Synthesis of amphiphilic seleninic acid derivatives with considerable activity against cellular membranes and certain pathogenic microbes.

Selenium compounds play a major role in Biology, where they are often associated with pronounced antioxidant activity or toxicity. Whilst most selenium compounds are not necessarily hazardous, their often selective cytotoxicity is interesting from a biochemical and pharmaceutical perspective. We have synthesized a series of amphiphilic molecules which combine a hydrophilic seleninic acid head group - which at the same time serves as thiol-specific warhead - with a hydrophobic tail. These molecules possess a surface activity similar to the one of SDS, yet their biological activity seems to exceed by far the one of a simple surfactant (e.g. SDS) or seleninic acid (e.g. phenyl seleninic acid). Such compounds effectively haemolyse Red Blood Cells and exhibit pronounced activity against Saccharomyces cerevisiae. From a chemical perspective, the seleninic warheads are likely to attack crucial cysteine proteins of the cellular thiolstat.

Synthetic polysulfane derivatives induce cell cycle arrest and apoptotic cell death in human hematopoietic cancer cells.

Natural polysulfanes including diallyltrisulfide (DATS) and diallyltetrasulfide (DATTS) from garlic possess antimicrobial, chemopreventive and anticancer properties. However these compounds exhibit chemical instability and reduced solubility, which prevents their potential clinical applicability. We synthesized six DATS and DATTS derivatives, based on the polysulfane motif, expected to exhibit improved physical and chemical properties and verified their biological activity on human leukemia cells. We identified four novel cytotoxic compounds (IC50 values: compound 1, 24.96±12.37 µM; compound 2, 22.82±4.20 µM; compound 3, 3.86±1.64 µM and compound 5, 40.62±10.07 µM, compared to DATTS: IC50: 9.33±3.86 µM). These polysulfanes possess excellent differential toxicity, as they did not affect proliferating mononuclear blood cells from healthy donors. We further demonstrated ability of active compounds to induce apoptosis in leukemia cells by analysis of nuclear fragmentation and of cleavage of effector and executioner caspases. Apoptosis was preceded by accumulation of cells in G2/M phase with a pro-metaphase-like nuclear pattern as well as microtubular alterations. Prolonged and persistent arrest of cancer cells in early mitosis by the benzyl derivative identifies this compound as the most stable and effective one for further mechanistic and in vivo studies.

Bilateral single cord of the brachial plexus in an adult female cadaver of South Indian origin.

The occurrence of a brachial plexus united into a single cord is very rare. During routine dissection of an elderly female cadaver, the brachial plexus united into a single cord was observed bilaterally. On the left side, C4, C5, and C6 roots combined to form the upper trunk, the C7 root continued as the middle trunk, and C8 and T1 united to form the lower trunk. All three trunks almost immediately fused to form a single cord. On the right side, C5 and C6 roots joined to form the upper trunk, which divided into anterior and posterior divisions. C7, C8, and T1 roots combined to form the lower trunk. The anterior and posterior divisions united with the lower trunk to form a single cord. On both sides, the subclavian artery was superior to the single cord. Supraclavicular brachial plexus injuries in such individuals may have serious clinical manifestations.

Antifungal activity of tetrasulfanes against Botrytis cinerea.

Various natural polysulfanes (RS(x)R', x > or = 3, R (double dagger) H), such as diallyltrisulfide and diallyltetrasulfide from garlic, are mostly harmless to humans, higher animals and plants, yet highly active against diverse microbes, including several fungi. Such natural organic sulfur compounds (OSCs) possess considerable practical potential against a wide range of agricultural pests. Unfortunately, their use is often hampered due to the inherently offensive smell, chemical instability and low water solubility. However, since the biological activity of polysulfanes is primarily based on their unique sulfur-sulfur motif, it is possible to preserve this motif and to modify the side-chain(s). Ultimately, such changes result in synthetic polysulfanes which retain or even exceed the activity of their natural analogues, and also show improved physico-chemical properties. The resulting acid-, ether- and ester-based tetrasulfanes synthesized as part of this study are odorless and highly active against the grey mold fungus Botrytis cinerea. Some, but not all, of the synthetic polysulfanes are recognized by an active fungal efflux mechanism mediated by the ABC transporter AtrB. Remarkably, some of them even induce transcription of the AtrB-encoding gene, mediated by transcription factor Mrr1. Taken together, the activity of synthetic polysulfanes against B. cinerea, combined with a likely low ecotoxicity of such sulfur compounds, bodes well for possible future applications against this and eventually other agronomically important plant pathogens.

Hepatitis B transmission event in an English prison and the importance of immunization.

Immunization against hepatitis B virus (HBV) is recommended for all sentenced prisoners and all new entrants to prison in the UK. In November 2008, acute hepatitis B was confirmed serologically in a 27-year-old man (Case 1) who had been incarcerated since February 2007. The cell mate of Case 1, a 26-year-old man was an established HBV carrier. A home-made tattoo gun was confiscated from their prison cell. In the absence of other clearly identifiable risk behaviours, tattooing was deemed to be a possible route of HBV transmission. Transmission of hepatitis B in a prison setting is a real concern and this report highlights the importance of immunizing prisoners against hepatitis B and should encourage health professionals to communicate the benefits of immunization to inmates to increase vaccine uptake.

The role of thought suppression in building mental blocks.

This research examined the role of thought suppression in the formation of mental blocks. In Experiment 1, participants were asked to generate a series of creative associates for two target words after initially suppressing a word that was semantically related to one of the two target words. Participants produced fewer responses, and experienced a greater sensation of being mentally blocked, when attempting to produce associates for the target word that was semantically related to the suppressed word. In Experiment 2, participants either thought about or suppressed a series of words prior to completing a word fragment completion task. Each word either corresponded exactly to one of the word fragment solutions (target primes) or resembled one of the solutions but was slightly different in its orthographic properties (negative primes). Participants performed most poorly on the items for which they had initially suppressed negative primes.