Reduced Ovulatory and Oestrous Activity in Zebu Heifers Following Trypanosoma vivax Infection

This paper describes a study on the oestrous and ovarian activity and responses to prostaglandin F2 (PGF2) administration and artificial insemination in zebu heifers.Four cycling heifers were artificially infected with 5×106 Trypanosoma vivax organisms. Two heifers served as controls. Two injections of PGF2 were given 11 days apart, commencing at the peak of parasitaemia in the infected animals, followed by artificial insemination 72 and 96 h after the second administration of PGF2. Sera were analysed for progesterone by radioimmunoassay, while ovarian activity and oestrus were determined by rectal palpation and visual observation, respectively. All the infected heifers developed the clinical disease. All control and infected heifers had progesterone profiles consistent with luteolysis and the occurrence of oestrus following the second administration of PGF2. Progesterone levels did not return to normal luteal values in infected animals, however, whilst they did so in control animals. No control or infected heifers became pregnant.The findings suggest that PGF2 will induce a non- fertile oestrus in zebu heifers acutely infected with T. vivax. Re-ovulation is also inhibited within 22 days in a majority of infected animals.     

Preliminary findings of altered follicular activity in Holstein cows with coagulation factor XI deficiency

Factor XI (F XI) deficiency is an autosomal recessive coagulopathy found in Holstein cattle. Affected animals have a 50% greater prevalence of repeat breeding. Therefore, several parameters describing ovarian function were studied. Daily blood sampling revealed that progesterone concentrations were slower to decline from a peak at day 16 (p<0.01) to values less than 3 nmol/L in F XI-deficient cows (5.14±0.69 days (mean ± SD) versus 4.05±0.63 days in control animals), resulting in an oestrous cycle length of 24.7±2.1 days compared to 22.9±3.0 days, respectively. This was not due to an alteration in the availability of prostaglandin F₂ (PGF₂) or oxytocin (OT) involved in luteolysis. No significant differences (p>0.05) were seen between normal (n=7) and F XI-deficient (n=7) cows in the peak values or the area under the curve for the pulse in 13,14-dihydro-15-keto PGF₂ in response to OT challenge or in the parameters describing the pulse of ovarian OT secretion after PGF₂ injection (n=7 for each) between days 12 and 14. Ovulatory follicular development was assessed by ultrasound monitoring and plasma 17-oestradiol values at 8-h intervals after a luteolytic injection of cloprostenol (n=6 for each). Follicular diameter was smaller (p<0.05) and accompanied by lower peak oestradiol values near the time of ovulation in F XI-deficient cows. The results suggest that the oestrous cycle in F XI-deficient cows is characterized by a slower process of luteolysis that may be associated with smaller follicular development.Abbreviations F XI factor XI - OT oxytocin - PGF₂ prostaglandin F₂ - PGFM 13,14-dihydro-15-keto-prostaglandin F₂ - i.m. intramuscularly     

Identification of Functional α-Adrenoceptor Subtypes in the Bovine Female Genital Tract During Different Phases of the Oestrous Cycle

The concentration and functionality of the -adrenoceptor (-AR) subtypes in the genital tract of cyclic heifers were investigated. In each tissue sample, a single class of ₁-ARs was observed, whereas two distinct classes of ₂-ARs were discriminated: low-affinity (LA) and high-affinity (HA) ₂-ARs. Statistical analysis showed the presence of significantly (p < 0.05) higher concentrations of all -AR subtypes in the follicle than in the corpus luteum. No significant differences were found in the ovary or myometrium between the luteal and follicular phases. In the ovary, the density of ₁-ARs was significantly (p < 0.05) higher than that of ₂-ARs. By contrast, there were significantly (p < 0.05) more ₂-ARs than ₁-ARs in the myometrium. As far as ₂-ARs are concerned, LA ₂-ARs were significantly (p < 0.05) higher than HA ₂-ARs in all tested tissues. Competition studies suggested that the rank order of potency of antagonists for ₁-ARs was prazosin > phentolamine > yohimbine, whereas for ₂-ARs the order of potency was yohimbine phentolamine > prazosin. Functional assays performed on myometrium showed that noradrenaline, phenylephrine and clonidine elicited concentration-dependent contractions only in dioestrus and pro-oestrus preparations and that clonidine was more effective than phenylephrine as a contractile agent. It appeared that there were no significant modifications in -AR affinity or concentration during the different stages of bovine oestrous cycle, whereas the uterine spontaneous activity and the responsiveness to -adrenergic stimulation was strongly influenced by hormonal levels. The modifications of uterine contractility observed during the oestrous cycle may be related to modifications induced in the transductional mechanisms of -ARs.     

