Chiral mesoporous silica nano-screws as an efficient biomimetic oral drug delivery platform through multiple topological mechanisms

In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws (CMSWs) with ideal topological structures (e.g., small section area, relative rough surface, screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bio-adhesion, mucus-penetration and cellular uptake (contributed by the macropinocytosis and caveolae-mediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres (CMSSs) and chiral mesoporous silica nanorods (CMSRs), achieving extended retention duration in the gastrointestinal (GI) tract and superior adsorption in the blood circulation (up to 2.61- and 5.65-times in AUC). After doxorubicin (DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier (IEB), and resulted in satisfactory oral bioavailability of DOX (up to 348%). CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.

Intranasal temperature-sensitive hydrogels of cannabidiol inclusion complex for the treatment of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD. Mice model of PTSD was established with conditional fear box. CBD TSGs could significantly improve the spontaneous behavior, exploratory spirit and alleviate tension in open field box, relieve anxiety and tension in elevated plus maze, and reduce the freezing time. Hematoxylin and eosin and c-FOS immunohistochemistry slides showed that the main injured brain areas in PTSD were the prefrontal cortex, amygdala, and hippocampus CA1. CBD TSGs could reduce the level of tumor necrosis factor-

AncPhore: A versatile tool for anchor pharmacophore steered drug discovery with applications in discovery of new inhibitors targeting metallo-

We herein describe AncPhore, a versatile tool for drug discovery, which is characterized by pharmacophore feature analysis and anchor pharmacophore (

Notoginsenoside Ft1 acts as a TGR5 agonist but FXR antagonist to alleviate high fat diet-induced obesity and insulin resistance in mice

Obesity and its associated complications are highly related to a current public health crisis around the world. A growing body of evidence has indicated that G-protein coupled bile acid (BA) receptor TGR5 (also known as Gpbar-1) is a potential drug target to treat obesity and associated metabolic disorders. We have identified notoginsenoside Ft1 (Ft1) from

Escape from abluminal LRP1-mediated clearance for boosted nanoparticle brain delivery and brain metastasis treatment

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.

A facile and universal method to achieve liposomal remote loading of non-ionizable drugs with outstanding safety profiles and therapeutic effect

Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs, but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents, thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy. In this study, a series of weak acid drug derivatives were designed by a simplistic one step synthesis, which could be remotely loaded into liposomes by pH gradient method. Cabazitaxel (CTX) weak acid derivatives were selected to evaluate regarding its safety profiles, pharmacodynamics, and pharmacokinetics. CTX weak acid derivative liposomes were superior to Jevtana® in terms of safety profiles, including systemic toxicity, hematological toxicity, and potential central nerve toxicity. Specifically, it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus neurons. Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.

Redox-sensitive prodrug nanoassemblies based on linoleic acid-modified docetaxel to resist breast cancers

Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione (GSH) and reactive oxygen species (ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system, we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge linoleic acid (LA) and docetaxel (DTX). This mono thioether-linked conjugates (DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients. The mono thioether endowed the nanoparticles redox sensitivity resulting in specific release at the tumor tissue. Our studies demonstrated that the nanoassemblies had uniform particle size, high stability and fast release behavior. DTX-S-LA nanoassemblies outperformed DTX solution in pharmacokinetic profiles for it had longer circulation time and higher area under curve (AUC). Compared with DTX solution, the redox dual-responsive nanoassemblies had comparable cytotoxic activity. Besides, the antitumor efficacy was evaluated in mice bearing 4T1 xenograft. It turned out this nanoassemblies could enhance anticancer efficacy by increasing the dose because of higher tolerance. Overall, these results indicated that the redox sensitivity nanoassemblies may have a great potential to cancer therapy.

