Quantitative Estimation of Urate Transport in Nephrons in Relation to Urinary Excretion Employing Benzbromarone-Loading Urate Clearance Tests in Cases of Hyperuricemia

Background: A four-component system for urate transport in nephrons has been proposed and widely investigated by various investigators studying the mechanisms underlying urinary urate excretion. However, quantitative determinations of urate transport have not been clearly elucidated yet. Methods: The equation Cua = {Ccr(1 – R1) + TSR}(1 – R2) was designed to approximate mathematically urate transport in nephrons, where R1 = urate reabsorption ratio; R2 = urate postsecretory reabsorption ratio; TSR = tubular secretion rate; Cua = urate clearance, and Ccr = creatinine clearance . To investigate relationships between the three unknown variables (R1, R2, and TSR), this equation was expressed as contour lines of one unknown on a graph of the other two unknowns. Points at regular intervals on each contour line for the equation were projected onto a coordinate axis and the high-density regions corresponding to high-density intervals of a coordinate were investigated for three graph types. For benzbromarone (BBR)-loading Cua tests, Cua was determined before and after oral administration of 100 mg of BBR and CuaBBR(∞) was calculated from the ratio of CuaBBR(100)/Cua. Results: Before BBR administration, points satisfying the equation on the contour line for R1 = 0.99 were highly dense in the region R2 = 0.87–0.92 on all three graphs, corresponding to a TSR of 40–60 ml/min in hyperuricemia cases (HU). After BBR administration, the dense region was shifted in the direction of reductions in both R1 and R2, but TSR was unchanged. Under the condition that R1 = 1 and R2 = 0, urate tubular secretion (UTS) was considered equivalent to calculated urinary urate excretion (Uex) in a model of intratubular urate flow with excess BBR; CuaBBR(∞) = TSR was deduced from the equation at R1 = 1 and R2 = 0. In addition, TSR of the point under the condition that R1 = 1 and R2 = 0 on the graph agreed with TSR for the dense region at excess BBR. TSR was thus considered approximately equivalent to CuaBBR(∞), which could be determined from a BBR-loading Cua test. Approximate values for urate glomerular filtration, urate reabsorption, UTS, urate postsecretory reabsorption (UR2), and Uex were calculated as 9,610; 9,510; 4,490; 4,150, and 440 µg/min for HU and 6,890; 6,820; 4,060; 3,610, and 520 µg/min for normal controls (NC), respectively. The most marked change in HU was the decrease in TSR (32.0%) compared to that in NC, but UTS did not decrease. Calculated intratubular urate contents were reduced more by higher UR2 in HU than in NC. This enhanced difference resulted in a 15.4% decrease in Uex for HU. Conclusion: Increased UR2 may represent the main cause of urate underexcretion in HU

Multiple inflammatory cytokine-productive ThyL-6 cell line established from a patient with thymic carcinoma

Thymic epithelial cells can produce many kinds of cytokines, and interleukin (IL)-6-producing thymic carcinoma cases have been reported. However, a cytokine-producing human thymic tumor cell line has not previously been established. In this paper, we report a novel, multiple inflammatory cytokine-productive cell line that was established from a patient with thymic carcinoma. This cell line, designated ThyL-6, positively expressed epithelial membrane antigen, cytokeratins, vimentin intermediate filament and CD5, although hematological markers were not present in the cells. Cytokine antibody array analysis showed that the cells secreted several cytokines including IL-1α, IL-6, IL-8, RANTES, soluble TNFα-receptor 1, VEGF and CTLA into the culture medium. The addition of ThyL-6-cultured supernatant supported the growth of human myeloma ILKM-3 cells, which require the presence of IL-6 in the culture medium for the maintenance of cell growth, suggesting that the secreted IL-6 from ThyL-6 cells was biologically active. Chromosome analysis demonstrated that ThyL-6 cells had complex karyotype anomalies, including der(16)t(1;16); the latter has been recognized in thymic squamous cell carcinoma and thymic sarcomatoid carcinoma cases, as well as in several other kinds of malignancies. Heterotransplantation of the cells into nude mice showed tumorigenesis with neutrophil infiltration and liquefactive necrosis. These findings suggest that ThyL-6 cells will provide us with a new experimental tool for investigating not only the pathogenesis, biological behavior, chromo-somal analysis and therapeutic reagents of human thymic carcinoma, but also for studying cytokine-chemokine network systems

