Absorption and pharmacokinetics of green tea catechins in beagles

The present study evaluates for the first time in dogs, the kinetics of green tea catechins and their metabolic forms in plasma and urine. Ten beagles were administered 173 mg (12·35 mg/kg body weight) of catechins as a green tea extract, in capsules. Blood samples were collected during 24 h after intake and urine samples were collected during the following periods of time: 0-2, 2-6, 6-8 and 8-24 h. Two catechins with a galloyl moiety and three conjugated metabolites were detected in plasma. Most of the detected forms in plasma reached their maximum plasma concentration (Cmax) at around 1 h. Median Cmax for (2)-epigallocatechin-3-gallate (EGCG), (2)-epicatechin-3-gallate (ECG), (2)-epigallocatechin glucuronide (EGCglucuronide), (2)-epicatechin glucuronide (EC-glucuronide), (2)-epicatechin sulphate (EC sulphate) were 0·3 (range 0·1-1·9), 0·1 (range 0-0·4), 0·8 (range 0·2-3·9), 0·2 (range 0·1 1·7) and 1 (range 0·3-3·4) mmol/l, respectively. The areas under the plasma concentration v. time curves (AUC0!24) were 427 (range 102-1185) mmol/l £ min for EGC-glucuronide, 112 (range 53-919) mmol/l £ min for EC-sulphate, 71 (range 26-306) mmol/l £ min for EGCG, 40 (range 12-258) mmol/l £ min for EC-glucuronide and 14 (range 0·1-124) mmol/l £ min for ECG. The values of mean residence time (MRT0!24) were 5 (range 2-16), 2 (range 1-11), 10 (range 2-13), 3 (range 2-16) and 2·4 (range 1-18) h for EGCG, ECG, EGC-glucuronide, EC-glucuronide and EC sulphate, respectively. In urine, catechins were present as conjugated forms, suggesting bile excretion of EGCG and ECG. Green tea catechins are absorbed following an oral administration and EGC-glucuronide is the metabolic form that remains in the organism for a longer period of time, suggesting that this compound could suffer an enterohepatic cycle.

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Peroxisome proliferator-activated receptors (PPARs) are ligand activated transcription factors belonging to the nuclear hormone receptor superfamily. PPARγ is involved in many different activities in the epidermis, such as keratinocyte differentiation, permeability barrier recovery, dermal wound closure, sebaceous gland formation, sebocyte differentiation, and melanogenesis. Preclinical studies with PPARγ ligands on various skin diseases have been performed and they could represent a new strategy in the treatment of scarring alopecia. PPARγ deserves further studies as therapeutic target, likely not with the current drugs, but with future new classes of safer molecules and in combined therapies.

Establishment of an In Vitro Photoallergy Test Using NCTC2544 Cells and IL-18 Production

Differentiation between photoallergenic and phototoxic reactions induced by low molecular weight compounds represents a current problem. The use of eratinocytes as a potential tool for the detection of photoallergens as opposed to photoirritants is considered an interesting strategy for developing in vitro methods. We have previously demonstrated the possibility to use the human keratinocyte cell line NCTC2455 and the production of interleukin-18 (IL-18) to screen low molecular weight sensitizers. The purpose of this work was to explore the possibility to use the NCTC2544 assay to identify photoallergens and discriminate from phototoxic chemicals. First, we identified suitable condition of UV-irradiation (3.5 J/cm2) by investigating the effect of UVAirradiation on intracellular IL-18 on untreated or chloropromazine (a representative phototoxic compound)- treated NCTC2544 cells. Then, the effect of UVA-irradiation over NCTC2544 cells treated with increasing concentrations of 15 compounds including photoallergens (benzophenone, 4-ter-butyl-4-methoxydibenzoylmethane, 2-ethylexyl-p-methoxycinnamate, ketoprofen, 6-methylcumarin); photoirritant and photoallergen (4-aminobenzoic acid, chlorpromazine, promethazine); photoirritants (acridine, ibuprofen, 8-methoxypsoralen, retinoic acid); and negative compounds (lactic acid, SDS and p-phenilendiamine) was investigated. Twenty-four hours after exposure, cytotoxicity was evaluated by the MTT assay or LDH leakage, while ELISA was used to measure the production of IL-18. At the maximal concentration assayed with non-cytotoxic effects (CV80 under irradiated condition), all tested photoallergens induced a significant and a dose-dependent increase of intracellular IL-18 following UVA irratiation, whereas photoirritants failed. We suggest that this system may be useful for the in vitro evaluation of the photoallergic potential of chemicals.