Desempenho de índices de gravidade na predição de complicações e mortalidade hospitalar de vítimas de trauma: estudo de coorte retrospectivo / Severity scores performance in predicting complications and hospital mortality of trauma victims: retrospective cohort study

Introdução: os índices de trauma são ferramentas metodológicas essenciais para estratificação da gravidade e previsão de desfechos de vítimas de trauma. Analisar o desempenho dos índices na predição de complicações e mortalidade hospitalar é fundamental para auxiliar no alcance e manutenção da qualidade da assistência. Objetivo: avaliar o desempenho de índices de gravidade na predição de complicações e mortalidade de vítimas de trauma durante a internação hospitalar. Método: estudo de coorte retrospectivo, realizado por meio da análise de prontuários de vítimas de trauma, com idade 16 anos, atendidas entre 2017 e 2018 em um hospital privado da cidade de São Paulo, Brasil. As variáveis analisadas contemplaram dados sociodemográficos, informações relacionadas ao evento traumático, ao atendimento hospitalar e à ocorrência de complicações (gerais, infecciosas e não infecciosas) e mortalidade, além dos índices de gravidade Injury Severity Score (ISS), New Injury Severity Score (NISS), Revised Trauma Score (RTS), modified Rapid Emergency Medicine (mREMS), Trauma and Injury Severity Score (TRISS), New Trauma and Injury Severity Score (NTRISS), TRISS-like, NTRISS-like, TRISS SpO2 e NTRISS-like SpO2. Os testes Exato de Fisher e Qui- Quadrado de Pearson, além de Receiver Operating Characteristic Curves e análise da área sob a curva (AUC), foram realizados, com nível de significância de 5%. Resultados: a casuística foi composta por 837 pacientes (62,0% homens; idade média 51,3 anos). As quedas (44,7%) prevaleceram na amostra. As médias dos índices RTS, mREMS, ISS e NISS foram: 7,7 (±0,7), 2,3 (±2,4), 7,9 (±6,7) e 10,7 (±9,2), respectivamente. Com exceção do TRISS SpO2 (87,3±16,0), a média de probabilidade de sobrevida prevista em todos os demais índices mistos foi superior a 96,0%. Aproximadamente 17,0% das vítimas tiveram complicação, com destaque às não infecciosas (n=128), especialmente delirium (n=41) e lesão renal aguda (n=34). A taxa de mortalidade hospitalar foi de 2,9%. Houve diferença significativa entre o desfecho clínico dos pacientes e a ocorrência de complicações em geral (p<0,001) e não infecciosas (p<0,001). Na análise do desempenho dos índices para cada tipo de complicação infecciosa e não infecciosa avaliada individualmente, observou-se que os valores preditivos positivos (VPP) foram sempre muito baixos, contraindicando a sua aplicação na prática clínica. Na predição de complicações em geral (n=141) e não infecciosas (n=128), o TRISS (AUC 0,793 e 0,787, respectivamente) e o NTRISS (AUC 0,792 e 0,783, respectivamente) apresentaram os melhores desempenhos, com aumento importante dos VPP. Para os desfechos complicações infecciosas e mortalidade, nenhum dos índices apresentou boa capacidade preditiva nessa amostra, dados os VPP baixos. Conclusão: O TRISS e o NTRISS apresentaram melhor desempenho na predição de complicações em geral e não infecciosas dos pacientes da amostra. Considerando que o TRISS é um índice reconhecido e aplicado mundialmente, sugere-se seu uso na predição desses desfechos em vítimas de trauma atendidas em instituição privada, cujos resultados podem auxiliar em estratégias de programas de prevenção, pautados no melhor custo-benefício e na segurança do doente.

