Preparation of the pentasaccharide hapten of the GPL of Mycobacterium avium serovar 19 by achieving the glycosylation of a tertiary hydroxyl group

The chemical synthesis of the glycopeptidolipid-type pentasaccharide hapten of Mycobacterium avium serovar 19 with a trifluoroacetamido spacer at the reducing end is described. The spacer-armed pentasaccharide 31, when conjugated to an immunogenic protein, can be applied to the serodiagnosis of mycobacterial infections. The questionable structure of the penultimate monosaccharide unit was clarified as 6-deoxy-3-C-methyl-2,4-di-O-methyl-L-mannopyranose. The occurrence of the 6-deoxy-3-C-methyl-2,4-di-O-methyl-L-talopyranose could be excluded by the presence of the large H-1'-H-2' coupling constant, which proves the 4C1 (L) conformation as the favoured one.     

Role of chemical structure in molecular recognition by transferrin

Studies of molecular recognition of chiral compounds by proteins are of importance from many points of view. The biological role of proteins in their interaction with small molecules is of fundamental interest and can be used in many different fields, for instance for in vitro analysis of optically active compounds. Studies in these areas need a detailed study of the interaction sites on the protein surface and the relationship between chemical structure and the complex formation ability of small molecules, such as drugs. The electrophoretic migration of charged compounds through a protein zone may provide information about the surface properties of the macromolecule in the interaction site. The interaction of human serum transferrin with tryptophan-methyl- (TME), ethyl- (TEE) and butyl-esters (TBE) has been investigated by capillary electrophoresis (CE) and model calculations. Differences in the separation of tryptophan derivatives were obtained by varying experimental parameters such as, pH, ionic strength of background electrolyte and the length of transferrin zone. Limited separation of the enantiomer pairs were observed at pH 5 and 7 with a maximum resolution at pH 6. The size of the ligands coupled to the chiral centre has importance in stereoselective recognition; however, a direct comparison of resolution different in same runs may lead to false conclusion if the experimental conditions are not comparable. With a careful evaluation of the data we obtained significant differences between the resolution of the smallest enantiomer pair compared to those of tryptophan derivatives with longer alkyl chains.     

Surgical outcomes of the brachial plexus lesions caused by gunshot wounds in adults

Background

The management of brachial plexus injuries due to gunshot wounds is a surgical challenge. Better surgical strategies based on clinical and electrophysiological patterns are needed. The aim of this study is to clarify the factors which may influence the surgical technique and outcome of the brachial plexus lesions caused by gunshot injuries.

Methods

Two hundred and sixty five patients who had brachial plexus lesions caused by gunshot injuries were included in this study. All of them were male with a mean age of 22 years. Twenty-three patients were improved with conservative treatment while the others underwent surgical treatment. The patients were classified and managed according to the locations, clinical and electrophysiological findings, and coexisting lesions.

Results

The wounding agent was shrapnel in 106 patients and bullet in 159 patients. Surgical procedures were performed from 6 weeks to 10 months after the injury. The majority of the lesions were repaired within 4 months were improved successfully. Good results were obtained in upper trunk and lateral cord lesions. The outcome was satisfactory if the nerve was intact and only compressed by fibrosis or the nerve was in-contunuity with neuroma or fibrosis.

Conclusion

Appropriate surgical techniques help the recovery from the lesions, especially in patients with complete functional loss. Intraoperative nerve status and the type of surgery significantly affect the final clinical outcome of the patients.     

Allosteric modulation of adenosine receptors

Allosteric modulators for adenosine receptors may have potential therapeutic advantage over orthosteric ligands. Allosteric enhancers at the adenosine A₁ receptor have been linked to antiarrhythmic and antilipolytic activity. They may also have therapeutic potential as analgesics and neuroprotective agents. A₃ allosteric enhancers are postulated to be useful against ischemic conditions or as antitumor agents. In this review, we address recent developments regarding the medicinal chemistry of such compounds. Most efforts have been and are directed toward adenosine A₁ and A₃ receptors, whereas limited or no information is available for A_2A and A_2B receptors. We also discuss some findings, mostly receptor mutation studies, regarding localization of the allosteric binding sites on the receptors.     

