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BACKGROUND: Parkinson's disease ranks second, after Alzheimer's as the major neurodegenerative disorder, for which no cure or disease-modifying therapies exist. Ample evidence indicate that PD manifests as a result of impaired anti-oxidative machinery leading to neuronal death wherein Cullin-3 has ascended as a potential therapeutic target for diseases involving damaged anti-oxidative machinery. OBJECTIVE: The design of target specific inhibitors for the Cullin-3 protein might be a promising strategy to increase the Nrf2 levels and to decrease the possibility of "off-target" toxic properties. METHODS: In the present study, an integrated computational and wet lab approach was adopted to identify small molecule inhibitors for Cullin-3. The rational drug designing process comprised homology modeling and derivation of the pharmacophore for Cullin-3, virtual screening of Zinc natural compound database, molecular docking and Molecular dynamics based screening of ligand molecules. In vivo validations of an identified lead compound were conducted in the PD model of C. elegans. RESULTS AND DISCUSSION: Our strategy yielded a potential inhibitor; (Glide score = -12.31), which was evaluated for its neuroprotective efficacy in the PD model of C. elegans. The inhibitor was able to efficiently defend against neuronal death in PD model of C. elegans and the neuroprotective effects were attributed to its anti-oxidant activities, supported by the increase in superoxide dismutase, catalase and the diminution of acetylcholinesterase and reactive oxygen species levels. In addition, the Cullin-3 inhibitor significantly restored the behavioral deficits in the transgenic C. elegans. CONCLUSION: Taken together, these findings highlight the potential utility of Cullin-3 inhibition to block the persistent neuronal death in PD. Further studies focusing on Cullin-3 and its mechanism of action would be interesting.

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In response to mating, the Drosophila female undergoes a series of rapid molecular, morphological, behavioral and physiological changes. Studies in Drosophila and other organisms have shown that stimuli received during courtship and copulation, sperm, and seminal fluid are needed for the full mating response and thus reproductive success. Very little is known, however, about how females respond to these male-derived stimuli/factors at the molecular level. More specifically, it is unclear what mechanisms regulate and mediate the mating response, how the signals received during mating are integrated and processed, and what network of molecules are essential for a successful mating response. Moreover, it is yet to be determined whether the rapid transition of the reproductive tract induced by mating is a general phenomenon in insects. This review highlights current knowledge and advances on the developmental switch that rapidly transitions the female from the 'unmated' to 'mated' state.

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BACKGROUND: Adequate colon preparation is essential for the quality and accuracy of colonoscopy and has a significant influence on related costs. The aim of this study was to assess the efficacy and safety of a novel attachable colon-cleaning device used during colonoscopies in porcine colon. METHODS: The ClearPath device consists of a multilumen extruded tube with channels for water irrigation and evacuation designed to allow the break up and removal of stool remnants during colonoscopy. Seven female domestic swine underwent several series of experiments in which partial bowel preparation followed by a sedated colonoscopy using the new device was performed. RESULTS: Between February 2008 and October 2008, a total of 57 colonoscopic procedures were conducted. The device enabled rapid cleaning of the partially prepared porcine colon with no immediate or delayed adverse consequences. CONCLUSIONS: Use of the ClearPath device was found to be a simple, reliable, and safe method for intraprocedural cleaning of partly prepared porcine colon. These experiments support a potential role for ClearPath in cleaning the colon in unprepared or poorly prepared human patients.

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Peripheral-type benzodiazepine receptors (PBR) have been implicated in cell proliferation. The aim of the present study was to test the effect of the PBR ligands PK 11195 and Ro 5-4864 and the central-type benzodiazepine receptor ligand clonazepam on breast carcinoma cell proliferation, using [3H] thymidine incorporation. We then carried out a study to identify where the PBR-specific ligands Ro 5-4864 and PK 11195 act in the cell cycle, using flow cytometric analysis. We found PBR expression in the malignant breast cancer tumors, representing various levels of estrogen and/or progesterone receptors, as well as in the MCF-7 breast carcinoma cell line. PK 11195 and Ro 5-4864 inhibited cell proliferation at concentrations of 10(-5) to 10(-4) M, while clonazepam (the central-type benzodiazepine receptor-specific ligand) had no effect. In this same concentration range, PK 11195 and Ro 5-4864, in contrast to clonazepam, induced an accumulation of MCF-7 cells in both the G0-G1 and G2-M phases of the cell cycle. The present study demonstrates that PBR ligands play a role in regulating cell proliferation in the human breast carcinoma cell line MCF-7.

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We present a case of Munchausen syndrome by proxy (MBP) in a symbiotic relationship between a 34-year-old man and his two female partners. In the past, MBP has only been identified in mother-child relationships. The present case, however, extends the syndrome to relationships between adults as well.

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