Development of a Colon Delivery Capsule and the Pharmacological Activity of Recombinant Human Granulocyte Colony-stimulating Factor (rhG-CSF) in Beagle Dogs

A peroral dosage form was examined to deliver recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the colon in beagle dogs. A new gelatin capsule with its inside surface coated with ethylcellulose was prepared for this purpose. RhG-CSF was dissolved with propylene glycol and was filled in the capsule. Several kinds of ethylcellulose-gelatin capsules with an ethylcellulose layer of thickness 46 to 221 mm were used. The capsule was filled with propylene glycol solution containing fluorescein as an absorption marker, castor oil derivative and citric acid. The hardness of the capsule was tested after the gelatin layer was dissolved using a hardness tester and was dependent on the thickness of the ethylcellulose layer of the capsule. The time, T_max, at which plasma fluorescein level reaches its maximum following oral administration of ethylcellulose capsules was used as a parameter for the in-vivo disintegration time of the ethylcellulose capsule into the colon. Capsules of thickness 84 mm with a T_max of 4–6 h were filled with rhG-CSF solution containing fluorescein and were administered to dogs. After administration, blood samples were collected for 96 h and the blood total leucocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The maximum BTL count appeared at 10 h then gradually decreased and returned to its normal level at 48 h. These results suggest the usefulness of ethylcellulose capsules for the delivery of rhG-CSF to the colon and the possibility of a new oral rhG-CSF dosage form has been elucidated.     

Clinical Structural Anatomy of the Inferior Pyramidal Space Reconstructed Within the Cardiac Contour Using Multidetector‐Row Computed Tomography

Although many studies have described the detailed anatomy of the inferior pyramidal space, it may not be easy for cardiologists who have few chances to study cadaveric hearts to understand the correct morphology of the structure. The inferior pyramidal space is the part of extracardiac fibro‐adipose tissue wedging between the 4 cardiac chambers from the diaphragmatic surface of the heart. Many cardiologists have interests in pericardial adipose tissue, but the inferior pyramidal space seems to have been neglected. A number of important structures, including the coronary sinus, atrioventricular node, atrioventricular nodal artery, membranous septum, muscular atrioventricular sandwich (previously called the “muscular atrioventricular septum”), atrial septum, ventricular septum, aortic valvar complex, mitral valvar attachment, and tricuspid valvar attachment are associated with the inferior pyramidal space. We previously revealed its 3‐dimensional live anatomy using multidetector‐row computed tomography. Moreover, the 3‐dimensional understanding of the anatomy in association with the cardiac contour is important from the viewpoints of clinical cardiac electrophysiology. The purpose of this article is to demonstrate extended findings regarding the clinical structural anatomy of the inferior pyramidal space, which was reconstructed in combination with the cardiac contour using multidetector‐row computed tomography, and discuss the clinical implications of the findings.     

Performance evaluation of newly developed portable aerosol sizers used for nanomaterial aerosol measurements

Nanomaterial particles exhibit a wide range of sizes through the formation of agglomerates/aggregates. To assess nanomaterial exposure in the workplace, accurate measurements of particle concentration and size distribution are needed. In this study, we evaluated the performance of two recently commercialized instruments: a portable scanning mobility particle sizer (SMPS) (NanoScan, TSI Inc.), which measures particle size distribution between 10 and 420 nm and an optical particle sizer (OPS, TSI Inc.), which measures particle size distribution between 300 and 10,000 nm. We compared the data measured by these instruments to conventional instruments (i.e., a widely used laboratory SMPS and an optical particle counter (OPC)) using nano-TiO₂ powder as test aerosol particles. The results showed obvious differences in the size distributions between the new and old SMPSs. A possible reason for the differences is that the cyclone inlet of the new SMPS (NanoScan) acted as a disperser of the weakly agglomerated particles and consequently the concentration increased through the breakup of the agglomerates. On the other hand, the particle concentration and size distributions measured by the OPS were similar to the OPC. When indoor aerosol particles were measured, the size distribution measured by the NanoScan was similar to the laboratory SMPS.     

Minimal invasiveness and effectivity of subinguinal microscopic varicocelectomy: a comparative study with retroperitoneal high and laparoscopic approaches

