Effects of Outdoor-Grown Royal Sun Medicinal Mushroom Agaricus brasiliensis KA21 (Agaricomycetes) Fruiting Body on Canine Malassezia Dermatitis.

Brazil-grown outdoor-cultivated Agaricus brasiliensis KA21 fruiting body (KA21) significantly increases the production of serum anti-beta-glucan antibody. Therefore, KA21 ingestion may be useful for the prevention and alleviation of fungal infections. This study aimed to determine the effects of KA21 in fungal infections in animals. KA21 was administered to nine dogs infected with Malassezia. Notably, the anti-beta-glucan antibody titer remained unchanged or tended to decrease in the oral steroid arm, whereas in the non-steroid arm, antibody titer increased in almost all animals after KA21 ingestion. Dogs showing improved clinical symptoms exhibited increased anti-beta-glucan antibody titers. The results of this study suggest that KA21 ingestion may alleviate the symptoms of Malassezia and other fungal infections and that continuous ingestion may help prolong recurrence-free intervals. Additionally, the ingestion of KA21 during oral steroid dosage reduction or discontinuation may enable smoother steroid withdrawal.

Dectin-1 Reactivity to Paramylon Derived from Euglena gracilis EOD-1.

Euglena gracilis is a microalga that has recently attracted attention because of its bioactivities. Paramylon (PM), a major ß-1,3-glucan, constitutes 70-80% of the cells of the E. gracilis EOD-1 strain. Dectin-1 is a pattern recognition receptor that recognizes ß-glucan. However, it is unclear whether PM binds to dectin-1. In this study, we investigated the reactivity of EOD1PM with dectin-1 by analyzing the binding of soluble murine and human dectin-1-Fc fusion protein (m dectin-1 Fc, h dectin-1 Fc) to EOD1PM using flow cytometry and enzyme-linked immunosorbent assay (ELISA). m Dectin-1 Fc bound to EOD1PM particles when m dectin-1-Fc is added. Furthermore, the binding specificity was examined in a competitive reaction following addition of a soluble antigen. It was found that the binding of m dectin-1-Fc to EOD1PM was not inhibited by the addition of dextran or ovalbumin but by the addition of solubilized EOD1PM or Candida cell wall- solubilized ß-glucan. In addition, the h dectin-1-Fc fusion protein was found to specifically bind to EOD1PM. These results suggest that dectin-1 recognizes and binds to the ß-glucan structure of EOD1PM. Dectin-1 is expressed in leukocytes as a ß-glucan receptor and is involved in the expression of various biological activities; therefore, the dectin-1 pathway may be involved in the biological activity of EOD1PM.

Factors Influencing Cardiac Sympathetic Nervous Function in Patients With Severe Aortic Stenosis: Assessment by 123I-Metaiodobenzylguanidine Myocardial Scintigraphy.

BACKGROUND: Numerous studies have shown that 123I-metaiodobenzylguanidine (MIBG) scintigraphy, an index of cardiac sympathetic nervous (CSN) activity, is useful for predicting prognosis in patients with heart failure. However, the factors influencing the CSN activity of patients with severe aortic stenosis (AS) remain unclear. METHODS: We enrolled 91 patients with severe AS who underwent 123I-MIBG scintigraphy, coronary computed tomography (CCT), and transthoracic echocardiography. When CCT angiography (CCTA) showed an obstructive epicardial artery, invasive coronary angiography was performed within 1 week of CCTA. RESULTS: There were 21 male and 70 female patients with a mean age of 84±5 years. Eighty-five (85) patients (93%) had hypertension and 13 patients (14%) had diabetes. Two (2) patients (2%) had previous myocardial infarction and eight (9%) had a previous coronary intervention. All patients had severe AS: aortic valve area was 0.63±0.18 cm2 and the mean pressure gradient was 56±19 mmHg. Regarding 123I-MIBG parameters, early heart-to-mediastinum (H/M) ratio was 3.1±0.5, delayed H/M ratio was 2.8±0.6, and the washout rate (WR) was 35%±13%. Multivariable linear regression analysis showed that coronary artery disease (ß=-0.30, p=0.002) was an independent predictor of delayed H/M ratio, and that aortic valve area (ß=-0.20, p=0.048) was an independent predictor of WR. CONCLUSIONS: Our findings suggest that coronary artery disease is an independent predictor of delayed H/M ratio, and aortic valve area is an independent predictor of WR in patients with severe AS.

