Breed-specific hematologic reference intervals in healthy adult Dogues de Bordeaux.

BACKGROUND: There is an increasing interest for breed-specific reference intervals in veterinary medicine. In a previous study, breed-specific biochemical reference intervals (RIs) have been established for Dogues de Bordeaux (DDBs). This breed is predisposed to familial juvenile glomerulonephropathy and hypothyroidism, and would benefit from hematologic RI. OBJECTIVE: The purpose was de novo establishment of breed-specific hematologic RIs for the DDB in accordance with the International Federation of Clinical Chemistry and Clinical and Laboratory Standards Institute guidelines. METHODS: One hundred and twenty DDBs from France and Belgium were recruited. CBCs were determined with the Sysmex XT-2000iV analyzer within 12 hours of blood collection. RIs were determined using the nonparametric method. Effects of sex, age, and face mask color were studied. RESULTS: RIs were determined in 58 healthy dogs. DDBs had higher RIs for HGB, HCT, MCV, MCHC, and mean platelet volume, and lower RIs for reticulocytes counts, platelets by impedance (PLT-I) and optical count (PLT-O), and plateletcrit when compared with generic canine RIs. Age significantly affected RIs for HGB, HCT, MCHC, WBC, neutrophil, lymphocyte, and monocyte counts. CONCLUSION: The generic canine RIs established in the same laboratory with analogous preanalytical and analytical variations did not differ significantly from breed-specific RIs, and thus have no significant impact on clinical decision making; however, breed-specific RIs are advised for some RBC and all platelet-related variables to avoid erroneous suspicion of polycythemia and thrombocytopenia when using general canine RIs for evaluation of DDB.

CGS 8216: receptor binding characteristics of a potent benzodiazepine antagonist.

CGS 8216 is a novel nonbenzodiazepine that inhibited 3H-flunitrazepam (3H-FLU) binding to rat synaptosomal membranes in vitro at subnanomolar concentrations. It prevented the in vivo labeling of brain benzodiazepine receptors by 3H-FLU with the same potency as diazepam when given orally to mice. Pharmacologic tests showed that it was devoid of benzodiazepine-like activity but it antagonized the actions of diazepam in these tests. It did not interact with alpha- or beta- adrenergic, H1-histaminergic or GABA receptors but it inhibited adenosine-activation of cyclic AMP formation. Studies with 3H-CGS 8216 demonstrated that it bound specifically and with high affinity to rat forebrain membranes and was displaced by drugs with an order of potencies similar to that observed when 3H-diazepam and 3H-FLU were used as radioligands. The regional distribution of 3H-CGS 8216 binding sites in the brain was also similar to that of 3H-FLU. Dissociation of 3H-CGS 8216 binding was slow at 0 degrees C but increased with temperature and was almost complete within 1 min at 37 degrees C. Scatchard analyses were linear, yielding KD values of 0.044, 0.11 and 0.18 nM at 0, 25 and 37 degrees C, respectively; the Bmax value did not change appreciably with temperature and was approximately 1000 fmoles/mg protein. Using 3H-FLU, the value for Bmax as well as for the KD increased with temperature. The total number of binding sites determined for 3H-FLU was greater than that for 3H-CGS 8216 at each temperature. CGS 8216 exhibited mixed-type inhibition of 3H-FLU binding. GABA did not stimulate 3H-CGS 8216 binding whereas it enhanced 3H-FLU binding. CGS 8216 may be a useful ligand for probing the antagonist properties of the benzodiazepine receptor and is likely to exhibit interesting therapeutic effects.

Syntheses, analgetic activity, and physical dependence capacity of 5-phenyl-6,7-benzomorphan derivatives.

The synthesis, analgetic activity, and physical dependence capacity of a large number of 5-phenyl-6,7-benzomorphan derivatives are described. Observations made during the Stevens' rearrangement of 1-benzyl-1-methyl-delta 3-piperidinium salt derivatives (V) under various conditions are discussed. The absolute configuration of the 9-demethyl series and the 2'-deoxy series is established by comparison of their ORD and CD spectra with those of 49, whose absolute configuration was previously established by X-ray crystallography. A convenient synthesis of 3H-labeled phenols using 3H3PO4 is described, as well as the preparation of 14C-labeled compounds by conventional methods.