Introduction: trauma scores are essential methodological tools to stratify the severity and to predict the outcomes of trauma victims. Analyzing the score performance in predicting complications and hospital mortality is fundamental to aid in achieving and maintaining the quality of care. Objective: to evaluate the performance of the severity scores in predicting the complications and mortality of trauma victims during hospitalization. Method: retrospective cohort study conducted by analysis of records of trauma victims, aging 16 years old, attended between 2017 and 2018 in a private hospital at São Paulo city, Brazil. The analyzed variables included sociodemographic data; information related to the trauma event, the hospital attendance, and the occurrence of complications (general, infectious, and noninfectious); and mortality; besides the severity scores Injury Severity Score (ISS), New Injury Severity Score (NISS), Revised Trauma Score (RTS), modified Rapid Emergency Medicine (mREMS), Trauma and Injury Severity Score (TRISS), New Trauma and Injury Severity Score (NTRISS), TRISS-like, NTRISS-like, TRISS SpO2, and NTRISS-like SpO2. Fisher's Exact Test and Pearson's Chi-Square Test, besides Receiver Operating Characteristic Curves and area the under curve analysis (AUC), were performed, with a 5% significance level. Results: the sample was composed by 837 patients (62.0% males; mean age of 51.3 years old). Falls (44.7%) prevailed in the sample. The mean RTS, mREMS, ISS, and NISS scores were: 7.7 (±0.7), 2.3 (±2.4), 7.9 (±6.7), and 10.7 (±9.2), respectively. Except for TRISS SpO2 (87.3±16.0), the mean survival probability predicted in all other mixed scores was higher than 96.0%. Approximately 17.0% of the victims presented a complication, highlighting the non-infectious ones (n=128), especially delirium (n=41) and acute kidney injury (n=34). The hospital mortality score was 2.9%. There was a significant difference between the clinical outcome of the patients and occurrence of general (p <0.001) and non-infectious (p <0.001) complications. In the score performance analysis individually assessed for each infectious and non-infectious complication, it was verified that the positive predictive values (PPV) were always very low, contraindicating their application in the clinical practice. In the prediction of general (n=141) and non-infectious (n=128) complications, TRISS (AUC of 0.793 and 0.787, respectively) and NTRISS (AUC of 0.792 and 0.783, respectively) presented the best performances, with a significant increase in PPV. For the outcomes infectious complications and mortality, no score presented good predictive capability in this sample, considering the low PPV. Conclusion: TRISS and NTRISS presented better performance in predicting general and non-infectious complications in the patients in the sample. Considering that TRISS is a recognized score that is applied worldwide, its use is suggested to predict such outcomes in trauma victims in private institutions, which results might aid in prevention program strategies, guided by the best costbenefit and the patient safety.

Exploration of gene functions for esophageal squamous cell carcinoma using network-based guilt by association principle

Gene networks have been broadly used to predict gene functions based on guilt by association (GBA) principle. Thus, in order to better understand the molecular mechanisms of esophageal squamous cell carcinoma (ESCC), our study was designed to use a network-based GBA method to identify the optimal gene functions for ESCC. To identify genomic bio-signatures for ESCC, microarray data of GSE20347 were first downloaded from a public functional genomics data repository of Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) between ESCC patients and controls were identified using the LIMMA method. Afterwards, construction of differential co-expression network (DCN) was performed relying on DEGs, followed by gene ontology (GO) enrichment analysis based on a known confirmed database and DEGs. Eventually, the optimal gene functions were predicted using GBA algorithm based on the area under the curve (AUC) for each GO term. Overall, 43 DEGs and 67 GO terms were gained for subsequent analysis. GBA predictions demonstrated that 13 GO functions with AUC>0.7 had a good classification ability. Significantly, 6 out of 13 GO terms yielded AUC>0.8, which were determined as the optimal gene functions. Interestingly, there were two GO categories with AUC>0.9, which included cell cycle checkpoint (AUC=0.91648), and mitotic sister chromatid segregation (AUC=0.91597). Our findings highlight the clinical implications of cell cycle checkpoint and mitotic sister chromatid segregation in ESCC progression and provide the molecular foundation for developing therapeutic targets.