The Monocyte to High-Density Lipoprotein Cholesterol Ratio Is Associated with Left Ventricular Diastolic Function in Patients with No Significant Perfusion Abnormality.

The monocyte to high-density lipoprotein cholesterol (HDL-C) ratio has been considered to be a prognostic marker. Whether this ratio is associated with left ventricular (LV) diastolic function remains undetermined. We tested the hypothesis that the monocyte to HDL-C ratio is associated with LV diastolic parameters derived from gated myocardial perfusion single-photon emission computed tomography (SPECT) in patients with no significant perfusion abnormality.The study population included 196 patients with no significant perfusion abnormalities and preserved ejection fraction. The peak filling rate (PFR) and one-third mean filling rate (1/3 MFR) were obtained as LV diastolic parameters using gated SPECT. Monocyte counts and plasma HDL-C levels were also examined.Significant associations were observed between the monocyte to HDL-C ratio and PFR (r = -0.20; P = 0.005) and 1/3 MFR (r = -0.19; P = 0.009). Multivariate linear regression analysis was performed to determine factors associated with LV diastolic parameters. Age (ß = -0.27; P < 0.001), LV end-diastolic volume (ß = -0.19; P = 0.034), and monocyte to HDL-C ratio (ß = -0.15; P = 0.027) were determined to be significantly associated with PFR. Moreover, age (ß = -0.13; P = 0.007), LV mass index (ß = -0.18; P = 0.037), and the monocyte to HDL-C ratio (ß = -0.13; P = 0.045) were significantly associated with 1/3 MFR.These results demonstrated that the monocyte to HDL-C ratio is associated with LV diastolic function, as derived from gated SPECT in patients with no significant perfusion abnormality.

Development of a Highly Sensitive ß-Glucan Detection System Using Scanning Single-Molecule Counting Method.

To overcome the limitations of the Limulus amebocyte lysate (LAL) assay method for the diagnosis of invasive fungal infection, we applied a reaction system combining recombinant ß-glucan binding proteins and a scanning single-molecule counting (SSMC) method. A novel (1→3)-ß-D-glucan recognition protein (S-BGRP) and a (1→6)-ß-glucanase mutant protein were prepared and tested for the binding of (1→6)-branched (1→3)-ß-D-glucan from fungi. S-BGRP and (1→6)-ß-glucanase mutant proteins reacted with ß-glucan from Candida and Aspergillus spp. Although LAL cross-reacted with plant-derived ß-glucans, the new detection system using the SSMC method showed low sensitivity to plant (1→3)-ß-D-glucan, which significantly improved the appearance of false positives, a recognized problem with the LAL method. Measurement of ß-glucan levels by the SSMC method using recombinant ß-glucan-binding proteins may be useful for the diagnosis of fungal infections. This study shows that this detection system could be a new alternative diagnostic method to the LAL method.

Associations of frontal QRS-T angle with left ventricular volume and function derived from ECG-gated SPECT in patients with advanced chronic kidney disease.

BACKGROUND: The frontal QRS-T angle is one of markers of ventricular repolarization. We investigated whether or not the frontal QRS-T angle could predict left ventricular (LV) volume and function derived from ECG-gated SPECT in patients with advanced chronic kidney disease (CKD). METHODS: Two hundred and twelve patients with advanced CKD defined as estimated glomerular filtration rate of < 45 ml min-1/1.73 m2 were enrolled. Wide QRS-T angle was defined as its angle of > 90°, and was considered abnormal. Enlarged LV end-diastolic volume (LVEDV) was defined as LVEDV index of > 76 ml m-2 in men and > 57 ml m-2 in women. Reduced LV ejection fraction (LVEF) was defined as LVEF of < 40%. RESULTS: Fifty-one patients (24%) had wide QRS-T angle, and 161 patients (76%) had normal QRS-T angle. Patients with wide QRS-T angle had larger SSS [9 (5-16) vs 4 (1-9), p < 0.001], larger LVEDV index (69 ± 29 vs 50 ± 18 ml m-2, p < 0.001) and lower LVEF (47 ± 13 vs 59 ± 12%, p < 0.001) than those with normal QRS-T angle. Multivariate analysis showed that wide QRS-T angle (odds ratio 5.93; 95% CI 2.55-14.33; p < 0.001) was significantly associated with enlarged LVEDV, whereas SSS severity was not. Severely abnormal SSS (odds ratio 3.80; 95% CI 1.16-14.05; p < 0.03) and wide QRS-T angle (odds ratio 5.67; 95% CI 2.10-16.22; p < 0.001) were significantly associated with reduced LVEF. CONCLUSIONS: Our results suggest that wide QRS-T angle is associated with LV remodeling such as enlarged LVEDV or reduced LVEF in patients with advanced CKD.

