A deep learning-based automated diagnosis system for SPECT myocardial perfusion imaging.

Images obtained from single-photon emission computed tomography for myocardial perfusion imaging (MPI SPECT) contain noises and artifacts, making cardiovascular disease diagnosis difficult. We developed a deep learning-based diagnosis support system using MPI SPECT images. Single-center datasets of MPI SPECT images (n = 5443) were obtained and labeled as healthy or coronary artery disease based on diagnosis reports. Three axes of four-dimensional datasets, resting, and stress conditions of three-dimensional reconstruction data, were reconstructed, and an AI model was trained to classify them. The trained convolutional neural network showed high performance [area under the curve (AUC) of the ROC curve: approximately 0.91; area under the recall precision curve: 0.87]. Additionally, using unsupervised learning and the Grad-CAM method, diseased lesions were successfully visualized. The AI-based automated diagnosis system had the highest performance (88%), followed by cardiologists with AI-guided diagnosis (80%) and cardiologists alone (65%). Furthermore, diagnosis time was shorter for AI-guided diagnosis (12 min) than for cardiologists alone (31 min). Our high-quality deep learning-based diagnosis support system may benefit cardiologists by improving diagnostic accuracy and reducing working hours.

Serum Apolipoprotein-A2 Levels Are a Strong Predictor of Future Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Because apolipoprotein-A2 (ApoA2), a key component of high-density lipoprotein cholesterol (HDL-C), lacks clear clinical significance, we investigated its impact on cardiovascular events in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: We examined 638 patients who underwent PCI with a new-generation drug-eluting stent for acute or chronic coronary syndrome and had their apolipoprotein levels measured between 2016 and 2021. The patients were divided into 2 groups based on the median serum ApoA2 values, and the incidence of major adverse cardiovascular events (MACE) was assessed. Of the 638 patients, 563 (88%) received statin treatment, with a median serum LDL-C level of 93 mg/dL. Furthermore, 137 patients (21.5%) experienced MACE, and Kaplan-Meier analysis revealed that the higher ApoA2 group had a significantly lower incidence of MACE than the lower ApoA2 group (30.9% vs. 41.6%). However, the other apolipoproteins, including ApoA1, ApoB, ApoC2, ApoC3, and ApoE, showed no significant differences in MACE. Multivariable Cox hazard analysis indicated that ApoA2 was an independent predictor of MACEs (hazard ratio, 0.666; 95% confidence interval, 0.465-0.954). Furthermore, ApoA2 levels exhibited the strongest inverse association with high-sensitivity C-reactive protein levels (rs=-0.479). CONCLUSIONS: Among all the apolipoproteins, the serum ApoA2 level may be the strongest predictor of future cardiovascular events and prognosis in patients undergoing PCI.

Analysis of patch testing with cocamidopropyl betaine and its impurities in patients with intractable scalp dermatitis in a single clinic in Japan.

BACKGROUND: The allergen responsible for cocamidopropyl betaine (CAPB) allergies has been debated. OBJECTIVES: To investigate the sensitizing agents of CAPB, the patch test positivity rates of impurities were examined in Japanese patients with CAPB-related allergic contact dermatitis. MATERIALS AND METHODS: Thirty patients with scalp dermatitis and positive patch tests for CAPB and/or lauramidopropyl betaine (LAPB) were enrolled in this study. They were patch tested with the detergents that they had been using at the time of their first visit and with the impurities dimethylaminopropylamine (DMAPA) and lauramidopropyl dimethylamine (LAPDMA). RESULTS: The positivity rate in patch tests of the 37 detergents that the patients had been using was 78.4% (29/37). The positivity rates of DMAPA 1% pet., 1% aq. and 0.2% aq. were 32.1% (9/28), 14.3% (4/28) and 13.3% (4/30), respectively, whereas those of LAPDMA 0.1% and 0.05% were 30.0% (9/30) and 16.7% (5/30), respectively. Among the 30 patients, 6 exhibited positive results for both DMAPA and LAPDMA, 3 showed positive results for DMAPA alone and 6 produced positive results for LAPDMA alone. CONCLUSION: Patch tests produced an overall positivity rate for DMAPA, LAPDMA or both of 50.0% (15/30) in patients with scalp dermatitis and positive patch test results for CAPB and/or LAPB.