Implementing action for acute stroke based on Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease in Tokushima

Cerebrovascular and cardiovascular disease are the main causes of death in Japan. The leading causes of the need for long-term care in Japan are also cerebrovascular and cardiovascular disease, which together account for more than one-fourth of the total. The Cerebrovascular and Cardiovascular Disease Control Act, of Japanese national law, was promulgated by a legislative act in 2018. On the basis of the Cerebrovascular and Cardiovascular Disease Control Act, the Ministry of Health, Labour and Welfare, Japan, published the Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease （Japanese National Plan） in 2020. By the example of the Japanese National Plan, Tokushima prefecture established a cerebrovascular and cardiovascular disease countermeasure promotion plan to progress cerebrovascular and cardiovascular disease measures according to their own circumstances. One of the important measures of the plan is improving emergency transportation systems. Patients with intracranial large vessel occlusion strokes should be served by direct transfer to endovascular capable centers avoiding delays by misguided transfer to primary stroke centers. Considering the limited availability of endovascular capable centers, accurate identification of patients with high probability of having large vessel occlusion strokes in the prehospital setting is importance. To address this problem, we introduced prehospital scale called Field Assessment Stroke Triage for Emergency Destination （FAST-ED） on emergency transportation systems in Tokushima city

Clinical Characteristics and Outcomes in 314 Japanese Patients with Bacterial Endophthalmitis : A Multicenter Cohort Study from J-CREST

Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus, Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment

Antimicrobial resistance profiles of vancomycin-resistant Enterococcus species isolated from laboratory mice

Isolates of 24 enterococci, 5 Enterococcus casseliflavus and 19 Enterococcus gallinarum, possessing vanC genes and showing low-level resistance to vancomycin were obtained from mice from commercial mouse breeding companies. Since some of these isolates showed resistance to other antibiotics, the purpose of this study was to clarify the resistant profiles of these isolates. One E. casseliflavus isolate showed resistance to erythromycin with a minimal inhibitory concentration (MIC) of 8 μg/mL and also showed apparent resistance to fluoroquinolones with an MIC of 32 μg/mL for ciprofloxacin. The MICs of 2 other fluoroquinolone-resistant E. casseliflavus and E. gallinarum isolates were 3 and 6 μg/mL, respectively. These 3 resistant isolates showed an absence of macrolide- and fluoroquinolone-resistant genes, including amino acid substitutions in the quinolone resistance determining regions of DNA gyrase and topoisomerase IV. Resistance to tetracycline was detected in 2 E.gallinarum isolates that were highly resistant, exhibiting MICs of 48 and 64 μg/mL and possessing tet(O) genes.The results indicate that antibiotic-resistant enterococci are being maintained in some laboratory mouse strains that have never been treated with an antibiotic

Case Report Successful Administration of Recombinant Human Soluble Thrombomodulin α (Recomodulin) for Disseminated Intravascular Coagulation during Induction Chemotherapy in an Elderly Patient with Acute Monoblastic Leukemia Involving the t(9;11)(p22;q23)

Patients with acute myelogenous leukemia complicate with disseminated intravascular coagulation (DIC), not only at the time of the initially leukemia diagnosis, but also during induction chemotherapy. In Japan, recently, a recombinant human soluble thrombomodulin alpha (Recomodulin) has been introduced as a new type of anti-DIC agent for clinical use in patients with hematological cancer or infectious disease. We describe a 67-year-old female case in which 25,600 units of Recomodulin for 6 days were successfully administered for both initially complicating and therapy-induced DIC without any troubles of bleeding in an acute monoblastic leukemia (AML-M5a) patient with the MLL gene translocation. Furthermore, the levels of DIC biomarkers recovered rapidly after the Recomodulin treatment. Our case suggests that DIC control using Recomodulin is one of the crucial support-therapies during remission induction chemotherapy in patients with acute leukemia of which type tends to complicate extramedullary or extranodal infiltration having potential to onset DIC