Feed intake and rumen motility in dwarf goats. Effects of some α-adrenergic agonists,prostaglandins and posterior pituitary hormones

The purpose of the present investigation was to test the hypothesis that drug-induced changes in rumen contractions influence feed intake in dwarf goats. Intravenous (i.v.) administration of clonidine (1 g kg^-1 min^-1 for 10 min), xylazine (1 g kg^-1 min^-1 for 10 min), and PGF-2 (10 g kg^-1 min^-1 for 15 min) caused bradycardia and inhibition of rumen contractions. However, no appetite-stimulating effect of these drugs was observed. Other clinical changes induced by the ₂-adrenergic agonists included slight sedation and a decrease in body temperature; all clinical effects of clonidine and xylazine were partly antagonized by tolazoline pretreatment (10 g kg^-1 min^-1 for 30 min). These results suggest that the CNS control of feeding differs in ruminants and monogastric species.In dwarf goats fasted for 2 h, i.v. administration of oxytocin (0.01 IU kg^-1 min^-1 for 15 min), vasopressin (0.01 IU kg^-1 min^-1 for 15 min), octapressin (0.003 IU kg^-1 min^-1 for 15 min) or PGE (0.8 g kg^-1 min^-1 for 15 min) did not change feeding behaviour during the two observation periods (0–30 min and 180–210 min after drug infusion, respectively). In previous studies, similar doses of these drugs induced changes in heart rate and inhibition of rumen contraction in goats. These findings demonstrate that drug-induced changes in forestomach contractions do not simply cause changes in feeding behaviour. The i.v. infusion of the PGF₂ analogues etiproston (10 g kg^-1 min^-1 for 15 min), luprostiol (30 g kg^-1 min^-1 for 15 min), cloprostenol (1 g kg^-1 min^-1 for 15 min) and tiaprost (1 g kg^-1 min^-1 for 15 min) induced hypophagic effects and stimulated intestinal propulsion.     

Bovine Immunodeficiency Virus Expression in Vitro is Reduced in the Presence of β-Chemokines,MIP-1α, MIP-1β and RANTES

The inhibition of HIV expression in vitro by a cocktail of the -chemokines MIP-1, MIP-1 and RANTES provided the initial evidence that HIV utilizes chemokine receptors as co-receptors for infection of cells. Bovine immunodeficiency virus (BIV), a lentivirus, infects a wide variety of leukocyte populations, but the cellular receptor(s) utilized by this virus for infection of cells is not known. The purpose of this study was to determine whether MIP-1, MIP-1 and RANTES affect BIV expression in vitro, as a prelude to identifying the cellular receptors utilized by this virus. Fetal bovine lung (FBL) cells were pretreated with serial dilutions of a cocktail of the chemokines, and then the cells were infected with BIV. Virus expression in these cells was determined by counting the syncytia that had developed in the cultures by five days after infection. A significant decrease in syncytium formation, corresponding to increasing concentrations of the chemokines, was the result. Reacting the chemokines with chemokine-specific neutralizing antibodies prior to treatment of the cells neutralized the effect of the chemokines on virus replication in a dose-dependent manner, restoring viral expression to a level similar to that of untreated cells. The presence of a CCR5 homologue on the surface of FBL cells was confirmed using an anti-CCR5 monoclonal antibody and FACS analysis. Collectively, these data provide preliminary evidence that BIV may utilize the CCR5 receptor for infection of cells in vitro, but additional studies are necessary to confirm this.     

