Finding Eden - alternative transplantation sites for pancreatic islets.

Pancreatic islets transplantation is an established treatment method for type 1 diabetic patients with the hypoglycemia unawareness syndrome in whom a therapy with modern technologies fails. Islet transplantation is most commonly done using an interventional radiology method: a tissue suspension of pancreatic islets is applied into a branch of the portal vein through a percutaneously installed catheter. Although being minimally invasive unlike pancreas organ transplant, this method is associated with many technical difficulties. Possible complications of the procedure include hemorrhage and portal vein thrombosis. Unlike their natural dispersed localization in exocrine pancreas, isolated pancreatic islets are exposed to hypoxia, toxins and immunosuppressive drugs in the liver parenchyma. Direct contact with the recipients blood causes an instant blood mediated inflammatory reaction (IBMIR) resulting in the death of more than half of the pancreatic islets shortly after their application. Therefore the size of the islet graft is often insufficient and a number of transplanted patients require administration of exogenous insulin. All of these are reasons for seeking an alternative transplantation site with more hospitable conditions for long-term islet survival. Various transplantation sites have been tested in experimental and clinical research. The advantages and disadvantages of some of them are summarized in this paper. Currently, transplantation into the greater omentum seems most promising, which has already been used in clinical practice at several institutions.

[Two-Year Follow-up Results of Patients with Macular Oedema Due to Retinal Vein Occlusion Treated with Ranibizumab]. / Dvouleté zkusenosti s intravitreální lécbou makulárního edému ranibizumabem u pacientu s okluzí retinální vény.

PURPOSE: To evaluate 2-year follow-up results of patients with macular oedema (ME) caused by central (CRVO) and branch (BRVO) retinal vein occlusion treated with intravitreal ranibizumab at the Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic. METHODS: Retrospective study. RESULTS: The 2-year follow-up was completed by 18 patients with ME caused by CRVO and 16 patients with ME caused by BRVO. In CRVO group mean age at diagnosis was 63 years, mean interval from diagnosis to the beginning of treatment was 3,6 months. During the first year of treatment the mean improvement of best corrected visual acuity (BCVA) was 17,4 letters of Early Treatment Diabetic Retinopathy Study (ETDRS) optotype, during the second year +2,4 letters. Mean number of injections was 6,8 in the first and 3,6 in the second year of treatment, mean total of 10,2 injections. In BRVO group the mean age at diagnosis was 68 years, mean interval from diagnosis to the beginning of treatment 6 month, mean gain in BCVA was +18,7 letters in the first and +1 letters in the second year of treatment, mean number of injections was 7 and 3,2 respectively, mean total of 9,6 injections. In both groups neither ocular nor systemic serious adverse effects were noted. CONCLUSION: According to our results intravitreal ranibizumab is a safe and effective treatment for ME caused by retinal vein occlusion. Our results in BRVO group were in accordance with published international studies - BRAVO (BRVO) +18,3 letters, HORIZON -0,7 and even slightly better in CRVO group - CRUISE (CRVO) +13,9 letters, HORIZON study -4,1 lettersKey words: macular oedema, ranibizumab, retinal vein occlusion, central retinal vein occlusion, branch retinal vein occlusion, 2-year follow-up.

Characteristics of titanium dioxide microdispersions with different photo-activity suitable for sunscreen formulations.

The aim of the study was the comparison of photo-activity of three types of titanium dioxide (TiO2) micro-dispersions intended for use as UV filters for cosmetic sunscreen products. The dispersions were also investigated with regard to their influence on the stability of photo-protective systems in cosmetic emulsions, their skin penetration/absorption and their photo-toxicity for humans and skin bacterial flora. All the tested micro-dispersions of rutile TiO2 type (agglomerates with diameter 120-150 nm), with primary particle size lower than 100 nm, demonstrated no phototoxic effect and insignificant antimicrobial behaviour. On the other hand, TiO2 with insufficient deactivation of photo-activity had significant negative impact on the stability of other organic UV filters and therefore on the stability of declared UV protective factors (SPF, UVA-PF). The study demonstrated that the level of deactivation of TiO2 is one of the highly important factors for evaluation of UV filters used as sunscreens.

CD 127- and FoxP3+ expression on CD25+CD4+ T regulatory cells upon specific diabetogeneic stimulation in high-risk relatives of type 1 diabetes mellitus patients.

Abnormalities in CD4+CD25+ regulatory T cells (Treg) may contribute to type 1 diabetes (T1D) development. First-degree relatives of T1D patients are at increased risk especially when they carry certain HLA II haplotypes. Using two novel markers of CD4+CD25+ Treg (CD127- and FoxP3+ respectively), we evaluated number and function of Treg after specific stimulation with diabetogeneic autoantigens in 11 high-risk (according to HLA-linked risk) relatives of T1D patients and 14 age-matched healthy controls using a cytokine secretion assay based on interferon-gamma (IFN-gamma) production. High-risk relatives of T1D patients had significantly lower pre- and post-stimulatory number of CD127- Treg than that of healthy controls (P < 0.05). Labelling Treg with FoxP3+ demonstrated similar trend but did not reach statistical significance. Although the stimulation with diabetogenic autoantigens did not lead to a significant change in number of Treg in both groups, the defective function of Treg was performed by significantly higher activation of diabetogeneic T cells in high-risk relatives of T1D patients compared to healthy controls (P < or = 0.02). Individuals at increased HLA-associated genetic risk for T1D showed defects in Treg.

Cord blood cytokine profile detection in neonates with T1D parents -- monitoring of cellular auto-reactivity using protein microarray.

Type 1 diabetes (T1D) is a great medical challenge and its incidence rises rapidly. T lymphocytes and their cytokine production are supposed to play a major role in T1D development. So far, there is no potent tool to recognize the early signs of cellular auto-reactivity which leads to beta-cell damage. The naïve immune system of the newborn (not yet influenced by external factors) can be used as an important model for T1D pathogenesis studies. Cord blood samples of 22 healthy neonates born at term to a diabetic parent (T1DR) and 15 newborns with no family history of any autoimmune disease (controls) were collected. Determination of 23 cytokines was performed before and after the stimulation with diabetogenic autoantigens using protein microarray. We observed lower basal production of all detected cytokines in the T1DR group - granulocyte/macrophage colony-stimulating factor (GM-CSF) (P = 0.025), growth regulated protein (GRO) (P = 0.002), GRO-alpha (P = 0.027), interleukin (IL)-1-alpha (P = 0.051), IL-3 (P = 0.008), IL-7 (P = 0.027), IL-8 (P = 0.042), monocyte chemoattractant proteins (MCP)-3 (P = 0.022), monokine-induced by IFN-gamma (MIG) (P = 0.034) and regulated upon activation normal T-cell express sequence (RANTES) (P = 0.004). Exclusively lower post-stimulative levels of G-CSF (P = 0.030) and GRO-alpha (P = 0.04) were observed in controls in comparison with the basal levels. A significant post-stimulative decrease in G-CSF (P = 0.030) and MCP-2 (P = 0.009) levels was observed in controls in comparison with T1DR neonates. We also observed the interesting impact of the risky genotype on the protein microarray results. Protein microarray seems to be a useful tool to characterize a risk pattern of the immune response for T1D also in newborns.