Binding Specificity of a New Artificial ß-Glucan Recognition Protein and Its Application to ß-Glucan Detection in Mushroom Extracts.

ß-1,3-D-glucan (BG) activates innate immunity and enhances immune responses. Fungi, such as mushrooms, produce a relatively large amount of BG, the structure and molecular weight of which varies depending on the species of fungi. This study was conducted to develop a detection probe for quantifying or detecting BG from fungi using BG-binding proteins. The binding properties of a new ß-glucan recognition protein (BGRP) against various BGs were compared. With reference to the amino acid sequences of BGRP in insects, an artificial BGRP (supBGRP) was designed with higher production efficiency using gene recombination technology. SupBGRP was produced in Escherichia coli with high efficiency, and its reactivity with BG from fungi was the highest among the BG-binding proteins examined. SupBGRP exhibited high reactivity with 1,6-branched BG and will be useful for the quantification and detection of fungal BG.

Possibility of Japanese Cedar Pollen Causing False Positives in the Deep Mycosis Test.

Because Japanese cedar pollen (JCP) contains beta-1,3-d-glucan (BG), there is concern that its lingering presence in the atmosphere, especially during its scattering period, may cause false positives in the factor-G-based Limulus amebocyte lysate (LAL) assay used to test for deep mycosis (i.e., G-test). Hence, we examined whether the LAL assay would react positively with substances contained in JCP by using the G-test to measure JCP particles and extracts. BG was purified from the JCP extract on a BG-specific affinity column, and the percentage extractability was measured using three different BG-specific quantitative methods. The G-test detected 0.4 pg BG in a single JCP particle and 10 fg from a single particle in the extract. The percentage extractability of JCP-derived BG was not significantly different among the three quantitative methods. As the JCP particles should technically have been removed during serum separation, they should be less likely to be a direct false-positive factor. However, given that the LAL-assay-positive substances in the JCP extract were not distinguishable by the three BG-specific quantitative methods, we conclude that they may cause the background to rise. Therefore, in Japan false positives arising from JCP contamination should be considered when testing patients for deep mycosis.

Open-Label Study of the Influence of Food Containing the Royal Sun Mushroom, Agaricus brasiliensis KA21 (Agaricomycetes), on ß-Glucan-Specific Antibody Production in Healthy Human Volunteers.

The edible mushroom Agaricus brasiliensis contains a large amount ß-glucan, which is mainly composed of a ß-1,6-glucan structure. In this study, we investigated the effect of A. brasiliensis strain KA21 on the anti-ß-glucan antibody titer in healthy humans and the role of antibodies as an immunomodulator. Twenty-two healthy volunteers were fed the dried fruiting body of A. brasiliensis (900 or 1500 mg/day) for 12 weeks. The anti-ß-glucan antibody titer in the serum was determined by enzyme-linked immunosorbent assay. Immunoglobulin G (IgG) against ß-glucan was significantly upregulated after intake of A. brasiliensis. Murine experiments demonstrated improvement of anti-ß-glucan antibody production after intraperitoneal injection of Agaricus-derived ß-glucan. To understand the role of antibody against ß-glucan in exclusion of pathogenic fungi, we examined the interaction between HL-60 cells and antibody-treated heat-killed Candida albicans. Flow cytometry analysis indicated the upregulation of Candida-positive HL-60 cells after treatment with human IgG, whereas the competitive assay demonstrated that the main epitope of Candida-reacted IgG was the ß-1,6-glucan structure. Binding between HL-60 and IgG-opsonized C. albicans was suppressed by anti-Fcγ receptor 1 (FcγRI) neutralizing antibody. Finally, using FcγRI-expressed cells with the nuclear factor of activated T-cell reporter assay, we demonstrated that higher titers of anti-ß-glucan IgG can induce stronger Fc receptor-mediated cell activation through the formation of an antibody-ß-glucan complex. In conclusion, oral ingestion of A. brasiliensis KA21 promotes anti-ß-glucan antibody production and may contribute to preventing fungal infection through the activation of immune cells by forming antibody-ß-glucan complexes via an FcγR-dependent pathway.

