Phenytoin as a novel anti-vitiligo weapon

Vitiligo is a psychologically devastating clinical conundrum which affects approximately 1% of the general population. The exact cause of the illness is an enigma, but several hypotheses about its pathogenesis are advanced.The autoimmune hypothesis proposes an autoimmune attack against melanocytes. Although anti-melanocyte autoantibodies have been demonstrated in vitiligo, recent research casts doubt on their pathogenic role and instead supports the involvement of cell-mediated autoimmune response in the pathobiology of this disorder, which is characterized by increase of suppressor T-cells and decrease of the helper/suppressor ratio in association with the presence of type-1 cytokine secreting cytotoxic T cells in the vicinity of disappearing melanocytes.The neural hypothesis proposes that increased release of norepinephrine, a melanocytotoxin, from the autonomic nerve endings in the microenvironment of melanocytes injures these cells. Moreover, norepinephrine induces the catecholamine degrading enzyme monoamine oxidase (MAO), which favors the formation of toxic levels of hydrogen peroxide in the vicinity of melanocytes.Another theory suggests that abnormal permeability of melanosome membrane, which normally prevents the diffusion of toxic melanin precursors into the cytoplasm, may cause melanocyte damage.Phenytoin, the widely-used anticonvulsant, has been employed both topically and systemically in the treatment of some dermatological disorders. The drug has been shown to significantly suppress mitogen-induced activation of lymphocytes and cytotoxic T lymphocyte activity and to polarize the immune response toward the type-2 pathway. It also significantly decreases suppressor T cells and increases the helper/suppressor ratio.At high concentrations, the drug inhibits the release of norepinephrine and the activity of MAO. Moreover, phenytoin is suggested to interact with membrane lipids, which may promote stabilization of the membranes.The hydantoin moiety of phenytoin exerts a direct stimulatory action on melanocytes; facial hyperpigmentation is a recognized side effect of orally administered phenytoin.Altogether, the above evidence suggests that phenytoin could be therapeutically effective against vitiligo. As phenytoin stimulates collagen production and inhibits its breakdown, its concomitant use with topical steroids could prevent steroid-induced skin atrophy while potentiating the anti-vitiligo effect of these agents.     

Squamous cell carcinoma in a tuatara (Sphenodon punctatus)

CASE HISTORY: A mature male tuatara was presented with a history of recurrent cloacal prolapse.

CLINICAL AND PATHOLOGICAL FINDINGS: The prolapsed tissue included a 12 mm diameter mass, which histologically showed cords and nodules of neoplastic epithelial cells.

DIAGNOSIS: The mass was diagnosed as a squamous cell carcinoma with ulceration of the overlying stratified squamous epithelium and diffuse inflammation of the surrounding dermis.

CLINICAL RELEVANCE: This case presented a rare opportunity to investigate squamous cell carcinoma in a long-lived lower vertebrate species. Future recurrence or metastasis of the mass may add useful information to the current base of knowledge of the behaviour of malignant neoplasms in reptiles.     

Bacterial sinusitis as a cause of beak deformity in an Antipodes Island parakeet (Cyanoramphus unicolor)

CASE HISTORY: From 26 days of age, an Antipodes Island parakeet (Cyanoramphus unicolor) was noted to have a severe beak deformity and reduced bodyweight gain compared to its nest mate. The bird was euthanised at 43 days of age.

CLINICAL AND PATHOLOGICAL FINDINGS: The beak abnormality consisted of distortion of the right nares and severe shortening resulting in deviation of the upper maxilla to the right and cranially. On sectioning the head, copious mucoid material was found in the infraorbital sinus and the bony sinus architecture was disrupted. Histopathological examination of the infraorbital sinuses revealed a large focus of chronic but active inflammation, bony lysis on the right side and pockets of a mixed population of bacteria.

DIAGNOSIS: Severe beak deformity, likely secondary to bacterial sinusitis.

CLINICAL RELEVANCE: The case illustrates the need to look for underlying aetiologies to beak malformation, particularly in young parrots.     

Bosonic stimulation in the formation of a bose-einstein condensate

The formation of a Bose-Einstein condensate of a dilute atomic gas has been studied in situ with a nondestructive, time-resolved imaging technique. Sodium atoms were evaporatively cooled close to the onset of Bose-Einstein condensation and then suddenly quenched to below the transition temperature. The subsequent equilibration and condensate formation showed a slow onset distinctly different from simple relaxation. This behavior provided evidence for the process of bosonic stimulation, or coherent matter-wave amplification, crucial to the concept of an atom laser.     

