Discovery of (R)-1-[2-hydroxy-3-(4-hydroxy-phenyl)-propyl]-4-(4-methyl-benzyl)-piperidin-4-ol: a novel NR1/2B subtype selective NMDA receptor antagonist.

Starting from Ro-25-6981 as a lead compound, highly potent and selective NR1/2B subtype selective NMDA receptor antagonists, with low activity at alpha(1) adrenergic receptors were developed.

Identification and verification of the anabolic steroid boldenone in equine blood and urine by HPLC/ELISA.

An enzyme linked immunosorbent assay (ELISA) was developed to detect the anabolic steroid boldenone in equine blood and urine. The polyclonal antiserum was raised in rabbits, employing boldenone-17-hemisuccinate-bovine serum albumin as antigen. Boldenone-17-hemisuccinate-horseradish peroxidase served as enzyme conjugate. Sensitivity of the assay was 26.0 +/- 3.0 pg/well. Among the endogenous steroids tested only progesterone and testosterone exhibited moderate cross-reactivities, 3.4 and 2.5%, respectively. These cross-reactivities are of no importance for the boldenone assay. For the reduction of background levels, screening for boldenone of equine serum was performed after extraction. Urine samples were determined directly after dilution, omitting hydrolysis of boldenone conjugates. Positive screening results were confirmed by means of two independent HPLC systems combined with off-line detection, employing the boldenone ELISA. Methandienone served as internal standard to ascertain retention factors. In horses treated with boldenone-17-undecylenate the presence of boldenone in serum was confirmed up to 28 days and in unhydrolyzed urine up to 56 days post applicationem.

[Equine influenza outbreaks with viral antigenic drift in Berlin 1988-1991]. / Beobachtungen bei equinen Influenza-Epidemien mit viraler Antigendrift in Berlin 1988-1991.

In this paper three outbreaks of equine influenza in Berlin (Germany) in the years of 1988, 1989 and 1991 are discussed, reporting mainly clinical, hematological, virological and some epizootiological aspects. We have detected variations from the traditional pattern of equine influenza, whereby the main clinical symptoms like cough or fever were absent in several cases. If cough was found, it was moist. Furthermore a mucous nasal discharge was present in a number of cases for a period of 4-5 days. Extreme neutropenia, lymphocytosis and predominantly an unchanged level of monocytes were observed. Several horses became ill, in spite of having been regularly vaccinated against equine influenza. As cause, a high antigenic drift of the influenza virus isolated from 1989 and 1991 is assumed in comparison to the strains that are used for the influenza vaccines available. The origin of the viruses which had caused the influenza outbreaks described could not be elucidated.

[Clinical chemistry in leukosis of horses (review)]. / Zur klinischen Chemie bei der Leukose des Pferdes (Ubersicht).

Clinicopathological aspects of equine leukosis are discussed in a review. Among various other findings, only hypercalcaemia accompanied by paraneoplastic syndrome in the course of equine leukosis, increased values of alkaline phosphatase as usual in tumorous diseases, and hypalbuminaemia and hypergammaglobulinaemia in mesentric and intestinal forms of equine leukosis seem to have some diagnostic and pathogenetic significance. Changed values of further parameters are more or less non-specific concomitant signs, indicating that other organs or organ systems have been affected. However, in case of suspicion of equine leukosis furthermore clinicopathological investigations are recommended particularly for differential-diagnostic reasons.

[Hematology and cytodiagnosis of leukosis of the horse (review)]. / Hämatologie und Zytodiagnostik bei der Leukose des Pferdes (Ubersicht).

In a review supplementary to prior evaluations further hematological or cytodiagnostic aspects respectively of equine leucosis are discussed. Leukemic nature of the disease is characterized by increased count of normal blood cells or by the presence of morphologically non-differentiated cells in circulating blood or by disorder or loss of function of blood cells respectively. Thrombocytopenia in the most cases is accompanied by anemia, leukemia and tumor cell infiltration in bone marrow. Tumor cells in circulating blood indicate their presence in bone marrow too. In cases of equine leucosis with effusions in thoracic and/or in abdominal cavities tumor cells seem to be present more frequently in hydrothorax than in ascites.

