Investigation of Ground- and Excited-State Photophysical Properties of 5,10,15,20-Tetra(4-pyridyl)-21H,23H-porphyrin with Ruthenium Outlying Complexes

The present work employs a set of complementary techniques to investigate the influence of outlying Ru(II) groups on the ground- and excited-state photophysical properties of free-base tetrapyridyl porphyrin (H(2)TPyP). Single pulse and, pulse train Z-scan techniques used M association with laser flash photolysis, absorbance and fluorescence spectroscopy, and fluorescence decay measurements, allowed us to conclude that the presence of outlying Ru(II) groups causes significant changes on both electronic structure and vibrational properties of porphyrin. Such modifications take place mainly due to the activation of. nonradiative decay channels responsible for the emission, quenching, as well as by favoring some vibrational modes in the light absorption process, It is also observed that, differently from what happens when the Ru(II) is placed at the center of the macrocycle, the peripheral groups cause an increase of the intersystem crossing processes, probably due to the structural distortion of the ring that implies a worse spin orbit coupling, responsible for the intersystem crossing mechanism.

Loss of Interleukin-10 Signaling and Infantile Inflammatory Bowel Disease: Implications for Diagnosis and Therapy

BACKGROUND & AIMS: Homozygous loss of function mutations in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) cause severe infantile (very early onset) inflammatory bowel disease (IBD). Allogeneic hematopoietic stem cell transplantation (HSCT) was reported to induce sustained remission in 1 patient with IL-10R deficiency. We investigated heterogeneity among patients with very early onset IBD, its mechanisms, and the use of allogeneic HSCT to treat this disorder. METHODS: We analyzed 66 patients with early onset IBD (younger than 5 years of age) for mutations in the genes encoding IL-10, IL-10R1, and IL-10R2. IL-10R deficiency was confirmed by functional assays on patients' peripheral blood mononuclear cells (immunoblot and enzyme-linked immunosorbent assay analyses). We assessed the therapeutic effects of standardized allogeneic HSCT. RESULTS: Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency: 3 patients had mutations in IL-10, 5 had mutations in IL-10R1, and 8 had mutations in IL-10R2. Refractory colitis became manifest in all patients within the first 3 months of life and was associated with perianal disease (16 of 16 patients). Extraintestinal symptoms included folliculitis (11 of 16) and arthritis (4 of 16). Allogeneic HSCT was performed in 5 patients and induced sustained clinical remission with a median follow-up time of 2 years. In vitro experiments confirmed reconstitution of IL-10R-mediated signaling in all patients who received the transplant. CONCLUSIONS: We identified loss of function mutations in IL-10 and IL-10R in patients with very early onset IBD. These findings indicate that infantile IBD patients with perianal disease should be screened for IL-10 and IL-10R deficiency and that allogeneic HSCT can induce remission in those with IL-10R deficiency.

Selection of Top 10 Quality Indicators for Nutrition Therapy

Background: The identification of useful quality indicators for nutrition therapy (QINTs) is of great interest and a challenge. This study attempted to identify the 10 QINTs that best suit the practice of quality control in nutrition therapy (NT) by evaluating the opinion of experts in NT with the use of psychometric techniques and statistical tools. Methods: Thirty-six QINTs available for clinical application in Brazil were assessed in 2 distinct phases. In phase 1, 26 nutrition experts ranked QINTs by scoring 4 attributes (utility, simplicity, objectivity, low cost) to assess each QINT on a 5-point Likert scale. The top 10 QINTs were identified from the 10 best scores obtained, and the reliability of expert opinion for each indicator was assessed by Cronbach's alpha. In phase 2, experts provided feedback regarding the selected top 10 QINTs by answering 2 closed questions. Results: The top 10 QINTs, in descending order, are the frequency of nutrition screening of hospitalized patients, diarrhea, involuntary withdrawal of enteral feeding tubes, feeding tube obstruction, fasting longer than 24 hours, glycemic dysfunction, estimated energy expenditure and protein needs, central venous catheter infection, compliance of NT indication, and frequency of application of subjective global assessment. Opinions were consistent among the interviewed experts. During feedback, 96% of experts were satisfied with the top 10 QINTs, and 100% had considered them in accordance with their previous opinion. Conclusion: The top 10 QINTs were identified according to their usefulness in clinical practice by obtaining adequate agreement and representativeness of opinion of nutrition experts. (Nutr Clin Pract. 2012;27:261-267)

Chiral HPLC analysis of donepezil, 5-O-desmethyl donepezil and 6-O-desmethyl donepezil in culture medium: application to fungal biotransformation studies

