Targeting of pancreatic and prostate cancer stem cell characteristics by Crambe crambe marine sponge extract

Cancer stem cells (CSCs) are suggested as reason for resistance of tumors toward conventional tumor therapy including pancreatic and advanced prostate cancer. New therapeutic agents are urgently needed for targeting of CSCs. Marine sponges harbor novel and undefined compounds with antineoplastic activity but their potential to eliminate CSC characteristics is not examined so far. We collected 10 marine sponges and one freshwater sponge by diving at the seaside and prepared crude methanolic extracts. The effect to established pancreatic and prostate CSC lines was evaluated by analysis of apoptosis, cell cycle, side population, colony and spheroid formation, migratory potential in vitro and tumorigenicity in vivo. While each sponge extract at a 1:10 dilution efficiently diminished viability, Crambe crambe marine sponge extract (CR) still strongly reduced viability of tumor cells at a dilution of 1:1,000 but was less toxic to normal fibroblasts and endothelial cells. CR inhibited self-renewal capacity, apoptosis resistance, and proliferation even in gemcitabine-selected pancreatic cancer cells with acquired therapy resistance and enhanced CSC characteristics. CR pretreatment of tumor cells diminished tumorigenicity of gemcitabine-resistant tumor cells in mice and totally abolished tumor take upon combination with gemcitabine. Our data suggest that CR contains substances, which render standard cancer therapy more effective by targeting of CSC characteristics. Isolation of bioactive metabolites from CR and evaluation in mice are required for development of new CSC-specific chemotherapeutic drugs from a marine sponge.     

Treatment of gingival recession using platelet concentrate with a bioabsorbable membrane and coronally advanced flap: a report of two cases

The aim of this report is to present a new treatment strategy for gingival recession. The use of platelet concentrate gel in a collagen sponge carrier combined with a bioabsorbable membrane and coronally advanced flap procedure is demonstrated in two patients. In both patients, the recession defects treated were equal to or greater than 2 mm. Complete root coverage was achieved in both cases. The patients were satisfied with the esthetic result and appreciated the excellent soft tissue contour and texture. This technique requires further investigation.     

The impact of orthodontic treatment on the quality of life in adolescents: a case-control study

The aim of this case-controlled study was to assess the effect of orthodontic treatment on the quality of life of Brazilian adolescents. Two hundred and seventy-nine 'cases' (106 males and 173 females) and 558 controls (246 males and 312 females) were randomly selected from 15- to 16-year-old adolescents attending all secondary schools in Bauru, S?o Paulo, Brazil. A case was defined as having at least one condition-specific impact (CSI) attributed to malocclusion during the previous 6 months, based on the Oral Impact on Daily Performances index. Conversely, a control was defined as having no CSI attributed to malocclusion during the same period. Adolescents were also clinically examined for orthodontic treatment need using the Index of Orthodontic Treatment Need (IOTN) and asked about previous orthodontic treatment. Binary logistic regression was used for statistical analysis. Females and adolescents with a definite normative orthodontic treatment need were more likely to report CSI than males and adolescents with no normative need [odds ratio (OR) = 1.48, 95 per cent confidence interval (CI) = 1.08-2.02 and OR = 2.02, 95 per cent CI = 2.09-4.47, respectively], whereas adolescents with a history of orthodontic treatment were less likely to report CSI than their counterparts (OR = 0.15, 95 per cent CI = 0.07-0.31). Furthermore, there was an interaction between a history of orthodontic treatment and the current level of normative need. Brazilian adolescents with a history of orthodontic treatment were less likely to have physical, psychological, and social impacts on their daily performances associated with malocclusion than those with no history of orthodontics. Gender was a confounding factor, whereas current level of normative orthodontic treatment need was an effect modifier. Prospective studies are needed to corroborate the present findings.     

Barrier function and water-holding and transport properties of infant stratum corneum are different from adult and continue to develop through the first year of life

Skin water barrier development begins in utero and is believed to be complete by week 34 of gestational age. The goal of this investigation was to assess the dynamic transport and distribution of water of the stratum corneum of infants and compare it to those of adults. The interaction of water with the stratum corneum was assessed by measuring capacitance, transepidermal water loss (TEWL), rates of absorption-desorption as well as Raman spectra as a function of depth (a total of 124 infants (3-12 months) and 104 adults (14-73 years)). The results show that capacitance, TEWL, and absorption-desorption rates had larger values consistently for infant stratum corneum throughout the first year of life and showed greater variation than those of adults. The Raman spectra analyzed for water and for the components of natural moisturizing factor (NMF) showed the distribution of water to be higher and have a steeper gradient in infants than in adults; the concentration of NMF was significantly lower in infants. The results suggest that although the stratum corneum of infants may appear intact shortly after birth (<1 month), the way it stores and transports water becomes adult-like only after the first year of life.     

Colchicine in the management of mucous membrane pemphigoid

Mucous membrane pemphigoid (MMP) usually runs a chronic and potentially devastating course. Its management requires long-term oral corticosteroids. Safe and effective adjuvant or steroid-sparing agents are needed. In this retrospective observational study with a follow-up extending to 16 years (mean: 4 years), 60% (9/15) of all patients with MMP were lesion-free under oral steroid therapy combined with a second immunosuppressant agent. Colchicine was the most effective, clearing from at least one individual mucosal site lesions in 67% (8/12) of patients. Colchicine may be suggested as a first-line corticosteroid-sparing regimen in the management of MMP.     

Preparation and characterization of technetium and rhenium tricarbonyl complexes bearing the 4-nitrobenzyl moiety as potential bioreductive diagnostic radiopharmaceuticals. In vitro and in vivo studies

The synthesis of a ligand containing a nitrobenzyl group as bioreductive pharmacophore and the preparation of the corresponding technetium and rhenium complexes are presented. (99m)Tc labelling was performed in high yield (>90%) by ligand substitution using fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) as precursor. The structure of the technetium complex was established by chromatographic comparison with the analogous rhenium compound which was fully characterized by elemental analysis, spectroscopic methods and X-ray crystallography. Reduction potential of the rhenium complex was in the characteristic range for bioreductive compounds. Biodistribution in normal mice was characterized by fast blood and soft tissue depuration and combined excretion via the hepatobiliary and urinary systems. Tumour uptake was low, probably due to low lipophilicity but tumour/muscle ratios were favourable as a consequence of high excretion.     

Repeated transchoroidal implantation and explantation of compound subretinal prostheses: An exploratory study in rabbits

Purpose  

For human trials with retinal prostheses it is mandatory to develop procedures to safely explant and possibly reimplant the devices. This prompted us to investigate in a small exploratory study the safety of repeated transchoroidal implantation and explantation procedures of complex subretinal devices in laboratory animals.