AIM: The standard management of varicocele repair is the subject of ongoing controversy. We retrospectively evaluated three surgical methods of varicocele treatment to determine the minimally invasive and most effective procedure. METHODS: We performed 144 varicocelectomies on infertile patients with left clinical varicocele. Of the patients, 50 were treated with retroperitoneal high ligation under lumbar anesthesia, 33 with laparoscopic ligation under general anesthesia, and 61 with subinguinal microscopic ligation under local anesthesia. Operative time, hospital days, and clinical outcomes were compared between these techniques. RESULTS: The operating time and hospitalization period required for subinguinal microscopic ligation was signi fi cantly shorter compared to those for the other procedures. All patients treated with subinguinal microscopic ligation could achieve normal activity as soon as they returned to their rooms. Postoperative complications were observed in fi ve (10.0%) cases treated with high ligation and three (9.1%) laparoscopic cases, but were not observed after the subinguinal procedure. There were six cases (12.0%) of recurrence in the high ligation group and six (6.1%) in the laparoscopic group, but none in the subinguinal group. Sperm density was signi fi cantly improved in all procedures postoperatively, but sperm motility was not improved. The two-year pregnancy rate calculated by the Kaplan-Meier method was 35.8% for high ligation, 40.4% for laparoscopic ligation and 50.9% for subinguinal microscopic ligation, although there were no statistical differences between the three groups. CONCLUSION: We concluded that subinguinal microscopic varicocelectomy could be a minimally invasive procedure compared to the other two techniques and a worthy method for treating male infertility due to clinical varicocele.     

Right atrial contractile performance in patients with myocardial infarction

To evaluate right atrial (RA) contractile performance in patientswith myocardial infarction, we validated a cineangiographicmethod of RA volume measurement, and investigated RA volumechange in ‘normal’ individuals and patients witha previous myocardial infarction. Sixteen silicone rubber RAcasts made from human cadavers were filmed in the postero-anteriorand left lateral projections. The cast volumes calculated followingSimpson's rule were in good agreement with those measured bywater replacement (r=0.992, P<.001). At cardiac catheterization,biplane RA cineangiography was performed in 19 ‘normal’individuals (N group), in 14 patients with a previous antero-septalinfarction (AM1 group) and in seven patients with apreviousinferior infarction (IMI group). The RA volume-time curve wasconstructed at 20–40 ms intervals for one cardiac cycle.RA volume at the beginning of the atrial contraction (RAVd),which was defined as the ‘preload’ of the RA, tendedto be larger in both the AMI and IMI groups compared with ‘normal’individuals. The RA ejection volume was significantly largerin both the AMI (18.4 ± 2.1 ml. m^–2, P <0.01)and IMI groups (l9.4±2.8, P<0.01) than in the N group(14.5±1.9), even for a comparable level of RAVd (rangefrom 26 to 36ml.m^–2) (18.6±2.1, P<0.01, 18.2±2.0,P<0.01, 14.7±1.9, respectively). These results suggestthat RA contraction increases in patients with myocardial infarctionby increasing both the ‘preload’ and ‘contractility’of the RA.     

The relationship among sleep reactivity,job-related stress,and subjective cognitive dysfunction: a cross-sectional study using path analysis

Insomnia, job-related stress, and cognitive dysfunction affect the mental health of workers. However, the relationships among sleep reactivity, job-related stress, and subjective cognitive dysfunction in workers remains not fully understood. Therefore, this study seeks to investigate the relationships among these variables in Japanese adult workers. In total, 536 adult workers in Japan were evaluated using the Japanese version of Ford Insomnia Response to Stress Test, Brief Job Stress Questionnaire, and Cognitive Complaints in Bipolar Disorder Rating Assessment to assess sleep reactivity, job-related stress, and subjective cognitive function, respectively. Path analysis was also carried out. The results of the path analysis showed that sleep reactivity significantly influenced on subjective cognitive dysfunction directly and indirectly via job stressors and stress reaction. Our results may not be generalizable to underage workers because only adult workers were included, which is a limitation of this study. The results of the present study suggest that job-related stress mediates the effect of sleep reactivity on subjective cognitive dysfunction in Japanese adult workers. This underscores the need to evaluate the mediating effect of job-related stress in addressing the subjective cognitive dysfunction associated with insomnia in workers.     

Exposure assessment of nanotitanium oxide powder handling using real-time size-selective particle number concentration measurements and X-ray fluorescence spectrometry —The possibility of exposure to nonagglomerated nanomaterials during the handling of nanomaterial fine powders—

In this study, airborne particles were collected using filters, and the particle number concentrations were measured in two nanotitanium dioxide (nanoTiO₂)-manufacturing plants. Real-time particle size measurements were performed using both optical and scanning mobility particle sizer and X-ray fluorescence spectrometry (XRF). The respirable particles collected using filters were used to analyze Ti concentrations in the workplace air of two factories engaged in nanoTiO₂ powder bagging processes. The XRF analysis revealed sufficient sensitivity to measure 0.03 mg/m³, which is 1/10 the concentration of the recommended occupational exposure limit of nanoTiO₂ in both stationary sampling and personal exposure sampling settings. In a factory where outside air was directly introduced, micron-sized aggregated particles were generated because of factory operations; however, nanosized and submicron-sized particles were not observed owing to high background concentrations of incidental nanoparticles. Alternatively, in another factory where particles from the outside air were removed using a high-efficiency particulate air filter, work-related nanoparticles were released. The findings of this study suggest that in nanoparticle powder handling processes, a nanoparticle exposure risk exists in the form of nonagglomerated state in nanoparticle powder handling processes.