Chemotaxis in Boyden's chamber: a comparison of the double and single filter techniques.

In the Boyden's chamber method to assess chemotaxis, when used to detect drug induced impairment of chemotaxis, the double filter counting method shows no advantage over the single filter technique.

Inhibition of virus-encoded thymidine kinase suppresses herpes simplex virus replication in vitro and in vivo.

Both herpes simplex virus type 1 (HSV-1) and HSV-2 encode a thymidine kinase enzyme which differs from cellular thymidine kinase in substrate specificity. Viral thymidine kinase enables the virus to replicate in cells that lack cellular thymidine kinase, namely those of the sensory neurons where the virus establishes, and periodically reactivates from, a latent state. Thymidine kinase-dependent HSV replication following viral reactivation at the site of latency is thought to precede the emergence of virus at mucosal surfaces. The ability to inhibit such an essential viral enzyme would potentially prevent HSV from replicating within neuronal tissue, and thus stop the recurrent disease cycle. Ro 32-2313 was designed as a selective and competitive inhibitor of HSV thymidine kinase and in vitro studies have confirmed this mechanism of action. In vivo evaluation of a soluble prodrug of Ro 32-2313, Ro 32-4397, was undertaken in murine models where pathogenesis was dependent upon viral replication in neuronal tissue. It was shown that in vivo administration of Ro 32-4397 (i) significantly reduced the viral titre detected in isolated dorsal root ganglia; (ii) prevented HSV-2-induced lethality in a systemic infection model; and (iii) reduced zosteriform lesion development in a model of dermal infection. Administration of Ro 32-4397 produced dose-related changes in viral pathogenicity towards those of the phenotype of a thymidine kinase-deficient virus. Overall, the study confirmed that thymidine kinase inhibitors can suppress the replication of HSV in vivo, and suggest that such inhibitors may reduce reactivation of the virus from latency if used prophylactically in recurrent HSV infection.

The effect of methotrexate and hydroxyurea on neutrophil chemotaxis.

Methotrexate depresses motility of neutrophils in chamber membranes, but does not interfere with random motility in tubes. Hydroxyurea has no such effect. The therapeutic response to methotrexate in psoriasis may be due in part to a reduction in migration of neutrophils into the epidermis.