Arabinoxylans (AX) microcapsules loaded with insulin were prepared by enzymatic gelation of AX, using a triaxial electrospray method. The microcapsules presented a spherical shape, with an average ...size of 250 µm. The behavior of AX microcapsules was evaluated using a simulator of the human intestinal microbial ecosystem. AX microcapsules were mainly (70%) degraded in the ascending colon. The fermentation was completed in the descending colon, increasing the production of acetic, propionic, and butyric acids. In the three regions of the colon, the fermentation of AX microcapsules significantly increased populations of Bifidobacterium and Lactobacillus and decreased the population of Enterobacteriaceae. In addition, the results found in this in vitro model showed that the AX microcapsules could resist the simulated conditions of the upper gastrointestinal system and be a carrier for insulin delivery to the colon. The pharmacological activity of insulin-loaded AX microcapsules was evaluated after oral delivery in diabetic rats. AX microcapsules lowered the serum glucose levels in diabetic rats by 75%, with insulin doses of 25 and 50 IU/kg. The hypoglycemic effect and the insulin levels remained for more than 48 h. Oral relative bioavailability was 13 and 8.7% for the 25 and 50 IU/kg doses, respectively. These results indicate that AX microcapsules are a promising microbiota-activated system for oral insulin delivery in the colon.
Introduction
Research into the transplantation of solid organs from animals (xenotransplantation) is generating interest and curiosity given that this could be a way of resolving the shortage in ...transplant organs. However, the fact is that currently xenotransplantation is far from becoming a clinical practice.
Objective
To analyse the attitude of medical students from Spanish universities towards the donation of organs from animals and to determine the factors affecting their attitudes.
Material and Methods
Type of study: A sociological, interdisciplinary, observational and multicentre study in Spain. Study population: Students enrolled on the medical degree in Spain (n = 34 000). Sample size: A sample of 9598 students (a confidence level of 99% and precision of ± 1%) stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ xenotransplantation (PCID‐XenoTx RIOS) which was self‐administered and completed anonymously.
Results
A completion rate of 95.7% (n = 9275) was obtained. If the results of xenotransplantation were as good as in human donation, 81% (n = 7491) would be in favour, 3% (n = 308) against and 16% (n = 1476) undecided. The following variables affected this attitude: sex (P < 0.001); academic year (P < 0.001); discussion of transplantation with one's family (P < 0.001) and friends (P < 0.001); the opinion of one's partner (P < 0.001); the respondent's attitude towards organ donation (P < 0.001); religion (P < 0.001); and participation in altruistic activities (P < 0.001). The following variables persisted in the multivariate analysis: (1) being a female (OR = 1.794; P < 0.001); (2) academic year (OR = 2.487; P < 0.001); (3) having spoken about the issue with one's family (OR = 1.200; P = 0.019); (4) the favourable opinion of one's partner (OR = 1.526; P = 0.028); (5) an attitude in favour of donation (OR = 2.087; P < 0.001); (6) being an atheist/agnostic, (OR = 2.5; P < 0.001); and (7) a belief that one's religion is in favour of transplantation (OR = 1.317; P = 0.005).
Conclusions
Spanish medical students have a favourable attitude towards xenotransplantation. This willingness and interest could be a decisive platform for the development and strengthening of research, both for centres with a pre‐clinical xenotransplantation programme and new healthcare centres.
•Covalently crosslinked arabinoxylans (AX) gels with different structure were obtained.•AX gels were biodegradable by mixture of two Bifidobacterium.•Changes in microstructure of AX gels allowed ...different degradation profiles.•AX gels could be used as microflora-activated system for colon delivery.
