Determination of immunoglobulin concentrations and genetic parameters for colostrum and calf serum in Charolais animals.

Colostrum samples from 366 Charolais primiparous cows, as well as serum from their calves at 24 to 48 h of age, were collected to gain an overview of the situation regarding passive immune transfer in beef cattle, from both the phenotypic and genetic points of view. All samples were analyzed to quantify their G1 immunoglobulins by radial immunodiffusion (RID) and their IgG, IgA, and IgM using ELISA. The average concentrations obtained in colostrum were 84 mg/mL for RID-IgG1, and 158 mg/mL, 4.5 mg/mL and 10.8 mg/mL for ELISA-IgG, -IgA, and -IgM, respectively. The corresponding values in calf serum were 19.9, 30.6, 1.0, and 1.9 mg/mL. Apart from the general environmental effect (farm-year combination and laboratory conditions), the characteristics of the dams tested did not reveal any influence on colostrum immunoglobulin concentrations. Calving difficulty, as well as the birth weight and sex of calves, were found to be associated with serum concentrations in some cases. Heritability estimates were low to moderate, with the highest being for RID-IgG1 in colostrum (h2 = 0.28, standard error = 0.14) and serum (h2 = 0.36, standard error = 0.18). Phenotypic correlations among the different immunoglobulins were generally positive or null, and none of the genetic correlations were significant due to large standard errors. The phenotypic correlation between dam colostrum and calf serum values was 0.2 for RID-IgG1 and null for the 3 ELISA measurements. The correlation between RID-IgG1 and ELISA-IgG was, unexpectedly, null for colostrum and 0.4 for serum. Increased RID-IgG1 levels in calf serum were associated with improved survival, as well as better early growth and fewer health problems. These results thus showed that despite generally higher concentrations in beef than in dairy cattle, passive transfer was unsuccessful in a considerable number of calves. This should be brought to the attention of breeders to avoid negative effects on survival and subsequent performance. The heritability estimates were encouraging; however, obtaining phenotypes on a large scale constitutes a real limitation regarding these traits.

Assessment of different on-farm measures of beef cattle temperament for use in genetic evaluation.

The aim of this study was to find a simple measure for calf temperament discrimination, which can be useful as a selection criterion for on-farm French beef cattle breeding schemes. Behavioral records were registered at an average age of 5 and 7 mo, respectively, for 1,282 and 1,440 Limousin calves born in 24 French farms between August 2007 and April 2008. Measures were repeated for 810 calves at the 2 ages. The test procedure consisted of individually restraining the calves in a chute, then exposing them to a stationary human situated in front of the chute for 10 s. For every calf and each period of the test, the number of rush movements and the total number of movements were scored by visual appraisal using a continuous scale ranging from 0 (no movements) to 60 (continuous movements). Initial scores were also transformed to categorical scores and analyzed. Genetic correlation across ages were very high for all the traits (above 0.84 ± 0.20) suggesting that these traits are governed by the same pool of genes at the 2 ages. The corresponding phenotypic correlations were about 0.3 for all the measures. Heritabilities were moderate for all measures (from 0.11 to 0.31) with the total number of movements during weighing measured at 7 mo being the greatest. All the measures were highly correlated (from 0.73 ± 0.26 to 0.99 ± 0.02). Genetic correlation across sexes was not statistically different from 1. However, traits measured during weighing showed different genetic variance estimates for females and males. Similar results were obtained for the transformed categorical scores. According to these results, the total number of movements during weighing seems to be the most promising trait for on-farm genetic evaluation of French beef cattle temperament.

Synthesis, analgesic activity and computational study of new isothiazolopyridines of Mannich base type.

A series of new 4-arylpiperazine derivatives of isothiazolopyridine of Mannich base type and their non-4-arylpiperazine analogues (3 and 4) were synthesized and assayed as potential analgesic agents. Pharmacological assay demonstrated that all the compounds prepared, without exception, displayed significant activity in the mouse writhing assay. The analgesic action, expressed as ED50, was found to be 2-10 times more potent than that of acetylsalicylic acid and 1.5-10 times weaker than that of morphine, these being used as standards. The toxicities (LD50) of the investigated derivatives varied and ranged from 250 to 2000 mg/kg. Additionally, the computational investigations were performed in order to find correlation between molecular structure and biological effects (toxicity, analgesic action) of discussed compounds. Useful model was found for toxicity assessment.

Synthesis and analgesic action of N-(substituted-ethyl)pyrrole-3,4-dicarboximides.

We prepared a series of new N-[2-(4-substitutedpiperazin-1-yl)ethyl]-1-(n-butyl or phenyl)-2,5-dimethyl-3,4-pyrroledicarboximides 3 and the related products 4 and 5, nine representatives of which were evaluated as potential analgesic agents in an animal model (mice). The new pyrroledicarboximides were not toxic (LD50 > or = 1466 mg/kg) and eight of them displayed analgesic activity approximately 1.5-5 times superior to that of ASA in the writhing test. However, the compounds were found to be unstable in methanol solution and in dilute bases (methanol/NaOMe). The S-A relationship is discussed.

Synthesis and properties of N-methyl and N-phenyl derivatives of 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d]pyridazines.

