[Anti-diabetic effect of ethanol extract of Cyclolepis genistoides D. Don (Palo azul), made in Paraguay].

Extract of Cyclolepis genistoides D. Don (vernacular name Palo azul; Palo) are traditionally consumed in the Republic of Paraguay in South America for the treatment of diabetes and kidney disease, and is sold in Japan as dietary supplement. This study aimed to elucidate the mechanism of anti-diabetes activity of Palo, especially focused on insulin resistance. Palo promoted adipocytes differentiation and regulated adipokine profiles in 3T3-L1 adipocytes by modulation of PPARγ, a major regulator of adipose differentiation. Human adipocyte showed almost similar profile with 3T3-L1 against Palo treatment. Furthermore, Palo treatment (250 or 1000 mg/kg) was performed with C57BL/6J mice for 14 weeks, being fed high-fat-diet (HFD60) simultaneously. Palo 250 mg/kg exhibited a tendency to decrease subcutaneous adipose volume along with increase of PPARγ and its target, adiponectin mRNA expression. In addition, as the other insulin targeted cell, effect on muscle differentiation was examined. Palo increased differentiation of C2C12 mouse muscle myoblasts by increase of IGF-1, myogenin, and myosine heavy chain (MHC) as well as 5'-AMP-activated protein kinase (AMPK) activation. Palo subsequently promoted myotube formation under differentiation condition. From the above, it was clarified that Palo acts variously on the differentiation and maturation of both adipocytes and muscle cells, and from the viewpoint of the regulatory mechanism for adipocytes, PPARγ-inducing action was shown to be a mechanism that acts across species.

Endoscopic removal of foreign bodies: A retrospective study in Japan.

BACKGROUND: The ingestion of foreign bodies (FBs) and food bolus impaction (FBI) in the digestive tract are commonly encountered clinical problems. Methods to handle such problems continue to evolve offering advantages, such as the avoidance of surgery, reduced cost, improved visualization, reduced morbidity, and high removal success rate. However, to date, no studies have evaluated the endoscopic management of FBs in Japan. AIM: To elucidate level of safety and efficacy in the endoscopic management of FBs and FBI. METHODS: A total of 215 procedures were performed at Keio University Hospital between November 2007 and August 2018. Data were collected from medical charts, and endoscopic details were collected from an endoscopic reporting system. Procedures performed with a flexible gastrointestinal endoscope were only taken into account. Patients who underwent a technique involving FB or FBI from the digestive tract were only included. Data on patient sex, patient age, outpatient, inpatient, FB type, FB location, procedure time, procedure type, removal device type, success, and technical complications were reviewed and analyzed retrospectively. RESULTS: Among the 215 procedures, 136 (63.3%) were performed in old adults (≥ 60 years), 180 (83.7%) procedures were performed in outpatients. The most common type of FBs were press-through-pack (PTP) medications [72 (33.5%) cases], FBI [47 (21.9%)], Anisakis parasite (AP) [41 (19.1%) cases]. Most FBs were located in the esophagus [130 (60.5%) cases] followed by the stomach [68 (31.6%) cases]. AP was commonly found in the stomach [39 (57.4%) cases], and it was removed using biopsy forceps in 97.5% of the cases. The most common FBs according to anatomical location were PTP medications (40%) and dental prostheses (DP) (40%) in the laryngopharynx, PTP (48.5%) in the esophagus, AP (57.4%) in the stomach, DP (37.5%) in the small intestine and video capsule endoscopy device (75%) in the colon. A transparent cap with grasping forceps was the most commonly used device [82 (38.1%) cases]. The success rate of the procedure was 100%, and complication were observed in only one case (0.5%). CONCLUSION: Endoscopic management of FBs and FBI in our Hospital is extremely safe and effective.

Expression of precipitating factors of pruritus found in humans in an imiquimod-induced psoriasis mouse model.

AIMS: To use a mouse model of imiquimod-induced psoriasis to investigate the relationship between pruritus and mast cells, nerve growth factor (NGF) and endogenous pruritogenic peptides, which are highly expressed in the skin of psoriasis patients. MAIN METHODS: We developed a mouse model of imiquimod-induced psoriasis and measured the frequency and duration of the model animals' self-scratching behavior using the SCLABA®-Real real-time scratch counting system. We then harvested the ears and subjected them to toluidine blue staining and real-time PCR. KEY FINDINGS: Topical application of imiquimod increased the Psoriasis Area and Severity Index score as well as the frequency and duration of self-scratching. Regarding internal factors, increases in mast cells number and mRNA expression of NGF and endogenous pruritogenic peptide precursor were confirmed. SIGNIFICANCE: Self-scratching behavior is accompanied by increased number of mast cells and expression of NGF and endogenous pruritogenic peptides in our imiquimod-induced psoriasis model. The expression of these factors was consistent with the features in patients with pruritic psoriasis, suggesting that our model reflects at least some of the precipitating factors of pruritus found in humans.

