Efficacy of cabergoline in a double-blind randomized clinical trial on milk leakage reduction at drying-off and new intramammary infections across the dry period and postcalving.

The abrupt cessation of milking at dry-off may induce milk leakage, which may increase the risk of new intramammary infections (IMI). This study assessed the efficacy of 1 i.m. injection of 5.6 mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France) at drying-off on milk leakage after dry-off and new IMI across the dry period and postcalving compared with a placebo (negative control) and an intramammary antibiotic treatment (positive control) under field conditions. The study was a double-blind, randomized, 3-arm, multicenter, clinical trial performed under Good Clinical Practice conditions. Data from 900 dairy cows of various breeds from 63 farms in France, Germany, and Hungary were analyzed. Only quarters with no bacterial growth at drying-off and a cow somatic cell count ≤200,000 cells/mL were included. Quarters infected with major or minor pathogens or cows with high somatic cell count at time of inclusion were excluded. Cows that qualified for the study were visited 7 times in total before and after drying-off and after calving. Presence (yes/no) of milk leakage was recorded on the day after dry-off. A new infected quarter (new IMI) was defined as one with a major pathogen present in any one of the 2 postcalving samples. Two mixed logistic regression models were fitted to the data to evaluate the efficacy of cabergoline in the reduction of milk leakage and new IMI. One i.m. injection of cabergoline at drying-off significantly reduced the incidence of milk leakage the day after dry-off compared with both placebo and antibiotic treatment. Cabergoline-treated cows significantly reduced the risk of new IMI by major pathogens across the dry period and postcalving by 21% when compared with placebo cows (20.5 vs. 26.0%, respectively). However, when milk leakage was added to the model, the significance of cabergoline was reduced. We interpreted this to show that milk leakage is an intervening variable between treatment with cabergoline and lower risk of new IMI. The antibiotic treatment significantly decreased the odds of new IMI compared with both cabergoline and placebo. However, because several countries are currently disallowing the preventive use of antibiotics at dry-off in noninfected quarters, the dry-off facilitator cabergoline may therefore be of particular value to reduce the risk of new IMI across the dry period.

Cabergoline inhibits prolactin secretion and accelerates involution in dairy cows after dry-off.

Dairy cattle require a dry period between successive lactations to ensure optimal milk production. Because prolactin (PRL) is necessary for the initiation and maintenance of milk production, strategies that can inhibit PRL secretion might hasten the involution process. The objective of this study was to determine the effect of the PRL release inhibitor cabergoline on markers of mammary gland involution during the early dry period. To assess the effect of cabergoline treatment on mammary gland involution, 14 Holstein dairy cows in late lactation were treated with either a single i.m. administration of 5.6mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France, n=7) or placebo (n=7) at the time of dry-off. Blood samples and mammary secretion samples were collected 6d before dry-off and again 1, 2, 3, 4, 8, and 14d following the abrupt cessation of lactation. Blood samples were used to determine plasma PRL concentrations. Mammary secretion samples were used to determine somatic cell count, milk fat, lactose, true protein content, and concentrations of α-lactalbumin, lactoferrin, and citrate. Following the cessation of lactation, changes in mammary secretion composition indicated diminished milk synthesis, including reduced concentrations of α-lactalbumin, citrate, and lactose. In contrast, milk somatic cell count, percent total protein, percent fat content, and lactoferrin concentrations significantly increased as involution progressed. Cabergoline treatment decreased the plasma PRL concentrations during the first week of dry-off, compared with the control treatment. No significant differences in citrate, α-lactalbumin, or protein content were observed between treatment groups. The most dramatic changes in secretion composition as a consequence of cabergoline treatment occurred during the first week of the dry period, when lactose concentrations and the citrate:lactoferrin molar ratio were lower and lactoferrin concentrations higher than in the control cows. Cabergoline treatment also tended to increase fat content and somatic cell count more rapidly following dry-off compared with the control group. These changes in mammary secretion composition following the abrupt cessation of lactation indicate that cabergoline treatment facilitated dry-off and effectively accelerated mammary gland involution.

[French validation of the Anger Rumination Scale]. / Validation française de l'échelle de rumination de colère (ARS).