Planning and reporting of quality-of-life outcomes in cancer trials.

BACKGROUND: Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN: Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS: Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS: About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.

Revisão radiológica de 173 casos consecutivos de paracoccidioidomicose

OBJETIVO: Revisar e determinar a incidência dos achados radiológicos mais importantes da paracoccidioidomicose, e verificar as possíveis variantes de suas apresentações. MATERIAIS E MÉTODOS: Foram revistos 173 casos consecutivos de paracoccidioidomicose, atendidos no período de 1970 a 1980. Os estudos radiológicos direcionados a cada caso foram reanalisados por no mínimo dois radiologistas experientes. RESULTADOS: Foram encontrados 94 casos de acometimento pulmonar isolado e 38 de acometimento pulmonar associado a lesões ganglionares, viscerais, ósseas e à tuberculose. Sem envolvimento pulmonar foram encontrados 41 casos, com lesões intestinais, viscerais, ósseas ou combinadas. Os principais achados radiológicos da forma pulmonar foram opacidade intersticial reticular e nodular bilateral, seguida por consolidação, também bilateral. As formas visceral e intestinal apresentaram lesões predominantes no fígado, jejuno e íleo. Na forma ganglionar houve predominância do comprometimento difuso abdominal e periférico, e no ósseo, áreas de lise principalmente em ossos longos e clavícula. CONCLUSÃO: A paracoccidioidomicose é doença granulomatosa comum no Brasil, acometendo principalmente o pulmão, tendo como porta de entrada a inalação dos esporos do fungo. Outras formas desta doença, menos freqüentes ou raras, devem ser permanentemente lembradas no diagnóstico diferencial.

Gertrud Hällström 18 3/9 73

Simananniemen käsikirjoituskokoelma.

Congenital anomalies associated with trisomy 18 or trisomy 13: A registry-based study in 16 european countries, 2000-2011.

The aim of this study was to examine the prevalence of trisomies 18 and 13 in Europe and the prevalence of associated anomalies. Twenty-five population-based registries in 16 European countries provided data from 2000-2011. Cases included live births, fetal deaths (20+ weeks' gestation), and terminations of pregnancy for fetal anomaly (TOPFAs). The prevalence of associated anomalies was reported in live births. The prevalence of trisomy 18 and trisomy 13 were 4.8 (95%CI: 4.7-5.0) and 1.9 (95%CI: 1.8-2.0) per 10,000 total births. Seventy three percent of cases with trisomy 18 or trisomy 13 resulted in a TOPFA. Amongst 468 live born babies with trisomy 18, 80% (76-83%) had a cardiac anomaly, 21% (17-25%) had a nervous system anomaly, 8% (6-11%) had esophageal atresia and 10% (8-13%) had an orofacial cleft. Amongst 240 Live born babies with trisomy 13, 57% (51-64%) had a cardiac anomaly, 39% (33-46%) had a nervous system anomaly, 30% (24-36%) had an eye anomaly, 44% (37-50%) had polydactyly and 45% (39-52%) had an orofacial cleft. For babies with trisomy 18 boys were less likely to have a cardiac anomaly compared with girls (OR = 0.48 (0.30-0.77) and with trisomy 13 were less likely to have a nervous system anomaly [OR = 0.46 (0.27-0.77)]. Babies with trisomy 18 or trisomy 13 do have a high proportion of associated anomalies with the distribution of anomalies being different in boys and girls. © 2015 Wiley Periodicals, Inc.

Transition of young people with chronic conditions: a cross-sectional study of patient perceptions before and after transfer from pediatric to adult health care.