Trichostatin A modulates cellular metabolism in renal cell carcinoma to enhance sunitinib sensitivity.

Although sunitinib is the first-line drug for progressive renal cell carcinoma (RCC), most patients experience its tolerance. One possible way of overcoming drug resistance is combination therapy. Epigenetic modifier is one of the candidate drug group. A recent evidence suggests that cell metabolism is regulated by epigenetic mechanisms. Epigenetic abnormalities lead to changes in metabolism and may contribute to drug resistance and progression of RCC. Consequently, we investigated whether trichostatin A (TSA), a potent histone-deacetylase (HDAC) inhibitor, alters sunitinib-induced cytotoxicity and metabolism in RCC cells at epigenetic regulatory concentrations. Combined metabolome and transcriptome analysis suggested that TSA impacts on energy productive metabolic pathways, such as those involving TCA cycle and nucleotide metabolism especially for increase of hyperphosphorylated form. Combination of sunitinib and TSA increased cell death with PARP cleavage, an early marker of mitochondrial apoptosis, whereas receptor tyrosine kinase signaling, which is the target of sunitinib, was not altered by TSA. Finally, the established sunitinib resistant-RCC cell (786-O Res) was also exposed to sunitinib and TSA combination, resulting in significant growth inhibition. In summary, it was suggested that TSA reduces sunitinib resistance by triggering intracellular metabolome shifts regarding energy metabolism, that is the first recognized mechanism as an HDAC inhibitor.

Sodium butyrate enhances the growth inhibitory effect of sunitinib in human renal cell carcinoma cells.

Sunitinib (SU) is a small molecule that inhibits the receptor tyrosine kinase (RTK) signaling pathway, and has been clinically used to treat advanced renal cell carcinoma (RCC). However, SU is not always effective as RCC is a highly chemoresistant type of cancer. One of the factors that confer chemoresistance to RCC is a hypoxic condition. Lack of oxygen activates hypoxia-inducible factor (HIF) protein, which is followed by the upregulation of growth factors, including vascular endothelial growth factor and activation of the RTK signaling pathway. In this context, histone deacetylase inhibitors (HDACIs) are considered prominent combined agents for SU as they downregulate the expression of HIFs. Therefore, the present study aimed to investigate the effectiveness of combined treatment with SU and sodium butyrate (NaBu), an HDACI. Long-term exposure to these agents exerted a stronger growth inhibitory effect in RCC cell lines compared with single treatment groups. Furthermore, combined treatment suppressed HIF-2α protein, which was induced under hypoxic conditions. In addition, this combination sustained the activity of the RTK signaling pathway to the level of intact cells, although a single treatment with SU or NaBu was demonstrated to increase this activity. Overall, it is suggested that the combination of SU and NaBu is effective for overcoming drug resistance in RCC.

Connexin 43 enhances Bax activation via JNK activation in sunitinib-induced apoptosis in mesothelioma cells.

The constituent protein of gap junctions, connexin (Cx), interacts with various proteins via its C-terminus region, including kinases, cell-adhesion proteins, and a pro-apoptotic protein, Bax. This molecular interaction may affect expression and functioning of the interacting proteins and modulate the cellular physiology. In our previous work, Cx43 was found to interact directly with Bax and in the presence of sunitinib, lead to the Bax-mediated apoptosis in mesothelioma cells. In this study, we investigated the mechanism of how Cx43 promotes Bax-mediated apoptosis using the same cell line. Treatment with sunitinib increased the expression of the active conformation of the Bax protein, which was predominantly localized at the mitochondria, only in Cx43-transfected cells. Bax oligomerization and decrease in the mitochondrial membrane potential were also observed. The involvement of c-Jun N-terminal kinase (JNK) in the interaction of Cx43 and Bax was further examined. Treatment with sunitinib increased the expression of phosphorylated (active) form of JNK only in the Cx43-transfected cells. Phosphorylated JNK and active Bax were co-localized, and the co-localization was suppressed by the knockdown of Cx43. Moreover, JNK inhibition clearly suppressed Bax activation. In conclusion, we identified a novel Cx43-JNK-Bax axis regulating the process of apoptosis for the first time.