[Clinical diagnostic keys and special manifestations in equine leukosis]. / Klinischer Diagnoseschlüssel und besondere Manifestationen der Leukose beim Pferd.

The literature contains about 500 cases of equine leucosis, though the reports are deposited in a great number of journals and vary considerably concerning particular topics. During the last years there has been a remarkable increase of publications about this syndrome in the equine. The clinical leucosis key recommended by us has been confirmed in principle considering the latest literature. In about 70 individual symptoms which can be clinically observed in equine with leucosis 11 can be considered as main symptoms because of their frequency; they are again classified in primary (lymph node tumours including splenomegaly--loss of condition, weakness--cachexia, weight loss, periphery oedema), secondary (anorexia, inappetence--fever--paleness of mucous membrane--anaemia--tachycardia) and accessory (incoordination--tachypnoea, dyspnoea--apathy, lethargy) main symptoms. Furthermore in future it will be necessary to take into more consideration the symptoms "recurrent colic" and "hydrothorax" within differential diagnosis. The main symptom "incoordination" (ataxia, asynergy, paresis, paralysis) is used by us more precisely only in case of impairment of nervous system by neoplastic infiltrations and does not signify as possible symptoms of general physical weakness, for example faltering, staggering, tumbling or lameness. The morphological classification follows further on our previous recommendation. There exist generalized forms with tumour infiltrations in abdominal and in thoracic cavity as well as especially in peripheral lymph nodes. On the other hand there are characteristic manifestations in certain regions of the body, which establish distinctly the clinical symptomatology. They are marked as regional multicentric forms with the main localizations "mediastinal", "splenic", "mesenteric" or "intestinal".(ABSTRACT TRUNCATED AT 250 WORDS)

[Training-induced changes of reference vectors in the QRS complex of the EKG of young trotting horses]. / Trainingsinduzierte Anderungen von Bezugsvektoren im QRS-Komplex des EKG junger Trabrennpferde.

After the onset of training ("breaking") in young standardbred horses within continuing investigations changes of vectors in the QRS-complex were considered. These changes accomplished in two stages. Mainly within the first three months of training the vector R (VR) in limb leads changed to the left and to caudal and dorsal. In a second interval between five and seven months after breaking the vector S (VS) changed to cranial. As main cause the different character of training in both phases is discussed. Additional indicators of age- or development-related causes were not found.

[The diagnosis of morbus maculosus in horses]. / Ein Beitrag zum Krankheitsbild des Morbus maculosus equorum.

This is a review on Morbus maculosus equorum (purpura haemorrhagica) on the base of literature data and of a case report on 13 own patients. It is shown, that the clinical picture of this disease has not changed within the last 150 years. Clinical main symptoms are haemorrhagic diathesis (petechiae, ecchymosis, suggillations) as well as peripheral edema and fever. The main haematological findings are neutrophilia, mostly going along with shift to the left and lymphopenia. In the last few years thrombocytopenia was also described in some cases. Basic therapeutics are glucocorticoids and penicillins. Problems of differential diagnosis and of nomenclature are discussed.

Pharmacokinetics of ascorbic acid in horses.

The pharmacokinetics of ascorbic acid were studied in 29 horses after intravenous (iv), subcutaneous, intramuscular (im) and oral administration. Following iv injection of 5 and 10 g ascorbic acid, respectively, a biphasic decline of ascorbic acid serum levels was found, indicating that the vitamin distributes in the body according to a two-compartment open model. The apparent volume of distribution (average value for Vd(ss) = 0.6 litre/kg) was approximately equivalent to the volume of total body water. The terminal half-life of the biexponential serum level-time curve (t1/2 beta) varied between 5 and 17 h. Both distribution and elimination were found to be positively correlated with the iv dose administered. Following subcutaneous and im injection, the average bioavailability of ascorbic acid amounted to 82 and 61 per cent, respectively. However, both routes of administration gave rise to marked local irritation. Following oral administration, the systemic availability of ascorbic acid was very poor. Serum levels in most experiments were not increased above the endogenous pre-administration values of the vitamin. Thus, in horses iv injection appears to be the only satisfactory route of administration of ascorbic acid if supplementation is required.