UNLABELLED: The aim of this study was to compare perceived barriers to and the most preferred age for successful transition to adult health care between young people with chronic disorders who had not yet transferred from pediatric to adult health care (pre-transfer) and those who had already transferred (post-transfer). In a cross-sectional study, we compared 283 pre-transfer with 89 post-transfer young people, using a 28-item questionnaire that focused on perceived barriers to transition and beliefs about the most preferred age to transfer. Feeling at ease with the pediatrician was the most important barrier to successful transition in both groups, but was rated significantly higher in the pre-transfer compared to the post-transfer group (OR = 2.03, 95 %CI 1.12-3.71). Anxiety and lack of information were the next most important barriers, rated equally highly by the two groups (OR = 0.67, 95 %CI 0.35-1.28 and OR = 0.71, 95 %CI 0.36-1.38, respectively). More than 80 % of the respondents in both groups reported that 16-19 years was the most preferred age to transfer; more than half of all the respondents reported 18-19 years and older as the most preferred age. CONCLUSION: Better transition planning through the provision of regular and more detailed information about adult health-care providers and the transition process could reduce anxiety and contribute to a more positive attitude to overcome perceived barriers to transition from young people's perspective. Young people's preferences about transferring to adult health care provide a challenge to those children's hospitals that transfer to adult health care at a younger age.

[(18)F]FDG-PET/CT metabolic parameters as useful prognostic factors in cervical cancer patients treated with chemo-radiotherapy.

BACKGROUND: To compare the prognostic value of different anatomical and functional metabolic parameters determined using [(18)F]FDG-PET/CT with other clinical and pathological prognostic parameters in cervical cancer (CC). METHODS: Thirty-eight patients treated with standard curative doses of chemo-radiotherapy (CRT) underwent pre- and post-therapy [(18)F]FDG-PET/CT. [(18)F]FDG-PET/CT parameters including mean tumor standardized uptake values (SUV), metabolic tumor volume (MTV) and tumor glycolytic volume (TGV) were measured before the start of CRT. The post-treatment tumor metabolic response was evaluated. These parameters were compared to other clinical prognostic factors. Survival curves were estimated by using the Kaplan-Meier method. Cox regression analysis was performed to determine the independent contribution of each prognostic factor. RESULTS: After 37 months of median follow-up (range, 12-106), overall survival (OS) was 71 % [95 % confidence interval (CI), 54-88], disease-free survival (DFS) 61 % [95 % CI, 44-78] and loco-regional control (LRC) 76 % [95 % CI, 62-90]. In univariate analyses the [(18)F]FDG-PET/CT parameters unfavorably influencing OS, DFS and LRC were pre-treatment TGV-cutoff ≥562 (37 vs. 76 %, p = 0.01; 33 vs. 70 %, p = 0.002; and 55 vs. 83 %, p = 0.005, respectively), mean pre-treatment tumor SUV cutoff ≥5 (57 vs. 86 %, p = 0.03; 36 vs. 88 %, p = 0.004; 65 vs. 88 %, p = 0.04, respectively) and a partial tumor metabolic response after treatment (9 vs. 29 %, p = 0.0008; 0 vs. 83 %, p < 0.0001; 22 vs. 96 %, p < 0.0001, respectively). After multivariate analyses a partial tumor metabolic response after treatment remained as an independent prognostic factor unfavorably influencing DFS and LRC (RR 1:7.7, p < 0.0001, and RR 1:22.6, p = 0.0003, respectively) while the pre-treatment TGV-cutoff ≥562 negatively influenced OS and DFS (RR 1:2, p = 0.03, and RR 1:2.75, p = 0.05). CONCLUSIONS: Parameters capturing the pre-treatment glycolytic volume and metabolic activity of [(18)F]FDG-positive disease provide important prognostic information in patients with CC treated with CRT. The post-therapy [(18)F]FDG-PET/CT uptake (partial tumor metabolic response) is predictive of disease outcome.

Psychomotor Development of 18-Months Children With Orofacial Clefts

Objective - To describe the global and language development of children with cleft palate or cleft lip and palate at the age of 18 months, and to evaluate whether the type of cleft has an impact on psychomotor development. Study Design - Prospective cohort study. Settings - Tertiary care hospital Patients - All children born between December 2002 and November 2009 with an orofacial cleft, operated and seen at the developmental unit (UD) of the same hospital at the age of 18 months. Outcome Measures - Developmental quotients of the Griffiths Mental Development Scale and the French Communicative Development Inventory (IFDC) were used to assess the overall and language development of the children. Statistics- The population characteristics were described with means for continuous variables, and frequencies for binary or categorical variables. Chi-squared and regression analysis were used to analyse the results. Results - 69 children with clefts were examined at the age of 18 months with the IFDC and the Griffith test. The results showed that there was no significant difference in the test results of language development and global psychomotor development between the children with different types of clefts, and all were within the normal range. Conclusion - Psychomotor development is not affected by orofacial clefts, and there is no difference between children with cleft palate or cleft lip and palate.