Stitching Flexible Electronics into the Brain.

Understanding complex neuronal networks requires monitoring long-term neuronal activity in various regions of the brain. Significant progress has been made in multisite implantations of well-designed probes, such as multisite implantation of Si-based and polymer-based probes. However, these multiprobe strategies are limited by the sizes and weights of interfaces to the multiple probes and the inability to track the activity of the same neurons and changes in neuronal activity over longer time periods. Here, a long single flexible probe that can be implanted by stitching into multiple regions of the mouse brain and subsequently transmit chronically stable neuronal signals from the multiple sites via a single low-mass interface is reported. The probe at four different sites is implemented using a glass capillary needle or two sites using an ultrathin metal needle. In vitro tests in brain-mimicking hydrogel show that multisite probe implantations achieve a high connection yield of >86%. In vivo histological images at each site of probes, implanted by stitching using either glass capillary or ultrathin metal insertion needles exhibit seamless tissue-probe interfaces with negligible chronic immune response. In addition, electrophysiology studies demonstrate the ability to track single neuron activities at every injection site with chronic stability over at least one month. Notably, the measured spike amplitudes and signal-to-noise ratios at different implantation sites show no statistically significant differences. Multisite stitching implantation of flexible electronics in the brain opens up new opportunities for both fundamental neuroscience research and electrotherapeutic applications.

Effect of A. polygama APEE (Actinidia polygama ethanol extract) or APWE (Actinidia polygama water extract) on wrinkle formation in UVB-irradiated hairless mice.

BACKGROUND: Actinidia polygama (silver vine) is considered a medical plant which has been used in oriental medicine. It has been used for the treatment of pain, gout, rheumatoid arthritis, and inflammation. Few studies reported on the effect of Actinidia polygama (silver vine) on skin photoaging. OBJECTIVE: To evaluate the anti-photoaging effect of the ethanol and water extracts of A. polygama (APEE and APWE, respectively) in UVB-irradiated hairless mice. METHODS: SKH-1 hairless mice were exposed to UVB irradiation (30-60 mJ/cm2 ), following orally APEE or APWE oral administration for 10 weeks. We examined the effect on winkle improvement by a measuring Fullscope, PRIMOS, Craniometer, and Cutometer. Furthermore, we analyzed histological changes in mouse dorsal skin through hematoxylin and eosin (H&E) and Masson's trichrome (MT) staining. The expression of matrix metalloproteinase (1, 3, and 9) was analyzed by immunoblotting. RESULTS: Oral administration of APEE or APWE at 100 or 200 mg/kg in UVB-irradiated mice alleviated the symptoms of skin aging, such as wrinkling, epidermal hyperplasia, and water loss. In addition, the APEE or APWE oral administration increased skin elasticity by enhancing the production of type I collagen, elastin, and hyaluronic acid synthase and downregulating matrix metalloproteinase (1, 3, and 9) expression. CONCLUSION: Based on results for our study, APEE or APWE could protect the UVB-mediated skin wrinkle and is new target for the developing anti-wrinkle cosmetics.

Melittin-derived peptides exhibit variations in cytotoxicity and antioxidant, anti-inflammatory and allergenic activities.

Melittin is a major component of bee venom; it is widely used in traditional medicine because of its therapeutic effects, such as anti-inflammatory effects. However, melittin has limited medical applications owing to its adverse effects, such as high cytotoxicity. In this study, we investigated the physiological activities of various hydrolyzed melittin-derived peptides to eliminate the cytotoxicity of melittin and enhance its efficacy. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay confirmed that melittin-derived peptides showed antioxidant activity comparable to that of melittin. Moreover, unlike melittin, which showed high cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, the melittin-derived peptides showed negligible cytotoxicity. Among the melittin-derived peptides, the peptide composed of sequence TTGLPALISWIKRKRQQ (P1) showed inhibitory effects on the mRNA expression of inflammatory cytokines and phosphorylation of IκBα, similar to the effects of melittin in RAW 264.7 cells. Degranulation of RBL-2H3 cells was analyzed using a ß-hexosaminidase release assay to confirm the allergenic activity of melittin and P1, which showed remarkably reduced allergenicity of P1 compared to that of melittin. These results indicate that P1 maintained the anti-inflammatory effects of melittin while reducing its cytotoxicity and allergic reactions. In conclusion, the melittin-derived peptide P1 efficiently decreased the adverse effects while maintaining the beneficial effects of melittin, making it suitable for therapeutic applications.