Ethanol extract of Cyclolepis genistoides D. Don (palo azul) induces formation of myotubes, which involves differentiation of C2C12 myoblast cells.

In this study, we examined the cell differentiation effect of an ethanol extract of Cyclolepis genistoides D. Don, a herbaceous perennial belonging to the family Asteraceae (vernacular name: palo azul). Palo azul has numerous physiological effects that contribute to the prevention of metabolic syndromes, although the mechanism remains unclear. We previously suggested that palo azul has antidiabetic activity via an adipose differentiation effect. Here, we focused on whether palo azul promoted the differentiation of myoblasts. The mouse muscle myoblast cell line C2C12 was cultured and differentiated using horse serum with or without an ethanol extract of palo azul (12.5-200 µg/mL). Quantitative real-time polymerase chain reaction was performed to evaluate differentiation markers, including insulin-like growth factor-1 and myogenin. To evaluate myotube formation, myosin heavy-chain (MHC) expression and localization were detected by immunohistochemistry. Palo azul increased the expression of the differentiation markers. Furthermore, immunohistochemistry analysis revealed increased formation of MHC myotubes after palo azul treatment along with increased diameter and fusion indices of the myotubes. The expression level of MHC was also increased. In conclusion, palo azul may increase muscle mass in the body and improve insulin resistance conditions by facilitating the formation of myotubes by promoting myocyte differentiation.

Crowned dens syndrome: reports of six cases and review of the literature.

Case: We have reported six cases of Crowned dens syndrome (CDS) diagnosed by computed tomography (CT). Presenting cases were three male and three female, aged from 45 to 89 (averaged in 72). Outcome: All cases showed calcification around the dens of axis in CTs. Neck pain in all cases relieved within at least 10 days, treated by non-steroidal anti-inflammatory drugs (NSAIDs) in five cases, and one by acetaminophens. Conclusion: Bouvet et al. first reported CDS in 1985, as acute pseudogout of the neck, which causes neck pain. CDS is a radioclinical syndrome defined by the radiographic calcifications in a crown-like configuration around the odontoid process, accompanied clinically by acute neck pain, often with neck stiffness, fevers and raised inflammatory markers. CDS is thought to be a rare condition; however, it is frequently misdiagnosed. CDS is an important differential diagnosis in patients presenting with acute neck pain.

Protective effect of young green barley leaf (Hordeum vulgare L.) on restraint stress-induced decrease in hippocampal brain-derived neurotrophic factor in mice.

BACKGROUND: Many health experts support the hypothesis that stressful lifestyles are the leading cause of illness, like depression. Therefore, from the standpoint of preventive medicine, it is important to reduce stress. Young green barley leaves are a good natural source of vitamins and minerals, and their juice is widely consumed as a functional food for health reasons in Japan. This study investigated the protective effect of young green barley leaves for stress control. MATERIALS AND METHODS: ICR outbred mice were exposed to 3-h sessions of restraint stress. Young green barley leaves (400 and 1,000 mg/kg) were administered orally 1 h before the sessions for 5 days. To analyze voluntary behavior, wheel-running activity was monitored during the dark period. Brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) expression in the whole hippocampus was measured by real-time quantitative polymerase chain reaction. RESULTS: Restraint stress resulted in a significant decrease in voluntary wheel-running behavior, but this decrease was ameliorated by the administration of young green barley leaves. The leaves also enhanced the decreased levels of BDNF mRNA induced by restraint stress; in particular, a significant protective effect was shown in the exon IV variant as compared to vehicle control mice. CONCLUSION: The findings suggest that young green barley leaves have potent anti-stress properties, as evidenced by preventing decreases in the levels of voluntary wheel-running activity and hippocampal BDNF mRNA in response to restraint stress. Our findings support the possibility that supplementation with young green barley leaves might be beneficial for preventing stress-related psychiatric disorders like depression.

Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells.

Connexin (Cx) makes up a type of intercellular channel called gap junction (GJ). GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43) (the most ubiquitous Cx subtype) expression on sunitinib (SU)-induced cytotoxicity in malignant mesothelioma (MM) cells. Increased Cx43 expression in an MM cell line (H28) improved the ability of SU to inhibit receptor tyrosine kinase (RTK) signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active) form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells.