Effects of macronutrients in mixed meals on postprandial glycemic response / 한국영양학회지

PURPOSE: The aim of study was to determine the effects of carbohydrate, fat, protein, and fiber contents on glycemic responses in a single food item or meal. METHODS: Glycemic responses were measured in 30 healthy young adults (17 males and 13 females) with various test foods, including rice, egg whites, bean sprouts, olive oil, noodles, prune, broccoli, Korean dishes, Western dishes, and salad dishes, etc. Test foods were designed to contain various carbohydrate, fat, protein, and fiber contents in single or mixed foods or dishes. After 12 hours of fasting, participants consumed test foods, and the glycemic response was measured for a subsequent 120 min (0, 15, 30, 60, 90, and 120 min). Three hundred and fifty three glycemic responses from 62 foods were collected. The incremental area under the curve (AUC) was calculated for each test food for each subject to examine glycemic responses. Statistical analysis was conducted to identify which macronutrient (carbohydrate, fat, protein and fiber) affected the AUC using a mixed model. RESULTS: Carbohydrates (β= 37.18, p < 0.0001) significantly increased while fat (β= −32.70, p = 0.0054) and fiber (β= −32.01, p = 0.0486) significantly reduced the glycemic response. CONCLUSION: It can be concluded that the glycemic response of a meal can be modified depending on the fat and fiber contents of ingredient foods, even though carbohydrate content is maintained.

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients

BACKGROUND: Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference. METHODS: Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. RESULTS: A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity. CONCLUSION: We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day.

Reference value range of pulse oximetry plethysmographic waveform parameters in the normal adults / 中华急诊医学杂志

Objective To Pulse oximetry saturation has been wildly used clinically.It has been reported that pulse oximetry plethysmographic waveform (POP) reflected the peripheral tissue perfusion.In this study,we parameterized POP,observed the value of POP parameters in normal adults,and established the normal reference value range.Methods A multi-center prospective descriptive study.Total of 1 019 adult volunteers with normovolemia from 7 cities were enrolled in this study.Sex,age,height,weight and pulse oximetry data in awake and spontaneous breathing under in quiet conditions in the room temperature were collected.POP parameters and perfusion index were analyzed using MATLAB 2012a software.The normal reference value ranges of POP parameters,including the amplitude of POP (Amp) and the area under the curve of POP (AUC),were formulated.Results Statistical differences of POP parameters were detected between men and women in the normal adult.The 95％ confidence reference value of POP parameters in normal population was as follows:Amp (104.8-2298.7) PVA and AUC (3265.8-6028.5) PVPGin total,Amp (129.4-2433.6) PVA and AUC (3319.0-5862.2) PVPG in male;Amp (89.5-2138.2) PVA and AUC (3163.9-5929.9) PVPG in female.Conclusions POP,including the amplitude of POP (Amp) and the area under the curve of POP (AUC),had normal reference value ranges in normal adults.

Evaluation of a Novel Glucose Area Under the Curve (AUC) Monitoring System: Comparison with the AUC by Continuous Glucose Monitoring

BACKGROUND: Management of postprandial hyperglycemia is a key aspect in diabetes treatment. We developed a novel system to measure glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET) for simple monitoring of postprandial glucose excursions. In this study, we evaluated the relationship between our system and continuous glucose monitoring (CGM) by comparing glucose AUC obtained using MIET with that obtained using CGM for a long duration. METHODS: Twenty diabetic inpatients wearing a CGM system were enrolled. For MIET measurement, a plastic microneedle array was applied to the skin as pretreatment, and hydrogels were placed on the pretreated area to collect interstitial fluid. Hydrogels were replaced every 2 or 4 hours and AUC was predicted on the basis of glucose and sodium ion levels. RESULTS: AUC predicted by MIET correlated well with that measured by CGM (r=0.93). Good performances of both consecutive 2- and 4-hour measurements were observed (measurement error: 11.7%±10.2% for 2 hours and 11.1%±7.9% for 4 hours), indicating the possibility of repetitive measurements up to 8 hours. The influence of neither glucose fluctuation nor average glucose level over the measurement accuracy was observed through 8 hours. CONCLUSION: Our system showed good relationship with AUC values from CGM up to 8 hours, indicating that single pretreatment can cover a large portion of glucose excursion in a day. These results indicated possibility of our system to contribute to convenient monitoring of glucose excursions for a long duration.

