicroCT and classical histology prove that surface modifications of the titanium implant significantly influence the bone formation. Using SRmicroCT, the preparation artefacts due to cutting and polishing are excluded.

Stimulation of feeding in lean but not in obese Zucker rats by a selective neuropeptide Y Y5 receptor agonist.

Obese Zucker rats are characterized by a reduced hypothalamic NPY receptor density. We tested the effects of intracerebroventricular injections of human NPY (hNPY) and [D-Trp32]NPY, a weak but selective NPY Y5 receptor agonist, on food intake in lean and obese Zucker rats. The effect of a maximal dose of hNPY (10 microg) on feeding was more pronounced in lean than in obese rats. [D-Trp32]NPY (10 microg) stimulated feeding in lean but not in obese Zucker rats. It did not affect the feeding response to hNPY, excluding the activation of an inhibitory receptor. These results are in favor of a down-regulation of the NPY 'feeding' receptor in the obese rat, which is suggested to be the Y5 subtype.

Benzoporphyrin derivative: a potent photosensitizer for photodynamic destruction of rabbit endometrium.

OBJECTIVES: To determine the optimal pharmacokinetic characteristics for photodynamic endometrial destruction using topically applied benzoporphyrin derivative and to evaluate long-term morphologic effects in a rabbit model. METHODS: Benzoporphyrin derivative pharmacokinetics were measured by analyzing frozen tissue sections 1.5-12 hours following topical administration. Photodynamic therapy was induced intraluminally 1.5 hours after drug application, and tissue morphology was evaluated by light and scanning electron microscopy 1 and 4 weeks after treatment. RESULTS: The highest glandular and stromal fluorescence was observed 1.5 hours after topical administration. Relative fluorescence of the endometrial glands significantly exceeded that of stroma and myometrium mainly at 1.5 and 3 hours (P < .0001). Histology revealed persistent epithelial destruction with minimal regeneration. Stroma resembled scar tissue in the majority of sections. The bordering myometrium was loosened and invaded by connective tissue. CONCLUSION: Topically applied benzoporphyrin derivative can be used for highly effective, long-lasting photodynamic destruction of rabbit endometrium. However, optical dosimetry can vary, particularly in the rabbit model, and this appears to affect long-term reepithelialization.

DNA probes for identification of the ectomycorrhizal fungus Tuber magnatum Pico.

The random amplified polymorphic DNA (RAPD) technique was used to develop DNA probes for the identification of ectomycorrhizal fungi belonging to the genus Tuber. RAPD fingerprinting revealed a high degree of interspecific variability and a low degree of intraspecific variability. One band (approximately 1.5 kb), consistently appearing when genomic DNA was amplified with an aspecific primer (OPA-18), was found to be a good marker for Tuber magnatum, and was used as a probe in Southern hybridization experiments. The specificity of the results suggests that this probe may be useful in developing specific primers for PCR amplifications.

The pharmacology of neuropeptide Y (NPY) receptor-mediated feeding in rats characterizes better Y5 than Y1, but not Y2 or Y4 subtypes.

Thirteen neuropeptide Y (NPY) agonists were administered intracerebroventricularly (i.c.v.) in rats (full dose-response curves) to estimate their half-effective dose (ED50) on feeding. These values were compared to their binding affinities (IC50) for rat NPY receptor subtypes Y1, Y2, Y4 and Y5 in vitro. Correlations between in vivo ED50 and in vitro IC50 were strong for the Y5 (r = 0.87; P < 0.01), weak for the Y1 (r = 0.48; P < 0.04) and non-significant for the Y2 and Y4 receptor subtypes. In vitro, h[D-Trp32]NPY was found to be a Y5-selective ligand and a full agonist in Y5-expressing cells. In vivo, it dose-dependently stimulated feeding, but failed to induce the full maximal response observed with pNPY. It did not antagonize pNPY-induced feeding and overfeeding in 24 h fasted rats. These findings demonstrate a role for the Y5, or possibly Y5 in combination with Y1, but not Y2 or Y4 receptor subtypes in feeding. No evidence was found for the existence of an additional, as yet undescribed, NPY feeding receptor.

Interaction of quaternary ammonium compounds with acetylcholinesterase: characterization of the active site.

The relation of the structure of 31 quaternary ammonium compounds (28 inhibitors; 3 substrate analogues) with their effects on the activity of acetylcholinesterase (EC 3.1.1.7; AChE) was studied. The compounds were structurally related to the natural substrate acetylcholine (ACh). All bear a trimethylammonium moiety as cationic head. The inhibitors include a variety of functional groups instead of an electrophilic ester group, making these substances suitable to probe the esteratic subsite. The inhibition constants and Km values were determined in kinetic experiments under steady state conditions (pH-stat method). Most of the substances acted as reversible, competitive inhibitors with KI in the range of 10(-6)-10(-3) M. The substrate analogues had Km values between (1.2-2.2) X 10(-4) M. The data allow the following main conclusions: (1) The quaternary trimethylammonium group of ACh is of high importance for substrate binding to AChE. It mediates association at the anionic site. (2) A poorer contribution to binding (two orders of magnitude lower) is attributable to the apolar methylene chain in ACh. It can be related to a hydrophobic interaction of the hydrocarbon chain at a region neighbouring the anionic site. (3) The ester group (both C = O and O) does not contribute to substrate binding. It is only responsible for reactivity.