2-Methoxy- and 2-ethoxy-6-methyl-3,4-pyridinedicarboximides (XI, XII) reacted with N-methylhydrazine giving 2- and 3-methyl derivatives of the appropriate 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d]pyridazines (XV, XIII and XVI, XIV). In both cases 3-methyl isomer (XIII, XIV) was formed in higher yield than 2-methyl derivative (XV, XVI). Reaction of the imide XII with N-phenylhydrazine gave the salts of the suitable N-phenyldihydropyrido[3,4d]pyridazines with NH2-NHC6H5 (XXI and XXII) which transformed into N-phenylaminoimide (XXIII) during the boiling in 80% CH3COOH. Imide XXIII isomerized to the appropriate 2-phenyl and 3-phenylpyrido[3,4-d]pyridazines (XXIV - main reaction product and XXV) under the influence of heating in ethanolic solution of C2H5ONa. Some of N-phenylpiperazinylhydroxyalkyl(alkyl) derivatives of compound XXIV (XXVII, XXVIII) were pharmacologically active.

Synthesis and properties of tetra(hexa)hydropyrazolo [1,2-a]pyrido[3,4-d]pyridazine derivatives.

The synthesis of tetra(hexa)hydropyrazolo[1,2-a]pyrido[3,4-d]pyridazine derivatives (14-21) and the results of pharmacological screening are described in this paper. All compounds tested were non-toxic and showed a significant analgesic action. The analgesic effects were associated with the suppression of the spontaneous locomotor activity. Furthermore most of the synthesized compounds displayed a weak antimycobacterial action in the preliminary screening.

Preparation of novel derivatives of pyridothiazine-1,1-dioxide and their CNS and antioxidant properties.

Starting from isothiazolopyridine-1,1-dioxide (1), corresponding derivatives of 3-aryl-4-hydroxypyrido[3,2-e]-1,2-thiazine-1,1-dioxide (6) possessing the 3-[4-(substituted-phenyl)piperazinyl]propyl or 3-(4-substituted-piperidinyl)propyl side chain by the nitrogen atom of the thiazine ring were prepared. Under pharmacological central nervous system (CNS) screening in animal models (mice), all of the six pyridothiazines 6 tested exhibited analgesic action as the predominant profile of their activity ('writhing' test 12.5-50 mg/kg). Moreover, the radical scavenging activity against peroxyl radicals of the representative pyridothiazines 6 was evaluated in vitro in water environment and some of them proved to be moderate antioxidants.

Synthesis and properties of 2-(4-substituted)butyl derivatives of some 2,3-dihydro-1,3-dioxo-1H-pyrrolo[3,4-c]pyridines.

The synthesis of 2-(4-substituted)butyl derivatives of 4-alkoxy-2,3-dihydro-6-methyl-1,3-dioxo-1H-pyrrolo[3,4-c]pyridine (10-15) and the results of preliminary pharmacological screening are described in this paper. All the compounds tested showed a strong analgesic action, suppressed spontaneous locomotor activity and prolonged barbiturate sleep. Except 10, all significantly decreased systolic and diastolic blood pressure.

Effect of monoterpene derivative KP-19 on the pressor activity of catecholamines in rats.

The present study investigated the influence of KP-19, the propranolol analogue, bearing natural monoterpene moiety in its structure, on the blood pressure and respiration, the effect on the isolated heart rhythm disturbances induced by occlusion and reperfusion and on the pressor activity of catecholamines in normotensive rats.

Search for new antiarrhythmic and hypotensive compounds. Synthesis, antiarrhythmic, antihypertensive, and alpha-adrenoceptor blocking activity of novel 1-[(2-hydroxy-3-amino)]-propylpyrrolidin-2-one derivatives.

A series of the derivatives of 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl])propyl]-pyrrolidin-2- one (MG-1) was synthesized and tested for electrocardiographic, antiarrhythmic, and antihypertensive activity as well as for alpha 1- and alpha 2-adrenoceptors binding affinities. Some of the compounds of this series slightly decreased the heart rate, prolonged P-Q, Q-T intervals and QRS complex. Only compound 7 (1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-pyrrolidine) possesses potent antiarrhythmic and a slight hypotensive properties, and affinity for alpha 1- and alpha 2-adrenoceptor. The results suggest that the antiarrhythmic and hypotensive effect of compound 7 and MG-1 is related to their adrenolytic properties, and that those properties depend on the presence of a phenylpiperazine moiety.

Synthesis and properties of some aminoalkanolic derivatives of xanthone.

A series of appropriate aminoalkanolic derivatives of xanthone III-VIII was synthesized and evaluated as potential antiarrhythmic agents. They were also tested for the effect on the cardiovascular system. The structure of the synthesized compounds was verified by IR 1H NMR, 13C NMR and mass spectral data.

Individual differences in docility in Limousin cattle.

Docility tests were performed over 3 yr on 906 Limousin heifers sired by 34 males. The heifers were tested individually when they were 10 to 11 mo old in a pen with a handler who had 2 min to lead the animal to a corner, keep it there for 30 consecutive seconds, and then to stroke it. Behaviours of the animals were recorded and scores calculated. The first score (docility score) was a continuous variable combining the greatest possible information. The second score (docility criterion) was a categorical trait with four classes. Tests were performed by seven different handlers. The effects of handler, year, birth period, dam parity, birth region, husbandry system, and sire were estimated. Handlers, birth period, husbandry system, and sire had significant effects. In particular, animals that were managed indoors were more docile than those reared out-of-doors at least part of the time. Heritability estimates of the docility score (.22) and docility criterion (.18) seem sufficient to select for docility traits.