Effects of Oral Administration of Lactiplantibacillus Plantarum APsulloc 331261 (GTB1TM) Isolated from Green Tea on Atopic Dermatitis (AD)-like Skin Lesion Mouse Models.

Background: Probiotics are known to improve atopic dermatitis (AD) by inhibiting T helper 2 (Th2)-related reactions, restoring the Th2/T helper1 (Th1) cytokine ratio. The most popular probiotic is Lactiplantibacillus plantarum (L. plantarum), which is widely used in the food and pharmaceutical industries. L. plantarum APsulloc 331261 (GTB1) used in this study was isolated from green tea. Materials and Methods: The effectiveness of oral GTB1 administration in improving AD was evaluated by visual evaluation, comparison of the lymph node sizes and spleen weights, histological evaluation, RT-qPCR, ELISA, and IHC analysis in the mouse model. Results: GTB1 improved AD symptoms, reduced epidermal thickness and mast cell numbers, decreased lymph node size and the spleen weight, increased filaggrin and loricrin protein levels, downregulated Th2 expression, and upregulated Th1 expression in a colony-forming unit-dependent manner. Conclusion: Oral administration of GTB1 isolated from green tea (Camellia sinensis) improved the AD symptoms, reduced hypersensitivity reaction, and increased the skin barrier function. Finally, it is involved in AD improvement by restoring the Th2/Th1 cytokine balance.

The Low-Fluence Q-Switched Nd:YAG Laser Treatment for Melasma: A Systematic Review.

Melasma is a common pigmentary disorder with a complex pathogenesis, of which the treatment is challenging. Conventional treatment often leads to inconsistent results with unexpected pigmentary side effects and high recurrence rates. Recently, the low-fluence Q-switched Nd:YAG laser (LFQSNY) has been widely used for treating melasma, especially in Asia. We reviewed literatures on the LFQSNY treatment of melasma published between 2009 and May 2022 to evaluate the efficacy and adverse events, including its combination therapy. A systematic PubMed search was conducted and a total of 42 articles were included in this study. It was hard to summarize the heterogenous studies, but LFQSNY appeared to be a generally effective and safe treatment for melasma considering the results of previous conventional therapies. However, mottled hypopigmentation has been occasionally reported to develop and persist as an adverse event of LFQSNY, which may be associated with the high accumulated laser energy. When used aggressively, even LFQSNY can induce hyperpigmentation via unwanted inflammation, especially in darker skin. Although few studies have reported considerable recurrence rates three months after treatment, unfortunately, there is a lack of the long-term follow-up results of LFQSNY in melasma. To enhance the effectiveness and reduce the adverse events, LFQSNY has been used in combination with other treatment modalities in melasma, including topical bleaching agents, oral tranexamic acid, chemical peeling, or diverse energy-based devices, which generally reduced side effects with or without significant superior efficacy compared to LFQSNY alone.

Intergenerational Taekwondo Program: A Narrative Review and Practical Intervention Proposal.

Taekwondo is a modernized martial art that includes various combinations of hand and kicking techniques and core values of Taekwondo philosophy such as courtesy, mutual respect, and self-control. Physical inactivity is highly prevalent among older adults and is a major contributor to health-related problems. Intergenerational physical activity programs are used as an effective tool to make a positive connection between generations and provide additional health benefits for both generations. This review study aimed to examine the theories of intergenerational physical activity programs and propose the Intergenerational Taekwondo Program (ITP). Various theories such as the transtheoretical model, contact theory, social capital theory, situated learning theory, human development theory, personality theory, and whole-person wellness model have been adopted in intergenerational physical activity programs. Our review suggests that to develop the Intergenerational Taekwondo Program, instructors should (1) establishing common goals, (2) understand differences in physical and mental abilities, and (3) offer incentives to encourage participants in physical activity programs. The proposed ITP program has the potential to not just provide unique inherent values and improving physical functions, but also to form generational connections.