A phylogenetic analysis of Bovine Viral Diarrhoea Virus (BVDV) isolates from six different regions of the UK and links to animal movement data

Bovine Viral Diarrhoea Virus (BVDV) is a pestivirus which infects cattle populations worldwide and is recognised as a significant source of economic loss through its impact on health and productivity. Studies investigating the molecular epidemiology of BVDV can give invaluable information about the diversity of viral strains present in a population and this, in turn, can inform control programs, drive vaccine development and determine likely infection sources. The current study investigated 104 viral isolates from forty farms across the UK. Through phylogenetic and nucleotide sequence analysis of the 5′UTR and N^pro regions of the isolates investigated, it was determined that BVDV 1a was the predominant sub-genotype. However, BVDV 1b, 1e and 1i were also identified and, for the first time in the UK, BVDV 1d. Through analysis of animal movement data alongside the phylogenetic analysis of these BVD isolates, it was possible to link animal movements to the viral isolates present on several premises and, for the first time, begin to elucidate the routes of viral transmission. With further work, this type of analysis would enable accurate determination and quantification of the true biosecurity risk factors associated with BVDV transmission.     

Mesenchymal Stem/Stromal-Like Cells from Diploid and Triploid Human Embryonic Stem Cells Display Different Gene Expression Profiles

Background:hESCs-MSCs open a new insight into future cell therapy applications, due to their unique characteristics, including immunomodulatory features, proliferation, and differentiation. Methods:Herein, hESCs-MSCs were characterized by IF technique with CD105 and FIBRONECTIN as markers and FIBRONECTIN, VIMENTIN, CD10, CD105, and CD14 genes using RT-PCR technique. FACS was performed for CD44, CD73, CD90, and CD105 markers. Moreover, these fibroblast-like cells, due to multipotent characteristics, differentiated to the osteoblast. Results:MSCs were derived from diploid and triploid hESC lines using sequential 3D and 2D cultures and characterized with the specific markers. IF showed the expression of FIBRONECTIN and CD105 in hESCs-MSCs. Flow cytometry data indicated no significant difference in the expression of MSC markers after 6 and 13 passages. Interestingly, gene expression profiles revealed slight differences between MSCs from diploid and triploid hESCs. The hESCs-MSCs displayed osteogenic differentiation capacity, which was confirmed by Alizarin red staining. Conclusion:Our findings reveal that both diploid and triploid hESC lines are capable of forming MSCs; however, there are some differences in their gene expression profiles. Generation of MSCs from hESCs, as a non-invasive procedure in large scale, will lend itself for the future cell-based therapeutic applications. Key Words: Human embryonic stem cells, Mesenchymal stem/stromal cells, Regenerative medicine     

Characterisation of adult green lacewing (Chrysoperla carnea) digestive physiology: impact of a cysteine protease inhibitor and a synthetic pyrethroid

BACKGROUND: In spite of concern regarding potential non‐target effects of GM crops, few studies have compared GM pest control with conventional methods. The impacts of cypermethrin and oilseed rape expressing oryzacystatin‐1 (OC‐1) were compared in this study on the predator Chrysoperla carnea (Stephens). RESULTS: Adults fed purified rOC‐1 showed a subtle shift in digestive protease profile, with an increasing reliance on serine proteases (chymotrypsin), increase in aspartic proteases and a slight reduction in elastase activity. Although there were no effects on mortality, onset of oviposition was delayed; however, once egg production commenced, egg laying and hatching success rates were comparable with those of controls. Oryzacystatin‐1 expressed in pollen showed no detrimental effects. Cypermethrin had no effect on mortality owing to high levels of non‐specific esterase activity resulting in partial breakdown of the insecticide. In spite of this, there was a significant delay in onset of oviposition and a significant reduction in egg production and viability. CONCLUSION: This study demonstrates the potential for pest management to impact on predators, but importantly it highlights the ability of the predator to detoxify/respond to treatments with different modes of action. In this case, exposure to an insecticide carried a greater fitness cost than exposure to a protease inhibitor expressed in transgenic crops. Copyright © 2009 Society of Chemical Industry     

An outbreak of avian malaria in captive yellowheads/mohua (Mohoua ochrocephala)

CASE HISTORY: Eight mohua, or yellowheads (Mohoua ochrocephala), were held in a large open aviary over the summer months of 2003–2004, following their capture for captivebreeding purposes. Two birds died of transportation trauma shortly after arrival, one became ill and died a month later, and another four died within a 2-week period in February 2004. The eighth bird also became ill at this time but survived for a year following treatment with chloroquine and doxycycline.

CLINICAL AND PATHOLOGICAL FINDINGS: The affected birds were depressed, lethargic and dyspnoeic. Necropsy of three birds showed a slightly pale and swollen liver and spleen. Impression smears of the liver of one bird revealed schizonts resembling Plasmodium spp. within the cytoplasm of many hepatocytes, which was confirmed histopathologically. Similar protozoal organisms were seen within splenic histiocytes and pulmonary endothelial cells of 5/6 birds. Electron microscopy identified these as protozoal schizonts containing merozoites of similar size and structure to those of Plasmodium spp.

DIAGNOSIS: The birds were infected with a protozoal haemoparasite resembling Plasmodium spp.; asexual stages within hepatocytes and endothelial cells of the lung and spleen were typical of this organism.

CONCLUSIONS AND CLINICAL RELEVANCE: The mohua captured from west Otago were highly susceptible to avian malaria as they came from an isolated population that was likely to be naïve and have had no previous contact with this organism. The birds were probably infected by bites from mosquitoes feeding off local populations of blackbirds subsequently found to be infected with Plasmodium spp.