Synergistic Effect of Detection and Separation for Pathogen Using Magnetic Clusters.

Early diagnosis of infectious diseases is important for treatment; therefore, selective and rapid detection of pathogenic bacteria is essential for human health. We report a strategy for highly selective detection and rapid separation of pathogenic microorganisms using magnetic nanoparticle clusters. Our approach to develop probes for pathogenic bacteria, including Salmonella, is based on a theoretically optimized model for the size of clustered magnetic nanoparticles. The clusters were modified to provide enhanced aqueous solubility and versatile conjugation sites for antibody immobilization. The clusters with the desired magnetic property were then prepared at critical micelle concentration (CMC) by evaporation-induced self-assembly (EISA). Two different types of target-specific antibodies for H- and O-antigens were incorporated on the cluster surface for selective binding to biological compartments of the flagella and cell body, respectively. For the two different specific binding properties, Salmonella were effectively captured with the O-antibody-coated polysorbate 80-coated magnetic nanoclusters (PCMNCs). The synergistic effect of combining selective targeting and the clustered magnetic probe leads to both selective and rapid detection of infectious pathogens.

Integrative Korean Medicine Treatment for Obesity and Overweight in Children and Adolescents: A Multicenter Retrospective Chart Review Study.

Introduction: Integrative Korean medicine treatment (IKM), including herbal medicine (HM) and acupuncture, has been widely used for obesity and overweight in children and adolescents in South Korea. We investigated the real-world usage status and the potential effect of the IKM for obesity and overweight in children and adolescents. Methods: Multicenter medical charts were retrospectively reviewed of obese and overweight children and adolescents who visited Korean medicine institutions with the goal of weight control for the first time and received IKM, to analyze the usage status and effect of IKM. We defined IKM responders as those with an improved obesity grade on the body mass index (BMI) percentile and analyzed their characteristics. Results: Medical charts of 209 patients (183 obese and 26 overweight) with a mean age of 11.45 years were examined. Patients visited the institution a mean of 5.95 times, and HM alone and HM plus acupuncture were frequently used IKM. HM was prescribed to 205 patients, 167 of whom received an HM prescription containing Ephedrae Herba. An HM of the decoction type was prescribed to 189 patients, and the average treatment duration was 76.54 days. After IKM, the percentile and z-score of BMI and weight significantly declined and height percentile and z-score were significantly enhanced, without serious adverse events. In the IKM responders, age, and the proportion of girls and overweight were significantly higher, and the percentile and z-score of height, weight, and BMI were significantly lower. Conclusion: This is the first study to examine the real-world usage of IKM for obesity and overweight in children and adolescents. A significant improvement in obesity-related outcome measures after IKM, illustrated the potential effect of IKM.

Synthesis and size characterization of silica nanospheres using sedimentation field-flow fractionation (SdFFF).

Silica nanoparticles were synthesized by a conventional emulsion polymerization by mixing ethanol, ammonium hydroxide, water and tetra ethyl orthosilicate (TEOS). A new reaction apparatus was assembled for a large scale synthesis of silica nanospheres in the laboratory, which was designed for uniform mixing of the reactants. The apparatus was equipped with a disc type agitator with six rectangular propellers. The new apparatus allowed high reproducibility in terms of the mean size and the size distribution of the silica nanoparticles with the relative standard deviation of less than about 6%. Sedimentation field-flow fractionation (SdFFF) was employed for determination of the size distribution of the silica nanoparticles. SdFFF provided size-based separation of the silica nanoparticles, with the retention time increasing with the size. When SdFFF analysis was repeated three times for the same sample, the standard deviation was less than 4%, showing reliability of SdFFF in size measurement. SdFFF seems to provide more accurate size distribution than DLS, particularly for those having broad and multimodal size distributions. Change in the agitation speed resulted in significant change in the mean diameter of the silica nanoparticles. Agitation speed of 400 rpm in 3 L reaction vessel yielded silica particles of about 100 nm in diameter, while at 200 rpm in 1 L vessel yielded those of about 500 nm.

Renoprotective effect of Tanshinone IIA, an active component of Salvia miltiorrhiza, on rats with chronic kidney disease.

