Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils

BACKGROUND: We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. METHODS: Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. RESULTS: Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. CONCLUSIONS: Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases.     

Maximal isometric force and neural activity during bilateral and unilateral elbow flexion in humans

We investigated maximal isometric force and electromyographic (EMG) activity of the biceps brachii muscle during rapid bilateral (BL) and unilateral (UL) elbow flexion in 11 right-handed subjects. The BL exhibited a deficit in force for both arms and more so for the right than the left arm during the rising phase of force generation. The EMG of the left biceps brachii muscle was similar during UL and BL, but for the right arm EMG was lower during BL than during UL for the rising phase of force generation. The BL to UL ratio of mean power frequency of the EMG was lower for the right than for the left arm. The data would suggest that the relatively small BL strength was associated with a equally small EMG and a shift to a lower mean power frequency especially for the fast motor units of the dominant muscle.     

Chronologic changes of activities of naphthol AS-D acetate esterase and other nonspecific esterases in the mononuclear phagocytes of tuberculous lesions.

Nonspecific esterases of mononuclear phagocytes (MNs) were studied histochemically in the developing and healing tuberculous lesions produced in rabbit skin by bacille Calmette Guérin (BCG). Nonspecific esterases were assayed with the following substrates: naphthol AS-D acetate (AS-D), naphthol AS-D chloroacetate (AS-D Chl), naphthol AS acetate (AS) and alpha-naphthyl acetate (alpha-N), beta-Galactosidase, a lysosomal enzyme of MNs, was also assayed as a marker of MN activation. The number of MNs hydrolyzing AS-D Chl, AS, and alpha-N increased for 2 to 4 weeks after infection. These chronologic changes were similar to that of beta-galactosidase. In contrast, MNs hydrolyzing AS-D appeared predominantly in the healing lesions five to six weeks after infection. These MNs had the morphologic features of balloon-like cells. They contained few lysosomes and gathered in clumps far from the caseous center. The activity of the AS-D esterase was almost completely inhibited by various trypsin inhibitors, but not by the serine esterase inhibitor of phenylmethylsulfonyl-fluoride. These results suggest that the AS-D esterase is a trypsin-like esterase which participates in the healing of tuberculous lesions.     

Peripheral low-density area of hepatic tumors: CT-pathologic correlation

To aid in the distinction between colorectal cancer metastasis to the liver and hepatocellular carcinoma, findings on computed tomographic (CT) scans taken more than 5 minutes after contrast material administration ("late-enhanced CT scans") and pathologic findings were compared. Late-enhanced CT scans of metastatic adenocarcinoma showed a peripheral low-density area (PLDA) that corresponded to viable tumor and a central high-density area that represented fibrous connective tissue. This phenomenon was recognized in 15 of 20 (75%) patients with metastatic adenocarcinoma and in one of 50 (2%) patients with hepatocellular carcinoma. Late-enhanced CT scans may be useful in distinguishing between metastatic nonmucinous colorectal cancer and hepatocellular carcinoma.     

Competition and physician-induced demand in a healthcare market with regulated price: evidence from Ghana

International Journal of Health Economics and Management - Using panel data of administrative claims spanning 36 months (2017–2019) and an instrumental variable method, this study...     

Retrosigmoid Approach in the Supine Position Using ORBEYE: A Consecutive Series of 14 Cases

One of the merits of recently introduced exoscopes, including ORBEYE, is that they are superior to a conventional microscope in terms of ergonomic features. Taking advantage of it, the retrosigmoid approach can be performed in the supine position using ORBEYE. We report a consecutive series of 14 operations through the retrosigmoid approach in the supine position using ORBEYE. Fourteen consecutive patients who underwent surgery through the retrosigmoid approach for cerebellopontine (CP) angle lesions in the supine position using ORBEYE were targeted, and surgical outcomes and complications were examined. We evaluated the posture of the operator and the surgical field during this approach compared with those using a conventional microscope. In all 14 cases, all operative procedures were accomplished only using the ORBEYE. There were no operative complications due to this approach. Using ORBEYE, even when the angle of the operative visual axis was horizontal, the operators could manipulate in a comfortable posture. They were not forced to be in an uncomfortable posture that extended their arms, as is often the case with a conventional microscope. Therefore, they could use shorter surgical instruments. As the cerebellum shifted downward with gravity even using slight retraction during this approach, the working space of the surgical field was easily secured. Through this approach, the operators can perform stable microsurgery of CP angle lesions in a comfortable posture. This approach can reduce the burden on the operator and the patient, leading to a refined surgical procedure.     