Acute and Subacute Metabolic and Endocrine Effects of Clenbuterol in Female Pigs

The aim of the study was to assess the relationship between acute and subacute metabolic and endocrine effects after intravenous administration of the ₂-adrenergic agonist clenbuterol in a growth-promoting dose to female pigs. Acute metabolic and endocrine effects were assessed by measuring the blood glucose, serum insulin and nonesterified fatty acid (NEFA) concentrations during 300 min after a single administration of clenbuterol. Significantly higher serum insulin and NEFA concentrations (19.90±2.50 U/ml, p<0.01, and 0.69±0.04 mmol/L, p<0.001, respectively) were measured 30 min after the preprandial administration of clenbuterol in female pigs. Over the same period, the levels of blood glucose (4.42±0.30 mmol/L) showed no difference from those of control pigs. The postprandial serum NEFA concentration decreased moderately during 210 min after feeding. Postprandial blood glucose and insulin concentrations increased and reached maximal levels 120 min after clenbuterol administration (10.91±0.60 mmol/L and 85.22±7.24 U/ml, respectively), and returned to basal levels at 300 min (4.20±0.21 mmol/L and 7.75±1.60 U/ml, respectively) after the administration of clenbuterol. Subacute metabolic and endocrine effects were assessed by measuring the blood glucose, serum insulin and NEFA concentrations for 21 days after the repeated doses of clenbuterol. In addition, the influence of clenbuterol administration on the endocrine regulation of the onset of the next expected oestrus in female pigs was assessed by measuring their serum 17-oestradiol and progesterone concentrations. Blood glucose, serum insulin and NEFA concentrations after the last administration of clenbuterol did not differ significantly from those in control animals. The onset of the next expected oestrus occurred regularly without any significant difference in serum 17-oestradiol or progesterone concentrations between the treated (9.83±2.60 pg/ml and 0.15±0.03 ng/ml) and control pigs (8.52±2.70 pg/ml and 0.25±0.06 ng/ml). The study results suggest the duration of intravenous administration of clenbuterol in a growth-promoting dose necessary to influence the metabolic and endocrine activities in female pigs.     

Detection of β2-agonists in milk replacer

₂-Agonist drugs may be illegally used as growth promoters for feedlot calves, when mixed into milk replacer immediately before feeding. To check for the presence of clenbuterol, salbutamol and terbutaline in such food, an analytical system was established using a screening method based on two commercial qualitative competitive ELISA tests, with antibodies raised against the arylamino group and thet-butyl group. The extraction procedure was based on precipitation of the milk samples with acetonitrile followed by filtration. The absence of any significant interference by other substances in the filtrate allowed detection of ₂-agonist drugs in spiked samples at the lowest concentration having a repartitioning effect (50 ppb for clenbuterol, mabuterol and terbutaline, 500 ppb for salbutamol). In view of a false positive response with tetracycline in milk samples and a cross-reaction between clenbuterol and mabuterol, an HPLC-MS technique was developed which, after extraction and purification of the samples with SPE C18 Polar Plus, was able to confirm the presence of these drugs. The good recovery after extraction (ranging from 84% to 90.2%) and the low detection limit with this method (250 ng/ml for clenbuterol, mabuterol and terbutaline, and 2.5 µg/ml for salbutamol) allowed easy confirmation and simultaneous detection of the four ₂-agonists at the lowest concentrations at which they are used in adulterated milk for calves.Abbreviations B optical density of the sample - B maximal optical density in total absence of competition - %B/B ₀ percentage of inhibition - ELISA enzyme-linked immunosorbent assay - EIA enzyme immunoassay - HPLC-MS high-performance liquid chromatography-mass spectrometry - m/z mass to charge ratio - ppb parts per billion - ppm parts per million - SPE solid-phase extraction     

Plasma,Urinary and Biliary Residues in Cattle Following Intramuscular Injection of Nortestosterone Laurate