Arabinoxylan gels with different cross-linking densities, swelling ratios, and rheological properties were obtained by increasing the concentration of arabinoxylan from 4 to 6% (w/v) during oxidative gelation by laccase. The degradation of these covalently cross-linked gels by a mixture of two Bifidobacterium strains (Bifidobacterium longum and Bifidobacterium adolescentis) was investigated. The kinetics of the evolution of structural morphology of the arabinoxylan gel, the carbohydrate utilization profiles and the bacterial production of short-acid fatty acid (SCFA) were measured. Scanning electron microscopy analysis of the degraded gels showed multiple cavity structures resulting from the bacterial action. The total SCFA decreased when the degree of cross-linking increased in the gels. A slower fermentation of arabinoxylan chains was obtained for arabinoxylan gels with more dense network structures. These results suggest that the differences in the structural features and properties studied in this work affect the degradation time of the arabinoxylan gels.
Vitamins and type 2 diabetes mellitus Valdés-Ramos, Roxana; Guadarrama-López, Ana Laura; Martínez-Carrillo, Beatriz Elina ...
Endocrine, metabolic & immune disorders drug targets,
01/2015, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The present review evaluates the relationship between type 2 diabetes mellitus and individual or combined vitamins. Antioxidant vitamins A, C and E are found decreased in diabetic subjects, possibly ...due to an increased need to control the excessive oxidative stress produced by abnormalities in glucose metabolism. On the other hand, retinol binding protein exerts a modulating effect, as it has adipokine functions. With respect to the B group vitamins, thiamin, pyridoxine and biotin have been found decreased but the mechanisms are not clear, however supplementation has shown some improvement of the metabolic control in diabetic patients. The absorption of folic acid and vitamin B12 is importantly decreased by the prolongued use of metformin, which is the first choice drug in uncomplicated diabetes, thus these two nutrients have been found deficient in the disease and most probably need to be supplemented regularly. On the other hand, vitamin D is considered a risk factor for the development of diabetes as well as its complications, particularly cardiovascular ones. Although some studies have found an association of vitamin K intake with glucose metabolism further research is needed. Studies on the use of multivitamin supplements have shown unconclusive results. After reviewing the evidence, no real recommendation on the use of vitamin supplements in type 2 diabetes mellitus can be issued, however patients using metformin during prolongued periods may need folic acid and vitamin B12.
Summary
The Latin American (LA) population has similarities with the Spanish population which makes its integration into Spanish society easier. Objective: to analyze the attitude toward organ ...donation among Latin American citizens residing in Spain, to determine the psychosocial variables which affect this attitude, and to examine the correlation between donation rates of LA citizens in Spain and in their countries of origin. A random sample of LA residents in Spain was taken and stratified according to the respondent's nationality (n = 1.314), in the year 2010. Attitude was assessed using a validated questionnaire (PCID‐DTO Dr Rios). The survey was self‐administered and completed anonymously. Statistical analysis: Student's t‐test, the χ2 test, and logistic regression analysis. There was a 94% completion rate (n = 1.237). Attitude toward donation was favorable in 60% of cases (n = 745), 12% (n = 145) were against, and 28% (n = 347) were undecided. The following variables were associated with attitude toward donation: sex (P = 0.038), level of formal education (P < 0.001), country of origin (P = 0.002), attitude toward the donation of a family member's organs (P < 0.001), having discussed donation with the family (P < 0.001), carrying out prosocial activities (P = 0.025), attitude toward cremation of the body (P < 0.001), attitude toward burial of the body (P < 0.001), attitude toward having an autopsy carried out (P < 0.001), previous experience of the organ donation and transplantation process (P < 0.001), fear of mutilation after donation (P < 0.001), knowledge that the Church has a positive attitude toward organ donation and transplantation (P < 0.001), knowledge of one's partner's attitude toward organ donation (P < 0.001), and a belief that one might need a transplant in the future (P < 0.001). The donation rates in this population group in Spain are higher than those recorded in their countries of origin (55.76 vs. <10 pmp; P < 0.001). The attitude toward organ donation among LA citizens residing in Spain is slightly worse than that reported in the native Spanish population and is determined by many psychosocial factors. The donation rates of LA citizens in Spain are higher than those in their countries of origin.