BACKGROUND: The aim of this study was to propose a French version of the Anger Rumination Scale (ARS). The main contribution of this scale is to evaluate cognitive responses involved in rumination experience related to anger. The rumination experience is assessed through four scales: angry afterthoughts, thoughts of revenge, angry memories and understanding of causes. Because anger rumination is related to anger experience, it is usually understood to be a dysfunctional or unconstructive behavior. However, because the rumination involves cognitive activity, it can be assimilated as a cognitive strategy to cope with a negative event in a specific context. The ARS seems to be useful in understanding the rumination effects both on anger experience as well as on aggressive behaviors. METHOD: The original scale was translated following scientific recommendations for cultural adaptation of questionnaires. Six hundred and seventeen voluntary undergraduate students were asked to complete the ARS-French version. Among these 617 students: 305 completed the French ARS version twice over a 1-month period to test the reliability of the French version; 361 filled out both the French ARS version and the STAXI-II; 342 filled out both the French ARS version and the Aggression Questionnaire (AQ). The Total Sample was randomly split into two groups. An exploratory factor analysis (EFA) was conducted with group I's data. The confirmatory factor analysis (CFA) was conducted with group II's data. RESULTS: The EFA revealed a four factors solution close to the original version. The CFA confirmed a good model fit for the original four factors solution (χ(2)146: 302.14 CFI: 0.96 RMSEA: 0.058). A one factor model was tested, but was not retained. The ARS's internal consistency coefficients replicated those of the literature: alpha coefficients ranged from 0.60 to 0.86, and test-retest correlation coefficients ranged from 0.65 to 0.70. External validity indices conformed to previous studies, both for gender differences and for relationship with STAXI-II and AQ. CONCLUSION: Results of the present study support the validity and the reliability of the French version of the ARS. This validation provides a multifactorial scale for assessing anger rumination. This scale could be used, for example, to explore processes leading to aggressive behavior in several contexts in which overt behavior is prohibited or detrimental to performance.

The efficacy of an oral treatment with paromomycin against an experimental infection with Giardia in calves.

A controlled and blinded study was conducted to evaluate the efficacy and safety of a treatment with paromomycin sulphate against an experimental Giardia infection in calves. Animals were infected with 10(5)Giardia cysts of cattle origin and were either treated 11 days later with 25, 50 or 75 mg paromomycin/(kg body weight per day) during 5 consecutive days or not treated (control group). Efficacy was evaluated based on reduction in cyst excretion. Furthermore weight gain and diarrhea scores were monitored. In the group treated with 75 mg/kg per day there was a 100% reduction in cyst excretion until 9 days after the start of the treatment (D9) and a very high reduction (> or =98%) until D13. There was a high reduction (> or =93%) until D9 and D13 in the groups treated with 25 and 50 mg/kg, respectively. The cumulative cyst excretion on D13 was significantly (P<0.05) lower in the groups treated with 75 and 50 mg/kg compared to the control group. Although there was a trend towards higher weight gain and less diarrhea in the treated groups, differences between groups were not significant. No adverse reactions to the paromomycin treatment were recorded. Furthermore, the need for reliable parameters for evaluation of treatments against protozoal infections is emphasised.

Analysis of the QUESTOR water quality model using a Fourier amplitude sensitivity test (FAST) for two UK rivers.

This paper presents the sensitivity analysis of a well-known in-stream water quality model, QUESTOR (QUality Evaluation and Simulation TOol for River systems) as applied to two rivers of contrasting land-use in the northeast of England: the 'rural' Ouse and the 'urban' Aire. The analysis employed a version of the Fourier Amplitude Sensitivity Test (FAST) that quantifies the contribution of changes in individual parameters and combination of parameters to the variance of the model output (here the Nash-Sutcliffe) in an efficient way. The quantification of the sensitivity of the model output to the parameters led to the identification of the most influential parameters. Differences between the Aire and the Ouse were found, reflecting their different water quality regime. Results highlighted the importance of interactions between two, or more, parameters on the model output. It led to question the one-at-a-time calibration method currently applied with QUESTOR and underlined the importance of including interactions between parameters in sensitivity analyses. Comparison of the relative influence of parameters versus input data showed contrasting results. In the urban system, the inputs from discharges (sewage treatment works and industrial effluents) were highly influential on model outputs and generally more important than the model parameters. For the rural river, the tributary discharges were most influential, but only at a similar or a lower level than the model parameters.

A 13C solid-state NMR study of the structure and auto-oxidation process of natural and synthetic melanins.

This paper presents a 13C CP/MAS NMR study of the melanin pigments obtained through natural and synthetic origins: sepia-melanin from squid ink and three synthetic 5,6-dihydroxyindole-melanins prepared using different non-enzymatic oxidation pathways. The synthetic pigments can be distinguished from natural melanin by the absence of aliphatic carbons, thereby confirming the unreacted 3,4-dihydroxyphenylalanine and the proteinaceous origins of the aliphatic resonances in natural eumelanin. The spectra of selected non-protonated carbon resonances and those with only protonated carbon signals led to a quantitative analysis. An auto-oxidative experiment using a synthetic melanin, over a period of 130 h, has shown an unusually slow disappearance of hydrogen peroxide formed in situ. The 13C-NMR spectrum of the insoluble oxidized synthetic melanin compared to that before auto-oxidation clearly demonstrates that the oxidation process is associated with chemical changes within the pigment; i.e., carbonyl functional group formation and an increase of the non-protonated carbons fraction.

