Novel diarylheptanoids as inhibitors of TNF-α production

Synthesis and anti-inflammatory activity of novel diarylheptanoids [5-hydroxy-1-phenyl-7-(pyridin-3-yl)-heptan-3-ones and 1-phenyl-7-(pyridin-3-yl)hept-4-en-3-ones] as inhibitors of tumor necrosis factor-α (TNF-α) production is described in the present article. The key reactions involve the formation of a β-hydroxyketone by the reaction of substituted 4-phenyl butan-2-ones with pyridine-3-carboxaldehyde in presence of LDA and the subsequent dehydration of the same to obtain the α,β-unsaturated ketones. Compounds 4i, 5b, 5d, and 5g significantly inhibit lipopolysaccharide (LPS)-induced TNF-α production from human peripheral blood mononuclear cells in a dose-dependent manner. Of note, the in vitro TNF-α inhibition potential of 5b and 5d is comparable to that of curcumin (a naturally occurring diarylheptanoid). Most importantly, oral administration of 4i, 5b, 5d, and 5g (each at 100 mg/kg) but not curcumin (at 100 mg/kg) significantly inhibits LPS-induced TNF-α production in BALB/c mice. Collectively, our findings indicate that these compounds may have potential therapeutic implications for TNF-α-mediated auto-immune/inflammatory disorders.     

Biological Assessment of Water Pollution Using Periphyton Productivity and Standing Crop in the Linggi River,Malaysia

Many assessments of water pollution in aquatic ecosystem have focused mainly on physical and chemical characteristics. However, until recently, biological aspects have been given little attention. Although physical and chemical methods of assessing water pollution are relatively simple to interpret, biological assessments have many strong merits. Therefore an attempt was made to use periphyton productivity (in terms of biomass ash‐free dry weight, AFDW) and chlorophyll‐a content (measured from periphyton colonized on glass microscope slides) to assess water pollution in the Linggi river. The Linggi River is a tropical lotic system in the country of Malaysia. As a result of increased nutrient enrichment due to sewage and agro‐industrial wastes, analyses of accumulated periphyton on glass slides showed increased biomass AFDW from an unpolluted upstream reach to the highly polluted downstream reach of the river. In contrast to biomass, the chlorophyll‐a content of the accumulated periphyton was not always directly related to the AFDW of the biomass. Though the highly polluted Station 4 showed high biomass AFDW and chlorophyll‐a, due to increased nutrient enrichment. The chlorophyll‐a values at slightly polluted Station 2 were lower than at the unpolluted Station 1. Meanwhile, the mean chlorophyll‐a content observed in Linggi river was relatively high as compared to previous studies carried out in Malaysia. When the Water Quality Index (WQI) was calculated using key chemical parameters linked to organic pollution, there was a significant correlation between chemical parameters, biomass AFDW, and chorophyll‐a. Though the chlorophyll‐a content increased with decreases in the WQI, similar to the biomass AFDW, the chlorophyll‐a values were found to be lower in slightly polluted Station 2 than unpolluted Station 1. Therefore it was not necessary that an increase in the biomass AFDW, due to nutrient enrichment, would always increase the chlorophyll‐a in accumulated periphyton (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Sex-specific genetic structure and social organization in Central Asia: insights from a multi-locus study

In the last two decades, mitochondrial DNA (mtDNA) and the non-recombining portion of the Y chromosome (NRY) have been extensively used in order to measure the maternally and paternally inherited genetic structure of human populations, and to infer sex-specific demography and history. Most studies converge towards the notion that among populations, women are genetically less structured than men. This has been mainly explained by a higher migration rate of women, due to patrilocality, a tendency for men to stay in their birthplace while women move to their husband's house. Yet, since population differentiation depends upon the product of the effective number of individuals within each deme and the migration rate among demes, differences in male and female effective numbers and sex-biased dispersal have confounding effects on the comparison of genetic structure as measured by uniparentally inherited markers. In this study, we develop a new multi-locus approach to analyze jointly autosomal and X-linked markers in order to aid the understanding of sex-specific contributions to population differentiation. We show that in patrilineal herder groups of Central Asia, in contrast to bilineal agriculturalists, the effective number of women is higher than that of men. We interpret this result, which could not be obtained by the analysis of mtDNA and NRY alone, as the consequence of the social organization of patrilineal populations, in which genetically related men (but not women) tend to cluster together. This study suggests that differences in sex-specific migration rates may not be the only cause of contrasting male and female differentiation in humans, and that differences in effective numbers do matter.     

