Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice

Chia-Che Tsai1, Chih-Hsien Chang1, Liang-Cheng Chen1, Ya-Jen Chang1, Keng-Li Lan2, Yu-Hsien Wu1, Chin-Wei Hsu1, I-Hsiang Liu1, Chung-Li Ho1, Wan-Chi Lee1, Hsiao-Chiang Ni1, Tsui-Jung Chang1, Gann Ting3, Te-Wei Lee11Institute of Nuclear Energy Research, Taoyuan, 2Cancer Center, Taipei Veterans General Hospital, Taipei, 3National Health Research Institutes, Taipei, Taiwan, ROCBackground: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of 188Re-labeled nanoliposomes (188Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated.Methods: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM® computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared.Results: In biodistribution, the highest uptake of 188Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of 188Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of 188Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the 188Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with 188Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU).Conclusion: The use of 188Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that 188Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.Keywords: biodistribution, dosimetry, 5-fluorouracil, micro-SPECT/CT, 188Re-liposome

High-resolution spatial and genomic characterization of coral-associated microbial aggregates in the coral Stylophora pistillata

Bacteria commonly form aggregates in a range of coral species [termed coral-associated microbial aggregates (CAMAs)], although these structures remain poorly characterized despite extensive efforts studying the coral microbiome. Here, we comprehensively characterize CAMAs associated with Stylophora pistillata and quantify their cell abundance. Our analysis reveals that multiple Endozoicomonas phylotypes coexist inside a single CAMA. Nanoscale secondary ion mass spectrometry imaging revealed that the Endozoicomonas cells were enriched with phosphorus, with the elemental compositions of CAMAs different from coral tissues and endosymbiotic Symbiodiniaceae, highlighting a role in sequestering and cycling phosphate between coral holobiont partners. Consensus metagenome--assembled genomes of the two dominant Endozoicomonas phylotypes confirmed their metabolic potential for polyphosphate accumulation along with genomic signatures including type VI secretion systems allowing host association. Our findings provide unprecedented insights into Endozoicomonas-dominated CAMAs and the first direct physiological and genomic linked evidence of their biological role in the coral holobiont

The Atacama Large Millimeter/submillimeter Array (ALMA) Band-1 Receiver

The Atacama Large Millimeter/submillimeter Array(ALMA) Band 1 receiver covers the 35-50 GHz frequency band. Development of prototype receivers, including the key components and subsystems has been completed and two sets of prototype receivers were fully tested. We will provide an overview of the ALMA Band 1 science goals, and its requirements and design for use on the ALMA. The receiver development status will also be discussed and the infrastructure, integration, evaluation of fully-assembled band 1 receiver system will be covered. Finally, a discussion of the technical and management challenges encountered will be presented

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Acute Effects of Dual-chamber Pacing on the Left Ventricular Systolic Function and Relaxation in Patients with Advanced AV Block and Sick Sinus Syndrome

Abnormal activation of the ventricles via right ventricular apical pacing deteriorates cardiac function, which may explain the increased mortality of patients with congestive heart failure receiving permanent pacemakers. We hypothesized that pacing at alternative sites may cause less detrimental effects on the cardiac function. Methods: Five symptomatic patients with either advanced AV block (n = 4) or sick sinus syndrome with normal left ventricular (LV) function (n = 1) were studied. During cardiac catheterization, LV pressure was recorded with a high-fidelity catheter-tipped transducer. Baseline rhythms were sinus rhythm or VVI pacing. Sequential VDD pacing with variable AV intervals was performed at the right ventricular apex (RVA), right ventricular septum (RVS), right ventricular outflow tract (RVOT) and coronary sinus (CS). LV systolic function was assessed by calculating dP/dtmax and LV diastolic function was indexed by calculating the exponential isovolumic relaxation constant (Tau). Percentage changes (mean ± SE) from baseline to pacing were measured. Results: RVA pacing reduced dP/dtmax (-0.8 ± 8.4%) and prolonged Tau (7.0 ± 5.6%); RVS pacing enhanced dP/dtmax (20.7 ± 15.3%) and shortened Tau (-10.4 ± 9%); RVOT pacing reduced dP/dtmax (-8.0 ± 20.0%) and shortened Tau (-6.0 ± 12.2%); CS pacing reduced dP/dtmax (-11.7 ± 13.0%) and prolonged Tau (10.5 ± 11.9%). Our results demonstrated that different pacing sites have different effects on LV contractility and relaxation in patients with normal LV function. Conclusion: Since pacing at the RVS preferably increased LV dP/dtmax and shortened Tau, it may be a better alternative than the RVA

A Novel Intensity-Based Approach to Increasing Prefrontal Cerebral Oxygenation by Walking Exercise

Regional cerebral blood flow (rCBF) increases after moderately intense exercise and is significantly correlated with cognitive function. However, no intensity-based physiological indicator for enhancing rCBF during low- to-moderate-intensity exercise has been proposed. The purpose of this study was to develop a physiological indicator housed in a wearable device to determine whether low-to-moderate intensity walking can increase rCBF. A cross-sectional study with four parallel arms was performed. Each of 114 participants was randomly assigned to either the moderate, low-to-moderate, low, or very low walking intensity groups. A novel dynamic cardiac force meter (CFM) was used to quantify walking intensity. Heart rate and hemoencephalography (HEG) were measured during each phase of the session. Compared to baseline, HEG significantly increased in both the submaximal exercise and recovery phases in members of the low-to-moderate intensity group but not the very low intensity group. Low-to-moderate intensity walking improves prefrontal cerebral blood oxygenation. The present results demonstrate the usefulness of a dynamic CFM housed in a wearable device for quantifying the intensity of walking exercise aimed at increasing prefrontal blood oxygenation. The results of the study may help guide further development of exercise strategies for brain disease patients and the ageing population

A Novel Intensity-Based Approach to Increasing Prefrontal Cerebral Oxygenation by Walking Exercise

Regional cerebral blood flow (rCBF) increases after moderately intense exercise and is significantly correlated with cognitive function. However, no intensity-based physiological indicator for enhancing rCBF during low- to-moderate-intensity exercise has been proposed. The purpose of this study was to develop a physiological indicator housed in a wearable device to determine whether low-to-moderate intensity walking can increase rCBF. A cross-sectional study with four parallel arms was performed. Each of 114 participants was randomly assigned to either the moderate, low-to-moderate, low, or very low walking intensity groups. A novel dynamic cardiac force meter (CFM) was used to quantify walking intensity. Heart rate and hemoencephalography (HEG) were measured during each phase of the session. Compared to baseline, HEG significantly increased in both the submaximal exercise and recovery phases in members of the low-to-moderate intensity group but not the very low intensity group. Low-to-moderate intensity walking improves prefrontal cerebral blood oxygenation. The present results demonstrate the usefulness of a dynamic CFM housed in a wearable device for quantifying the intensity of walking exercise aimed at increasing prefrontal blood oxygenation. The results of the study may help guide further development of exercise strategies for brain disease patients and the ageing population