Latent 1,3-ß-D-glucan acts as an adjuvant for allergen-specific IgE production induced by Japanese cedar pollen exposure.

BACKGROUND: The pollen grains of several plant species contain 1,3-ß-D-glucan (BG). BG activates dendritic cells (DCs) and subsequently regulates the innate immune responses. Within Japan, the most common disease associated with type-I hypersensitivity is Japanese cedar pollinosis. However, the role of BG in Japanese cedar pollen (JCP) remains unclear. This study examined the localization and immunological effects of BG in JCP. METHODS: The localization of BG in JCP grain was determined by immunohistochemical staining using a soluble dectin-1 protein probe and a BG recognition protein (BGRP). The content of BG extracted from JCP was measured by a BGRP-based ELISA-like assay. The cytokine production by bone marrow-derived DCs (BMDCs) obtained from wild-type and BG receptor (dectin-1) knock-out mice was examined in vitro. The mice were intranasally administered JCP grains and the specific serum Ig levels were then quantified. RESULTS: BG was detected in the exine and cell wall of the generative cell and tube cell of the JCP grain. Moreover, BG in the exine stimulated production of TNF-α and IL-6 in the BMDCs via a dectin-1-dependent mechanism. Meanwhile, JCP-specific IgE and IgG were detected in the serum of wild-type mice that had been intranasally administered with JCP grains. These mice also exhibited significantly enhanced sneezing behavior. However, dectin-1 knock-out mice exhibited significantly lower JCP-specific IgE and IgG levels compared to wild-type mice. CONCLUSIONS: Latent BG in JCP can act as an adjuvant to induce JCP-specific antibody production via dectin-1.

Aortic valve calcium is associated with left ventricular diastolic function in patients without evidence of ischaemic heart disease: assessment by gated single-photon emission computed tomography.

BACKGROUND: Several studies have shown that aortic valve calcium (AVC) is associated with cardiovascular events. Furthermore, the extent of AVC is associated with adverse prognosis even in patients without significant aortic stenosis. We investigated the relationship between AVC and left ventricular (LV) diastolic parameters determined by gated single-photon emission computed tomography (SPECT) in patients with no evidence of ischaemic heart disease. METHODS: This study included 157 patients with no evidence of ischaemic heart disease who underwent both coronary computed tomography and gated SPECT. The AVC scores were calculated by the Agatston method, and peak filling rate (PFR) and one-third mean filling rate (1/3 MFR) were determined as LV diastolic parameters. RESULTS: There were 93 (59%) and 64 (41%) patients with and without AVC, respectively, and the AVC scores ranged from 0 to 1251. There was no significant difference in LV end-diastolic volume (EDV) (60 ± 18 vs 62 ± 25 mL, p = 0.52) or LV ejection fraction (67% ± 10% vs 66% ± 8%, p = 0.60) between the two groups. Patients with AVC had lower PFR (2.2 ± 0.5 vs 2.4 ± 0.5 EDV/s, p = 0.002) and 1/3 MFR (1.3 ± 0.3 vs 1.5 ± 0.4 EDV/s, p = 0.003) than those without AVC. Multivariate linear regression analysis showed that ln(AVC score + 1) was significantly associated with PFR and 1/3 MFR. CONCLUSION: In patients without evidence of ischaemic heart disease, the extent of AVC was inversely correlated with gated SPECT-derived parameters of LV diastolic function.

Effects of Newly Developed Right Versus Left Bundle Branch Block on the QRS Axis, T-wave Axis and Frontal QRS-T Angle in Patients with a Narrow QRS.

Objective The QRS-T angle has been established as a repolarization marker. In the present study, we determined whether or not newly developed bundle branch block (BBB) affected the QRS-T angle in patients with a narrow QRS. Methods Twenty-four patients with newly developed BBB and no adverse cardiac events were retrospectively included. The frontal QRS-T angle was defined as the absolute value of the difference between the frontal plane QRS axis and the T-wave axis. These electrocardiogram parameters were serially measured in the settings of narrow QRS and BBB. Results Twelve patients had newly developed right BBB (RBBB), and 12 had newly developed left BBB (LBBB). The development of RBBB did not affect the QRS axis, T-wave axis of QRS-T angle (41° ±42° to 53° ±65°, p = 0.63). In contrast, the development of LBBB shifted the QRS axis to the left (25° ±29° to -18° ±31°, p = 0.003), resulting in an increased QRS-T angle (72° ±50° to 123° ±39°, p = 0.001). Regarding RBBB, an excellent correlation and agreement were found between the QRS-T angles in the setting of narrow QRS and RBBB (r = 0.88; p <0.001; bias, 2.9° ±20.9°). However, there was a significant bias between the QRS-T angles in the setting of narrow QRS and LBBB (51.9° ±40.4°; p = 0.001). Conclusion Our data suggested that the QRS-T angle in the setting of RBBB reflected the original QRS-T angle in the setting of narrow QRS well, whereas the QRS-T angle in the setting of LBBB did not.