Nitrate tolerance does not increase production of peroxynitrite in the heart

Clinical studies have suggested that long-term nitrate treatment does not improve and may even worsen cardiovascular mortality, and the possible role of nitrate tolerance has been suspected. Nitrate tolerance has been recently shown to increase vascular superoxide and peroxynitrite production leading to vascular dysfunction. Nevertheless, nitrates exert direct cardiac effects independent from their vascular actions. Therefore, we investigated whether in vivo nitroglycerin treatment leading to vascular nitrate tolerance increases cardiac formation of nitric oxide (NO), reactive oxygen species, and peroxynitrite, thereby leading to cardiac dysfunction. Nitrate tolerance increased bioavailability of NO in the heart without increasing formation of reactive oxygen species. Despite elevated myocardial NO, neither cardiac markers of peroxynitrite formation nor cardiac mechanical function were affected by nitroglycerin treatment. However, serum free nitrotyrosine, a marker for systemic peroxynitrite formation, was significantly elevated in nitroglycerin-treated animals. This is the first demonstration that, although the systemic effects of nitroglycerin may be deleterious due to enhancement of extracardiac peroxynitrite formation, nitroglycerin does not result in oxidative damage in the heart.     

H2O2 feeding enables LPMO-assisted cellulose saccharification during simultaneous fermentative production of lactic acid

Simultaneous saccharification and fermentation (SSF) is a well-known strategy for valorization of lignocellulosic biomass. Because the fermentation process typically is anaerobic, oxidative enzymes found in modern commercial cellulase cocktails, such as lytic polysaccharide monooxygenases (LPMOs), may be inhibited, limiting the overall efficiency of the enzymatic saccharification. Recent discoveries, however, have shown that LPMOs are active under anoxic conditions if they are provided with H₂O₂ at low concentrations. In this study, we build on this concept and investigate the potential of using externally added H₂O₂ to sustain oxidative cellulose depolymerization by LPMOs during an SSF process for lactic acid production. The results of bioreactor experiments with 100 g/L cellulose clearly show that continuous addition of small amounts of H₂O₂ (at a rate of 80 µM/h) during SSF enables LPMO activity and improves lactic acid production. While further process optimization is needed, the present proof-of-concept results show that modern LPMO-containing cellulase cocktails such as Cellic CTec2 can be used in SSF setups, without sacrificing the LPMO activity in these cocktails.     

Fungal Elicitor-Mediated Induction of Innate Immunity in Catharanthus roseus Against Leaf Blight Disease Caused by Alternaria alternata

Journal of Plant Growth Regulation - Catharanthus roseus (L.) G. Don has a broad range of medicinal importance besides its ornamental exterior. In the present work, biotic (fungal) elicitor was...     

Nitrone derivatives of trolox as neuroprotective agents

Synthesis of nitrone derivatives of trolox is described. Their biological evaluation was performed in vitro for scavenging different free radicals, inhibiting Fe(2+)-induced lipid peroxidation, and in vivo in a permanent middle cerebral artery occlusion model in mice. New compounds exert pharmacological activities comparable to or better than those of trolox or nitrone-type reference compounds.     

The Expression of Psoriasin (S100A7) and CD24 Is Linked and Related to the Differentiation of Mammary Epithelial Cells

Psoriasin (S100A7), a member of the S100 family of calcium-binding proteins, is highly expressed in high-grade ductal carcinoma in situ (DCIS) and in the benign hyperproliferative skin disorder psoriasis. The gene that encodes psoriasin and many other S100 genes are located within a gene cluster on chromosome region 1q21, known as the epidermal differentiation complex. This cluster contains genes for several differentiation markers that play important roles in the terminal differentiation of the epidermis. The purpose of the present study was to evaluate the role of psoriasin in the differentiation process of mammary epithelial cells. Normal mammary epithelial cells (MCF10A) cultured in confluence and suspension, conditions known to induce psoriasin expression, demonstrated a shift towards a more differentiated phenotype indicated by an increase in the expression of the luminal differentiation markers CD24 and MUC1 and the reduced expression of the breast stem cell marker CD44. The expression of psoriasin and MUC1 was most pronounced in the CD24⁺-enriched fraction of confluent MCF10A cells. The shift towards a more differentiated phenotype was abolished upon the downregulation of psoriasin using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Using specific inhibitors, we showed that psoriasin and CD24 expression was regulated by reactive oxygen species (ROS) and the nuclear factor (NF)-κB signaling pathways. While immunohistochemical analyses of DCIS showed heterogeneity, the expression of psoriasin and CD24 showed a similar staining pattern. Our findings suggest that the expression of psoriasin is linked to the luminal differentiation marker CD24 in mammary epithelial cells. Psoriasin demonstrated an essential role in the shift towards a more differentiated CD24⁺ phenotype, supporting the hypothesis that psoriasin plays a role in the differentiation of luminal mammary epithelial cells.