A simplified direct radioimmunoassay for urinary aldosterone (author's transl)]

A simplified direct radioimmunoassay for urinary acid labile aldosterone was developed. One ml of urine was hydrolysed with 2 ml of 0.2N HCL at 30 degrees C for 16hrs. One tenth ml of hydrolysed urine diluted 10 times with charcoal treated aldosterone-free calf serum was used for the radioimmunoassay. The radioimmunoasssay was done with a specific antibody, 125I-aldosterone, as the labeled antigen and polyethylene glycol for bound-free separation. There were excellent correlations between the present methods and other methods, i.e., i) a method using dichloromethane extraction before the assay as well as pre-extraction before hydrolysis and ii) a commercial kit using 3H-aldosterone. The intra-assay coefficient of variation was 5.8%, and the inter-assay coefficient of variation was 9.5%. The normal value of urinary aldosterone was excretion was 3.7 plus or minus 2.5 micrograms/day by the present method, and values of patients with primary aldosteronism were between 24 to 43 micrograms/day.     

CCL2 is critical for immunosuppression to promote cancer metastasis

We previously found that cancer metastasis is accelerated by immunosuppression during Snail-induced epithelial-to-mesenchymal transition (EMT). However, the molecular mechanism still remained unclear. Here, we demonstrate that CCL2 is a critical determinant for both tumor metastasis and immunosuppression induced by Snail⁺ tumor cells. CCL2 is significantly upregulated in various human tumor cells accompanied by Snail expression induced by snail transduction or TGFβ treatment. The Snail⁺ tumor-derived CCL2 amplifies EMT events in other cells including Snail^? tumor cells and epithelial cells within tumor microenvironment. CCL2 secondarily induces Lipocalin 2 (LCN2) in the Snail⁺ tumor cells in an autocrine manner. CCL2 and LCN2 cooperatively generate immunoregulatory dendritic cells (DCreg) having suppressive activity accompanied by lowered expression of costimulatory molecules such as HLA-DR but increased expression of immunosuppressive molecules such as PD-L1 in human PBMCs. The CCL2/LCN2-induced DCreg cells subsequently induce immunosuppressive CD4⁺FOXP3⁺ Treg cells, and finally impair tumor-specific CTL induction. In murine established tumor model, however, CCL2 blockade utilizing the specific siRNA or neutralizing mAb significantly inhibits Snail⁺ tumor growth and metastasis following systemic induction of anti-tumor immune responses in host. These results suggest that CCL2 is more than a chemoattractant factor that is the significant effector molecule responsible for immune evasion of Snail⁺ tumor cells. CCL2 would be an attractive target for treatment to eliminate cancer cells via amelioration of tumor metastasis and immunosuppression.     

Ultra-Early Induction of General Anesthesia for Reducing Rebleeding Rates in Patients with Aneurysmal Subarachnoid Hemorrhage

ObjectiveRebleeding of aneurysmal subarachnoid hemorrhage (aSAH) is one of the significant risk factors for poor clinical outcome. The rebleeding risk is the highest during the acute phase with an approximate rebleeding rate of 9-17% within the first 24 h. Theoretically, general anesthesia can stabilize a patient's vital signs; however, its effectiveness as initial management for preventing post-aSAH rebleeding remains unclear. The purpose of this study was to determine the feasibility and safety of ultra-early general anesthesia induction for reducing the rebleeding rates among patients with aSAH.Materials and methodsWe retrospectively evaluated patients with aSAH who were admitted to our department between January 2013 and December 2019. All the patients underwent ultra-early general anesthesia induction as initial management regardless of their severity. We evaluated the rebleeding rate before definitive treatment, factors influencing rebleeding, and general anesthesia complications.ResultsWe included 191 patients with two-third of them having a poor clinical grade (World Federation of Neurological Society [WFNS] grade IV or V). The median duration from admission to general anesthesia induction was 22 min. Rebleeding before definitive treatment occurred in nine patients (4.7%). There were significant differences in the Glasgow Coma Scale score (p = 0.047), WFNS grade (p = 0.02), and dissecting aneurysm (p <0.001) between the rebleeding and non-rebleeding patients. There were no cases of unsuccessful tracheal intubation or rebleeding during general anesthesia induction.ConclusionUltra-early general anesthesia induction could be performed safely in patients with aSAH, regardless of the WFNS grade; moreover, it resulted in lower rebleeding rate than that reported in previous epidemiological reports.     

