Ocular neuroprotection by siRNA targeting caspase-2

Retinal ganglion cell (RGC) loss after optic nerve damage is a hallmark of certain human ophthalmic diseases including ischemic optic neuropathy (ION) and glaucoma. In a rat model of optic nerve transection, in which 80% of RGCs are eliminated within 14 days, caspase-2 was found to be expressed and cleaved (activated) predominantly in RGC. Inhibition of caspase-2 expression by a chemically modified synthetic short interfering ribonucleic acid (siRNA) delivered by intravitreal administration significantly enhanced RGC survival over a period of at least 30 days. This exogenously delivered siRNA could be found in RGC and other types of retinal cells, persisted inside the retina for at least 1 month and mediated sequence-specific RNA interference without inducing an interferon response. Our results indicate that RGC apoptosis induced by optic nerve injury involves activation of caspase-2, and that synthetic siRNAs designed to inhibit expression of caspase-2 represent potential neuroprotective agents for intervention in human diseases involving RGC loss

Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Ophthalmic techniques described by Şerefeddin Sabuncuoglu (1385-1468 AD)

PubMedID: 15068438Şerefeddin Sabuncuoglu (1385-1468 AD) was a Turkish surgeon who lived in the Ottoman Empire during the fifteenth century, a time of progressive expansion. When in his eighties, he wrote Cerrahiyyetü'l-Haniyye, which means Imperial Surgery. His book is the first example of an illustrated surgical textbook in the Turkish-Islamic medical literature. The importance of his book rests upon the inclusion of colour miniatures of the surgical procedures, incisional techniques and instruments, all drawn by Sabuncuoglu himself. Only three hand-written copies exist, two of which were originally written by the author and are currently exhibited in Paris and Istanbul. The book was rediscovered in 1936, but some parts of it are still suspected to be missing. At present, the book consists of three chapters divided into 193 known sections, The sections deal with all fields of surgery including ophthalmology, and cite relevant Greek, Arabic and Persian textbooks. In this historical article the sections of Cerrahiyyetü'l-Haniyye pertinent to ophthalmology are critically reviewed, including a selection of the coloured drawings

Natural radioactivity and radon specific exhalation rate of zircon sands

The study focuses on the radon emanation from zircon sands and their derivatives, which are widely used in many sectors of industry. In particular, the results obtained by experimental measurements on samples of zircon sands and zircon flours commonly used in Italian ceramic industries are reported. Zircon sands contain a significant concentration of natural radioactivity because Th and U may substitute zirconium in the zircon crystal lattice. The relevant routes of exposure of workers to TENORM from zircon materials are external radiation and internal exposure, either by inhalation of aerosols in dusty working conditions or by inhalation of radon in workplaces. The main objective of this investigation is to provide experimental data able to better calculate the internal exposure of workers due to radon inhalation. Zircon samples were surveyed for natural radioactivity, radon specific exhalation rate and emanation fraction. Measurements of radioactivity concentration were carried out using γ-spectrometry. Methods used for determining radon consisted in determining the 222Rn activity accumulated in a vessel after a given accumulation build-up time. The average activity concentrations of 238U and 232Th in samples result about 2600 and 550 Bq kg-1, respectively; these concentrations are significantly higher than the world average noticed in soils, rocks and Earth\u2019s crust. The 222Rn specific exhalation rates result very low probably due to the low porosity of the material and the consequent difficulty for radon to be released from the zircon crystal lattice

Ophthalmic techniques described by Serefeddin Sabuncuoglu (1385-1468 AD)

WOS: 000220627500015PubMed ID: 15068438Serefeddin Sabuncuoglu (1385-1468 AD) was a Turkish surgeon who lived in the Ottoman Empire during the fifteenth century, a time of progressive expansion. When in his eighties, he wrote Cerrahiyyetu'l-Haniyye, which means Imperial Surgery. His book is the first example of an illustrated surgical textbook in the Turkish-Islamic medical literature. The importance of his book rests upon the inclusion of colour miniatures of the surgical procedures, incisional techniques and instruments, all drawn by Sabuncuoglu himself. Only three hand-written copies exist, two of which were originally written by the author and are currently exhibited in Paris and Istanbul. The book was rediscovered in 1936, but some parts of it are still suspected to be missing. At present, the book consists of three chapters divided into 193 known sections. The sections deal with all fields of surgery including ophthalmology, and cite relevant Greek, Arabic and Persian textbooks. In this historical article the sections of Cerrahiyyetu'l-Haniyye pertinent to ophthalmology are critically reviewed, including a selection of the coloured drawings