Administration of Jerusalem artichoke reduces the postprandial plasma glucose and glucose-dependent insulinotropic polypeptide (GIP) concentrations in humans.

Background: The consumption of Jerusalem artichoke has multiple beneficial effects against diabetes and obesity. Objective: The aim of this study was to determine the effect of a single administration of Jerusalem artichoke tubers on postprandial glycemia and the concentrations of incretin hormones in humans. Method: Grated Jerusalem artichoke was administered prior to a meal (Trial 1; white rice for prediabetic participants, n = 10). Dose-dependent effect of Jerusalem artichoke (Trial 2; white rice for prediabetic participants, n = 4) and effect prior to the fat-rich meal were also investigated (Trial 3; healthy participants, n = 5) in this pilot study. Circulating glucose, insulin, triglyceride, glucagon, active glucagon-like peptide-1 (GLP-1), and active glucose-dependent insulinotropic polypeptide (GIP) concentrations were subsequently measured in all the trials. Results: Jerusalem artichoke significantly reduced the glucose and GIP concentrations after the consumption of either meal in Trial 1 and Trial 3, whereas there were no differences in the insulin, glucagon, and active GLP-1 concentrations. Also, there was no significant difference in the triglyceride concentration after the ingestion of the fat-rich meal in Trial 3. The glucose and GIP-lowering effects were dose-dependent, and the consumption of at least 100 g of Jerusalem artichoke was required to have these effects in Trial 2. Conclusion: This study demonstrates that a single administration of Jerusalem artichoke tubers reduces postprandial glucose and active GIP concentrations in prediabetic and healthy individuals.

Catheter failure in the administration of hyperosmotic drugs through a peripheral vein and vascular selection: A retrospective cohort study.

This study aimed to determine whether the placement of a peripheral intravenous catheter (PIVC) in the cephalic vein of the forearm could prevent PIVC failure in patients receiving hyperosmotic drugs through the peripheral vein. This retrospective cohort study included patients aged ≥ 20 years who had received infusion therapy via a PIVC in our institution between July and November 2017. Patients were divided into groups according to PIVC insertion into the cephalic, basilic, and medial veins. PIVCs used to administer drugs with osmotic pressure ratios > 2.0 were included. The primary outcome was survival time to catheter failure. Catheter failure was defined as accidental and unplanned catheter removal. We set the cephalic vein and other veins, including the medial and basilic veins, in the forearm as cohort groups. We used the Kaplan-Meier survival curves to compare the time until catheter failure in the cohort groups. The Cox proportional hazard models were fitted, and the hazard ratios were calculated. A total of 46 catheters with hyperosmotic agents were included in the analysis. Catheter failure was observed in 25 (54.3%) cases. Time to catheter failure in patients receiving high-dose drugs via the cephalic vein was significantly longer than that in the other two groups (p < 0.01). Thus, the cephalic vein, which has a high blood flow, is the ideal site of PIVC insertion in patients receiving high drug concentrations to prevent catheter failure.

Modeling for Change of Daily Nurse Calls After Surgery in an Orthopedics Ward Using Bayesian Statistics.

Nurse call data may be used to evaluate the quality of nursing. However, traditional frequency-based statistics may not easily apply to nurse calls due to the large individual variability and daily call changes. We intended to propose a probabilistic modeling of nurse calls based on Bayesian statistics. We constructed the model including nurse call daily changes, individual variability, and adjustment according to characteristics (age and sex). Nurse call differences after surgery were analyzed based on data from the orthopedic ward from April 2014 to October 2017. Results show that there were differences in nurse calls from day 1 to day 10 after surgery between patients who had undergone orthopedic surgery and those who had undergone other surgeries such as tumor surgery. Furthermore, there were differences in nurse calls from day 1 to day 8 after surgery between patients who used extra pain relief medicine and those who did not. Although the analysis required multiple comparisons regarding daily nurse call changes and fixed data samples per day, our approach using Bayesian statistics could detect the periods and significant differences. This indicates that our nurse call modeling based on Bayesian statistics may be used to analyze nurse call changes.

Bayesian statistic model for nurse call data considering time-series, individual patient variabilities and massive zero-count call data.

Analysis of nurse call data is important to evaluate nursing management, because nurse calls reflect the fundamental demand of patients. However, the nurse call data include time-series properties and individual patient variabilities. In addition, the calls do not necessarily follow the common single distributions such as normal and Poisson distribution. These characteristics of the nurse call data cause the difficulty of applying traditional frequent statistics. To resolve this problem, we introduced Bayesian statistics and proposed a model including three elements: 1) transition, which represents time-series change of nurse calls, 2) random effect, which handles individual patient variabilities, and 3) zero inflated Poisson distribution, which is suitable for nurse call data including massive zero data. To evaluate the model, nurse call dataset containing total 3324 patients in orthopedics ward was used and the differences of nurse calls between the patients who had undergone orthopedics surgery and those who had undergone other surgeries were analyzed. The result in comparing all combinations of elements suggested that our model including all elements was the most fitting model to the dataset. In addition, the model could detect longer duration of nurse call difference existence than the other models. These results indicated that our proposed model based on Bayesian statistics may contribute to analyzing nurse call dataset.