Synthesis of O-β-d-mannopyranosyl-(1→4)-O-α-l-rhamnopyranosyl-(1→3)-d-galactopyranose,the trisaccharide repeating-unit of the O-specific polysaccharide from Salmonella anatum

Glycosylation of 1,2:5,6-di-O-isopropylidene-α-d-galactofuranose with 2,3-di-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-d-mannopyranosyl)-α-l-rhamnopyranosyl bromide, followed by removal of the protecting groups, gave O-β-d-mannopyranosyl-(1→4)-O-α-l-rhamnopyranosyl-(1→3)-d-galactose, which is the trisaccharide repeating-unit of the O-specific polysaccharide chain of the lipopolysaccharide from Salmonella anatum. The formation of the β-d-mannopyranosyl linkage was achieved by a glucose-mannose conversion via stereoselective reduction of the corresponding oxo-disaccharide.     

Utility of mean nuclear volume in predicting disease-free survival in locally advanced invasive cervical squamous cell carcinoma

OBJECTIVE: To evaluate mean nuclear volume (MNV) as a prognostic indicator in invasive squamous cell carcinoma of the uterine cervix. STUDY DESIGN: Forty-nine consecutive cases of invasive squamous cell carcinoma of the cervix diagnosed in 1995 were analyzed retrospectively for MNV and correlated with outcome at the end of a 5-year follow-up period. RESULTS: The average MNV among patients with a 5-year disease-free survival (DFS) and patients with disease recurrence within the same period was 1424.11 microm3 and 1401.49 microm3, respectively (P = .984, Mann-Whitney test), indicating a poor relationship between MNV and 5-year DFS. CONCLUSION: Estimation of MNV alone in cases of invasive squamous cell carcinoma of the cervix is not predictive of DFS.     

Specific and sensitive immunoassays detect multiple anti-ovarian antibodies in women with infertility.

Serum anti-ovarian antibodies (AOAs) have been shown in autoimmune premature ovarian failure and in vitro fertilization-embryo transfer (IVF-ET) cases. The specificity of assays detecting these antibodies has been questioned. Researchers have used several techniques (e.g., ELISA and indirect immunofluorescence). Few have reported on the non-specificity and the type of molecular and cellular targets. We reported earlier on the presence of naturally occurring anti-albumin antibodies as the likely factor for non-specificity. Having developed a novel blocking recipe, we show substantial elimination of this non-specificity. With these standardized tests, we hereby report multiple targets at protein and histological levels. In our study group, 15 of 50 (30%) patients with premature ovarian failure and 13 of 50 (26%) IVF-ET patients showed the presence of AOAs. Western blotting showed a large number of patients making AOAs to a 90-kDa protein, followed by 97- and 120-kDa proteins. Histochemically, it was evident that the sera of these patients predominantly react with the oocyte; other somatic cellular targets are also involved. The specific non-invasive test developed by us was found to be useful because it could carry out a reliable diagnosis of an autoimmune etiology that would be very helpful to select patients in whom immune-modulating therapy could be recommended, which in turn may restore ovarian function and fertility.     

