Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII8–12

A series of 13 compounds having a monoindolizine mono-salt skeleton was designed and synthesised in order to evaluate their antimycobacterial activity. The synthesis is efficient, involving only three steps: two alkylations and one 3?+?2 dipolar cycloaddition. The antimicrobial activity against Mycobacterium tuberculosis H37Rv grown under aerobic conditions was evaluated, eight compounds showing a very good antimycobacterial activity. SAR correlation reveals a certain influence of the R substituent from the para position of benzoyl moiety at position 3 of indolizine. The most active five compounds passed the second stage of anti-TB testing, the assay demonstrating that they are potent against both replicating and non-replicating Mtb, have a bactericidal mechanism of action, are active against drug-resistant Mtb strains, present a moderate to good activity against nontuberculous mycobacteria, a good intracellular activity, and a moderate to high cytotoxicity. For one compound showing a promising anti-TB profile, a complete ADMET study has been performed.     

Search for somatic DNA variation in the brain: investigation of the serotonin 2A receptor gene

Somatic DNA variation represents one of the most interesting but also one of the least investigated genetic phenomena. In addition to the classical case of DNA hypermutability at the V(D)J region, there is an increasing body of experimental evidence suggesting that genes other than immunoglobulin in tissues other than lymphocytes also exhibit nonuniformity of DNA sequence, which opens new opportunities for explaining various features of multicellular organisms. Identification of somatic DNA mutability, however, is not a trivial task and numerous confounding factors have to be taken into account. In this work we investigated putative DNA variation in the serotonin 2A receptor gene (HTR2A). A series of real-time PCR-based experiments was performed on DNA samples (n = 8) from human brain and peripheral leukocytes. Amplification of the target DNA sequences was carefully matched to that of the control plasmid containing the insert of HTR2A. Sequencing of nearly 500 clones containing a total of 150,000 nucleotides did not show any evidence for somatic DNA variation in the brain and peripheral leukocytes. It is argued in this article that although intraindividual DNA mutability may be a more common phenomenon than is generally accepted, some of the earlier claims of genetic nonidentity on the brain cells may be premature.     

Diazepam: A Preliminary Study of its Effects on Patients with Athetoid Cerebral Palsy

Diazepam was administered to seven severely affected athetoid children for a period of two to three months to determine whether beneficial effects could be demonstrated from its use. All patients were started on a daily dose of 2.5 mg. and the dose was increased as tolerated. The patients were assessed by a neurologist, an occupational therapist, a physiotherapist and a speech therapist before and after the trial.The dose of diazepam cannot be determined in advance. The optimum dose must be established by trial in each individual patient. No beneficial effects were noted in four of these children. One of those who showed improvement became significantly worse when the drug was withdrawn and it was necessary to reinstitute the drug. The response in any individual patient is unpredictable. The most significant side effect was drowsiness.     

First Report about Mineral Content,Fatty Acids Composition and Biological Activities of Four Wild Edible Mushrooms

The goal of this research was a comprehensive analysis of four wild edible mushroom species, Cantharellus cinereus, Clavariadelphus pistillaris, Clitocybe nebularis and Hygrocybe punicea, which have not been analyzed so far. Extracts of different polarities have been prepared and evaluated for their antioxidant activities by DPPH, ABTS, FRAP, TRP and CUPRAC methods. For all extracts, total phenolic content was determined. Based on the analysis, it was shown that solvent type had a significant effect on the antioxidant capacities of mushroom extracts, so water extracts showed the highest activity. Furthermore, the analysis includes determination of mineral composition, fatty acid profiles and antimicrobial activity. Unsaturated fatty acids, which are very important for human health, are dominant in the studied mushroom species. Linoleic and oleic acid consist of over 50 % of the total fatty acid composition. Seventeen biologically important and toxic elements have been analyzed by ICP‐OES and ICP‐MS and results showed that the element concentrations were species‐dependent. Also, it has been found that analyzed mushrooms did not show any antimicrobial activity. Chemometric analysis was used to understand the connection between the extracts of different polarities.     

Refusing to Sing: Gender,Kinship and Patriliny in Macedonia

The issue of whether formal kinship structures and sentiments reflect the reality of social relations was of particular concern to specialists at the height of the kinship debates in the 1960s and 1970s, as it continues to be in some contemporary studies. So too, the classifications ‘patrilineal’ or ‘matrilineal’ have clearly been shown to be problematic given that there are multiple levels of discourse and relational and ideational realities in any given society. For many contemporary kinship specialists in fact no simple correlation can be made between type of descent system and actual social relations, especially relations between men and women. However, some anthropologists continue to argue that patrilineal kinship systems are somehow indicative of control or domination by men or, put inversely, of women's lack of power and authority. It is argued in this paper that even where the formal kinship structures and ideological discourses are dominated by agnation as appears to be the case in south Slav societies generally, and Macedonian in particular, this is not automatically mirrored in gender relations between men and women. In short, there is a long leap from patriliny to patriarchy.