Efficacy of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Treatment for Repeated In-stent Restenosis in a Coronary Artery.

A 57-year-old woman experienced chest pain. A coronary angiogram revealed middle left anterior descending artery stenosis. Despite receiving adequate anti-hyperlipidemia treatment and undergoing percutaneous coronary intervention (PCI), she experienced angina and required PCI six more times for in-stent restenosis. As she had high lipoprotein (a) [LP-(a)] levels at the seventh PCI procedure, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) was administered, and a reduction in the LP-(a) and low-density lipoprotein cholesterol (LDL-C) values was observed. She experienced no recurrence of angina for five years with PCSK9i treatment. PCSK9i can reduce not only LDL-C but also LP-(a) levels, resulting in cardiac event risk reduction.

Subendocardial Infarction in Severe Bicuspid Aortic Stenosis without Coronary Stenosis Confirmed by Contrast-enhanced Computed Tomography and Autopsy.

A 59-year-old man with aortic stenosis (AS) showed cardiopulmonary arrest requiring extracorporeal circulation. Although coronary angiography did not show coronary artery stenosis, he had an elevated creatine kinase-myocardial band value of 1,298 U/L. Echocardiography revealed severe AS and global hypokinesia of the thickened myocardium. Contrast-enhanced computed tomography (CT) detected a circumferential subendocardial perfusion defect of the left ventricular myocardium. Eventually, the patient died from brain anoxia. Autopsy revealed circumferential subendocardial infarction of the left ventricular myocardium. This is the first case of circumferential subendocardial defect on CT corresponding to circumferential subendocardial infarction on autopsy in severe AS without coronary stenosis.

A cell-based evaluation of human tyrosinase-mediated metabolic activation of leukoderma-inducing phenolic compounds.

BACKGROUND: Chemical leukoderma is a skin depigmentation disorder induced through contact with certain chemicals, most of which have a p-substituted phenol structure similar to the melanin precursor tyrosine. The tyrosinase-catalyzed oxidation of phenols to highly reactive o-quinone metabolites is a critical step in inducing leukoderma through the production of melanocyte-specific damage and immunological responses. OBJECTIVE: Our aim was to find an effective method to evaluate the formation of o-quinone by human tyrosinase and subsequent cellular reactions. METHODS: Human tyrosinase-expressing 293T cells were exposed to various phenolic compounds, after which the reactive o-quinones generated were identified as adducts of cellular thiols. We further examined whether the o-quinone formation induces reductions in cellular GSH or viability. RESULTS: Among the chemicals tested, all 7 leukoderma-inducing phenols/catechol (rhododendrol, raspberry ketone, monobenzone, 4-tert-butylphenol, 4-tert-butylcatechol, 4-S-cysteaminylphenol and p-cresol) were oxidized to o-quinone metabolites and were detected as adducts of cellular glutathione and cysteine, leading to cellular glutathione reduction, whereas 2-S-cysteaminylphenol and 4-n-butylresorcinol were not. In vitro analysis using a soluble variant of human tyrosinase revealed a similar substrate-specificity. Some leukoderma-inducing phenols exhibited tyrosinase-dependent cytotoxicity in this cell model and in B16BL6 melanoma cells where tyrosinase expression was effectively modulated by siRNA knockdown. CONCLUSION: We developed a cell-based metabolite analytical method to detect human tyrosinase-catalyzed formation of o-quinone from phenolic compounds by analyzing their thiol-adducts. The detailed analysis of each metabolite was superior in sensitivity and specificity compared to cytotoxicity assays for detecting known leukoderma-inducing phenols, providing an effective strategy for safety evaluation of chemicals.

[A CASE OF ALLERGIC CONTACT DERMATITIS CAUSED BY DETERGENTS CONTAINING COCAMIDOPROPYL BETAINE IN WHICH AN IMPURITY WAS THE POSSIBLE CAUSATIVE AGENT].