Innovative next-generation monoclonal antibody purification using activated carbon: A challenge for flow-through and column-free processes.

Activated carbon (AC) is a porous solid with a larger surface area and lower cost than chromatography resins. AC has been used in the field of biopharmaceutical manufacturing for plasma-derived products and recombinant monoclonal antibodies (mAb). In our previous study, AC was employed in the purification process of therapeutic mAb as a replacement for Protein A affinity chromatography (PrA). In addition, we designed an all flow-through purification process using AC. In these investigations, greater effective clearance of high-molecular-weight species (HMW), low-molecular-weight species (LMW), host cell proteins (HCP), and DNA was observed compared to that of the conventional Protein A platform purification process. However, it was revealed that mAb recovery from the AC step was lower than that from the PrA step. In this work, to improve mAb recovery from the AC step while maintaining the effective removal of impurities, a pretreatment procedure conducted prior to the AC treatment was investigated. We found that both an ultrafiltration/dilution and reduction in the conductivity of the filtered cell culture supernatant after acid precipitation could improve both the impurity clearance and mAb recovery from the AC treatment. From the obtained results, we designed a two-step purification process in which AC treatment is followed by either cation exchange column chromatography or anion exchange column chromatography, and we compared this against the Protein A platform purification process. Excellent impurity clearance was achieved, even in the one-column process. Furthermore, we designed an innovative column-free flow-through purification process based on acid precipitation, clarification, ultrafiltration/dilution, and the implementation of an AC filter membrane and an anion exchange chromatography membrane. With this process in the pilot-scale, HCP level can be reduced to below 10 ng/mg, and HMW and LMW can be removed to below 1% while improving mAb recovery. From these results, it is strongly expected that AC is a promising candidate for the next generation of mAb purification processes to improve the economy and efficiency of the process.

Monoclonal antibody purification using activated carbon as a replacement for Protein A affinity chromatography.

Activated carbon (AC) is a porous solid with a higher surface area and a lower cost than chromatography resins. AC is widely used in the pharmaceutical field in applications such as the manufacturing of low-molecular and hematological drugs and as a treatment for oral poisoning and hemocatharsis. In this work, AC was employed in the purification process of therapeutic monoclonal antibodies (mAb). After screening several kinds of ACs, we investigated the selected AC used in a flow-through mode (with impurities binding) and as a replacement for Protein A affinity chromatography (PrA). The recovery, purity, and clearance of the impurities were examined compared with those obtained from the Protein A platform purification process (PrA followed by anion exchange chromatography (AEX) and cation exchange chromatography (CEX)). Comparable clearance of impurities, high-molecular-weight species (HMW), low-molecular-weight species (LMW), host cell proteins (HCP), and DNA were observed in the purification processes, which were AC followed by AEX and CEX. In addition, we designed all flow-through processes using AC. Effective HMW, LMW, and HCP clearance were also obtained in this manner. From these results, it is expected that AC can be applied to industrial mAb purification as an alternative to PrA to improve process economy.

Developmental disorders and altered gene expression in the tropical clawed frog (Silurana tropicalis) exposed to 17α-ethinylestradiol.

Several endocrine-disrupting chemicals with estrogenic activity can affect sexual development and reproduction in aquatic wildlife. The occurrence of oocytes in the testis (testis-ova) is one reproductive disorder and can be used as a valid endpoint when studying disruptive effects of estrogenic chemicals. To elucidate the molecular basis of testis-ova induction, we conducted gene expression analysis in the gonads of Silurana tropicalis exposed to 0, 3, 10 and 30 ng l(-1) 17α-ethinylestradiol (EE2) from 2 days after fertilization to the juvenile stage (14 weeks after fertilization). The frequencies of testis-ova induction or male to female sex-reversal of the gonads increased in an EE2 dose-dependent manner. Microarray analysis showed that expressions of a large number of genes were significantly changed by EE2 exposure. Genes including egg envelope composition (zp4, zpax, zpc, zp3.2 and egg cortical granule lectin), 42S particle genes (42Sp50, 42Sp43 and 42Sp48) and regulation of female germ cells (figla) are associated with the testis-ova and sex-reversal situation in the gonads. Of those, expression of zpc and 42Sp50 genes is associated with testis-ova. Thus, we propose that these genes are useful biomarkers for toxicological research in amphibians developmentally exposed to estrogenic chemicals.

Application of metamorphosis assay to a native Japanese amphibian species, Rana rugosa, for assessing effects of thyroid system affecting chemicals.