The synthetic androgen 19-nortestosterone (-NT) has been used illegally as a growth promoter in cattle production in the European Union. Elimination of -NT and its metabolites in plasma, urine and bile was studied in three cattle with cannulated gallbladders following intramuscular injection at a single site of 500 mg of the laurate ester (NTL) containing 300.5 mg -NT. Using enzyme immunoassay quantification, plasma Cmax of free -NT was 0.5±0.15 g/L (mean±SEM). Concentrations of free -NT in plasma were consistently greater than the assay limit of quantification (0.12 g/L) for 32.7±13.42 days. Mean residence time for free -NT in plasma was 68.5±20.75 days. Following sample preparation by immunoaffinity chromatography, high-resolution GC-MS was used to quantify -NT and -NT in urine and bile. -NT was detected irregularly in urine from two of the three animals post injection. The principal metabolite present in the urine, -NT, was detected for 160.3±22.67 days post injection. Cmax for -NT in urine was 13.7±5.14 g/L. Mean urinary AUC0–183 days for -NT was 845.7±400.90 (g h)/L.In bile, -NT was the only metabolite detected for 174.3±8.67 days post treatment. Cmax for -NT in bile was 40.8±12.70 g/L and mean biliary AUC0–183 days for -NT was 1982.6±373.81 (g h)/L. Concentrations of -NT in bile samples were greater than those in urine samples taken at the same time. The mean ratio of biliary:urinary AUC0–183 days was 3.0±0.72. It is concluded that bile is a superior fluid for detection of -NT following injection of NTL, owing to the longer period during which residues may be detected after administration.     

Present Concepts on the Inflammatory Modulators with Special Reference to Cytokines*

The pro- and anti-inflammatory cytokines create a network of interactions between cells that lead to both stimulatory and inhibitory responses that maintain an effective homeostatic regulation. The anti-inflammatory cytokines are a family of peptides that modulate the pro-inflammatory cytokine response. Cytokines act in concert with non-cytokine mediators, such as prostaglandin E₂, glucocorticosteroids, lipocortins, and catecholamines. This review highlights new developments in our understanding of the pathophysiology of inflammation and gives an example of a more recent approach to the modulation of acute systemic inflammatory disorders: activation of ₂-adrenergic receptors on macrophages. In this respect the potent ₂-adrenergic agonist clenbuterol seems of therapeutic interest.     

Decreased number of α-motoneurons in the cervical intumescence of calves with Arthrogryposis Multiplex Congenita of both thoracic limbs

The number of -motoneurons in the spinal cord segments C6 to Th2 of five calves with Arthrogryposis Multiplex Congenita (AMC) and of five normal calves was compared. A statistically highly significant reduction in the number of -motoneurons in segment C6 was observed in the affected calves. Two hypotheses to explain the effect of these findings were proposed. Firstly, it was thought that AMC may result from paresis of some muscles of the girdle, shoulder and elbow. Secondly, it was postulated that the decrease in the number of -motoneurons in C6 may have induced a radial nerve dysfunction resulting in AMC.This work was supported by the IWONL, Brussels, Belgium.     

Evaluation of Synchronization of Oestrus Based on Gonadotrophin-releasing Hormone and Its Potential Use for Fixed-Time Breeding in Tuli Beef Cows

The objective of the experiment was to compare the reproductive post-partum performance of beef cows synchronized for oestrus using prostaglandin F₂ (PGF₂) alone or with a gonadotrophin-releasing hormone (GnRH)-based drug. Fifty-five post-partum lactating Tuli cows were randomly allocated to three groups. Two groups were synchronized using either two injections of PGF₂ (500 g Prosolvin per injection) given 11 days apart (group 1), or GnRH (12.5 g Receptal per injection) followed 6 days later by an injection of 500 g PGF₂ (group 2). The cows were bred by artificial insemination 12 h after they were observed in oestrus. Group 3 was synchronized as for group 2, but a second injection of GnRH was given 54 h after the PGF₂ injection, at which time the cows were bred by artificial insemination (AI) without detection of oestrus. Blood samples were taken from the cows in group 3 and analysed for progesterone concentration to establish which cows were cycling and in oestrus before and at the time of breeding. Detection of oestrus and breeding by AI was done over 60 days. There were no significant differences (p>0.05) among the three groups in the first service and total conception rates. The percentage of cows in oestrus within 10 days of the synchronization treatment was not significantly different (p>0.05) between groups 1 and 2. The progesterone concentrations in the cows in group 3 showed that only those that were cycling at the start of the experiment responded to the synchronization treatment and conceived after fixed-time breeding. These results suggest that combinations of PGF₂ and GnRH may be of value in synchronizing oestrus and controlling breeding in Tuli cows. However, the benefit might be greater if only cows that are known to be cycling are bred in this way.     

