Binding affinity of adenosine receptor agonists and antagonists at human cloned A3 adenosine receptors

The A3 adenosine receptor is one of the four adenosine receptors which have thus far been identified. Cloning of the A3 receptor from animal species such as rat, sheep and human has shown that there are interspecies differences in its peripheral distribution, and binding affinity for various adenosine receptor ligands. The adenosine derivative, 4-aminobenzyl-5'-N-methylcarboxamidoadenosine (AB-MECA), is a potent A3 receptor agonist which is used as a reference drug. In this report we have characterized the binding of selected adenosine receptor agonists and antagonists to HEK 293 cells transfected with the human A3 adenosine receptor using [125I]AB-MECA as radioligand. HE-NECA and NECA were the most potent compounds showing Ki values in the low nanomolar range, while the recently discovered non-xanthine A2A receptor antagonists ZM 241385, SCH 58261 and SCH 63390 showed affinity values in the micromolar range. These data further indicate the need to examine the affinity of new adenosine receptor ligands directly in human A3 receptors.     

Repair of a complex retinal detachment with proliferative vitreoretinopathy in an eye with extreme scleral thinning

Two new withanolides (steroidal lactones) named coagulin F [27-hydroxy-14,20-epoxy-1-oxo-(22R)-witha-3,5,24-trienolide] (1) and coagulin G [17beta,27-dihydroxy-14,20-epoxy-1-oxo-(22R)-witha-2,5, 24-trienolide] (2) were isolated from the whole plant of Withania coagulans, and their structures were deduced by spectral analysis.     

Lethal infection of newborn mice, caused by hepatitis C virus

Intracerebral infection of mice aged 2-3 days with hepatitis C virus (HCV) from chronically infected suckling mouse brain cultures and porcine embryo cells resulted in the death of animals after 12-14 days. Repeated passages of HCV in animals decreased the incubation period to just 3-4 days. Blood serum of surviving mice collected during the 4th week postinfection contained antiHCV antibodies detected by enzyme immunoassay and hemagglutination inhibition test. The results are proof of creation of a new in vivo model of experimental HCV infection.     

Cryoprecipitates as a source of fibrinogen in treatment of disseminated introvascular coagulation (DIC)

Cryoprecipitates, in addition to containing factor VIII, contain about one third of the fibrinogen in the plasma from which they were derived. This fibrinogen is functional, as established by successfully preparing two congenital hypofibrinogenemics for major surgery by infusing cryoprecipitates. Cryoprecipitates and platelet concentrates are also used for patients with low levels caused by disseminated intravascular coagulation (DIC). We feel that these patients benefit not only from the factor VIII in the cryoprecipitates, but from the fibrinogen, which adds its support to the fibrinogen in platelet infusions, plasma, and whole blood. Such support makes it possible to heparinize such patients more heavily than would be safe without such preparation. The authors report three patients with severe and life-endangering DIC who were heavily heparinized, and supported with cryoprecipitates, as well as other blood fractions. Response to this therapy was excellent.     

Two-dimensional analysis of the structure of human von Willebrand factor

Human von Willebrand factor (vWF) is synthesized as an extra large polymer; then, it is converted to lower molecular weight plasma multimers, originally composed of intact 225-kDa subunits, by a metalloproteinase. Proteolysis generates two fragments of 140-and 176-kDa, which originate from cleavage of peptide bond Tyr842-Met843 and which represent vWF residues 1-842 and 843-2050, respectively; a very small amount of 189-kDa fragment can also be found in normal plasma. We describe here a two-dimensional (2-D) method to analyze plasma vWF structure.     

Are frequent short gastro-oesophageal reflux episodes the cause of symptoms in patients with non-ulcer dyspepsia responding to treatment with ranitidine?

BACKGROUND: Patients with non-ulcer dyspepsia (NUD) responding to treatment with H2-receptor antagonists have no clinically useful characteristics. This trial compares the gastro-oesophageal reflux pattern as measured by 24-h oesophageal pH monitoring in patients responding to ranitidine with that of non-responders. METHODS: Thirty-one patients with NUD were randomized to 6 weeks' double-blind alternating treatment with 150 mg ranitidine twice daily or placebo and classified as responders or non-responders. RESULTS: Pathologic gastro-oesophageal reflux was seen in 3 of the 13 responders and 4 of the 18 no-responders (NS). The responders had frequent short reflux episodes (< 1 min in duration). When 4 patients with > or = 5 reflux episodes longer than 5 min were excluded, the number of short reflux episodes (median) in responders and non-responders was 32 and 14, respectively. The difference is statistically significant (p = 0.025). There were no other differences between the groups. CONCLUSIONS: In this study patients with NUD responding to ranitidine were characterized by frequent short reflux episodes in the absence of numerous long reflux episodes.