Drug-induced endocytosis of neonatal erythrocytes

The erythrocytes of the newborn infant have many properties that distinguish them from those of adults, and their membranes are also different from those of adult erythrocytes. We compared the ability of adult and neonatal RBCs to undergo endocytosis on exposure to drugs. Using a quantitative method, we showed that neonatal erythrocytes undergo a greater degree of endocytosis than do adult RBCs in response to primaquine, vinblastine, and chlorpromazine, and are sensitive to lower concentrations of the drugs. Some forms of drug-induced endocytosis are red cell age-dependent; when RBCs were separated by density gradient centrifugation, the membranes of the younger, less dense populations of both the neonatal and adult RBCs were capable of more extensive internalization than those of the denser, older RBCs. Neonatal RBCs of a given density undergo more endocytosis than do adult RBCs of the same density, suggesting that the membrane of the neonatal RBC is less stable and capable of more of the reorganization reflected in endocytosis than is the adult RBC membrane.     

Seropositivity of Chlamydophila pneumoniae immunoglobulin G antibody of HIV/AIDS patients in Abuja,Nigeria

ObjectiveTo detect IgG antibody to Chlamydophila pneumoniae (CP) in sera of HIV/AIDS patients and provide rationale for inclusion of routine screening for anti-CP antibodies and anti-chlamydial agents in the Nigerian National HIV/AIDS Management Plan.MethodsSerum samples from 34 consenting HIV/AIDS patients attended a Government-approved Antiretroviral Treatment Facility in Abuja were screened by enzyme-linked immunosorbent assay for anti-CP IgG antibody using ImmunoComb® Chlamydia Bivalent IgG Test kit (Orgenics, Israel).ResultsAnti-CP IgG antibody was detected in 20 (58.8%) of 34 patients tested. The detection rate was higher among the males (8/13; 61.5%) than the females (12/21; 57.1%). Patients of the age group 16-30 years had the highest (7/10; 70%) detection of anti-CP IgG antibody.ConclusionsThe result of the present study suggests the presence of anti-CP antibodies in sera of the HIV/AIDS patients, and reinforces the need for routine screening for anti-CP antibodies as a necessary intervention to reduce the burden of Chlamydophila pneumoniae (C. pneumoniae) infections and to reduce HIV-positive morbidity in Nigeria. The outcome of this study also provides justification for the possible inclusion of anti-chlamydial agents in the National HIV/AIDS Management Plan to provide prophylaxis against or treat active C. pneumoniae infections.     

Multiple organ failure in patients with hemoblastosis during long-term follow-up of treatment]

AIM: Investigation of the condition of the liver, gastrointestinal tract, heart in patients at the stage of clinicohematological remission after treatment for hemoblastosis (acute leukemia, Hodgkin's disease, non-Hodgkin's lymphoma). RESULTS: Marked functional-morphological changes were found: endomyocardial fibrosis, cardiopathy, pulmonary hypertension, chronic atrophic gastritis, colon lesions, dysbacteriosis, viral or drug-induced hepatitis. CONCLUSION: The above affections have developed because of the treatment: chemotherapy, radiotherapy, hemotransfusions, antibacterial drugs. They deteriorate life quality and require a special system of rehabilitation measures.     

A light-driven rhythm in neurotensin-like immunoreactivity in the chicken retina

Purpose: To determine if the pattern of release of neurotensin from the enkephalin-, neurotensin- and somatostatin-like immunoreactive amacrine cells in response to light and dark is the same as that of the enkephalins and somatostatin. Methods/Results: Both the enkephalins and somatostatin are released at high rates in the dark and at lower rates in the light, and these rate changes are reflected in increasing intracellular levels of the peptides in vivo in the light and decreasing levels in the dark The levels of neurotensin-like immunoreactivity show a similar diurnal light-driven and non-circadian rhythm in vivo. Conclusion: This implies that the actual release rates of neurotensin follow the same patterns as those demonstrated in vitro for the enkephalins and somatostatin.     