AIM: To analyze the attitude of Spanish medical students toward living liver donation(LLD) and to establish which factors have an influence on this attitude.METHODS: Study type: A sociological, ...interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain(n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire(PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student′s t test, χ2 test and logistic regression analysis.RESULTS: The completion rate was 95.7%(n = 9275). 89%(n = 8258) were in favor of related LLD, and 32%(n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude:(1) age(P = 0.008);(2) sex(P < 0.001);(3) academic year(P < 0.001);(4) geographical area(P = 0.013);(5) believing in the possibility of needing a transplant oneself in the future(P < 0.001);(6) attitude toward deceased donation(P < 0.001);(7) attitude toward living kidney donation(P < 0.001);(8) acceptance of a donated liver segment from a family member if one were needed(P < 0.001);(9) having discussed the subject with one’s family(P < 0.001) and friends(P < 0.001);(10) a partner’s opinion about the subject(P < 0.001);(11) carrying out activities of an altruistic nature; and(12) fear of the possible mutilation of the body after donation(P < 0.001).CONCLUSION: Spanish medical students have a favorable attitude toward LLD.
Introduction
The VELOUR study evaluated the efficacy and safety of adding aflibercept to FOLFIRI (fluorouracil, leucovorin, irinotecan) in second‐line therapy for metastatic colorectal cancer (mCRC). ...However, a nomogram that can stratify patients according to prognosis is unavailable, and the frequency and effect of the pragmatic use of modified schedules in actual practice remains unknown.
Method
The sample consists of 250 patients with mCRC treated with aflibercept and irinotecan‐based chemotherapy at nine Spanish academic centers between January 2013 and September 2015. The result of a Cox proportional hazards model regression for overall survival (OS), adjusted for covariates available in daily practice, was represented as a nomogram and web‐based calculator. Harrell's c‐index was used to assess discrimination.
Results
The prognostic nomogram for OS includes six variables: Eastern Cooperative Oncology Group performance status, tumor location, number of metastatic sites, mutational status, better response to previous treatment(s), and carcinoembryonic antigen. The model is well calibrated and has acceptable discriminatory capacity (optimism‐corrected c‐index, 0.723; 95% confidence interval CI, 0.666–0.778). Median OS was 6.1 months (95% CI, 5.1–8.8), 12.4 months (95% CI, 9.36–14.8), and 22.9 months (95% CI, 16.6–not reached) for high‐, intermediate‐, and low‐risk groups, respectively. Age, comorbidity, or use of modified FOLFIRI regimens did not affect prognosis in this series. Grade 3–4 adverse events were less common following modified schedules. The admission rate because of toxicity was higher in ≥65 years (9.7% vs. 19.6%; odds ratio, 2.26; p = .029).
Conclusion
We have developed and internally validated a prognostic model for use in individuals with colorectal cancer initiating therapy with FOLFIRI‐aflibercept to predict both OS and the effect of pragmatic modifications of the classic regime on efficacy and safety. This can aid in decision making and in designing future trials.
Implications for Practice
In this study, the authors developed and conducted the internal validation of a prognostic nomogram that makes it possible to stratify patients who are eligible for second‐line FOLFIRI‐aflibercept based on their probability of survival. This model was developed in a multicenter sample from nine Spanish hospitals. Furthermore, to increase the study's validity, the practical use of aflibercept in this setting was investigated, including doses or pragmatic modifications. The results suggest that the modified schedules often used in this daily clinical practice‐based patient population are associated with less severe toxicity without apparent detriment to survival endpoints. It is believed that these data complement the information provided by the VELOUR trial and are relevant for the oncologist in treating colon cancer in the second‐line setting.