The aims of this study were to assess the utility of a metamorphosis assay for detecting thyroid hormone-disrupting chemicals using Rana rugosa, a domestic frog species in Japan, and to compare species differences in sensitivity to thyroxine (T(4)) and propylthiouracil (PTU) among R. rugosa, Xenopus laevis and Xenopus (Silurana) tropicalis. Tadpoles of R. rugosa (TK stages III/IV) were exposed to standard test chemicals for acceleration (T(4)) and inhibition (PTU) of metamorphosis for 28 days in semi-static condition and total body length and developmental stage (TK stage) were recorded every week. T(4) (0.61 and 2.24 microg/L in actual concentrations) and PTU (19.73, 76.83, and 155.67 mg/L in actual concentrations) induced significant acceleration and inhibition of metamorphosis, respectively. The present results indicate that the metamorphosis assay is successfully applied to the domestic frog species, R. rugosa, suggesting this assay can be used for the assessment of chemicals on ecological impacts in wild frog species.

Effect of atrazine on metamorphosis and sexual differentiation in Xenopus laevis.

There is a growing international concern that commonly used environmental contaminants have the potential to disrupt the development and functioning of the reproductive system in amphibians. One such chemical of interests is the herbicide atrazine. Effects of atrazine on sex differentiation were studied using wild-type Xenopus laevis tadpoles and all-ZZ male cohorts of X. laevis tadpoles, produced by mating wild-type ZZ male to sex-reversed ZZ male (female phenotype). Stage 49 tadpoles were exposed to 0.1-100 ppb atrazine or 0.27 ppb (1 nM) 17beta-estradiol (E(2)) until all larvae completed metamorphosis (stage 66). Metamorphosis, gonadal morphology and histology, CYP19 (P450 aromatase) mRNA induction, and hepatic vitellogenin (VTG) induction were investigated. Effects of atrazine on VTG-induction were also assessed in vitro in primary-cultured X. laevis hepatocytes. Atrazine had no effect on metamorphosis of developing wild-type or all-male X. laevis larvae. Statistical increase in female ratios was observed in 10 and 100 ppb atrazine groups in comparison with control group. While no hermaphroditic froglet was observed in all atrazine groups. In ZZ males, sex reversal was induced by 0.27 ppb E(2), but not by atrazine at concentrations of 0.1 and 1.0 ppb. In addition, neither P450 aromatase mRNA in the gonad nor hepatic VTG were induced by atrazine. Furthermore, VTG was not induced by 1000 ppb atrazine in primary-cultured hepatocytes. Our results indicate that female ratios in developing X. laevis tadpoles were increased by 10 and 100 ppb atrazine under the present experimental conditions. While the other endpoints showed no effect in the range of 0.1-100 ppb atrazine. These results suggest that effect of atrazine on sexual differentiation was not caused by estrogenic action and has no induction ability of P450 aromatase gene in gonad.

Development of metamorphosis assay using Silurana tropicalis for the detection of thyroid system-disrupting chemicals.

The West African clawed frog (Silurana tropicalis), which resembles the South African clawed frog (Xenopus laevis), but is somewhat smaller, has a diploid genome and a shorter generation time. Therefore, S. tropicalis has the potential for use as a new model in ecotoxicology. We demonstrated a S. tropicalis metamorphosis assay based on Xenopus Metamorphosis Assay (XEMA) using 1 microg/L thyroxine (T4) and 75 mg/L propylthiouracil (PTU). Tadpoles at developmental stages 48-50 were exposed to chemicals for 28 days and total body length, developmental stage, and hind limb length were recorded every 7 days. Significant differences in developmental stage and total body length were found for both T4 and PTU after 7-day exposure, which were similar to the results of the XEMA ring-test using the same chemicals. Moreover, in the present study, we measured hind limb length as a new endpoint of thyroid axis. Significant differences in the hind limb length were encountered in both T4 and PTU treatments after 7 days of exposure. These results suggest that S. tropicalis can be used in a XEMA-like protocol to detect agonist and antagonist effects of chemicals on the thyroid system. Hind limb length is also a suitable endpoint in such protocols. A new test protocol detecting both thyroid disruption and reproductive effects of chemicals using S. tropicalis should be established in the near future.

All ZZ male Xenopus laevis provides a clear sex-reversal test for feminizing endocrine disruptors.

We investigated the possibility of using all ZZ male Xenopus laevis tadpoles produced by mating normal ZZ males with feminized ZZ males to detect estrogenic chemical activity. We examined the effects of 17beta-estradiol (E2) on sex differentiation by treating NF stage 49/50 to stage 57 tadpoles with 0.1, 1, 10, and 20 nM E2 for 4 weeks. Following this, the tadpoles were allowed to develop in clean water until the animals reached stage 66. Increased developmental abnormalities and mortality were not observed in all E2-exposed groups during metamorphosis. Feminization of gonads was detected at all E2 concentrations, whereas nonexposed controls developed testes. Morphological and histological analyses showed that feminized gonads were ovaries. Five and one hermaphroditic frogs were found in the 0.1 and 1 nM E2 groups, respectively, showing testicular as well as ovarian regions within one gonad. These results indicate that phenotypically normal females can be produced from genetic males and demonstrate the utility of a sex-reversal test based on all ZZ males for examining in vivo effects of chemicals with estrogenic activity. The testing of all ZZ male tadpoles might be a useful tool for assessment of feminizing compounds not only estrogenic substance.