Muscarinic receptor subtypes, β-adrenoceptors and cAMP in the tracheal smooth muscle of conventional and double-muscled calves

The total muscarinic (M₁ + M₂ + M₃) and -adrenergic receptors in the tracheal smooth muscle of conventional and double-muscled calves were identified and characterized with the non-specific antagonists [³H]quinuclidinyl benzilate ([³H]QNB) and [³H]dihydroalprenolol ([³H]DHA) respectively.Although the quantity of -adrenoceptors in double-muscled calves was 25% lower (p<0.05) than in conventional calves (B _max=327±89 fmol/mg protein), adenylate cyclase assays indicated that the basal adenylate cyclase activity and the (–)-isopropylnoradrenaline (ISO)- and sodium fluoride (NaF)-stimulated values were not significantly different between these calves. However, the density of muscarinic receptors in double-muscled calves was 40% higher (p<0.01) than in conventional calves (B _max=2955±625 fmol/mg protein). Subtypes of muscarinic receptors were studied with [³H]telenzepine (M₁-receptors), [³H]AF-DX 384 (M₂-receptors) and [³H]4DAMP (M₁ and M₃-receptors). It was found that in both double-muscled and conventional calves about 40% of the receptors were of the M₃-subtype, the remaining 60% being M₂-receptors.From these results, it is suggested that inflammation of the respiratory tract in double-muscled calves may be complicated by an imbalance between the cholinergic bronchoconstrictor and the -adrenergic bronchodilator components of the autonomic nervous system.     

A Comparison of the Concentrations of C-reactive Protein and α1-Acid Glycoprotein in the Serum of Young and Adult Dogs with Acute Inflammation

The concentrations of C-reactive protein (CRP) and ₁-acid glycoprotein (AAG) were evaluated in 1-, 3- and 18-month-old dogs (four of each age) that had been inoculated with turpentine oil. The CRP and AAG in 3-month-old and younger dogs subjected to surgery or inoculated with either Staphylococcus aureus or a viral vaccine were also evaluated. The average CRP concentration in the sera peaked 2 days after inoculation of turpentine oil. The peak CRP concentrations in 3- and 18-month-old dogs were significantly (p<0.05) greater than those in 1-month-old dogs. The average AAG concentration in the sera peaked 4 days after inoculation of turpentine oil. No significant difference was found in AAG concentrations between any of the age groups. When experimentally inoculated with S. aureus or subjected to oophorohysterectomy, the CRP and AAG concentrations increased in 3-month-old dogs, but they increased little in 1-month-old dogs. The CRP and AAG in dogs inoculated with the viral vaccine did not increase. In dogs with fractures or subjected to percutaneous gastrostomy, the CRP and AAG concentrations correlated with the condition of dogs.     

Food intake and rumen motility in dwarf goats. Effects of atipamezole on the inhibitory effects induced by detomidine,medetomidine and romifidine

The effects of some ₂-adrenoceptor agonists and of the ₂-adrenoceptor antagonist atipamezole on food intake and ruminal contractions were studied in dwarf goats. Detomidine, 0.2 µg/kg per min for 10 min, failed to modify food intake during either the first or second observation period (0–30 min and 180–210 min after drug infusion, respectively). Given at a higher dose rate (0.4 µg/kg per min for 10 min), the drug inhibited food consumption during the first observation period, but stimulated food intake during the second period. A similar pattern was observed after IV infusion with medetomidine (0.2 µg/kg per min for 10 min), romifidine (0.4 µg/kg per min for 10 min) or xylazine (1 µg/kg per min for 10 min). The ₂-antagonist atipamezole (2 µg/kg per min for 10 min) failed to modify food intake during either the first or second observation period. After treatment with atipamezole, the effects of ₂-agonists on feeding behaviour were completely antagonized.The ₂-agonists administered at similar dose rates to those used in the food intake experiments induced bradycardia, decreases in body temperature and inhibition of ruminal contractions. The inhibition of ruminal contractions induced by romifidine was partly antagonized by atipamezole pre-treatment. These findings demonstrate that the ₂-agonist-induced changes in ruminal contractions do not simply cause changes in feeding behaviour. The drop in body temperature induced by ₂-agonists was prevented by atipamezole pre-treatment, whereas the induced bradycardia was not modified by this ₂-antagonist.Abbreviations IV intravenous - SEM standard error of the mean     