Cocamidopropyl betaine (CAPB) is an amphoteric surfactant. It has several functions, including producing effervescence and washing effects, and thus, it is used in many cleansing products, such as shampoo and liquid body cleansers. Recently, it has become clear that some impurities that arise during the manufacturing process can have sensitizing effects. Herein, we report a case of allergic contact dermatitis caused by detergents containing CAPB, in which an impurity was determined to be the possible causative agent by patch testing and chemical analysis.A 64-year-old Japanese female developed a skin rash on the hairlines of her forehead and nuchal region one month before her first visit to our clinic. Later, the rashes, which were composed of desquamative erythema, expanded to her face, neck, upper back, and chest. Patch tests produced positive results for a shampoo and liquid body cleanser (1% aq.) that she had used as well as for CAPB (1% aq.); lauramidopropyl betaine (LAPB) (1% aq.); and lauramidopropyl dimethylamine (LAPDMA) (0.05% aq.), which is an impurity of CAPB. The rashes resolved completely after we instructed her to use products without CAPB and LAPB. When issuing such instructions, clinicians should have correct knowledge about surfactants, such as the differences between cosmetic ingredient names and quasi-drug ingredient names.

Ventricular septal perforation naturally reduced in takotsubo cardiomyopathy.

An 80-year-old female was transferred to our hospital with dyspnea. Chest X-ray showed severe pulmonary congestion and electrocardiogram showed ST-segment elevation, abnormal Q, and negative T waves in leads V1-4. Transthoracic echocardiography demonstrated left ventricular apical akinesia with apical ventricular septal perforation. Emergent coronary angiography showed no coronary artery stenosis, and right-heart catheterization revealed a pulmonary to systemic flow ratio (Qp/Qs) of 2.2 on oximetry run. She was diagnosed with takotsubo cardiomyopathy with an associated complication of ventricular septal perforation. Her cardiac function gradually improved with nonsurgical treatment. An oximetry run performed 67 days later revealed that Qp/Qs decreased to 1.2. The size of ventricular septal perforation associated with takotsubo cardiomyopathy reduces naturally by conservative treatment, unlike that in acute myocardial infarction. .

Correlation Between the Japanese Version of the High Bleeding Risk (J-HBR) Criteria and the PRECISE-DAPT Score, and Optimal J-HBR Cut-Off Score to Predict Major Bleeding.

Background: The correlation between the Japanese version of high bleeding risk (J-HBR) criteria and the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score is unknown, as is the relationship of both risk scores with ischemic events. Methods and Results: This study enrolled 842 patients who underwent percutaneous coronary intervention (PCI) between January 2016 and December 2020. The 2 bleeding risk scores at the time of PCI and the subsequent risk of bleeding and ischemic events over a 1-year follow-up were examined. The J-HBR score was significantly correlated with the PRECISE-DAPT score (r=0.731, P<0.001). However, 1 year after PCI, the J-HBR was not significantly associated with the incidence of major bleeding and ischemic events (log-rank, P=0.058 and P=0.351, respectively), whereas the PRECISE-DAPT score predicted both the incidence of major bleeding and ischemic events (log-rank, P=0.006 and P=0.019, respectively). According to receiver operating characteristic curve analysis, a J-HBR score ≥1.5 was significantly associated with a higher cumulative incidence of major bleeding, but not ischemic events (log-rank, P=0.004 and P=0.513, respectively). Conclusions: The J-HBR score is highly correlated with the PRECISE-DAPT score. A J-HBR score ≥1.5 can identify high bleeding risk patients without an increased risk of ischemic events.

HSPA8 Single-Nucleotide Polymorphism Is Associated with Serum HSC70 Concentration and Carotid Artery Atherosclerosis in Nonalcoholic Fatty Liver Disease.

There is an association between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis, but the genetic risk of atherosclerosis in NAFLD remains unclear. Here, a single-nucleotide polymorphism (SNP) of the heat shock 70 kDa protein 8 (HSPA8) gene was analyzed in 123 NAFLD patients who had been diagnosed using a liver biopsy, and the NAFLD phenotype including the maximum intima-media thickness (Max-IMT) of the carotid artery was investigated. Patients with the minor allele (A/G or G/G) of rs2236659 showed a lower serum heat shock cognate 71 kDa protein concentration than those with the major A/A allele. Compared with the patients with the major allele, those with the minor allele showed a higher prevalence of hypertension and higher Max-IMT in men. No significant associations between the HSPA8 genotype and hepatic pathological findings were identified. In decision-tree analysis, age, sex, liver fibrosis, and HSPA8 genotype were individually associated with severe carotid artery atherosclerosis (Max-IMT ≥ 1.5 mm). Noncirrhotic men aged ≥ 65 years were most significantly affected by the minor allele of HSPA8. To predict the risk of atherosclerosis and cardiovascular disease, HSPA8 SNP genotyping might be useful, particularly for older male NAFLD patients.

