Biologically active, non membrane-anchored precursors: an overview

Peptides function as chemical signals between cells of multicellular organisms via specific receptors on target cells. Many hormones, neuromodulators and growth factors are peptides. Peptide hormones and other biologically active peptides are synthesized as higher molecular weight precursor proteins (pro-hormones), which must undergo post-translational modification to yield the bioactive peptide(s). In many instances, more than one biologically active peptide is generated from one and the same precursor. In most cases, these precursors are biologically inert and their existence is confined to the membrane-enclosed subcellular compartments where processing of the pro-hormones takes place. A class of growth factors that derive from membrane-anchored precursors which themselves are biologically active constitute an exception to this model. The list of the membrane-anchored biologically active precursors has been the subject of specialized reviews. The present review focuses on precursors other than membrane-anchored precursors, which were found to be biologically active and which often display different biological activities, and may mediate their effects via receptors independent from those of their generated peptides.     

Determination,a l'equilibre,des constantes d'association de ligands radioactifs ou non radioactifs par une methode non graphique

The present work deals with the determination of association constants at equilibrium by a non-graphical method in binding systems containing one specific receptor. Equations have been derived from that originally described by Lea (Biochim. Biophys. Acta, 322, 68–74), the terms of which are obtained from the data of simple displacement curves of a bound radioactive ligand by unlabelled competitors identical or different in nature. By knowing the function relating the variations of the bound ligand (B) to the affinity constant (K_i) and the quantity (M_i) of competitor for a given system, it is possible to calculate any of these parameters when the two others are measured. Thus, it becomes easy to compare the relative affinities of differents receptors for the same ligand or that of one receptor for various labelled or unlabelled ligands. Furthermore, theoretical displacement curves can be drawn and compared to experimental data, when only knowing the affinity constant of a specific binding system in given conditions. These modes of calculation have been tested in a study of interactions between various steroids and a fraction of human serum proteins precipitated by ammonium sulfate (30–45%) and containing the sex hormone-binding globulin. Association constants thus obtained agree well with those reported in the literature and determined by graphical procedures.     

Natura non facit saltum

The suggestion that speciation involves non-adaptive processes needs further research, not more argument.
Mr Darwin's position might, we think, have been stronger than it is if he had not embarrassed himself with the aphorism, "Natura non facit salturn", which turns up so often in his pages. We believe…that Nature does make jumps now and then and a recognition of the fact is of no small importance in disposing of many minor objections to the doctrine of transmutation (i.e. speciation).     

Dermatophyte and non dermatophyte fungi in Riyadh City,Saudi Arabia

BackgroundDermatophytes are a scientific label for a group of three genera (Microsporum, Epidermophyton and Trichophyton) of fungus that causes skin disease in animals and humans. Conventional methods for identification of these fungi are rapid and simple but are not accurate comparing to molecular methods.ObjectiveThis study aimed to isolate human pathogenic dermatophytes which cause dermatophytosis in Riyadh City, Saudi Arabia and to identify these fungi by using conventional and molecular methods.MethodsThe study was conducted in Medical Complex, Riyadh and King Saud University. Samples of infected skin, hairs and nails were collected from 112 patients. Diagnosis of skin infections, direct microscopic test, isolation and identification of dermatophytes by conventional and molecular methods were carried out.ResultsThe results indicated that the tinea capitis infection had the highest prevalence among the patients (22.3%) while Tinea barbae had the lowest. In this study the identified dermatophyte isolates belong to nine species as Trichophyton violaceum, Trichophyton verrucosum, Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton schoenleinii, Trichophyton concentricum, Microsporum canis, Microsporum audouinii and Epidermophyton floccosum which cause skin infections were isolated during this study. Non dermatophyte isolates included 5 isolates from Aspergillus spp. 4 isolates from Acremonium potronii and 15 isolates from Candida spp. M. canis were the most common species (25% of isolated dermatophytes). Out of the 52 dermatophyte isolates identified by conventional methods, there were 45 isolates identified by the molecular method.ConclusionsThe results concluded that approximately M. canis caused a quarter of dermatophyte cases, tinea capitis infection was prevalent and the molecular method was more accurate than conventional methods.     

New non competitive AMPA antagonists

New halogen atom substituted 2,3-benzodiazepine derivatives condensed with an azole ring on the seven membered part of the ring system of type 3 and 4 as well as 5 and 6 were synthesized. It was found that chloro-, dichloro- and bromo-substitutions in the benzene ring and additionally imidazole ring condensation on the diazepine ring can successfully substitute the methylenedioxy group in the well known molecules GYKI 52466 (1) and GYKI 53773 (2) and the 3-acetyl-4-methyl structural feature in 2, respectively, preserving the highly active AMPA antagonist characteristic of the original molecules. From the most active compounds (3b,i) 3b (GYKI 47261) was chosen for detailed investigations. 3b revealed an excellent, broad spectrum anticonvulsant activity against seizures evoked by electroshock and different chemoconvulsive agents indicating a possible antiepileptic efficacy. 3b was found to be highly active in a transient model of focal ischemia predictive of a therapeutic value in human stroke. 3b also reversed the dopamine depleting effect of MPTP and antagonized the oxotremorine induced tremor in mice indicating a potential antiparkinson activity.     

DNA aneuploidia in cells of acute leukemia non B non T type in children

In 31 children with acute lymphoblastic leukemia of non B and non T type the cellular DNA amount using cytophotometric method was estimated. Parallely the computer microscopic image analysis was performed. These investigations were made using Morphoquant of C. Zeiss, Jena, GDR. The cells were studied before the introduction of therapy, after obtaining the first phase remission, during remission and at the relapse. DNA-diploidal type in 13 cases, aneuploidio-poliploidal in 8 cases and hipoploidal type in 13 cases. The survival time of investigated children was the largest in the case with diploidal and hyperploidal types of leukemic cells. The children with DNA-aneuploidopoliploidal type cells had the shortest survival time. Besides the estimation of the cellular DNA amount the defining of the percentage of the cells being in S phase seems to be very important. In differentiating between the normal and leukemic lymphocytes, containing the same amount of DNA as non neoplastic lymphocytes, it may be advisable to analyse the morphological picture, particularly of such parameters as chromatin compactness degree and the presence of nucleoli.