Elacridar enhances the cytotoxic effects of sunitinib and prevents multidrug resistance in renal carcinoma cells.

Intrinsic drug resistance occurs in many renal carcinomas and is associated with increased expression of multidrug resistant proteins, which inhibits intracellular drug accumulation. Multidrug resistant protein 1, also known as P-glycoprotein, is a membrane drug efflux pump belonging to the ATP-binding cassette (ABC) transporter superfamily. ABC Sub-family B Member 2 (ABCG2) is widely distributed and is involved in the multidrug resistant phenotype. Sunitinib is a tyrosine kinase inhibitor used to treat kidney cancer that disrupts signaling pathways responsible for abnormal cancer cell proliferation and tumor angiogenesis. Multiple drug resistance is important in tyrosine kinase inhibitor-induced resistance. We hypothesized that inhibition of multidrug resistant transporters by elacridar (dual inhibitor of P-glycoprotein and ABCG 2) might overcome sunitinib resistance in experimental renal cell carcinoma. Human renal carcinoma cell lines 786-O, ACHN, and Caki-1 were treated with sunitinib or elacridar alone, or in combination. We showed that elacridar significantly enhanced sunitinib cytotoxicity in 786-O cells. P-glycoprotein activity, confirmed by P-glycoprotein function assay, was found to be inhibited by elacridar. ABCG2 expression was low in all renal carcinoma cell lines, and was suppressed only by combination treatment in 786-O cells. ABCG2 function was inhibited by sunitinib alone or combination with elacridar but not elacridar alone. These findings suggest that sunitinib resistance involves multidrug resistance transporters, and in combination with elacridar, can be reversed in renal carcinoma cells by P-glycoprotein inhibition.

[Expression and function of the histamine receptors in dermal and articular tissues].

Histamine was first identified in 1910 as a physiologically active amine. It is now recognized for its multiple regulatory activities in the digestive, neuronal, and immune systems, and new roles are still being elucidated. Histamine exerts its effects through four distinct receptor subtypes. The histamine H4 receptor was identified in 2000 and is the most recently identified of the four histamine receptors. It is expressed primarily in immune cells and is involved in physiologic functions related to inflammation and allergy. Recently, the H4 receptor was highlighted as a promising therapeutic target in atopic dermatitis, asthma, and chronic arthritis. In fact, some H4 receptor antagonists have reached clinical trials for the treatment of asthma, atopic dermatitis, and allergic rhinitis. Based on an initial assessment of its distribution, the H4 receptor has been referred to as the histamine receptor of the hematopoietic system. However, the H4 receptor has also been implicated in the regulation of other non-hematopoietic systems. Here, I review the expression and function of the identified histamine receptors, including the H4 receptor with a focus on articular and dermal tissues. In articular tissue, H4 receptor expression has been detected in synovial cells. Chondrocytes, a major cell source for cartilage tissue engineering, also express the H4 receptor. In skin, the H4 receptor is expressed in both the epidermis and dermis, with stronger receptor expression in the epidermis. Further understanding of the functions of H4 receptors in non-hematopoietic cells might lead to novel treatments for diseases with unmet medical needs.

Sex hormones influence expression and function of peroxisome proliferator-activated receptor γ in adipocytes: pathophysiological aspects.

Abstract Adipose tissue plays important roles not only in storing fat but also in maintaining metabolic homeostasis by regulating hundreds of biological signaling events and the secretion of various cytokines. One of the central regulators of adipocyte differentiation is peroxisome proliferator-activated receptor γ (PPARγ), which promotes downstream transcriptional activities, such as adiponectin. Disruption of homeostasis leads to the onset of metabolic diseases such as type 2 diabetes and other triggers for metabolic syndrome. Males and post-menopausal females are more likely to be affected with metabolic diseases than pre-menopausal females, suggesting that sex hormones might be involved in the pathogenesis and development of metabolic diseases. Indeed, 17ß-estradiol, testosterone, dihydrotestosterone, and their receptors clearly play a role in adipose regulation: they can alter fat distribution and can modify the expression and activities of PPARγ and its downstream adipocytokines. Furthermore, sex hormones affect inflammatory factors such as nitric oxygen, nitric oxygen synthase, and their surrounding components. Sex hormones are also suggested to be involved with sex differences in the efficacy of the PPARγ agonist thiazolidinediones. Therefore, thorough investigation of how sex hormone-dependent regulation of metabolic homeostasis occurs is necessary in order to develop individualized clinical therapies optimized with regard to each patient's biological condition and drug sensitivities.