The Effectiveness of Ultrasound Deep Heat Therapy for Adhesive Capsulitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Adhesive capsulitis occurs with synovial inflammation and capsular fibrosis in the glenohumeral joint, leading to restriction of joint motion and pain. Heat therapy modalities, which aim at modifying dense collagenous tissues are commonly practiced interventions for patients with adhesive capsulitis; however, the effectiveness of ultrasound deep heat therapy (UST) on adhesive capsulitis is still unclear. PURPOSE: This systematic review and meta-analysis study was conducted to evaluate the effects of UST on the improvement of pain and glenohumeral joint function in adhesive capsulitis compared to (1) no treatment or placebo, and (2) any other therapeutic modalities. METHODS: A literature search was carried out in January 2021 in Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PEDro, Web of Science, and Google Scholar. The main outcomes of interest were self-reported pain scores, disability scores, and the range of motion. This study was conducted based on the guidelines of the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) protocols, using random-effects models. RESULTS: Seven studies were included in the systematic review with five studies forming the basis for meta-analyses. The effects of UST in patients with adhesive capsulitis were compared with placebo, shockwave therapy, corticosteroid injection, platelet-rich plasma injection, or cryotherapy. The results indicated that UST significantly improved pain scores when performed together with exercise and/or other physical modalities compared to placebo; however, whether UST provides benefits for the improvement of disability and/or the range of motion was uncertain in the present results. CONCLUSIONS: The present findings suggest that UST as a co-intervention combined with other physical modalities is an effective means of improving the overall pain in patients with adhesive capsulitis.

Phase II trial of bevacizumab and sorafenib in recurrent ovarian cancer patients with or without prior-bevacizumab treatment.

OBJECTIVE: To examine whether blocking multiple points of the angiogenesis pathway by addition of sorafenib, a multi-kinase inhibitor against VEGFR2/3, Raf, c-Kit, and PDGFR, to bevacizumab would yield clinical activity in ovarian cancer (OvCa). METHODS: This phase II study tested bevacizumab plus sorafenib in two cohorts; bevacizumab-naïve and bevacizumab-exposed patients. Bevacizumab (5 mg/kg IV every 2 weeks) was given with sorafenib 200 mg bid 5 days-on/2 days-off. The primary objective was response rate using a Simon two-stage optimal design. Progression-free survival (PFS) and toxicity were the secondary endpoints. Exploratory correlative studies included plasma cytokine concentrations, tissue proteomics and dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI). RESULTS: Between March 2007 and August 2012, 54 women were enrolled, 41 bevacizumab-naive and 13 bevacizumab-prior, with median 5 (2-9) and 6 (5-9) prior systemic therapies, respectively. Nine of 35 (26%) evaluable bevacizumab-naive patients attained partial responses (PR), and 18 had stable disease (SD) ≥ 4 months. No responses were seen in the bevacizumab-prior group and 7 (54%) patients had SD ≥ 4 months, including one exceptional responder with SD of 27 months. The overall median PFS was 5.5 months (95%CI: 4.0-6.8 months). Treatment-related grade 3/4 adverse events (≥5%) included hypertension (17/54 [31%]; grade 3 in 16 patients and grade 4 in one patient) and venous thrombosis or pulmonary embolism (5/54 [9%]; grade 3 in 4 patients and grade 4 in one patient). Pretreatment low IL8 concentration was associated with PFS ≥ 4 months (p = .031). CONCLUSIONS: The bevacizumab and sorafenib combination did not meet the pre-specified primary endpoint although some clinical activity was seen in heavily-pretreated bevacizumab-naive OvCa patients with platinum-resistant disease. Anticipated class toxicities required close monitoring and dose modifications.