Complex HeartWare left ventricular assist device infection treated with pump exchange: clinical alert for the driveline location

Journal of Artificial Organs - Infection is a major complication in patients with a left ventricular assist device (LVAD). Once a driveline exit-site infection (DLI) reaches the LVAD component,...     

Radical scavenging activity of carbon nanotubes: toward appropriate selection of a radical initiator

Radical scavenging activities are attractive properties not only for scientific fields e.g. biomedicine, but for the materials industry. In this study, we report that carbon nanotubes (CNTs) can scavenge radicals from organic peroxides, while radicals from azo-type radical initiators exhibit only a few effects from the presence of CNTs. In addition, experimental results suggest the possibility that captured peroxide radicals generate active radical sites on the CNT surface, from which polymerization can take place. These results indicate the importance of selecting an appropriate radical initiator.

Carbon nanotubes scavenge radicals preferentially from peroxides, and polymerization presumably takes place from generated active radical sites on the surface.     

Early and Long-Term Outcomes in Japanese Patients Aged 80 Years or Older Undergoing Conventional Aortic Valve Replacement

In this study, we investigated the early and long-term results of conventional aortic valve replacement (AVR) in very old patients.Methods: Seventy-five patients with aortic stenosis underwent conventional AVR for patients aged 80 years.We examined early death and major adverse cardiovascular and cerebrovascular event (MACCE).Results: The operative mortality was 0% for isolated AVR and 19.2% for concomitant surgery. The postoperative survival rate and MACCE free-rate were no significant differences between the isolated AVR and the concomitant surgery. Univariate analysis confirmed that cardiac dysfunction, severe chronic kidney disease (CKD), hemodialysis, + coronary artery bypass grafting, and norepinephrine use were risk factor of early death. Univariate analysis confirmed that severe CKD, BNP >1000 pg/ml, aortic cross clamping time (ACCT) >180 min, and non-use carperitide and multivariate analysis confirmed that ACCT >180 min, and non-use carperitide were risk factor of MACCE.Conclusions: This study showed that the results of conventional AVR in very old patients were not satisfactory. However, the results obtained with isolated AVR were favorable with no operative deaths. The present study demonstrated that preoperative cardiac function, preoperative renal function, and operative factors have an important impact on early mortality and MACCE.     

Cholestatic Liver Injury After Biliary Reconstruction Impairs Transplanted Islet Viability and Function

Islet autotransplantation following total pancreatectomy differs from allograft transplantation with respect to the requirement of biliary reconstruction. Although it is known that careful consideration should be given to postoperative cholestatic liver injury after biliary reconstruction, its direct effects on transplanted islets have not been completely elucidated. In this study, we developed a murine model of postoperative cholestatic liver injury after biliary reconstruction with islet autotransplantation that involved syngeneic intraportal islet transplantation into chemically induced diabetic mice and common bile duct ligation. We assessed the viability and function of the transplanted islets. The impaired viability of transplanted islets and increased blood glucose levels indicated restoration of the diabetic state after common bile duct ligation in this murine model. Furthermore, impaired islet viability and function occurred earlier in the transplanted islets than in the surrounding liver tissues, which was consistent with the faster and higher expression of oxidative stress markers in the transplanted islets. Transplanted islets may be more vulnerable to oxidative stress caused by cholestatic liver injury than the surrounding liver tissue. Therefore, patients should be intensively managed after total pancreatectomy with islet autotransplantation to preserve viability and function of the transplanted islets.