An high performance liquid chromatography (HPLC) method for the enantioselective determination of donepezil (DPZ), 5-O-desmethyl donepezil (5-ODD), and 6-O-desmethyl donepezil (6-ODD) in Czapek culture medium to be applied to biotransformation studies with fungi is described for the first time. The HPLC analysis was carried out using a Chiralpak AD-H column with hexane/ethanol/methanol (75:20:5, v/v/v) plus 0.3 % triethylamine as mobile phase and UV detection at 270 nm. Sample preparation was carried out by liquid-liquid extraction using ethyl acetate as extractor solvent. The method was linear over the concentration range of 100-10,000 ng mL(-1) for each enantiomer of DPZ (r a parts per thousand yenaEuro parts per thousand 0.9985) and of 100-5,000 ng mL(-1) for each enantiomer of 5-ODD (r a parts per thousand yenaEuro parts per thousand 0.9977) and 6-ODD (r a parts per thousand yenaEuro parts per thousand 0.9951). Within-day and between-day precision and accuracy evaluated by relative standard deviations and relative errors, respectively, were lower than 15 % for all analytes. The validated method was used to assess DPZ biotransformation by the fungi Beauveria bassiana American Type Culture Collection (ATCC) 7159 and Cunninghamella elegans ATCC 10028B. Using the fungus B. bassiana ATCC 7159, a predominant formation of (R)-5-ODD was observed while for the fungus C. elegans ATCC 10028B, DPZ was biotransformed to (R)-6-ODD with an enantiomeric excess of 100 %.

ENVIRONMENTAL TOBACCO SMOKE INDUCES OXIDATIVE STRESS IN DISTINCT BRAIN REGIONS OF INFANT MICE

Environmental tobacco smoke (ETS) leads to the death of 600,000 nonsmokers annually and is associated with disturbances in antioxidant enzyme capacity in the adult rodent brain. However, little is known regarding the influence of ETS on brain development. The aim of this study was to determine levels of malonaldehyde (MDA) and 3-nitrotyrosine (3-NT), as well as enzymatic antioxidant activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and superoxide dismutase (SOD), in distinct brain structures. BALB/c mice were exposed to ETS twice daily for 1 h from postnatal day 5 through postnatal day 18. Acute exposure was performed for 1 h on postnatal day 18. Mice were euthanized either immediately (0) or 3 h after the last exposure. Immediately after an acute exposure there were higher GR and GST activities and MDA levels in the hippocampus, higher GPx and SOD activities in the prefrontal cortex, and higher GST activity and MDA levels in the striatum and cerebellum. Three hours later there was an increase in SOD activity and MDA levels in the hippocampus and a decrease in the activity of all enzymes in the prefrontal cortex. Immediately after final repeated exposure there were elevated levels of GST and GR activity and decreased GPx activity in the hippocampus. Moreover, a rise was found in GPx and GST activities in the prefrontal cortex and increased GST and GPx activity in the striatum and cerebellum, respectively. After 3 h the prefrontal cortex showed elevated GR and GST activities, and the striatum displayed enhanced GST activity. Data showed that enzymatic antioxidant system in the central nervous system responds to ETS differently in different regions of the brain and that a form of adaptation occurs after several days of exposure.

Cephalometric effects of the use of 10-hour Force Theory for Class II treatment

OBJECTIVE: This study aimed to evaluate the cephalometric effects promoted by the orthodontic treatment of Class II malocclusion patients with the use of the 10-Hour Force Theory, that consists in the use of fixed appliances with 8 hours a day using a cervical headgear appliance and 16 hours a day using Class II elastics, 8 hours on the first mandibular molar and 8 hours in the second mandibular molar. METHODS: Sample comprised 31 patients with mean initial age of 14.90 years, final mean age of 17.25 years and mean treatment time of 2.35 years. The lateral cephalograms in pre-treatment and post-treatment stages were evaluated. Evaluation of cephalometric changes between initial and final treatment phases was performed by paired t test. RESULTS: The cases treated with the 10-Hour Force Theory presented a slight restriction of anterior displacement of the maxilla, increase in the effective length of the mandible, significant improvement of the maxillomandibular relationship, significant increase in anterior lower face height, distal tipping of the maxillary premolar crowns, extrusion and distal tipping of the roots of maxillary molars, significant proclination and protrusion of mandibular incisors, significant extrusion and mesialization of mandibular molars, besides a significant correction of the molar relationship, overjet and overbite. CONCLUSION: The use of the 10-Hour Force Theory in treatment of Class II malocclusion provided satisfactory results.

Activation of PAF-receptor induces regulatory dendritic cells through PGE2 and IL-10

Activation of the platelet-activating factor receptor (PAFR) in macrophages is associated with suppressor phenotype. Here, we investigated the PAFR in murine dendritic cells (DC). Bone marrow-derived dendritic cells (BALB/c) were cultured with GM-CSF and maturation was induced by LPS. The PAFR antagonists (WEB2086, WEB2170, PCA4248) and the prostaglandin (PG) synthesis inhibitors (indomethacin, nimesulide and NS-398) were added before LPS. Mature and immature DCs expressed PAFR. LPS increased MHCII, CD40, CD80, CD86, CCR7 and induced IL-10, IL-12, COX-2 and PGE2 expression. IL-10, COX-2 and PGE2 levels were reduced by PAFR antagonists and increased by cPAF. The IL-10 production was independent of PGs. Mature DCs induced antigen-specific lymphocyte proliferation. PAFR antagonists or PG-synthesis inhibitors significantly increased lymphocyte proliferation. It is proposed that PAF has a central role in regulatory DC differentiation through potentiation of IL-10 and PGE2 production.