Effects of upright T-wave in lead aVR on left ventricular volume and function derived from ECG-gated SPECT in patients with advanced chronic kidney disease.

BACKGROUND: Numerous studies have shown the association between chronic kidney disease (CKD) and adverse cardiac events. We investigated whether or not the upright T-wave in lead aVR (TaVR) could predict left ventricular (LV) volume and function derived from ECG-gated SPECT in patients with advanced CKD. METHODS: Two hundred and sixty-one patients with advanced CKD [estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2] were enrolled. Upright TaVR was defined as a wave with a positive deflection of > 0 mV. Enlarged LV end-diastolic volume (LVEDV) was defined as LVEDV index of > 76 ml/m2 in men and > 57 ml/m2 in women. Reduced LV ejection fraction (LVEF) was defined as LVEF of < 40%. RESULTS: Forty-six patients (18%) had upright TaVR, and 215 patients (82%) had negative TaVR. Summed redistribution score (SRS) [ 6 (1-12) vs. 2 (0-5), p < 0.001] and summed difference score (SDS) [4 (1-6) vs. 2 (0-4), p = 0.004] were significantly larger in patients with upright TaVR than those with negative TaVR. Patients with upright TaVR had larger LVEDV index (75 ± 33 ml/m2 vs. 50 ± 18 ml/m2, p < 0.001) and lower LVEF (43 ± 14% vs. 58 ± 11%, p < 0.001) compared to those with negative TaVR. After adjusted for other variables including SRS and SDS, upright TaVR remained a significant predictor of enlarged LVEDV (odds ratio 5.45; 95% CI 2.16-14.22; p < 0.001) and reduced LVEF (odds ratio 4.54; 95% CI 1.70-12.23; p = 0.003). CONCLUSIONS: Our data suggested that upright TaVR could predict LV volume and function derived from ECG-gated SPECT in patients with advanced CKD.

Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement on Changes in Cardiac Sympathetic Nervous Function.

The impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) on changes in cardiac sympathetic nervous (CSN) function remains unclear. Using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, we investigated the impact of PPM after TAVR on CSN activity.We enrolled 44 of 117 patients with severe aortic stenosis who underwent TAVR for analysis in the present study. We conducted 123I-MIBG scintigraphy at baseline and at about 9 months after TAVR. Differences between baseline and post-TAVR 123I-MIBG parameters were compared between cases with and without PPM.There were 17 and 27 patients with and without PPM, respectively. Those without PPM exhibited significantly decreased left ventricular mass index (122 ± 36 g/m2 versus 108 ± 30 g/m2, P < 0.001) following TAVR, whereas those with PPM did not (117 ± 21 g/m2 versus 110 ± 17 g/m2, P = 0.09). Significant improvements in delayed heart-to-mediastinum (H/M) ratio (2.8 ± 0.4 versus 3.0 ± 0.4, P = 0.004) and washout rate (WR) (33% ± 10% versus 24% ± 12%, P < 0.001) were observed after TAVR in patients without PPM but not in those with PPM. Multivariable linear regression analysis revealed PPM to be a negative predictor of improvements in delayed H/M ratio and WR.Delayed H/M ratio and WR improve significantly after TAVR in the absence of PPM, whereas these improvements are not observed in patients with PPM. Hence, the presence of PPM is a negative predictor of improvements in delayed H/M ratio and WR in patients undergoing TAVR.

Coronary Vasculitis Induced in Mice by Cell Wall Mannoprotein Fractions of Clinically Isolated Candida Species.