Identification of a predictive biomarker for the beneficial effect of keishibukuryogan, a kampo (Japanese traditional) medicine, on patients with climacteric syndrome.

Keishibukuryogan (KBG; Guizhi-Fuling-Wan in Chinese) is one of the Kampo (Japanese traditional) medicines used to treat patients with climacteric syndrome. KBG can be used by patients who cannot undergo hormone replacement therapy due to a history of breast cancer. We evaluated whether cytosine-adenine (CA) repeat polymorphism of the estrogen receptor ß gene can be a predictor of the beneficial effect of KBG on climacteric syndrome. We also investigated the relationship between CA repeat polymorphism, the patients' profiles, and the therapeutic effect. We found that CA was an SS, SL, or LL genotype according to the number of repeats. We studied 39 consecutive patients with climacteric disorders who took KBG for 12 weeks. The diagnosis of climacteric disorders was made on the basis of the Kupperman index. KBG significantly improved the patients' climacteric symptoms (i.e., vasomotor symptoms in the patients with the LL genotype and melancholia in the patients with the SL genotype). No relationship between the patients' profiles and CA repeat polymorphism was recognized. CA repeat polymorphism could thus be a potential biomarker to predict the efficacy of KBG in climacteric syndrome, and its use will help to reduce the cost of treating this syndrome by focusing the administration of KBG on those most likely to benefit from it.

Sex-related differences in SLIGRL-induced pruritus in mice.

AIMS: Pruritus is a common symptom of skin diseases, and is associated with impaired sleep quality and a considerable reduction in the patient's quality of life. Recently, it was reported that there are sex-specific differences in scratching behavior in chronic pruritus patients. Namely, female chronic pruritus patients scratch more and have significantly more scratch lesions than male patients. However, few animal studies have examined sex-related differences in scratching behavior. Thus, the present work investigated sex-related differences in animal pruritus using pruritogens, which are often used to create experimental animal models of itching. MAIN METHODS: Acute pruritus was induced in ICR mice by a single intradermal injection of histamine, 4-methylhistamine, serotonin, compound 48/80, substance P (SP), or the proteinase-activated receptor-2 (PAR-2)-activating peptide SLIGRL-NH2. Chronic pruritus was induced by 5 weeks of the repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) to BALB/c mice. KEY FINDINGS: Female mice showed significantly higher scratching counts in SLIGRL-NH2-induced pruritus than male mice. Conversely, there was no obvious sex-related difference in scratching behavior for the other pruritogens examined. SIGNIFICANCE: These results indicate that sex-related differences may exist in the pruritogen-responsive neurons that transmit the itch signal induced by SLIGRL-NH2, but not by histamine or 5-HT.

Increased expression of the histamine H4 receptor following differentiation and mediation of the H4 receptor on interleukin-8 mRNA expression in HaCaT keratinocytes.

Recent in vivo studies have demonstrated involvement of the histamine H4 receptor in pruritus and skin inflammation. We previously reported that an H4 receptor antagonist attenuated scratching behaviour and improved skin lesions in an experimental model of atopic dermatitis. We also reported the expression of the H4 receptor in human epidermal tissues. In this study, we investigated the expression of H4 receptor mRNA and the function of the receptor in a culture system that mimics in vivo inflammation on the HaCaT human keratinocyte cell line. Increased expression of the H4 receptor was observed in HaCaT cells following differentiation. Treatment of HaCaT cells with histamine and TNFα enhanced the mRNA expression of interleukin (IL)-8. These increases in expression were significantly inhibited by the H4 receptor antagonist JNJ7777120. Our results indicate that IL-8 mRNA expression might be enhanced by histamine and TNFα via H4 receptor stimulation in keratinocytes.

Sex differences in stress reactivity of hippocampal BDNF in mice are associated with the female preponderance of decreased locomotor activity in response to restraint stress.