Effect of Gossypol on Hepatic and Serum γ-glutamyltransferase Activity in Rats

A single intraperitoneal dose (25 mg/kg) of gossypol given to male Sprague-Dawley rats caused marked changes in the activity of the hepatic and serum -glutamyltransferase (GGT) and microsomal monooxygenases. The GGT activity in liver homogenate, S-9 supernatant fraction and microsomes was significantly depressed; however, the level of serum GGT was elevated. While the hepatic glutathione concentration was not greatly changed, the aminopyrine N-demethylase activity and microsomal cytochrome P450 content of the liver were significantly decreased in the treated rats. At necropsy, the livers of the treated rats appeared generally pale with distinct pinpoint foci. Histopathological examination of the liver showed degenerative changes and coagulative necrosis. The results indicate that gossypol is a strong hepatotoxic agent which can produce severe hepatic damage.     

Leukocyte and Cytokine Accumulation in the Ovine Teat and Udder during Endotoxin-Induced Inflammation

Persson Waller, K., Colditz, I.G., Flapper, P. and Seow, H.-F., 1997. Leukocyte and cytokine accumulation in the ovine teat and udder during endotoxin-induced inflammation. Veterinary Research Communications, 21 (2), 101-115The accumulation of leukocytes, ovine serum albumin and the cytokines interleukin-1 (IL-1), tumour necrosis factor- (TNF-), interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon- (IFN-) was studied during endotoxin-induced inflammation in lactating and dry ovine udders, and in the teat cisterns of dry ewes after surgical closure of the passage between the teat and udder cisterns. Samples were taken before infusion and hourly up to 10 h after infusion of 0.1, 1 or 10 µg of endotoxin, or infusion of pyrogen-free saline (PFS) as a control. Rectal temperatures were measured.A significant dose- and time-dependent accumulation of leukocytes, mainly neutrophils, was observed in the lactating udders and in the teat cisterns. In the dry udders, the leukocyte accumulation was significant for time but not for dose. Peak numbers of cells were reached at 3-4 h in the dry udders and in the teat cisterns, but not until 10 h after infusion in the lactating udders. The changes in the ovine serum albumin concentrations mostly paralleled changes in leukocyte numbers.A role was indicated for TNF-, IL-8 and GM-CSF, but not for IL-1 and IFN-, during endotoxin-induced inflammation in the ovine udder. Release of TNF-, IL-8 and GM-CSF was most prominent in lactating udders, peaking at 2 or 3 h after infusion, but was also detected in dry udders and teat cisterns. Detectable levels of IL-1 and IFN- were occasionally found in all three groups.     

The use of vitamin D metabolites and analogues for the prevention of milk fever in dairy cattle

During the past decade it has been discovered that vitamin D₃ (cholecalciferol) is converted into 25-hydroxycholecalciferol in the liver and that this compound in converted in the kidney into 1, 25-dihydroxycholecalciferol. These metabolites and particularly 1, 25-dihydroxycholecalciferol, rather than vitamin D itself, have powerful effects on calcium metabolism, stimulating the absorption of calcium from the gastrointestinal tract and the resorption of calcium from bone. A synthetic analogue of these metabolites, 1-hydroxycholecalciferol, is rapidly converted in the liver into 1, 25-dihycroxycholecalciferol. Thus the two metabolites and the synthetic analogue may be valuable for the prevention on treatment of milk fever.The three compounds, when administered in doses ranging from 0.5 to 32g/kg bodyweight increase the concentrations of calcium and phosphorus in the blood plasma of cattle more quickly than much larger doses of vitamin D₃. Their principal effect is to stimulate the absorption of calcium from the gastrointestinal tract. At the same time they decrease the plasma concentration of magnesium slightly. Trials of 25-hydroxycholecalciferol and 1-hydroxycholecalciferol in the prevention of milk fever have shown promising results.