Effects of consumption of coffee, tea, or soft drinks on open-angle glaucoma: Korea National Health and Nutrition Examination Survey 2010 to 2011.

We sought to investigate the association between consumption of coffee, tea, or soft drinks and risk of open-angle glaucoma (OAG) among Koreans using nationwide population-based data. This cross-sectional survey was performed through the Korea National Health and Nutrition Examination Survey 2010 to 2011. Participants older than 19 years were included in the sample for analysis after excluding those with any missing data. The diagnosis of OAG was based on the International Society of Geographical and Epidemiological Ophthalmology criteria, and participants without glaucomatous optic neuropathy served as controls. The frequency of beverage consumption during the past 12 months was obtained through a questionnaire. Multivariate logistic regression models were used to determine the relationship between consumption of each type of beverage and prevalence of OAG. A total of 6,681 participants was included in the analysis. The prevalence of OAG was 4.4% (n = 323), including 5.4% (n = 169) among men and 3.5% (n = 154) among women. After adjusting for multiple covariates, coffee consumption was significantly associated with OAG, while no significant association was found between consumption of tea or soft drinks and OAG. Participants who drank coffee had a higher risk of having OAG compared with those who did not drink coffee (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.22-4.72; p = 0.011). In sex-stratified analyses, the robust association of coffee consumption with OAG was observed in men (OR, 3.98; 95% CI, 1.71-9.25; p = 0.001) but not in women. Our results suggest that coffee consumption may affect the risk of OAG, particularly in men.

The Associations of Vitamin D Status with Athletic Performance and Blood-borne Markers in Adolescent Athletes: A Cross-Sectional Study.

The purpose of this study was to examine the associations of vitamin D status with athletic performance and blood-borne markers in adolescent athletes. This cross-sectional study included forty-seven Taekwondo athletes, aged 15-18 years old. Athletic performance was assessed using maximal oxygen consumption (VO2max), Wingate anaerobic power test, vertical jump, agility T-test, lower limb muscle strength, and fatigue resistance. Blood samples were collected to assess serum 25-hydroxyvitamin D [25(OH)D], free-testosterone, cortisol, creatine kinase, and urea. One-way ANOVAs were applied using Bonferroni adjusted alpha levels, which was 0.02 (i.e., 0.05/3). Multiple linear regressions analyses as well as Pearson and partial correlation analyses were used to examine the relationship among 25(OH)D concentration, athletic performance, and blood-borne markers. The participants 25(OH)D concentration were ranged from 16 to 73.25 nmol/L, indicating that 74.5% of the adolescent athletes have vitamin D insufficiency or deficiency. The vitamin D status did not show any significant effects on the performance factors or blood-borne markers. Serum 25(OH)D concentration was positively correlated with mean power output (r = 0.359, p < 0.05) and relative mean power output (r = 0.325, p < 0.05) after adjusting for bone age, height, weight, training experience, lean body mass, and fat mass. However, 25(OH)D concentration was not associated with other performance-related factors and blood-borne markers. In addition, multiple linear regressions analyses revealed that serum 25(OH)D concentration were not significant predictors of athletic performance in adolescent athletes. In conclusion, vitamin D status is weakly correlated with anaerobic capacity; moreover, the underlying mechanisms of how vitamin D influence anaerobic performance is unclear in the present study. Nevertheless, the importance of vitamin D on health benefits should not be underestimated, especially during growth periods.

Effects of Various Work-to-rest Ratios during High-intensity Interval Training on Athletic Performance in Adolescents.