Protonation of the imidazole ring prevents the modulation by histidine of oxidative DNA degradation.

When supercoiled DNA is incubated with Fe(II) at pH 7 in the presence of hydrogen peroxide, the rate of nicking first increases with increasing H2O2 concentration to reach a maximum, then decreases and eventually increases again. When 0.1 mM histidine is added at neutral pH at low H2O2 concentration (< 3 mM), it hinders the nicking of DNA; when it is added at high H2O2 concentrations (> 10 mM), it enhances the rate of nicking. When similar experiments are performed at slightly acidic pH (4.5) the biphasic behavior is maintained, independent of the presence of histidine. One can conclude that the protonation of imidazole (pK = 5.9) abolishes the capability of histidine to modulate the oxidative degradation of DNA. Results of electron spin resonance experiments suggest that at low H2O2 concentration, the protective effect of histidine could be the consequence of its capability to bind OH. radicals.

Physical activity and sport involvement in French high school students.

The links between morphological, biological, sociological, psychological, and environmental characteristics, the practice of organized sports, and moderate to vigorous physical activities were examined by means of a questionnaire given to 48 high-school students aged between 16 and 19 years and their continuous heart-rate monitoring. Few correlations appear between these characteristics and moderate to vigorous physical activities. Only maximal oxygen uptake is linked to this type of activity in girls. Concerning sport involvement, correlations were more numerous for girls than boys. Physical and sports activities of girls were linked with maximal oxygen uptake, sport involvement of father, support, and encouragements of practice, perception of own activity, and private environment. Among boys, physical and sport activities were only linked with sport involvement of friends and perception of own activity. Unlike boys, physical and sport activities among girls seemed more strongly linked to sociological characteristics than other ones.

Determinants of physical activity and physical and sports activities in French school children.

The influence of morphological, biological, sociological, psychological, and environmental factors on the practice of organized sports and the amount of moderate to vigorous physical activity was examined through a questionnaire and continuous heart-rate monitoring, for 80 schoolchildren, 11 to 16 years old. Sport-practicing boys had a lower percentage of fat mass. Sport-practicing girls had more frequently sport-practicing mothers and higher scores on achievement motivation than nonsport-practicing girls. Active boys had more frequently sport-practicing fathers than inactive boys. No statistically significant correlation was found between moderate to vigorous physical activity and organized sports. Those children who are the most involved in organized sports are thus not necessarily the most active ones.

Photostability assessment of sunscreens. Benzylidene camphor and dibenzoylmethane derivatives.

Synopsis A rapid method has been developed in order to compare the photostability of several sunscreen agents incorporated in the same type of emulsion. Thin films of the different preparations were spread on quartz plates and irradiated with a solar simulator. Differences in energy distribution according to wavelengths observed with solar simulator and sun radiation were taken into account. A kinetic study of absorption properties was carried out under solar simulator irradiation. A simple calculation gave the results which would be obtained under sunlight. This technique differentiated the reversible transformations of photoisomerizable compounds from an irreversible disappearance which resulted in a significant loss of protective power. Applied to benzylidene camphor derivatives, this technique showed the excellent photostability of these sunscreen agents.

Modulation by L-histidine of H2O2-mediated damage of cellular and isolated DNA.

The mechanism by which L-histidine modulates H2O2-induced damage to DNA has been investigated by alkaline and neutral gel electrophoresis of cellular DNA, by measuring the conversion of purified supercoiled DNA to its relaxed and linear forms and by the ESR spin-trapping technique. L-Histidine greatly increased the amount of H2O2-mediated DNA single-strand breaks. DNA double-strand breaks were produced only in cells exposed to H2O2 and L-histidine. The addition of a cell permeable chelator such as o-phenanthroline (unlike EDTA, DTPA and desferrioxamine) prevented both DNA single- and double-strand breakage induced by H2O2 plus L-histidine. In vitro, the profile of the dose-response curve for the ferrous iron-mediated, H2O2-dependent DNA nicking was modified by the addition of L-histidine. At low H2O2 concentrations, corresponding to the maximum extent of DNA cleavage, L-histidine was protective. At higher H2O2 concentrations L-histidine enhanced the formation of DNA single-stand breaks and produced DNA double-strand breaks. The increase in H2O2-mediated DNA nicking by L-histidine depended on the L-histidine:Fe(II) ratio, the maximal rate occurring at a molar ratio of 10(3):1 and being independent of the concentration of DNA. Thus, it appeared that intracellular iron mediated both DNA single- and double-strand breaks induced by H2O2 plus L-histidine. Results of ESR experiments seemed to rule out the involvement of the hydroxyl radical by itself in DNA cleavage mediated by the L-histidine:Fe(II):H2O2 system.