Plasmid profiles and randomly amplified polymorphic DNA analysis of Salmonella enterica serotype Enteritidis strains from outbreaks and sporadic cases in Turkey

The aim of the study was to investigate the characteristics of Salmonella serotype Enteritidis strains isolated from outbreaks and sporadic cases in Turkey by plasmid profiles and randomly amplified polymorphic DNA (RAPD) patterns. A total of 64 S. Enteritidis clinical strains were selected from the culture collection of the Enterobacteria Laboratory of Ankara University Medical School Department of Microbiology and Clinical Microbiology for molecular analysis using the plasmid profiles and RAPD method. Fifty-six isolates (88%) harbored one to four plasmids ranging in size from 2.5 to 100 kbp. 57 kbp plasmids were the most common plasmids, and forty-four strains (69%) carried 57 kbp plasmids alone or together with other plasmids. The outbreak strains carried the same plasmid profile: three plasmids sized 57, 40, 3.0 kbp. None of the strains analyzed displayed any RAPD bands with the primer OPB-17. By using primer p-1254, 42 strains (66%) were divided into fourteen RAPD patterns. Ten of the outbreak strains (77%) showed >80% similarity by cluster analysis program. Analysis of RAPD-PCR with primer p-1254 proved an easy, rapid and discriminative method complementing antibiogram and plasmid profiles in routine laboratories, and may contribute to the investigations of S. Enteritidis which still cause outbreaks in Turkey. This study presents the first report on S. Enteritidis isolates in Turkey investigated by plasmid profiles and RAPD methods.     

Molecular operation of metals into the function and state of photosystem II

Action sites of different metals in the electron transport reactions of Photosystem II (PS II) evaluated by delayed fluorescence in the ms range (ms DF) and pigment-pigment, pigment-protein and protein-protein interaction states by electrophoretic measurements are presented. The main targets for the metals action were shown to be:(i) Cd(2+), Ni(2+), Co(2+)-Y(z) or CaMn(4)-cluster on the donor site with dependence on pH;(ii) Ni(2+), Co(2+), Zn(2+), Al(3+), Mn(2+) between Q(A) and Q(B) on the acceptor site; effect of Al(3+) and Mn(2+) is observed only in acidic pH. Investigated metals bring about monomerization of oligomeric and dimeric chlorophyll-protein complexes (CPC) and destabilization of protein-protein interactions. Molecular mechanisms of metals interference with the structure of PS II are discussed.     

D-Alanine-Controlled Transient Intestinal Mono-Colonization with Non-Laboratory-Adapted Commensal E. coli Strain HS

Soon after birth the mammalian gut microbiota forms a permanent and collectively highly resilient consortium. There is currently no robust method for re-deriving an already microbially colonized individual again-germ-free. We previously developed the in vivo growth-incompetent E. coli K-12 strain HA107 that is auxotrophic for the peptidoglycan components D-alanine (D-Ala) and meso-diaminopimelic acid (Dap) and can be used to transiently associate germ-free animals with live bacteria, without permanent loss of germ-free status. Here we describe the translation of this experimental model from the laboratory-adapted E. coli K-12 prototype to the better gut-adapted commensal strain E. coli HS. In this genetic background it was necessary to complete the D-Ala auxotrophy phenotype by additional knockout of the hypothetical third alanine racemase metC. Cells of the resulting fully auxotrophic strain assembled a peptidoglycan cell wall of normal composition, as long as provided with D-Ala and Dap in the medium, but could not proliferate a single time after D-Ala/Dap removal. Yet, unsupplemented bacteria remained active and were able to complete their cell cycle with fully sustained motility until immediately before autolytic death. Also in vivo, the transiently colonizing bacteria retained their ability to stimulate a live-bacteria-specific intestinal Immunoglobulin (Ig)A response. Full D-Ala auxotrophy enabled rapid recovery to again-germ-free status. E. coli HS has emerged from human studies and genomic analyses as a paradigm of benign intestinal commensal E. coli strains. Its reversibly colonizing derivative may provide a versatile research tool for mucosal bacterial conditioning or compound delivery without permanent colonization.