Effect of brimonidine on rabbit trabecular meshwork hyaluronidase activity.

PURPOSE: To study the presence of hyaluronidase activity in the rabbit trabecular meshwork and its regulation by brimonidine. METHODS: A spectrophotometric assay that consists of the assessment of N-acetylhexosamine groups released from hyaluronic acid was used to examine hyaluronidase activity. Cyclic adenosine monophosphate (cAMP) levels were assessed by radioimmunoassay. RESULTS: Hyaluronidase activity was detected in the rabbit trabecular meshwork. Its optimal activity was in the acid range of pH 3.8. Brimonidine significantly increased trabecular hyaluronidase-specific activity and decreased cAMP accumulation. Yohimbine significantly inhibited the effect of brimonidine on both hyaluronidase activity and cAMP accumulation. CONCLUSIONS: The finding of endogenous hyaluronidase activity in rabbit trabecular meshwork supports the hypothesis that this tissue can metabolize its own glycosaminoglycan (GAG) products. The present results suggest, however, that the hypotensive effect of brimonidine could be mediated, at least in part, by its ability to increase GAG catabolism, probably through a cAMP-independent mechanism.

Dopamine decreases melatonin content in golden hamster retina.

Dopamine significantly decreased melatonin levels in Golden hamster retinas excised at noon and incubated under light. The effect of dopamine was reversed by spiperone and clozapine (selective antagonists for D(2) and for D(4)/D(2) dopaminergic receptors, respectively) but not by SCH 23390 (a selective D(1) dopamine receptor antagonist). Both clozapine and spiperone per se significantly increased melatonin levels, whereas SCH 23390 was ineffective. Quinpirole (an agonist for D(2)-subfamily dopaminergic receptor) decreased melatonin content in retinas excised at midday. Dopamine increased, whereas quinpirole decreased, cAMP accumulation in retinas excised at noon. Retinal dopaminergic turnover rate (assessed as the ratio of 3,4-dihydroxyphenylacetic acid to dopamine) was significantly higher at midday than at midnight. In retinas excised at midnight, melatonin content in vitro was unaffected by dopamine or quinpirole. At midnight, dopamine increased cAMP accumulation, whereas quinpirole was ineffective. When hamsters were kept under constant darkness for 48 h and sacrificed at subjective midday or midnight, dopamine increased cAMP accumulation at both times, whereas quinpirole decreased this parameter only at subjective midday. Dopaminergic turnover rate was significantly higher at subjective midday than at subjective midnight. These results show that dopamine regulates melatonin biosynthesis in the Golden hamster retina.

Effect of GABA on melatonin content in golden hamster retina.

The effect of GABA on melatonin content in vitro was studied in the golden hamster retina. GABA significantly increased melatonin levels in a dose-dependent manner, its effect being reversed by a GABA(A) receptor antagonist, bicuculline, but not by saclofen, a GABA(B) antagonist. Moreover, an equimolar concentration of muscimol, a GABA(A) receptor agonist, significantly increased retinal melatonin content, whereas baclofen, a GABA(B) receptor agonist, was ineffective. The darkness-induced increase in melatonin content in vitro was inhibited by bicuculline, whereas saclofen was ineffective. Retinal GABA turnover rate was significantly higher at midnight than at midday. GABA significantly decreased cyclic AMP and increased cyclic GMP accumulation in the golden hamster retina. The effect of GABA on both nucleotide levels was reversed by bicuculline, but baclofen had no effect. Cyclic GMP analogues (i.e., 8-bromoguanosine 3',5'-cyclic monophosphate and 2'-O-dibutyrylguanosine 3',5'-cyclic monophosphate) significantly increased retinal melatonin content in vitro. Taken together, these results support the hypothesis that GABA may be important for the "dark message" in the hamster retina.

Photic control of nitric oxide synthase activity in golden hamster retina.

A characterization of nitric oxide synthase (NOS) in the golden hamster retina was performed. Enzymatic activity was partially Ca2+ and calmodulin-dependent, required NADPH, and was inhibited by L-arginine analogs. Retinal NOS activity was higher at midnight than at midday. When the hamster were placed under constant darkness for 24 or 48 h, and killed at equivalent time points, representing subjective day and subjective night respectively, the differences in NOS activity disappeared. One hour of darkness during the day increased, while the same period of light during the night decreased, retinal NOS activity. From these results, it might be presumed that hamster retinal NOS activity is regulated by the photic stimulus.

Protection of mice and swine from pseudorabies virus conferred by vaccinia virus-based recombinants.

Glycoproteins gp50, gII, and gIII of pseudorabies virus (PRV) were expressed either individually or in combination by vaccinia virus recombinants. In vitro analysis by immunoprecipitation and immunofluorescence demonstrated the expression of a gII protein of approximately 120 kDa that was proteolytically processed to the gIIb (67- to 74-kDa) and gIIc (58-kDa) mature protein species similar to those observed in PRV-infected cells. Additionally, the proper expression of the 90-kDa gIII and 50-kDa gp50 was observed. All three of these PRV-derived glycoproteins were detectable on the surface of vaccinia virus-PRV recombinant-infected cells. In vivo, mice were protected against a virulent PRV challenge after immunization with the PRV glycoprotein-expressing vaccinia virus recombinants. The coexpression of gII and gIII by a single vaccinia virus recombinant resulted in a significantly reduced vaccination dose required to protect mice against PRV challenge. Inoculation of piglets with the various vaccinia virus-PRV glycoprotein recombinants also resulted in protection against virulent PRV challenge as measured by weight gain. The simultaneous expression of gII and gp50 in swine resulted in a significantly enhanced level of protection as evaluated by weight evolution following challenge with live PRV.

[Critical analysis of the arteriography of primary malignant tumors of the bones, on the occasion of 19 unedited cases]. / Analyse critique de l'artériographie des tumeurs malignes primitives des os á l'occasion de 19 observations inédites

From the analysis of a series of 62 unedited cases of arteriography of osseous tumors including 19 primary malignant tumors, it was confirmed that the majority of angiographic signs described as being characteristic of malignant tumors of the bones are not significant. They are found in benign tumors and in ordinary inflammatory phenomena: several cases of osteoid osteoma, myeloplax tumor or simply of osseous reconstruction permit one to make criticisms. On the other hand, one must endeavour to demonstrate, by means of a technique whose main elements are recalled, vascular abnormalities which are the only typical ones and which furthermore are found in "silent" tumors such as chondrosarcomas or fibrosarcomas. These vascular abnormalities are given in detail, and several examples of them are given.