摘要
介绍。VELOUR 研究对二线治疗中采用 FOLFIRI(氟尿嘧啶、甲酰四氢叶酸、伊立替康)联合阿帕西普治疗转移性结直肠癌 (mCRC) 的疗效和安全性进行了评估。然而，无法用列线图表示根据预后情况对患者进行的分层，且在临床实践中实际使用改良给药方案的频率和效果尚不可知。
方法。样本包括 2013 年 1 月至 2015 年 9 月期间，在西班牙 9 家学术中心接受阿帕西普和基于伊立替康化疗的 250 名mCRC患者。利用 Cox 比例风险回归模型得出的总生存期 (OS) 结果(根据临床实践中可用的协变量进行校正)可用列线图和基于网络的计算器表示。同时，利用 Harrell 的 C 指数来评估区分度。
结果。关于OS的预后列线图中包含六个变量:美国东部肿瘤协作组的体力状态、肿瘤位置、转移部位的数量、突变状态、对先前治疗的较好反应率及癌胚抗原。模型经过准确校准，具有合格的鉴别能力 乐观校正 C 指数为 0.723；95% 置信区间(CI)，0.666–0.778。高风险、中度风险及低风险组的中位OS分别为 6.1 个月(95% CI，5.1–8.8)、12.4 个月(95% CI，9.36–14.8)及 22.9 个月(95% CI，16.6–未达到)。年龄、合并症或使用改良的 FOLFIRI 方案对本组预后无影响。在使用经改良的给药方案后，3‐4 级不良事件较为罕见。在 65 岁(含)以上的患者中，因毒性反应而入院的比率更高(9.7% vs. 19.6%；比值比，2.26；p = 0.029)。
结论。我们开发了一个预后模型并进行了内部验证，此模型可针对启用 FOLFIRI 联合阿帕西普治疗的结直肠癌患者预测其OS及实际改良传统治疗方案对药物疗效和安全性的影响。这有助于制定医疗决策和设计未来的试验。《肿瘤学家》
实践意义:在本研究中，作者编制了一份预后列线图并进行了内部验证，以便能够基于生存概率对符合 FOLFIRI 联合阿帕西普二线治疗的患者进行分层。此模型由 9 家西班牙医院利用多中心样本进行开发。此外，为提高本研究的有效性，我们研究了在此种情况下使用阿帕西普的实际情况，包括剂量或务实性改良。结果表明，经改良的给药方案常用于基于日常临床实践的患者群体中，与较少的严重毒性反应相关，但不会明显损害生存终点。我们认为，这些数据补充了 VELOUR 试验所提供的信息，有助于肿瘤学家研究结肠癌的二线治疗。
This article reports on a prognostic model for use in patients with colorectal cancer initiating therapy with FOLFIRI/aflibercept to predict overall survival and aid in decision making, with the goal of optimizing treatment results in actual patient populations.
Summary
Multidrug‐resistant Candida auris has emerged as a cause of insidious hospital outbreaks and complicated infections. We present the analysis of an ongoing C. auris outbreak including the ...largest published series of C. auris bloodstream infection. All C. auris‐positive patients from April‐2016 to January‐2017 were included. Environmental, clinical and microbiological data were recorded. Definitive isolate identification was performed by ITS‐rDNA sequencing, and typing by amplified fragment length polymorphism fingerprinting. One hundred and forty patients were colonised by C. auris during the studied period (68% from surgical intensive care). Although control measures were implemented, we were not able to control the outbreak. Forty‐one invasive bloodstream infections (87.8% from surgical intensive care) were included. Clinical management included prompt intravascular catheter removal and antifungal therapy with echinocandins. All isolates were fluconazole‐ and voriconazole‐resistant, but echinocandin‐ and amphotericin B‐susceptible. Thirty‐day mortality rate was 41.4%, and severe septic metastasis as spondylodiscitis and endocarditis were observed in 5 patients (12%). C. auris was also recovered from inanimate patient surroundings and medical equipment. Despite antifungal treatment, high mortality and late complication rates were recorded. Molecular typing suggested a clonal outbreak different from those previously published.
PDF
