Effects of imidazoline and nonimidazoline α-adrenoceptor agonists and antagonists, including xylazine, medetomidine, dexmedetomidine, yohimbine, and atipamezole, on aggregation of feline platelets.

OBJECTIVE: To examine the effects of imidazoline and nonimidazoline α-adrenergic agents on aggregation of feline platelets. SAMPLE: Blood samples from 12 healthy adult cats. PROCEDURES: In 7 experiments, the effects of 23 imidazoline and nonimidazoline α-adrenoceptor agonists or antagonists on aggregation and antiaggregation of feline platelets were determined via a turbidimetric method. Collagen and ADP were used to initiate aggregation. RESULTS: Platelet aggregation was not induced by α-adrenoceptor agonists alone. Adrenaline and noradrenaline induced a dose-dependent potentiation of ADP- or collagen-induced aggregation. Oxymetazoline and xylometazoline also induced a small potentiation of ADP-stimulated aggregation, but other α-adrenoceptor agonists did not induce potentiation. The α2-adrenoceptor antagonists and certain imidazoline α-adrenergic agents including phentolamine, yohimbine, atipamezole, clonidine, medetomidine, and dexmedetomidine inhibited adrenaline-potentiated aggregation induced by ADP or collagen in a dose-dependent manner. The imidazoline compound antazoline inhibited adrenaline-potentiated aggregation in a dose-dependent manner. Conversely, α1-adrenoceptor antagonists and nonimidazoline α-adrenergic agents including xylazine and prazosin were ineffective or less effective for inhibiting adrenaline-potentiated aggregation. Moxonidine also was ineffective for inhibiting adrenaline-potentiated aggregation induced by collagen. Medetomidine and xylazine did not reverse the inhibitory effect of atipamezole and yohimbine on adrenaline-potentiated aggregation. CONCLUSIONS AND CLINICAL RELEVANCE: Adrenaline-potentiated aggregation of feline platelets may be mediated by α2-adrenoceptors, whereas imidazoline agents may inhibit in vitro platelet aggregation via imidazoline receptors. Imidazoline α-adrenergic agents may have clinical use for conditions in which there is platelet reactivity to adrenaline. Xylazine, medetomidine, and dexmedetomidine may be used clinically in cats with minimal concerns for adverse effects on platelet function.

Synthesis and biological evaluation of diaryl-substituted carboranes as inhibitors of hypoxia inducible factor (HIF)-1 transcriptional activity.

Diaromatic-substituted ortho- and meta-carboranes were synthesized as mimics of manassantin A. Among the carboranes synthesized, compounds 1 and 2 showed significant inhibition of hypoxia-induced HIF-1 transcriptional activity, with IC(50) values of 3.2 and 2.2 µM, respectively. Compounds 1 and 2 similarly suppressed hypoxia-induced HIF-1α accumulation in a concentration-dependent manner without affecting the expression level of HIF-1α mRNA. The hypoxia-induced accumulation and translocation of HIF-1α into nuclei were not observed in HeLa cells treated with compounds 1 and 2 by immunofluorescence analysis, revealing that the inhibition of hypoxia-induced HIF-1 transcriptional activity is induced by compounds 1 and 2 through a degradation pathway of the HIF-1α protein under hypoxic conditions.

Morphological, biochemical and mechanical features of the cranial cruciate and lateral collateral ligaments in dogs.

The cruciate ligament and the collateral ligament play key roles in stabilization of the knee joint. Cases of serious knee joint problems presented at the, the Veterinary Teaching Hospital of Rakuno Gakuen University, Japan mostly involved rupture of the cranial cruciate ligament (CCL). Disorders in structural and biochemical components of the CCL were thought to be the causes of the knee problems. Morphological, biochemical and biomechanical features of the CCL and the lateral collateral ligament (LCL) were therefore analyzed. In the CCL, fibroblasts with ovoid and enlarged nuclei were observed mainly at the periphery of collagen bundles. The array of collagen fibrils in the LCL was slightly disoriented, but that of the CCL was tight and regular. In the LCL, the major groups of collagen fibrils were those with diameters of 70-80 and 120-130 nm. Most collagen fibrils in the CCL had diameters of 70-80 nm. The mean collagen diameters were 90 nm in the CCL and 105 nm in the LCL. The ratios of the noncollagen area to the area occupied by collagen fibrils were 43% in the CCL and 55% in the LCL. There was no difference between the amounts of HA or between the amounts of DS in two ligaments. However, the amount of CS in the CCL was about 17-times greater than that in the LCL. The expansion of and the resistance to tension exerted onto the CCL were less than those of the LCL. A high concentration of CS and low tensile strength due to small-sized collagen fibrils cause the CCL to rupture easily, especially when overextension of the knee joint occurs.