Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis

Background: Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors. Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation. Psoriasis is an inflammatory disease also characterised in part by epidermal keratinocyte hyper-proliferation. Objective: We investigated the plant cannabinoids Delta-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors. Methods: A keratinocyte proliferation assay was used to assess the effect of treatment with cannabinoids. Cell integrity and metabolic competence confirmed using lactate-dehydrogenase and adenosine tri-phosphate assays. To determine the involvement of the receptors, specific agonist and antagonist were used in conjunction with some phytocannabinoids. Western blot and RT-PCR analysis confirmed presence of CB1 and CB2 receptors. Results: The cannabinoids tested all inhibited keratinocyte proliferation in a concentration-dependent manner. The selective CB2 receptor agonists JWH015 and BML190 elicited only partial inhibition, the non-selective CB agonist HU210 produced a concentration-dependent response, the activity of theses agonists were not blocked by either C81 /C82 antagonists. Conclusion: The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process. Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis. (c) 2006 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Can misalignments in typical infants be used as a model for infantile esotropia?

PURPOSE. To investigate the nature of early ocular misalignments in human infants to determine whether they can provide insight into the etiology of esotropia and, in particular, to examine the correlates of misalignments. METHODS. A remote haploscopic photorefraction system was used to measure accommodation and vergence in 146 infants between 0 and 12 months of age. Infants underwent photorefraction immediately after watching a target moving between two of five viewing distances (25, 33, 50, 100, and 200 cm). In some instances, infants were tested in two conditions: both eyes open and one eye occluded. The resultant data were screened for instances of large misalignments. Data were assessed to determine whether accommodative, retinal disparity, or other cues were associated with the occurrence of misalignments. RESULTS. The results showed that there was no correlation between accommodative behavior and misalignments. Infants were more likely to show misalignments when retinal disparity cues were removed through occlusion. They were also more likely to show misalignments immediately after the target moved from a near to a far position in comparison to far-to-near target movement. DISCUSSION. The data suggest that the prevalence of misalignments in infants of 2 to 3 months of age is decreased by the addition of retinal disparity cues to the stimulus. In addition, target movement away from the infant increases the prevalence of misalignments. These data are compatible with the notion that misalignment are caused by poor sensitivity to targets moving away from the infant and support the theory that some forms of strabismus could be related to failure in a system that is sensitive to the direction of motion.

Design, synthesis and in vitro degradation of a novel co-drug for the treatment of psoriasis

Psoriasis is a common, chronic and relapsing inflammatory skin disease. It affects approximately 2% of the western population and has no cure. Combination therapy for psoriasis often proves more efficacious and better tolerated than monotherapy with a single drug. Combination therapy could be administered in the form of a co-drug, where two or more therapeutic compounds active against the same condition are linked by a cleavable covalent bond. Similar to the pro-drug approach, the liberation of parent moieties post-administration, by enzymatic and/or chemical mechanisms, is a pre-requisite for effective treatment. In this study, a series of co-drugs incorporating dithranol in combination with one of several non-steroidal anti-inflammatory drugs, both useful for the treatment of psoriasis, were designed, synthesized and evaluated. An ester co-drug comprising dithranol and naproxen in a 1:1 stoichiometric ratio was determined to possess the optimal physicochemical properties for topical delivery. The co-drug was fully hydrolyzed in vitro by porcine liver esterase within four hours. When incubated with homogenized porcine skin, 9.5% of the parent compounds were liberated after 24 h, suggesting in situ esterase-mediated cleavage of the co-drug would occur within the skin. The kinetics of the reaction revealed first order kinetics, Vmax = 10.3 μM/min and Km = 65.1 μM. The co-drug contains a modified dithranol chromophore that was just 37% of the absorbance of dithranol at 375 nm and suggests reduced skin/clothes staining. Overall, these findings suggest that the dithranol-naproxen co-drug offers an attractive, novel approach for the treatment of psoriasis.