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Kurzfassung Im vergangenen Jahrzehnt hat man festgestellt, dass das Vitamin D₃ (Cholecalciferol) in der Leber in 25-Hydroxycholecalciferol umgewandelt wird und die Nieren diese Verbindung wiederum in 1, 25-Dihydroxycholecalciferol umbilden. Mehr noch als Vitamin D selbst zeigen diese Metaboliten und hier insbesondere das 1, 25-Dihydroxychlecalciferol umfangreiche Auswirkungen auf den Kalziummetabolismus, indem sie die Kalziumabsorption aus dem Magen-Darmtrakt und die Kalziumresorption der Knochen anregen. Ein synthetischer Analogstoff zu diesen Metaboliten, das 1- Hydroxycholecalciferol, wird in der Leber rasch in 1, 25-Dihydroxycholecalciferol umgewandelt. Die beiden Metaboliten und der synthetische Analogwirkstoff könnten daher für die Milchfieberprophylaxe bzw-therapie von Nutzen sein.Werden die drei Verbindungen in Dosen von 0,5 bis 32g/kg Körpergewicht verabreicht, so erhöht sich die Kalzium-und Phosphorkonzentration im Blutplasma der Kühe schneller als bei bedeutend höheren Dosen von Vitamin D₃. Ihre Hauptwirkung liegt in der Anregung der Kalzium-absorption aus dem Magen-Darmtrakt. Gleichzeitig bauen sie jedoch auch in geringfügigem masse die Magnesiumkonzentration im Plasma ab. Versuche mit 25-Hydroxycholecalciferol und 1-Hydroxycholecalciferol haben bei der Milchfieberprophylaxe vielversprechende Ergebnisse gezeigt.

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Resume Au cours de la dernière décennie, on a découvert que la vitamine D₃ (cholécalciférol) se transformait en 25-hydroxycholécalciférol dans le foie et que ce composé se transformait en 1, 25-dihydroxy-cholécalciférol dans le rein. Ces métabolites, et en particulier le 1, 25-dihydroxycholécalciférol, ont, plus que la vitamine D elle-même, des effets puissants sur le métabolisme du calcium: ils stimulent l'absorption du calcium de l'appareil gastrointestinal et la résorption du calcium des os. Une substance homologue synthétique de cés metabolites, le 1-hydroxycholécalciférol, se transforme rapidement en 1, 25-dihydroxycholécalciférol dans le foie. Les deux métabolites et la substance homologue synthétique peuvent donc s'avérer précieux dans la prévention ou le traitement de la fièvre laiteuse.Administrés en doses allant de 0,5 à 32g/kg de poids corporel, ces trois composés augmentent les concentrations de calcium et de phosphore dans le plasma sanguin du bétail plus rapidement que des doses beaucoup plus fortes de vitamine D₃. Ils ont pour principal effet de stimuler l'absorption du calcium de l'appareil gastro-intestinal. Simultanément, ils réduisent légèrement la concentration de magnésium dans le plasma. Les essais d'utilisation du 25-hydroxycholécalciférol et du 1-hydroxycholécalciférol pour la prévention de la fièvre laiteuse ont donné des résultats prometteurs.