Study of measles virus recombinant proteins and their immunobiological properties

Recombinant proteins rN (nucleocapsid) and rH/Nh (hemagglutinin) of the measles virus strain NovO/96 of genotype A were obtained. The immunobiological properties of the proteins were studied in the reaction with a panel of positive and negative sera. BALB/c mice were immunized with recombinant proteins and native antigen of the measles virus strain NovO/96 in order to obtain hyperimmune serum and its analysis using ELISA (enzyme-linked immunosorbent assay) and PRN (plaque reduction neutralization). The hyperimmune sera against recombinant proteins and native antigen of the measles virus strain NovO/96 were found to be highly active in ELISA. The antibodies against the proteins rN and rH/Nh were found to be capable of neutralizing the virus in titer 1 : 13.5 and 1 : 22.9, respectively. The neutralization titer of the antibodies generated against native antigen of the measles virus strain NovO/96 was 1 : 25.7.     

Biochemical and pharmacological characterization of AZD1981, an orally available selective DP2 antagonist in clinical development for asthma

Background and Purpose

The discovery of DP₂ as a second receptor for PGD₂ has prompted the search for antagonists as potential novel therapies based on the associations between PGD₂ and disease. Here we describe the biochemical and pharmacological properties of 4-(acetylamino)-3-[(4-chlorophenyl)thio]-2-methyl-1H-indole-1-acetic acid (AZD1981), a novel DP₂ receptor antagonist.

Experimental Approach

Binding to DP₂, functional receptor pharmacology and selectivity were studied in both human and animal systems.

Key Results

AZD1981 displaced radio-labelled PGD₂ from human recombinant DP₂ with high potency (pIC₅₀ = 8.4). Binding was reversible, non-competitive and highly selective against a panel of more than 340 other enzymes and receptors, including DP₁ (>1000-fold selective). AZD1981 inhibited DP₂-mediated shape change and CD11b up-regulation in human eosinophils, shape change in basophils and chemotaxis of human eosinophils and Th2 cells with similar potency. AZD1981 exhibited good cross-species binding activity against mouse, rat, guinea pig, rabbit and dog DP₂. Evaluation in mouse, rat or rabbit cell systems was not possible as they did not respond to DP₂ agonists. Agonist responses were seen in guinea pig and dog, and AZD1981 blocked DP₂-mediated eosinophil shape change. Such responses were more robust in the guinea pig, where AZD1981 also blocked DP₂-dependent eosinophil emigration from bone marrow.

Conclusions and Implications

AZD1981 is a DP₂ antagonist that blocks functional responses in eosinophils, Th2 cells and basophils. It exhibited similar potency irrespective of the cell type, DP₂ agonist or species used. This selective orally active agent is currently under clinical evaluation as a potential therapeutic agent in respiratory diseases including asthma.     

Localization of D, dopamine receptors in the chicken retina

Purpose: The localization of dopamine D| receptors (DIR) in the chicken retina was examined using an anti-human DI R. monoclonal antibody and PAP techniques. Results: A clear band of staining was seen in the outer plex-iform layer; as well as cellular staining in the outer-most part of the inner nuclear layer probably in a subset of horizontal cells. Many different amacrine cell bodies were labelled in the inner one-third of the inner nuclear layer. There was also extensive staining in the inner plexiform layer; which showed some striation. Occasional labelled ganglion cells were also detected. Conclusion: Localization of DI-dopamine receptors has     

A fundamental step-transition in retinal function at low light intensities

There appears to be a fundamental step-transition in retinal function at low light intensities, close to the scotopic-mesopic transition. This step-transition is observed for elements of the retinal dark-light switch, which has been described in the chicken retina. Over the same range of light intensities, there is a step-transition in photoreceptor retinomotor movements and in the coupling of horizontal and All amacrine cells, which suggests a switch in retinal circuitry from rod-processing to cone-processing regimes. A similar step-transition in pineal function suggests that the retinal step-transition signals to the central circadian systems. Finally, this step-transition may also inhibit eye growth, and thus be responsible for the reported diurnal rhythm in eye growth. Disturbances to this step-transition may be the initial cause of disordered eye growth in the form-deprivation myopia paradigm.