To examine the effect of high-intensity interval training (HIIT) with different work-to-rest ratios on athletic performance in athletes. Forty-seven male Taekwondo athletes (aged 15-18 yrs) were randomly assigned into 3 HIIT groups and a control group. Each group performed 6 and 8 bouts of HIIT: 1) 1:2 (30:60 s), 2) 1:4 (30:120 s), and 3) 1:8 (30:240 s) groups while the control group performed only Taekwondo training program. All HIIT groups completed 10 sessions over 4 weeks. Athletic performance tests including VO2max test, Wingate anaerobic test, vertical jump, and agility T-test were measured at both pre- and post-tests. Two-way repeated measures ANOVA were applied to examine the performance changes between protocols. VO2max improved significantly in all HIIT groups (p<0.01), and the post-hoc test indicated that the only 1:4 group showed significant improvement compared to the control group. The HIIT with 1:4 ratio showed the effective protocol for enhancing anaerobic capacity including relative peak and mean power compared to control (p<0.01). Ten sessions of HIIT involving the 1:4 group, lasting over a brief 4-week period revealed the effective protocol for enhancing both aerobic and anaerobic capacity. Our findings provide practical implications to develop a performance-enhancing program specialized for adolescent Taekwondo athletes.

LC-MS/MS Software for Screening Unknown Erectile Dysfunction Drugs and Analogues: Artificial Neural Network Classification, Peak-Count Scoring, Simple Similarity Search, and Hybrid Similarity Search Algorithms.

Screening and identifying unknown erectile dysfunction (ED) drugs and analogues, which are often illicitly added to health supplements, is a challenging analytical task. The analytical technique most commonly used for this purpose, liquid chromatography-tandem mass spectrometry (LC-MS/MS), is based on the strategy of searching the LC-MS/MS spectra of target compounds against database spectra. However, such a strategy cannot be applied to unknown ED drugs and analogues. To overcome this dilemma, we have constructed a standalone software named AI-SIDA (artificial intelligence screener of illicit drugs and analogues). AI-SIDA consists of three layers: LC-MS/MS viewer, AI classifier, and Identifier. In the second AI classifier layer, an artificial neural network (ANN) classification model, which was constructed by training 149 LC-MS/MS spectra (including 27 sildenafil-type, 6 vardenafil-type, 11 tadalafil-type ED drugs/analogues and other 105 compounds), is included to classify the LC-MS/MS spectra of the query compound into four categories: i.e., sildenafil, vardenafil, and tadalafil families and non-ED compounds. This ANN model was found to show 100% classification accuracy for the 187 LC-MS/MS modeling and test data sets. In the third Identifier layer, three search algorithms (pick-count scoring, simple similarity search, and hybrid similarity search) are implemented. In particular, the hybrid similarity search was found to be very powerful in identifying unknown ED drugs/analogues with a single modification from the library ED drugs/analogues. Altogether, the AI-SIDA software provides a very useful and powerful platform for screening unknown ED drugs and analogues.

Survival outcomes of hepatic resection compared with transarterial chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis.

BACKGROUND/AIMS: Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT. METHODS: Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II). RESULTS: The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ significantly between the latter two groups (p=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (p=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262, p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012). CONCLUSIONS: Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC.

Subchronic toxicity of Acorus gramineus rhizoma in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Acorus gramineus rhizoma (AGR) is the dry rhizome of Acorus gramineus Solander from the family Araceae that has been used as sedative, analgesic, diuretic, digestive and antifungal agent. AIM OF THE STUDY: To evaluate the no-observed-adverse-effect level (NOAEL) and the toxicity of AGR, following repeated oral administration to rats for 13 weeks. MATERIALS AND METHODS: AGR was administered by oral gavage to groups of rats (10 per group, each sex) at doses of 0 (control), 25, 74, 222, 667, or 2,000mg/kg/day, 5 times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology, sperm motility, sperm morphology, organ weights, gross and histopathological findings were compared between control and AGR groups. RESULTS: No mortality or remarkable clinical signs were observed during this 13-week study. No adverse effects on body weight, food consumption, urinalysis, hematology, serum chemistry, organ weights, gross lesion, histopathology, vaginal cytology, sperm motility or deformity were observed in any of the male or female rats treated with AGR. CONCLUSIONS: On the basis of these results, the NOAEL of AGR is determined to be 2,000mg/kg/day for male and female rats.