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Riassunto Nel corso dell'ultimo decennio si è scoperto che la vitamina D₃ (colecalciferolo) viene trasformata nel fegato in 25-idrossicolecalciferolo, il quale, a sua volta, si trasforma nel rene in 1, 25-diidrossicolecalciferolo. Detti metaboliti, ed in specie l'1, 25-diidrossicolecalciferolo., più che la stessa vitamina D, hanno potenti effetti sul metabolismo del calcio, poichè ne stimolano l'assorbimento da parte dell' apparato digerente e l'anabolizzazione da parte delle ossa. Un composto sintetico analogo di questi metobiliti, l'1, idrossicolecalciferolo, viene rapidamente trasformato nel fegato in 1, 25-diidrossicolecalciferolo. Perciò i due metaboliti e il composto sintetico analogo possono essere utili per la profilassi e la cura della febbre da latte.I tre composti, se somministrati in dosi da 0.5 a 32g/kg peso corporeo, aumentano la concentrazione del calcio e del fosforo nel plasma sanguigno del bestiame più rapidamente di dosi molto maggiori di vitamina D₃. Il loro effetto principale è quello di stimolare l'assorbimento del calcio da parte dell'apparato digerente. Contemporaneamente, essi riducono leggermente la concentrazione di magnesio nel plasma. Esperimenti con il 25-idrossicolecalciferolo nella profilassi della febbre da latte hanno dato risultati promettenti.

     

In vitro response to noradrenaline of small intestine taken from normal and grass sickness-affected horses

Small intestine was taken from the caudal flexure of the duodenum and the terminal ileum proximal to the ileocaecal fold of 25 horses, 9 with acute grass sickness (AGS), 12 with subacute grass sickness (SAGS) and 12 with chronic grass sickness (CGS). The motility in the samples was measured isometrically either within 1 h of death or after storage for 24 h at 4°C.In control tissue, noradrenaline produced contractions of muscle strips which did not involve a muscarinic cholinergic mechanism and which were unaffected by the 1 antagonist prazosin but were blocked by the 2 antagonist yohimbine. Pretreatment with the antagonist phentolamine prevented the contractile response to noradrenaline and the background contractions either continued at a reduced rate and amplitude or were abolished after a few minutes. Thus, following blockade, noradrenaline reduced the background contraction rate by an effect on inhibitory adrenoceptors. The rate of background contractions in duodenal preparations was significantly greater than that in control ileal preparations.Although cold storage for 24 h caused a reduction in the background contraction rates of the control preparations, there was no effect on the contractile responses to noradrenaline, the associated pharmacology being similar to that of fresh tissue. This suggests that noradrenaline-evoked contraction was not dependent on enteric neural elements.The response to noradrenaline by grass sickness-affected tissue was generally similar to that of tissue from control horses, with an immediate contraction which was 2 sensitive. The contractile response to noradrenaline after propranolol was significantly reduced in the CGS group and there were significant differences between the AGS, CGS and control groups. There was a significant difference between the ileal preparations from the control and SAGS groups in their response to noradrenaline following pretreatment with propranolol.     

Prostaglandin F2α metabolite levels in normal and uterine-infected postpartum cows

The stable metabolite of prostaglandin F₂, 15 keto-13, 14-dihydroprostaglandin F₂ (PGFM), was measured from peripheral blood samples collected at specified intervals postpartum from 7 normal dairy cows and 4 cows with apparent endometritis. Plasma PFGM levels were significantly (P<.05) elevated for the first 5 days postpartum in the cows with endometritis (ranging from 4.0 to 5.0 ng/ml) compared to the controls (approximately 1.0 ng/ml). Beyond 5 days postpartum, plasma PGFM levels were not significantly different and decreased to approximately 0.4 ng/ml by day 13 in both groups. Time to uterine involution was not different between groups (less than 30 days). Therefore, uterine infections in cows during the puerperium was associated with elevated circulating PGFM levels. These findings and the observation that PGF₂ is not uterotonic in the puerperal cow do not suggest a therapeutic use of PGF₂ in order to evacuate the uterus.     

The influence of clenbuterol on prostaglandin F2α-induced dyspnoea in calves

Pulmonary function tests were performed in six healthy calves. Prostaglandin F₂ causes severe narrowing of both upper and lower airways (total lung resistance increased, dynamic compliance decreased). Clenbuterol administered intravenously fifteen minutes prior to prostaglandin F₂ aerosol, and in increasing doses (0, 0.4, 0.8, 1.2 g/kg), on days 1, 2, 4 and 6 of the experiment, effectively but not entirely suppressed these responses.These data indicate that -adrenergic receptors are present in the bovine airways and that the use of clenbuterol (0.8 g/kg) may be effective in treating clinical respiratory disease such as bronchopneumonia in calves.