Effect of skin-capsular distance on controlled attenuation parameter for diagnosing liver steatosis in patients with nonalcoholic fatty liver disease.

The effect of the skin-capsular distance (SCD) on the controlled attenuation parameter (CAP) for diagnosis of liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD) remains unclear. The SCD was measured using B-mode ultrasound, and the CAP was measured using the M probe of FibroScan®. According to the indications of the M probe, 113 patients with an SCD of ≤ 25 mm were included in the present study. The association between the SCD and CAP was investigated, and the diagnostic performance of the SCD-adjusted CAP was tested. The SCD showed the most significant positive correlation with the CAP (ρ = 0.329, p < 0.001). In the multiple regression analysis, the SCD and serum albumin concentration were associated with the CAP, independent of pathological liver steatosis. According to the multivariate analysis, two different formulas were developed to obtain the adjusted CAP using the SCD and serum albumin concentration as follows: adjusted CAP (dB/m) = CAP - (5.26 × SCD) and adjusted CAP (dB/m) = CAP - (5.35 × SCD) - (25.77 × serum albumin concentration). The area under the receiver operating characteristic curve for diagnosis of a steatosis score ≥ 2 of adjusted CAP was 0.678 and 0.684 respectively, which were significantly greater than the original CAP (0.621: p = 0.030 and p = 0.024). The SCD is associated with the CAP independent of liver steatosis. Adjustment of the CAP using the SCD improves the diagnostic performance of the CAP in NAFLD.

Zebrafish as a new model for rhododendrol-induced leukoderma.

Idiopathic leukoderma is a skin disorder characterized by patchy loss of skin pigmentation due to melanocyte dysfunction or deficiency. Rhododendrol (RD) was approved as a cosmetic ingredient in Japan in 2008. However, it was shown to induce leukoderma in approximately 20,000 customers. The prediction of cytotoxicity, especially to melanocytes in vivo, is required to avoid such adverse effects. Since the use of higher vertebrates is prohibited for medicinal and toxicological assays, we used zebrafish, whose melanocytes were regulated by mechanisms similar to mammals. Zebrafish larvae were treated with RD in breeding water for 3 days, which caused body lightening accompanied by a decrease in the number of melanophores. Interestingly, black particles were found at the bottom of culture dishes, suggesting that the melanophores peeled off from the body. In addition, RT-PCR analysis suggested that the mRNA levels of melanophore-specific genes were significantly low. An increase in the production of reactive oxygen species was found in larvae treated with RD. The treatments of the fish with other phenol compounds, which have been reported to cause leukoderma, also induced depigmentation and melanophore loss. These results suggest that zebrafish larvae could be used for the evaluation of leukoderma caused by chemicals, including RD.

Prediction of Nonalcoholic Fatty Liver Disease Using Noninvasive and Non-Imaging Procedures in Japanese Health Checkup Examinees.

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index (p < 0.001) and FLI (p = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis.

A phase I/IIa double blind single institute trial of low dose sirolimus for Pendred syndrome/DFNB4.