Severe Endobronchial Inflammation Induced by Aspiration of a Ferrous Sulfate Tablet.

Iron supplements such as ferrous sulfate tablets are usually used to treat iron-deficiency anemia in some elderly patients with primary neurologic disorders or decreased gag reflexes due to stroke, senile dementia, or parkinsonism. While the aspiration of ferrous sulfate is rarely reported, it is a potentially life-threatening condition that can lead to airway necrosis and bronchial stenosis. A detailed history and high suspicion of aspiration are required to avoid delays in diagnosis and treatment. The diagnosis can be confirmed by bronchoscopic examination and a tissue biopsy. Early removal of the aspirated tablet prevents acute complications, such as bronchial necrosis, hemoptysis, and lobar consolidation. Tablet removal is also necessary to prevent late bronchial stenosis. We presented the first case in Korea of a ferrous sulfate tablet aspiration that induced severe endobronchial inflammation.

Petatewalide B, a novel compound from Petasites japonicus with anti-allergic activity.

ETHNOPHARMACOLOGICAL RELEVANCE: The giant butterbur Petasites japonicus is used to treat asthma and allergic diseases in traditional Korean, Japanese, and Chinese medicine. AIM OF THE STUDY: To elucidate the anti-allergic effect of Petasites genus, we studied effects of several compounds from Petasites japonicus leaves and found a novel bakkenolide-type sesquiterpine. In the present study, anti-allergic and anti-inflammatory effects of the new compound was examined using in vivo and in vitro experiments. MATERIALS AND METHODS: The novel compound was isolated from Petasites japonicus leaves and named petatewalide B. Antigen-induced degranulation and Ca(2+) mobilization were measured in RBL-2H3 mast cells by measuring ß-hexosaminidase activity and fluorescence change of Ca(2+) probe, fura-2. Induction of inducible nitric oxide synthase and cyclooxygenase 2 was measured by Western blotting in peritoneal macrophages. In addition, ovalbumin-induced asthma model was used for in vivo efficacy test of petatewalide B. Membrane potential was estimated by measuring fluorescence change of DiBAC in C6 glioma cells. RESULTS: Petatewalide B inhibited the antigen-induced degranulation of ß-hexosaminidase in RBL-2H3 mast cells, but did not affect antigen-induced Ca(2+) increase in the cells. Petatewalide B also showed inhibition of the LPS-induced induction of iNOS, but not COX-2 in mouse peritoneal macrophages. Nitric oxide production was also inhibited by petatewalide B in macrophages. In the ovalbumin-induced asthma model, petatewalide B strongly inhibited accumulations of eosinophils, macrophages, and lymphocytes in bronchoalveolar lavage fluid. Petatewalide B increased the membrane potential of C6 glioma cells in a concentration-dependent manner. CONCLUSION: Petatewalide B from Petasites genus not only has anti-allergic and anti-inflammatory effects but also induces a transient increase of membrane potential in C6 glioma cells.

Anti-allergic effect of α-cubebenoate isolated from Schisandra chinensis using in vivo and in vitro experiments.

AIM OF THE STUDY: In Oriental countries, the dried fruits of Schisandra chinensis are extensively used in traditional medicine to treat asthma, gonorrhea, and other diseases. Recently, α-cubebenoate was isolated as an anti-inflammatory component from Schisandra chinensis. In the present study, the authors examined the anti-allergic effect of α-cubebenoate using in vivo and in vitro experiments. MATERIALS AND METHODS: α-Cubebenoate was isolated from an extract of Schisandra chinensis fruits. Antigen-induced degranulation and Ca(2+) mobilization were measured in RBL-2H3 mast cells. In addition, BALB/c mice were sensitized with ovalbumin and aluminum hydroxide, and then challenged with ovalbumin for three consecutive days. α-Cubebenoate (1mg/kg) was administered intraperitoneally 30min before each ovalbumin challenge. RESULTS: In RBL-2H3 mast cells, α-cubebenoate inhibited antigen-induced degranulation and increase of intracellular Ca(2+) concentrations. In the ovalbumin-induced asthma model, α-cubebenoate suppressed bronchiolar structural changes induced by ovalbumin challenge. Furthermore, α-cubebenoate strongly inhibited accumulations of eosinophils, macrophages, and lymphocytes in bronchoalveolar lavage fluid. α-Cubebenoate also suppressed Th2 cytokines (IL-4 and IL-13) and TGF-ß1 in lung tissues and in immune cells at the mRNA and protein levels. CONCLUSION: α-Cubebenoate has an inhibitory effect on allergic inflammation and could be utilized as an agent for the treatment of asthma.

Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats.

Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.

Clinical experience with (18)F-fluorodeoxyglucose positron emission tomography and (123)I-metaiodobenzylguanine scintigraphy in pediatric neuroblastoma: complementary roles in follow-up of patients.

PURPOSE: To evaluate the potential utility of (123)I-metaiodobenzylguanine ((123)I-MIBG) scintigraphy and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) for the detection of primary and metastatic lesions in pediatric neuroblastoma (NBL) patients, and to determine whether (18)F-FDG PET is as beneficial as (123)I-MIBG imaging. METHODS: We selected 8 NBL patients with significant residual mass after operation and who had paired (123)I-MIBG and (18)F-FDG PET images that were obtained during the follow-up. We retrospectively reviewed the clinical charts and the findings of 45 paired scans. RESULTS: Both scans correlated relatively well with the disease status as determined by standard imaging modalities during follow-up; the overall concordance rates were 32/45 (71.1%) for primary tumor sites and 33/45 (73.3%) for bone-bone marrow (BM) metastatic sites. In detecting primary tumor sites, (123)I-MIBG might be superior to (18)F-FDG PET. The sensitivity of (123)I-MIBG and (18)F-FDG PET were 96.7% and 70.9%, respectively, and their specificity were 85.7% and 92.8%, respectively. (18)F-FDG PET failed to detect 9 true NBL lesions in 45 follow-up scans (false negative rate, 29%) with positive (123)I-MIBG. For bone-BM metastatic sites, the sensitivity of (123)I-MIBG and (18)F-FDG PET were 72.7% and 81.8%, respectively, and the specificity were 79.1% and 100%, respectively. (123)I-MIBG scan showed higher false positivity (20.8%) than (18)F-FDG PET (0%). CONCLUSION: (123)I-MIBG is superior for delineating primary tumor sites, and (18)F-FDG PET could aid in discriminating inconclusive findings on bony metastatic NBL. Both scans can be complementarily used to clearly determine discrepancies or inconclusive findings on primary or bone-BM metastatic NBL during follow-up.

Subchronic toxicity study of Coptidis rhizoma in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis Rhizoma (CR) is a medical herb from the family Ranunculacease that has been used to treat gastroenteritis, dysentery, diabetes mellitus, and severe skin diseases. AIM OF THE STUDY: To evaluate the no-observed-adverse-effect level (NOAEL) and the toxicity of CR, following repeat oral administration to rats for 13 weeks. MATERIALS AND METHODS: CR was administered by oral gavage to groups of rats (n=10/group, each sex) at dose levels of 0 (control), 25, 74, 222, 667 or 2000 mg/kg/day 5 times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology and sperm morphology, organ weights, gross and histopathological findings were compared between control and CR groups. RESULTS: Urinalysis showed a significant increase in N-acety1-ß-glucosaminidase in males in the 2000 mg/kg/day group (P<0.01). However, no mortality or remarkable clinical signs were observed during this 13-week study. No adverse effects on body weight, food consumption, hematology, serum chemistry, organ weights, gross lesion, histopathology, vaginal cytology, sperm motility, or deformity were observed in the males or female rats treated with CR. CONCLUSIONS: On the basis of these results, the NOAEL of CR is determined to be 667 mg/kg/day for males and 2000 mg/kg/day for females.