ESR study of hair and melanin-keratin mixtures - the effects of temperature and light.

Synopsis The ESR spectrum of hair presents a symmetrical absorption band with the same characteristics as pure melanin (g= 2.0030; deltaH= 5 G). Between 250 degrees K and 490 degrees K, the intensity of the signal increases as for pure melanin. This variation may be explained by a change in the moisture content of hair as function of the temperature. Below 250 degrees K, in a frozen medium, melanin-water interactions remain constant and the number of radicals is no longer a function of temperature. Under exposure to light of hair, melanin-derived radicals were formed. Stable and short-lived radicals were observed at lambda > 345 nm; only unstable radicals were formed at lambda > 450 nm. At shorter wavelengths (lambda > 280 nm), a new asymmetric signal (g= 2.0065H= 20 G) appeared on UV exposure of black, grey or white hair; this signal was attributed to radicals formed in the direct excitation of keratin amino acids.

Electron spin resonance of eumelanin from hair: photoinduced radicals in solid matrix.

KBr matrices appear to be convenient media to reveal the radicals formed on light exposure of eumelanin dispersions. The ESR signal of eumelanin dispersed at low concentration in KBr pellets is analyzed during and after irradiation at various wavelengths. Different types of radicals are observed. R'1- and R1-types of radicals are assigned, respectively, to neutral and deprotonated intrinsic phenoxy radicals of eumelanin. R'1 can be oxidized by oxygen as opposite to R1. R2- and R'2-types are formed in the indolic site. Water favours the conversion of R2, unreactive with oxygen, into R'2 which can be oxidized. R'1 and R2 result of an electron photoejection, respectively, from the phenolic and the indolic site. The R3-type radicals are associated with the band-to-band excitation of eumelanin considered as a semiorganized solid.

Electron spin resonance study of photoinduced radicals in various eumelanins in solid matrix.

The photoinduced radicals formed in eumelanin from hair at various excitation wavelengths, in KBr matrix, are compared with the photoinduced radicals observed with bovine eye iris and squid ink eumelanins. Qualitative similarities and quantitative differences are observed, specially on exposure at short wavelengths.

Study of the photochemical behaviour of sunscreens - benzylidene camphor and derivatives.

Synopsis Benzylidene camphor derivatives have been currently used as ultraviolet filters in sunscreen compositions. When solutions of these compounds are exposed to the light from a solar simulator, a photoinduced cis-trans isomerization is observed. The initial quantum yields of this photochemical isomerization of studied molecules have been determined in several solvents. Their photochemical behaviour depends neither on the concentration nor on the presence or absence of oxygen or other inhibitors such as isopropanol or biacetyl. It means that the lifetime of the precursor states of isomerization is about 10(-12)s, that is to say, too short for them to react with neighbouring molecules. For each compound, the ratio of the respective concentrations of 'E' and 'Z' forms was also determined by photostationary state. A good agreement between theoretical and experimental values of this ratio shows that the studied compounds are only very slightly photodegradable. This was confirmed by the low values of photodegradation quantum yields. In case of the studied compounds, the isomerization process observed is totally reversible. During irradiation a photostationary state is quickly reached, each isomer may change into the other form after absorption of a photon which leads to a mixture of isomers. In practice, it is this mixture of E and Z forms which acts as UV filters. It may be said that a very short lifetime of the excited states, a good light stability and a reaction inertia under light irradiation make these compounds excellent sunscreen agents.

Proposed protocol for determination of photostability Part I: cosmetic UV filters.

Synopsis The protocol described here has been developed to measure the stability of UV-B filters; a modified version is recommended for UV-A filters. It should be considered as a tool to predict the effectiveness remaining after exposure to UV-A and UV-B light. It is a simple and reliable in vitro model simulating conditions of actual use. The results show that each filter requires an appropriate choice and fine tuning of reproducible analytical conditions. While absolute values are directly influenced by uncertainties in irradiance (dosimetry), comparative measurements with respect to a known standard are very reliable.