Proceedings of the Ninth Annual Conference of the British Association for Biological Anthropology and Osteoarchaeology, Department of Archaeology, University of Reading

The Proceedings of the Ninth Annual Conference of the British Association for Biological Anthropology and Osteoarchaeology (BABAO) held at the University of Reading in 2007. Contents: 1) A life course perspective of growing up in medieval London: evidence of sub-adult health from St Mary Spital (London) (Rebecca Redfern and Don Walker); 2) Preservation of non-adult long bones from an almshouse cemetery in the United States dating to the late nineteenth to the early twentieth centuries (Colleen Milligan, Jessica Zotcavage and Norman Sullivan); 3) Childhood oral health: dental palaeopathology of Kellis 2, Dakhleh, Egypt. A preliminary investigation (Stephanie Shukrum and JE Molto); 4) Skeletal manifestation of non-adult scurvy from early medieval Northumbria: the Black Gate cemetery, Newcastle-upon-Tyne (Diana Mahoney-Swales and Pia Nystrom); 5) Infantile cortical hyperostosis: cases, causes and contradictions (Mary Lewis and Rebecca Gowland); 6) Biological Anthropology Tuberculosis of the hip in the Victorian Britain (Benjamin Clarke and Piers Mitchell); 7) The re-analysis of Iron Age human skeletal material from Winnall Down (Justine Tracey); 8) Can we estimate post-mortem interval from an individual body part? A field study using sus scrofa (Branka Franicevec and Robert Pastor); 9) The expression of asymmetry in hand bones from the medieval cemetery at Écija, Spain (Lisa Cashmore and Sonia Zakrezewski); 10) Returning remains: a curator’s view (Quinton Carroll); 11) Authority and decision making over British human remains: issues and challenges (Piotr Bienkowski and Malcolm Chapman); 12) Ethical dimensions of reburial, retention and repatriation of archaeological human remains: a British perspective (Simon Mays and Martin Smith); 13) The problem of provenace: inaccuracies, changes and misconceptions (Margaret Clegg); 14) Native American human remains in UK collections: implications of NAGPRA to consultation, repatriation, and policy development (Myra J Giesen); 15) Repatriation – a view from the receiving end: New Zealand (Nancy Tayles).

Phenotypic and genotypic characterization of avian Escherichia coli O86:K61 isolates possessing a gamma-like intimin

Escherichia coli O86:K61 has long been associated with outbreaks of infantile diarrhea in humans and with diarrheal disease in many animal species. Studies in the late 1990s identified E. coli 086:K61 as the cause of mortality in a variety of wild birds, and in this study, 34 E. coli 086:K61 isolates were examined. All of the isolates were nonmotile, but most elaborated at least two morphologically distinct surface appendages that were confirmed to be type I and curli fimbriae. Thirty-three isolates were positive for the eaeA gene encoding a gamma type of intimin. No phenotypic or genotypic evidence was obtained for elaboration of Shiga-like toxins, but most isolates possessed the gene coding for the cytolethal distending toxin. Five isolates were selected for adherence assays performed with tissue explants and HEp-2 cells, and four of these strains produced attaching and effacing lesions on HEp-2 cells and invaded the cells, as determined by transmission electron microscopy. Two of the five isolates were inoculated orally into 1-day-old specific-pathogen-free chicks, and both of these isolates colonized, invaded, and persisted well in this model. Neither isolate produced attaching and effacing lesions in chicks, although some pathology was evident in the alimentary tract. No deaths were recorded in inoculated chicks. These findings are discussed in light of the possibility that wild birds are potential zoonotic reservoirs of attaching and effacing E. coli.

Acts of estrangement: reading the psoriatic-skin

I am continually surprised by the acts of estrangement in which my body engages. All bodies do this to some extent – lungs breathe, hearts beat and so on, but with psoriasis, which my article is concerned with, these processes are highly visible. As a condition of the skin, it is a pathology which is enacted both within and without, visible to the social world as well emerging from some little understood inflammatory source within the body. This article will undertake a phenomenological exploration of my own skin and how my experience of my body is affected by its lack of compliance with medicine, cosmetics etc. By some unknown causation it flakes, breaks, itches constantly drawing attention to bodily limits and the limits of medical knowledge. I want to think through the meanings we ascribe to such inflammatory conditions in Western society, how my skin materialises at the nexus of industrialisation, medicine, class and capital. This investigation will emerge at the limit point, the thin skin between the subjective and objective, observing and theorising my skin in ways which dissolve disciplinary boundaries, to comprehend the cultural, biological and environmental forces that work upon my body, estranging it from me.