The incidence and prevalence of depression is higher in women than in men, but the cause of this sex discrepancy remains unknown. Brain-derived neurotrophic factor (BDNF) is a key protein for maintaining neuronal integrity. The purpose of this study was to investigate the female preponderance in behavioral responsivity to restraint stress focusing on the stress reactivity of BDNF in the hippocampus. Male and female ICR mice were exposed to a 3-h session of restraint stress. Plasma corticosterone was measured by high-performance liquid chromatography. BDNF mRNA expression in the whole hippocampus was measured by quantitative real-time reverse transcription-polymerase chain reaction. Wheel-running activity was monitored during the dark period. In response to restraint stress, the increase in levels of serum corticosterone was higher in female than in male mice. Restraint stress resulted in decreased voluntary wheel-running behavior that was greater in female than male animals. In addition to these sex differences in stress reactivity, we found a significant sex difference in BDNF levels in the hippocampus of restraint-stressed mice; total BDNF levels significantly decreased in female mice, but not in male mice in response to the stress. Furthermore, BDNF exon I and IV mRNA expression also showed the same tendency. These data indicate that the reduction in levels of voluntary wheel-running activity in response to stress can be significantly influenced by sex. Moreover, our findings suggest a link between the sex differences in this behavioral response to stress and differential stress reactivity in the production of BDNF in the hippocampus.

Cyclolepis genistoides D. Don (palo azul) promotes differentiation of adipocytes and regulates adipokine expression.

Cyclolepis genistoides D. Don is a herbaceous perennial belonging to the family Asteraceae, and its vernacular name is "palo azul" (palo). Palo has been reported to exhibit many physiological effects that contribute to the prevention of metabolic syndromes, although its mechanism is unclear. Among palo's various activities, we investigated the hypothesis that palo promotes adipocytes differentiation and regulates adipokine profiles in 3T3-L1 adipocytes by modulation of peroxisome proliferator-activated receptor (PPAR) γ, a major regulator of adipose differentiation. 3T3-L1 adipocytes were cultured and differentiated in Dulbecco modified Eagle medium with 50 to 200 µg/mL palo for 7 days or were cultured with palo without differentiation protocol for 14 days. Palo down-regulated the expression of 2 types of expressed/secreted adipokines, leptin and resistin, in a concentration-dependent manner. Under a nondifferentiated condition, palo promoted the accumulation of lipid droplets in cells. Real-time polymerase chain reaction and luciferase reporter assay showed that palo up-regulated expression and transcriptional activity of PPARγ. Furthermore, palo increased the expression of insulin-sensitizing adipokine, adiponectin, which is a directly target of PPARγ, both at the messenger RNA level and at the protein level. In summary, palo demonstrated the potential to improve insulin resistance by promoting adipocyte differentiation via PPARγ activation. Results suggest an increase in adiponectin secretion and a decrease in insulin-resistant factors such as leptin and resistin.

Difficulty for consumers in choosing commercial bilberry supplements by relying only on product label information.

BACKGROUND: Various kinds of bilberry supplements have recently become available on the market. However, it is doubtful whether consumers receive accurate information to be able to compare different supplements. OBJECTIVE: We aimed to investigate whether consumers can obtain the expected benefits by relying only on the information printed on the product labels of commercial bilberry supplements. MATERIALS AND METHODS: The quality of 20 supplements was investigated by the spectrophotometric method and ultra high performance liquid chromatography (UHPLC). Each peak was identified by liquid chromatography-mass spectrometry and quantified using an external standard. The percentage of the actual measured value relative to the indicated value on the product label was determined using the spectrophotometric method. The daily dosage was calculated from the total amount of anthocyanins quantified by UHPLC and information on the product label. RESULTS: In 14 of 20 supplements, the total anthocyanin content expressed as delphinidin equivalents was within 20% of the labeled value. However, the extent of degradation could not be determined by the spectrophotometric method. In fresh bilberry fruit, anthocyanidins were barely detected. In 8 of 20 supplements, the anthocyanidin content was >1.0%. The daily dosage of anthocyanins varied by about 66-fold among supplements, and the dosage of 6 supplements was less than the recommended level in Japan. CONCLUSIONS: Consumers cannot always obtain the expected benefits by relying only on product label information. Therefore, new rules concerning product label information are required to make it possible for consumers to take the equivalent amounts of anthocyanins for whichever bilberry supplement they choose.

[Accidents during bathing].

Sudden death during bathing accounts for 10 to 15% of all out-of hospital cardiac arrests in Japan. Surveys in Tokyo revealed 1,085 victims of accidents during bathing transported by ambulance from October 1999 to March 2000. 53% of them were cardiac arrest and 25% were those who needed rescue from bath tub because of consciousness disturbance (rescued group). Clinical observation of the rescued group patients indicated they suffered from transient loss of consciousness probably because of elevated body temperature. The current hypothesis of the accidents during bathing is a unique type of heat illness exposed by high water temperature(41-43 degrees C). Geriatric population is vulnerable to the bathing induced heat illness.