Kawasaki disease (KD) is an inflammatory disease that was identified by Professor Tomisaku Kawasaki in 1961. Candida albicans-derived substances (CADS) such as the hot water extract of C. albicans and Candida water-soluble fractions (CAWS) induce coronary vasculitis similar to KD in mice. An increasing proportion of deep-seated candidiasis cases are caused by non-albicans Candida and are often resistant to antifungal drugs. We herein investigated whether the mannoprotein fractions (MN fractions) of clinically isolated Candida species induce vasculitis in mice. We prepared MN fractions from 26 strains of Candida species by conventional hot water extraction and compared vasculitis in DBA/2 mice. The results obtained revealed that the induction of vasculitis and resulting heart failure were significantly dependent on the species; namely, death rates on day 200 were as follows: Candida krusei (100%), Candida albicans (84%), Candida dubliniensis (47%), Candida parapsilosis (44%), Candida glabrata (32%), Candida guilliermondii (20%), and Candida tropicalis (20%). Even for C. albicans, some strains did not induce vasculitis. The present results suggest that MN-induced vasculitis is strongly dependent on the species and strains of Candida, and also that the MN fractions of some non-albicans Candida induce similar toxicity to those of C. albicans.

Quantification of ß-Glucan from Culinary-Medicinal Mushrooms Using Novel Artificial ß-Glucan Recognition Protein.

(1->3)-ß-D-glucans (BGs), found in culinary-medicinal mushrooms, exhibit an immunostimulatory effect; hence, it is important to measure the content of BGs contained in mushrooms. BGs content in a mushroom extract was measured using a recombinant BG-binding protein, supBGRP, and compared with the existing BG assay using BGs antibody. The specificity of supBGRP enzyme immunoassay (EIA) was evaluated using a commercially available polysaccharide reagent. The supBGRP did not react to barley glucan, dextran, mannan, pustulan, and xylan, but reacted to sonifilan, and only slightly to curdlan. Among the BGs tested, supBGRP was most reactive to lentinan. The glucans were extracted using hot water and alkaline solution from the fruit body of the following edible mushrooms: Pleurotus ostreatus, Grifola frondosa, Lentinus edodes, Hypsizygus marmoreus, Flammulina velutipes, and Auricularia polytricha. All BGs extracted from edible mushrooms were detectable; in particular, the reactivity of supBGRP toward the alkaline-extracted fraction from Lentinus edodes was higher than that toward polyclonal antibody for BGs. The results suggest that supBGRP had a specific reaction to BG. The supBGRP seems to be superior to antibodies due to easy availability as a reagent and stability as a protein molecule for measurement of BGs.

Effects of aging on coronary flow reserve in patients with no evidence of myocardial perfusion abnormality.

Coronary flow reserve (CFR) reflects the functional capacity of microcirculation to adapt to blood demand during increased cardiac work. We tested the hypothesis that aging had impacts on coronary flow velocities and CFR in patients with no evidence of myocardial perfusion abnormality on single photon emission computed tomography (SPECT). Seventy-six patients undergoing transthoracic Doppler echocardiography with no evidence of myocardial perfusion abnormality on SPECT were enrolled in this study. CFR was defined as the ratio of hyperemic to resting peak diastolic coronary flow velocity. Patients were divided into the three groups based on age: 17 patients aged less than 70 years (Group I), 38 patients aged 70-79 years (Group II), and 21 patients aged 80 years or more (Group III). Compared with Group I, CFR was significantly lower in Group II (p < 0.01) and Group III (p < 0.01). Multivariate linear regression analysis showed that female (ß = - 0.26, p = 0.03), cigarette smoking (ß = - 0.32, p = 0.004), hemoglobin level (ß = - 0.40, p = 0.001) and LV mass index (ß = 0.24, p = 0.03) were determinants for resting coronary flow velocity. On the other hand, age (ß = -0.30, p = 0.008), hemoglobin level (ß = -0.47, p < 0.001) and LV mass index (ß = 0.24, p = 0.04) were determinants for hyperemic coronary flow velocity. Age was only determinant for CFR (ß = -0.48, p < 0.001). Our data suggested that that aging had a decreased effect on hyperemic coronary flow velocity rather than resting coronary flow velocity, and was further associated with impaired CFR in patients with no evidence of myocardial perfusion abnormality.

Outdoor-Cultivated Royal Sun Medicinal Mushroom Agaricus brasiliensis KA21 (Agaricomycetes) Reduces Anticancer Medicine Side Effects.