Epidemiology of heterogeneous vancomycin-intermediate Staphylococcus aureus from sterile body fluid specimens / 国际检验医学杂志

Objective To investigate the prevalence and molecular characteristic of heterogeneous‐ vancomycin intermediate Staphylococcus aureus(hVISA) among methicillin‐resistant Staphylococcus aureus (MRSA)strains isolated from sterile body fluid specimens from 2009 to 2013 in Huangzhou District People′s Hospital in Huanggang City .Methods The minimum inhibitory con‐centrations (MIC) of antibiotics was determined by agar dilution method .The hVISA strains were detected by population analysis profile/area under the curve method (PAP/AUC) .The staphylococcal cassette chromosome mec (SCCmec) ,multilocus‐sequence typing (MLST) ,accessory gene regulator (agr) and Staphylococcus aureus protein A(spa) typing of hVISA strains were detected using PCR method .Results 32 hVISA strains were detected among 285 MRSA strains ,the prevalence rate of hVISA was 11 .2% , and the detection rates of hVISA from 2009 to 2013 were 0 .0% ,6 .4% ,9 .0% ,14 .3% and 18 .8% ,respectively ,showed an increas‐ing trend .The main hVISA epidemic clone was ST239‐SCCmecIII‐ t030‐agrI type(28strains ,accounting for 87 .5% ) .Conclusion The detection rate of hVISA showed an increasing trend in the past 5 years ,should be paid attention to strictly control the utiliza‐tion of glycopeptide drugs .

Effects of antibiotic antitumor drugs on nucleotide levels in cultured tumor cells: an exploratory method to distinguish the mechanisms of antitumor drug action based on targeted metabolomics

Nucleotide pools in mammalian cells change due to the influence of antitumor drugs, which may help in evaluating the drug effect and understanding the mechanism of drug action. In this study, an ion-pair RP-HPLC method was used for a simple, sensitive and simultaneous determination of the levels of 12 nucleotides in mammalian cells treated with antibiotic antitumor drugs (daunorubicin, epirubicin and dactinomycin D). Through the use of this targeted metabolomics approach to find potential biomarkers, UTP and ATP were verified to be the most appropriate biomarkers. Moreover, a holistic statistical approach was put forward to develop a model which could distinguish 4 categories of drugs with different mechanisms of action. This model can be further validated by evaluating drugs with different mechanisms of action. This targeted metabolomics study may provide a novel approach to predict the mechanism of action of antitumor drugs.

Pharmacokinetic aspects and in vitro-in vivo correlation potential for lipid-based formulations

Lipid-based formulations have been an attractive choice among novel drug delivery systems for enhancing the solubility and bioavailability of poorly soluble drugs due to their ability to keep the drug in solubilized state in the gastrointestinal tract. These formulations offer multiple advantages such as reduction in food effect and inter-individual variability, ease of preparation, and the possibility of manufacturing using common excipients available in the market. Despite these advantages, very few products are available in the present market, perhaps due to limited knowledge in the in vitro tests (for prediction of in vivo fate) and lack of understanding of the mechanisms behind pharmacokinetic and biopharmaceutical aspects of lipid formulations after oral administration. The current review aims to provide a detailed understanding of the in vivo processing steps involved after oral administration of lipid formulations, their pharmacokinetic aspects and in vitro in vivo correlation (IVIVC) perspectives. Various pharmacokinetic and biopharmaceutical aspects such as formulation dispersion and lipid digestion, bioavailability enhancement mechanisms, impact of excipients on efflux transporters, and lymphatic transport are discussed with examples. In addition, various IVIVC approaches towards predicting in vivo data from in vitro dispersion/precipitation, in vitro lipolysis and ex vivo permeation studies are also discussed in detail with help of case studies.