INTRODUCTION: Pendred syndrome (PDS)/DFNB 4 is a disorder with fluctuating and progressive hearing loss, vertigo, and thyroid goiter. We identified pathophysiology of a neurodegenerative disorder in PDS patient derived cochlear cells that were induced via induced pluripotent stem cells and found sirolimus, an mTOR inhibitor, as an inhibitor of cell death with the minimum effective concentration less than 1/10 of the approved dose for other diseases. Given that there is no rational standard therapy for PDS, we planned a study to examine effects of low dose oral administration of sirolimus for the fluctuating and progressive hearing loss, and the balance disorder of PDS by daily monitor of their audio-vestibular symptoms. METHODS AND ANALYSIS: This is a phase I/IIa double blind parallel-group single institute trial in patient with PDS/DFNB4. Sixteen of outpatients with fluctuating hearing diagnosed as PDS in SLC26A4 genetic testing aged in between 7 and 50 years old at the time of consent are given either placebo or sirolimus tablet (NPC-12T). In NPC-12T placebo arm, placebo will be given for 36 weeks; in active substance arm, placebo will be given for 12 weeks and the NPC-12T for 24 weeks. Primary endpoints are safety and tolerability. The number of occurrences and types of adverse events and of side effects will be sorted by clinical symptoms and by abnormal change of clinical test results. A 2-sided 95% confidence interval of the incidence rate by respective dosing arms will be calculated using the Clopper-Pearson method. Clinical effects on audio-vestibular tests performed daily and precise physiological test at each visit will also be examined as secondary and expiratory endpoints. TRIAL REGISTRATION NUMBER: JMA-IIA00361; Pre-results.

Accuracy of the Enhanced Liver Fibrosis test, and combination of the Enhanced Liver Fibrosis and non-invasive tests for the diagnosis of advanced liver fibrosis in patients with non-alcoholic fatty liver disease.

AIM: The Enhanced Liver Fibrosis (ELF) test comprises a logarithmic algorithm combining three serum markers of hepatic extracellular matrix metabolism. We aimed to evaluate the performance of ELF for the diagnosis of liver fibrosis and to compare it with that of liver stiffness measurement (LSM) by FibroScan in non-alcoholic fatty liver disease. METHODS: ELF cut-off values for the diagnosis of advanced fibrosis were obtained using receiver operating characteristic analysis in patients with biopsy-confirmed non-alcoholic fatty liver disease (training set; n = 200). Diagnostic performance was analyzed in the training set and in a validation set (n = 166), and compared with that of LSM in the FibroScan cohort (n = 224). RESULTS: The area under receiver operating characteristic curve was 0.81 for the diagnosis of advanced fibrosis, and the ELF cut-off values were 9.34 with 90.4% sensitivity and 10.83 with 90.6% specificity in the training set, and 89.8% sensitivity and 85.5% specificity in the validation set. There was no significant difference in the area under the receiver operating characteristic curve between ELF and LSM (0.812 and 0.839). A combination of ELF (cut-off 10.83) and LSM (cut-off 11.45) increased the specificity to 97.9% and the positive predictive value, versus ELF alone. Sequential use of the Fibrosis-4 index (cut-off 2.67) and ELF (cut-off 9.34) increased the sensitivity to 95.9%. CONCLUSIONS: ELF can identify advanced liver fibrosis in non-alcoholic fatty liver disease, and its diagnostic accuracy is comparable to that of FibroScan. According to the clinical setting, combinations or sequential procedures using other non-invasive tests complement the diagnostic performance of ELF for the identification of advanced fibrosis.

Chronic pancreatitis and pancreatic pseudocyst with adult-onset type II citrullinemia.

Citrin deficiency, which is caused by a mutation of SCL25A13, can manifest in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD) and in adults as recurrent hyperammonemia with neuropsychiatric symptoms in adult-onset type II citrullinemia (CTLN2). FTTDCD and CTLN2 are known to complicate hypertriglyceridemia and chronic pancreatitis. Here we report, for the first time, the case of a patient with chronic pancreatitis and pancreatic pseudocyst with CTLN2 who was treated using endoscopic ultrasound-guided cyst drainage (EUS-CD). A 33-year-old woman with down syndrome presented to our hospital with complaints of fever, abdominal distention, and biliary vomiting for the previous 2 weeks. Owing to her difficulties in communication, although she had been taking a nutritionally balanced diet regardless of her preference, chronic pancreatitis and pancreatic stones had already been observed at the time of CTLN2 diagnosis at the age of 30 years. Three years later, a merged pancreatic pseudocyst was detected, and EUS-CD was successfully performed. A high-fat diet therapy for FTTDCD and CTLN2 may have caused the development of the pancreatic pseudocyst combined with chronic pancreatitis in this case. Pancreatic pseudocysts associated with FTTDCD or CTLN2 can be treated in a similar manner to those resulting from other causes.