We investigated whether outdoor-cultivated Agaricus brasiliensis (KA21) could reduce the side effects caused by the anticancer medicine 5-fluorouracil (5-FU). The adverse effects of 5-FU were analyzed in mice by orally administering the drug every day for 5 days. Leukopenia, diarrhea, body weight loss, anorexia, kidney injury, gastrointestinal tract injury, and hair loss were evaluated as side effects. We determined whether these side effects were reduced by the intake of outdoor-cultivated A. brasiliensis. The side effects were reduced in mice receiving the outdoor-cultivated A. brasiliensis but not in those receiving the indoor-cultivated A. brasiliensis. These results suggest that outdoor-cultivated A. brasiliensis is beneficial in reducing the side effects of the anticancer medicine and might, therefore, be useful in improving the quality of life of patients with cancer. Furthermore, because antioxidants have been reported to contribute to the suppression of the side effects of anticancer medicines, the antioxidant activities of different mushrooms were determined. The antioxidant activity of the outdoor-cultivated A. brasiliensis was the highest among all the tested mushrooms. These findings make it clear that the cultivation conditions of A. brasiliensis are important in suppressing the side effects of anticancer medicines. Strong antioxidant activity might be one of the mechanisms through which this pharmacological activity is mediated.

Non-Invasive Central Venous Pressure Measurement Using Enclosed-Zone Central Venous Pressure (ezCVPTM).

BACKGROUND: Central venous pressure (CVP) is measured to assess intravascular fluid status. Although the clinical gold standard for evaluating CVP is invasive measurement using catheterization, the use of catheterization is limited in a clinical setting because of its invasiveness. We developed novel non-invasive technique, enclosed-zone (ezCVPTM) measurement for estimating CVP. The purpose of this study was to assess the feasibility of ezCVP and the relationship between ezCVP and CVP measured by a catheter.Methods and Results:We conducted 291 measurements in 97 patients. Linear regression analysis revealed that ezCVP was significantly correlated with CVP (r=0.65, P<0.0001). The Bland-Altman analysis showed that ezCVP had an underestimation bias of -2.5 mmHg with 95% limits of agreement of -14.1 mmHg and 9.6 mmHg for CVP (P<0.0001). The areas under the curves of receiver operating curve with ezCVP to detect the CVP ≥12 cmH2O (8.8 mmHg) and CVP >10 mmHg were 0.81 or 0.88, respectively. The sensitivity, specificity and positive likelihood ratio of ezCVP for the CVP ≥8.8 mmHg and CVP >10 mmHg were 0.59, 0.96 and 14.8 with a cut-off value of 11.9 and 0.79, 0.97 and 26.3 with a cut-off value of 12.7. CONCLUSIONS: These findings suggest that ezCVP measurement is feasible and useful for assessing CVP.

Frontal QRS-T angle and left ventricular diastolic function assessed by ECG-gated SPECT in the absence of significant perfusion abnormality.

The frontal QRS-T angle, defined as the angle between QRS and T-wave axes, has recently become an area of research interest. We tested the hypothesis that the frontal QRS-T angle is associated with left ventricular (LV) diastolic function in the absence of significant perfusion abnormality using ECG-gated SPECT. One hundred twenty eight patients with no significant perfusion abnormality and preserved LV ejection fraction were enrolled. The peak filling rate (PFR) and the one-third mean filling rate (1/3 MFR) were obtained as LV diastolic parameters on ECG-gated SPECT. There were 115 male and 13 female patients with a mean age of 70 ± 9 years. The PFR and 1/3 MFR were 2.1 ± 0.4/s and 1.2 ± 0.3/s, respectively. The frontal QRS-T angle was 33° ± 31°, ranging from 0° to 151°. There were significant associations of frontal QRS-T angle with PFR (r = - 0.29, p = 0.001) and 1/3 MFR (r = - 0.30, p < 0.001). Multivariate linear regression analysis showed that age (ß = - 0.25, p = 0.003), heart rate (ß = 0.26, p = 0.002), LV ejection fraction (ß = 0.43, p < 0.001) and frontal QRS-T angle (ß = - 0.16, p = 0.03) were significant factors associated with PFR. Also, heart rate (ß = - 0.32, p < 0.001), LV mass index (ß = - 0.19, p = 0.03), LV ejection fraction (ß = 0.30, p < 0.001) and frontal QRS-T angle (ß = - 0.26, p = 0.002) were significant factors associated with 1/3 MFR. Our data suggested that the frontal QRS-T angle was associated with LV diastolic function in the absence of significant perfusion abnormality.