Development and Validation of Scoring Indication of Surgical Clipping and Endovascular Coiling for Aneurysmal Subarachnoid Hemorrhage from the Post Hoc Analysis of Japan Stroke Data Bank

There are no scoring methods for optimal treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). We developed a scoring model to predict clinical outcomes according to aSAH risk factors using data from the Japan Stroke Data Bank (JSDB). Of 5344 patients initially registered in the JSDB, 3547 met the inclusion criteria. Patients had been diagnosed with aSAH and treated with surgical clipping or endovascular coiling between 1998 and 2013. We performed multivariate logistic regression for poor outcomes at discharge, indicated by a modified Rankin Scale (mRS) score >2, and in-hospital mortality for both treatment methods. Based on each risk factor, we developed a scoring model assessing its validity using another dataset of our institution. In the surgical clipping group, scoring criteria for aSAH were age >72 years, history of more than once stroke, World Federation of Neurological Societies (WFNS) grades II–V, aneurysmal size >15 mm, and vertebrobasilar artery (VBA) aneurysm location. In the endovascular coiling group, scoring criteria were age >80 years, history of stroke, WFNS grades III–V, computed tomography (CT) Fisher group 4, and aneurysmal location in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). The rates of poor outcome of mRS score >2 in an isolated dataset using these scoring criteria were significantly correlated with our model’s scores, so this scoring model was validated. This scoring model can help in the more objective treatment selection in patients with aSAH.     

The effect of frailty on the quality of life and lower urinary symptoms following robot-assisted radical prostatectomy: A longitudinal analysis (FRARP-QL Study)

ObjectivesWe aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (CaP).Materials and MethodsWe longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 >14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP.ResultsThe median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients’ background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, P = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening.ConclusionsFrailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP.     

Prognostic significance of the Ki67 index and programmed death-ligand 1 expression after radical cystectomy in patients with muscle-invasive bladder cancer

ObjectivesTo investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.Materials and MethodsWe retrospectively evaluated 262 MIBC patients treated with RC between April 2004 and April 2020. The impact of Ki67 index and PD-L1 expression on prognosis was evaluated by univariate Cox regression analysis. In addition, a pathomolecular risk score, including Ki67 and PD-L1, was developed to predict prognosis and pathological factors. We also evaluated the link between the Ki67 index and PD-L1 under the IL-6 stimulation in the bladder cancer cell lines of T24 and 5637 cells.ResultsThe median age and follow-up period was 69 years and 52 months, respectively. Ki67 index and PD-L1 expression were significantly associated with tumor recurrence. Univariate Cox regression analysis showed that pT3–4, mixed histology, lymphovascular invasion positive (LVI+), pN+, Ki67-high (>17%), and PD-L1+ were significantly associated with recurrence-free survival (RFS). The pathomolecular risk score was developed using resection margin+ (1 point), mixed histology (1 point), LVI+ (1 point), pN+ (1 point), and Ki67-high (1 point). RFS and overall survival were significantly shorter in patients with higher pathomolecular risk scores (>1) than in those with lower risk scores (≤1). Cell proliferation was significantly increased in the T24 and 5637 cells under the IL-6 stimulation, while PD-L1 expression was not.ConclusionsA significant effect of Ki67-high and PD-L1 expression on poor prognosis was observed in patients with MIBC. Further studies are necessary to elucidate the precise mechanisms of cell proliferation and PD-L1 expression in patients with MIBC.