Impact of glycemic variability on myocardial infarct size in patients with ST-segment elevation myocardial infarction: quantitative assessment of left ventricular wall motion severity.

Glycemic variability (GV) is relevant to impaired myocardial salvage in acute ST-elevation myocardial infarction (STEMI). Severity of hypokinesis at the infarct site as assessed from contrast left ventriculography can reportedly predict infarct size in STEMI. We prospectively studied 58 consecutive patients (mean age, 63 ± 11 years) with anterior or inferior STEMI who underwent successful reperfusion therapy. Mean amplitude of glucose excursion (MAGE) was obtained from continuous glucose monitoring system. Patients were divided into the upper tertile of MAGE as Group H, and the other two-thirds as Group L. Serial regional wall motion severity at the infarct site was computed postprocedure and at follow-up using a quantitative left ventricular analysis system. Impaired myocardial salvage was defined as severity recovery ratio < 20%. Significantly shorter onset-to-balloon time (196.9 vs. 279.0 min, p = 0.033) and relatively lower postprocedural wall motion severity (2.4 vs. 2.9, p = 0.096) were observed in Group H, but absolute severity recovery was significantly smaller in Group H (0.5 vs. 1.3, p = 0.017). Multivariate analysis showed higher MAGE as predictive of impaired myocardial salvage (OR, 406.10; 95% CI, 4.41-37,366.60; p = 0.009). Recovery of reginal wall motion severity at the infarct site was compromised in STEMI patients with higher MAGE. Our results suggest that final infarct size is potentially larger than expected in STEMI patients with higher GV.

Supplementation with branched-chain amino acids ameliorates hypoalbuminemia, prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis induces marked metabolic disorders, protein-energy malnutrition, and sarcopenia. The objective of the study reported here was to investigate the effects of dietary branched-chain amino acids (BCAAs) on systemic glucose metabolism, skeletal muscle, and prognosis of patients with liver cirrhosis. METHODS: Japanese patients with liver cirrhosis (n = 21) were enrolled into a longitudinal study in which their diets were supplemented with BCAAs. We evaluated glucose metabolism and analyzed the skeletal muscle area index (SAI) and intramuscular adipose tissue content (IMAC) using computed tomography. RESULTS: After 48 weeks of supplementation with BCAAs, there were no changes in glucose metabolism and skeletal muscle findings. In patients with ameliorated hypoalbuminemia, IMAC was significantly decreased and SAI was preserved concomitant with decreasing 90- and 120-min post-challenge plasma glucose levels (P < 0.01 each). In patients without increased albumin levels, IMAC was significantly increased and the SAI was significantly decreased (P < 0.01 each). Liver-related event-free survival rates for 72 months were 63.6% in patients with decreased IMAC and 20.0% in patients with increased IMAC. CONCLUSIONS: Amelioration of hypoalbuminemia associated with BCAA supplementation correlated with decreased fat accumulation in skeletal muscle, maintenance of skeletal muscle mass, and improved glucose sensitivity, all factors which may contribute to improving the survival of patients with liver cirrhosis.

Risk assessment of skin lightening cosmetics containing hydroquinone.

Following reports on potential risks of hydroquinone (HQ), HQ for skin lightening has been banned or restricted in Europe and the US. In contrast, HQ is not listed as a prohibited or limited ingredient for cosmetic use in Japan, and many HQ cosmetics are sold without restriction. To assess the risk of systemic effects of HQ, we examined the rat skin permeation rates of four HQ (0.3%, 1.0%, 2.6%, and 3.3%) cosmetics. The permeation coefficients ranged from 1.2 × 10-9 to 3.1 × 10-7 cm/s, with the highest value superior than the HQ aqueous solution (1.6 × 10-7 cm/s). After dermal application of the HQ cosmetics to rats, HQ in plasma was detected only in the treatment by highest coefficient cosmetic. Absorbed HQ levels treated with this highest coefficient cosmetic in humans were estimated by numerical methods, and we calculated the margin of exposure (MOE) for the estimated dose (0.017 mg/kg-bw/day in proper use) to a benchmark dose for rat renal tubule adenomas. The MOE of 559 is judged to be in a range safe for the consumer. However, further consideration may be required for regulation of cosmetic ingredients.