Usefulness of testing histamine release from isolated human basophils in anti-allergic and anti-asthmatic drug assessment]

Histamine release from isolated human basophils test was used to evaluate an activity of: histamine receptors H1 and H2 blockers, agonists of beta-receptors, calcium channel blocking agents, hydrocortisone, and disodium cromoglycate (Intal). The study involved 84 patients hospitalized for the bronchial asthma. Basophils were isolated with Day's technique modified by Shov and Norn. Histamine was measured with Shov's spectrofluorimetric technique. It was found that histamine release from isolated human basophils may be used in both evaluation of the mechanism of action and efficiency of drugs used in allergic diseases therapy.     

Ten years of experience with specific desensitization in children with bronchial asthma

Hundred eighty five children, aged between 6 and 15 years, with bronchial asthma and diagnosed allergy to Dermatophagoides pteronyssinus were followed-up for 2-3 years between 1978 and 1988. Children were treated with HDM vaccine Bencard. Administered doses were increased gradually at the beginning of therapy whereas they remained the same for further 1-3 years. Excellent and favourable results were achieved in 78.4% of cases. The treatment as postponed in 36 children (19.4%) because of the lack of improvement after one year of the follow-up. Easily manageable adverse reactions and complications were seen in 4 patients (2.2%).     

A novel splicing variant encoding putative catalytic α subunit of maize protein kinase CK2

A cDNA highly homologous to the known catalytic α subunit of protein kinase CK2 was cloned from maize ( Zea mays ). It was designated ZmCK 2α-4 (accession no. AAF76187). Sequence analysis shows that ZmCK2α-4 and the previously identified ZmCK2α-1 (accession no. X61387) are transcribed from the same gene, ZmPKCK2AL (accession no. Y11649), but at different levels in various maize organs and at different stages of development. The cDNA encoding ZmCK2α-4 has three potential translation initiation sites. The three putative variants of ZmCK2α-4 were expressed in Escherichia coli as GST-fusion proteins and purified from bacterial extracts. In contrast to the previously characterized ZmCK2αs, the obtained GST:ZmCK2α-4 proteins were catalytically inactive as monomers or in the presence of equimolar amounts of the human CK2β. However, GST:ZmCK2α-4 did phosphorylate casein in the presence of a large excess of the β subunit. The activity of ZmCK2α-4 toward casein could also be stimulated by increasing ATP concentration. Modeling studies have shown that there is no interaction between the N-terminal segment of ZmCK2α-4 and the activation loop responsible for constitutive catalytic activity of CK2α. Preliminary results suggest that ZmCK2α-4 may function as a negative regulator of other CK2s, and at certain circumstances as a holoenzyme which catalytic activity is stimulated by specific regulatory subunit(s).     

Migration of Al(OH)3 in the bodies of experimental animals

The aim of this study was to observe aluminium hydroxide distribution in mice given this substance subcutaneously and intraperitoneally in various concentrations (0.03 mg-0.8 mg of Al3+ per dose). Each experimental group consisted of 5-6 mice of which brain, liver and kidney were isolated after 7, 14, 28, and 35 days after injection. Control group was composed of unvaccinated mice. Sera of animals vaccinated subcutaneously with the following doses: 0.2 mg, 0.4 mg and 0.8 mg were also tested. A distinct accumulation of Al3+ in liver after intraperitoneal injection with a tendency of rising after 28 days of observation was seen. The same was observed in kidneys after subcutaneous injection, especially doses of 0.4 mg Al3+ and 0.8 mg Al3+. The aluminium content in sera was high in an early period of observation only, and subsequently its elimination was fast.     

The decline of antibiotic era--new approaches for antibacterial drug discovery

Infectious diseases still remain the main cause of human premature deaths; especially in developing countries. The emergence and spread of pathogenic bacteria resistant to many antibiotics (multidrug-resistant strains) have created the need for the development of novel therapeutic agents. Only two new classes of antibiotics of novel mechanisms of action (linezolid and daptomycin) have been introduced into the market during the last three decades. The recent progress in molecular biology and bacterial genome analysis has had an enormous impact on antibacterial drug research. This review presents new achievements in searching a new bacterial essential genes, a potential targets for antibacterial drugs. Application of metagenomics strategy is also shown. Some recent technologies aimed at development of anti-pathogenic drugs such as inhibitors of quorum sensing process or histidine kinases are also discussed. Extensive research efforts have provided many details concerning structure of bacterial proteins playing an important role in pathogenesis such as adherence proteins or toxins, what allowed searching for antitoxin drugs or drugs interfering with bacterial adhesion. As an example, the review focuses on anthrax therapies under development. Additionally, the article presents the progress in phage therapy; using bacteriophages or their products such as lysins in antibacterial therapy.