Axillary lymphadenectomy--just how radical should it be?

UNLABELLED: To determine whether local axillary recurrences correlate with the number of lymph nodes extirpated, 779 cases of breast cancer were analysed in retrospect. RESULTS: The number of lymph nodes extirpated varied between 1 and 42 per axilla. The axillary recurrence rate of 5.5% showed a minimal correlation between the frequency of these recurrences and the number of lymph nodes removed. There is an equally insignificant correlation between the percentage of positive histological findings and the number of lymph nodes extirpated: The trend analysis shows that with fewer than five lymph nodes extirpated, 40% of positive histological findings can be expected, whereas with over 20 lymph nodes extirpated the percentage is 45%. CONCLUSION: The number of lymph nodes extirpated is an unsuitable indicator as to how radical axillary clearance is. Surgeons should rely on anatomical boundaries rather than focusing on the number of lymph nodes removed.

PEG-m-THPC-mediated photodynamic effects on normal rat tissues.

Photodynamic therapy (PDT) of malignancies uses light to activate a photosensitizer preferentially accumulated in cancer cells. The first pegylated photosensitizer, tetrakis-(m-methoxypolyethylene glycol) derivative of 7,8-dihydro-5,10,15,20-tetrakis(3-hydroxyphenyl)-21-23-[H]-porphyrin (PEG-m-THPC), was evaluated in non-tumor-bearing rats. The aim of this study was to assess the photodynamic threshold for damage and its sequelae in normal rat tissue. Thirty-five Fischer rats were sensitized with 3, 9 or 30 mg/kg body weight PEG-m-THPC. Colon, vagina and perineum were irradiated with laser light of 652 nm wavelength and an optical dose of 50, 150 or 450 J/cm fiber length. Temperature in the pelvis was measured during PDT. Three days following PDT the effect on skin, vagina, colon, striated muscle, connective tissue, nerves and blood vessels was assessed by histology. The healing of the above-mentioned tissues was assessed on two rats 3 and 8 weeks after PDT using 9 mg/kg PEG-m-THPC activated with 450 J/cm laser light. No dark toxicity was observed. PDT using 30 mg/kg PEG-m-THPC induced severe necrosis irrespective of the optical dose. Body weight of 9 or 3 mg/kg activated with less than 450 J/cm induced moderate or no damage. No substantial increase in body temperature was seen during PDT. Tissues with severe PDT-induced damage seem to have a good tendency to regenerate. We conclude that within the dose required for tumor treatment PEG-m-THPC is a safe photosensitizer with promising properties. PDT of the colon mucosa below 9 mg/kg PEG-m-THPC and 150 J/cm seems to be safe. All other tissues can be exposed to 9 mg/kg PEG-m-THPC activated with less than 450 J/cm laser light with little side effects.

From moclobemide to Ro 19-6327 and Ro 41-1049: the development of a new class of reversible, selective MAO-A and MAO-B inhibitors.

This study describes the serendipitous discovery of moclobemide, a short-acting MAO-A inhibitor which is in an advanced stage of clinical development as an antidepressant. The short duration of action of this MAO inhibitor containing a morpholine ring moiety is due to the complete reversibility (probably by metabolism of the inhibitory molecular species) of MAO-A inhibition. Since moclobemide is much more effective in vivo than expected from its in vitro activity, investigations to identify a possible metabolite(s) more active as MAO-A inhibitor than the parent compound were carried out. The study of the MAO inhibitory characteristics of several known and putative moclobemide metabolites did not allow the identification of a potent MAO-A inhibitor but led to the discovery of Ro 16-6491, a potent MAO-B inhibitor of novel chemical structure. Systematic chemical modification of the aromatic ring system of Ro 16-6491 finally provided Ro 19-6327 and Ro 41-1049 which are highly selective and reversible inhibitors of MAO-B and MAO-A, respectively. Tritiated derivatives of Ro 19-6327 and Ro 41-1049 were used in binding studies to elucidate their mechanisms of action and to study their cellular distribution by quantitative enzyme radioautography.

Determination of the optical properties of the human uterus using frequency-domain photon migration and steady-state techniques.

The optical properties (absorption and transport scattering coefficients) of freshly excised, bulk human uterine tissues were measured at 630 nm using frequency-domain and steady-state photon migration techniques. Measurements were made on both normal (pre- and post-menopausal) and non-neoplastic fibrotic tissues. The absorption coefficient of normal post-menopausal tissue (approximately 0.06 mm(-1)) was found to be significantly greater than that of normal pre-menopausal tissue (0.02-0.03 mm(-1)) and pre-menopausal fibrotic tissue (0.008 mm(-1)). The transport scattering coefficient was similar in all three tissue types considered (0.6-0.9 mm(-1)). From the preliminary results presented here, we conclude that optical properties can be reliably calculated either from the frequency-dependent behaviour of diffusely propagating photon density waves or by combining the frequency-independent photon density wave phase velocity with steady-state light penetration depth measurements. Instrument bandwidth and tissue absorption relaxation time ultimately determine the useful frequency range necessary for frequency-domain photon migration (FDPM) measurements. Based on the optical properties measured in this study, we estimate that non-invasive FDPM measurements of normal uterine tissue require modulation frequencies in excess of 350 MHz.