Comparison of different scoring systems evaluating short-term prognosis of patients with hepatitis B associated acute hepatic failure / 实用医学杂志

Objective To assessment short-term prognosis in patients with acute on chronic liver failure , several scoring systems were compared. Methods Two hundred and sixteen patients with acute on chronic liver failure were divided into survival group and death group according to the results of 90 days after admission.CTP , MELD,APACHEⅡ, SOFA and SMSVH score were calculated.After ROC curves were performed ,the areas under the curves of these scoring systems were compared. Results The areas under the ROC curves of MELD, APACHEⅡ, SOFA, CTP and SMSVH were 0.88, 0.76, 0.89,0.79and 0.69,respectively. The areas under the curves of SOFA and MELD were larger than the APACHEⅡ, CTP and SMSVH (P0.05). The area under the curve of CTP was larger than the APACHEⅡ, but there was no statistically significant difference (P > 0.05). The area under the curve of SMSVH were less than 0.7. Conclusions The SOFA, MELD,CTP and APACHEⅡcan predict the short-term prognosis of acute on chronic liver failure. The SOFA and MELD are the best scoring systems.CTP,APACHEⅡ are better than SMSVH. SMSVH fail to predict the prognosis of acute on chronic liver failure.

Effects of xylooligosaccharide-sugar mixture on glycemic index (GI) and blood glucose response in healthy adults / 한국영양학회지

PURPOSE: The objective of this study was to investigate the effects of xyloologosaccharide (XOS)-sugar mixture on glycemic index (GI) and blood glucose in human subjects. METHODS: Randomized double-blind cross-over studies were conducted to examine the effect of sucrose with 14% xyloologosaccharide powder (Xylo 14) and sucrose with 20% xylooligosaccharide powder (Xylo 20) on GI and postprandial glucose response at 15, 30, 45, 60, 90, and 120 min. RESULTS: GIs of Xylo 14 and Xylo 20 were 60.0 +/- 23.5 classified within medium GI range, and 54.3 +/- 17.7 within low GI range, respectively. Xylo 14 and Xylo 20 showed significantly lower area under the glucose curve (AUC) for 0-15 min (p = 0.0113), 0-30 min (p = 0.0004), 0-45 min (p < 0.0001), 0-60 min (p < 0.0001), 0-90 min (p < 0.0001), and 0-120 min (p = 0.0001). In particular, compared with glucose, the blood glucose levels of Xylo 14 and Xylo 20 were significantly lower at every time point between 15 and 120 min. CONCLUSION: The results of this study suggested that Xylo 14 and Xylo 20 had an acute suppressive effect on GI and the postprandial glucose surge.

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

BACKGROUND/AIMS: The dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT). METHODS: Two sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT. RESULTS: In the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively. CONCLUSIONS: A reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.

La importancia de los parámetros farmacocinéticos y farmacodinámicos en la prescripción de antibióticos / The importance of pharmacokinetic and pharmacodynamic parameters in antibiotic prescription

En el tratamiento del enfermo grave, la elección del antibiótico y su dosificación están determinados por factores relacionados al microorganismo, al fármaco y a las condiciones de salud del paciente. La relación de algunos parámetros farmacocinéticos y farmacodinámicos como la concentración máxima alcanzada (Cmáx), el área bajo la curva (ABC) y la concentración mínima inhibitoria (MIC) son determinantes en la toma de decisiones para seleccionar el fármaco y su posología. De acuerdo a estos parámetros, los antibióticos se clasifican en dependientes de tiempo y dependientes de concentración. Los primeros (betalactámicos, glucopéptidos) pueden requerir ajustes en el tiempo de infusión y los dependientes de concentración (aminoglucósidos, fluoroquinolonas) se basan en la Cmáx/MIC.

In the treatment of critically ill patient, antibiotic choice and dosage are influenced by factors related to the pathogen, the drug and the patient's health status. The relationship of pharmacokinetic and pharmacodynamic parameters such as maximum concentration (Cmax), area under the curve (AUC) and minimum inhibitory concentration (MIC) can assist in decision-making to choose the drug and the correct dose. According to these parameters, antibiotics are classified into time-dependent and concentration-dependent. The first ones (betalactams, glycopeptides) could require adjustments in the infusion time; while concentration-dependent ones (aminoglycosides, fluoroquinolones) are based on the Cmax / MIC.