Chronic kidney disease (CKD) is a common cause of end-stage renal disease. Antihypertensive agents are used clinically to inhibit the progression of CKD, but cannot prevent eventual renal failure. This study investigated the effect of Tanshinone IIA, an active component of Salvia miltiorrhiza, in rats suffering from CKD induced by 5/6 nephrectomy. After development of renal insufficiency, the rats were treated with Tanshinone IIA (10 mg/kg) for 8 weeks. Serum creatinine, angiotensin II (Ang II), transforming growth factor ß1 (TGF-ß1) and collagen IV levels were significantly reduced in Tanshinone IIA treated rats compared with a control group. In addition, Tanshinone IIA suppressed increases in urinary protein excretion in CKD rats. These findings suggest that chronic oral administration of Tanshinone IIA can improve renal dysfunction associated with CKD.

Comparative study on high fat diet-induced 4-hydroxy-2E-nonenal adducts in the hippocampal CA1 region of C57BL/6N and C3H/HeN mice.

In the present study, we investigated the influences of a high fat diet (HD) fed for 12 weeks, on lipid peroxidation and antioxidant enzyme using 4-hydroxy-2E-nonenal (HNE)-modified proteins (HNE-mp) and Cu,Zn-superoxide dismutase (SOD1) in the hippocampal CA1 region (CA1) in C57BL/6N and C3H/HeN mice. Body weights and body weight gains were significantly higher in HD fed C57BL/6N mice than in low fat diet (LD) fed C57BL/6N and LD or HD fed C3H/HeN mice. In the HD fed C57BL/6N and C3H/HeN mice, HNE-mp immunoreactivity and protein levels were much higher than in the LD fed C57BL/6N or C3H/HeN mice. In particular, HNE-mp immunoreactivity and protein levels in HD fed C57BL/6N mice was higher than that in the HD fed C3H/HeN mice. SOD1 immunoreaction was detected in the non-pyramidal cells of C57BL/6N mice, while in the C3H/HeN mice SOD1 immunoreaction was observed in CA1 pyramidal cells. The SOD1 immunoreactivity in the LD fed C57BL/6N and C3H/HeN mice was slightly, but not significantly decreased compared to that in the HD fed C57BL/6N and C3H/HeN mice, respectively. In addition, ionized calcium-binding adapter molecule 1 (Iba-1) immunoreactive microglia in the HD fed C57BL/6N showed hypertrophy of cytoplasm, which is the characteristics of activated microglia. These results suggest that HD fed C57BL/6N mice are more susceptible to lipid peroxidation in the CA1 than in LD fed C57BL/6N and LD or HD fed C3H/HeN mice without any differences of SOD1 expression.

Peroxisome proliferator-activated receptor-gamma Pro12Ala polymorphism is associated with the susceptibility to ischemic stroke in Taeeumin classified by Sasang medicine.

BACKGROUND: Sasang constitutional medicine classifies mankind into four constitutional types according to individual psychologic and physical traits. We hypothesized that differences among constitutional types might be explained by genetic variations. METHODS: To evaluate the hypothesis, we determined the possible association in ischemic stroke patients (n = 134) of peroxisome proliferator-activated receptor (PPAR)-gamma with four constitutional types of Sasang medicine. The constitutional type of each patient and control subject (n = 129) was classified and genotyped for PPAR-gamma polymorphism Pro12Ala by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) methods. RESULTS: The distribution of the Pro/Ala genotypes in the ischemic stroke patients was not significantly different from that of healthy controls [odds ratio (OR)= 0.46; p = 0.1214]. However, very interestingly, we observed that all six Pro/Ala genotypes in ischemic patients were Taeeumin, one of four constitutional types of Sasang medicine. Statistical analysis revealed that Pro/Ala genotype in Taeeumin increases almost 15-fold the susceptibility to ischemic stroke compared to other constitutional types, Taeyangin, Soyangin or Soeumin (OR= 14.72; p = 0.0110). CONCLUSION: From the results in this study, we might suggest that Pro/Ala genotype in Taeeumin is associated with the susceptibility to ischemic stroke. To the author's best knowledge, this is the first report to study on genetic level the potential relationship between ischemic stroke and Sasang constitutional medicine, one of traditional Korean medicines (TKM). Authors hope that this study could provide a new approach for the study of ischemic stroke and merit further research.

Narrow band CE-Chirp auditory steady-state response is more reliable than the conventional ASSR in predicting the behavioral hearing threshold.

OBJECTIVE: We evaluated conventional ASSR (Bio-logic MASTER II) and NB CE-Chirp ASSR thresholds as objective hearing measures in both normal and hearing loss subjects. METHODS: Patients with sensorineural hearing loss and volunteer normal hearing subjects were enrolled. Pure tone thresholds at 0.5, 1, 2 and 4 kHz were compared with the corresponding thresholds measured using Bio-logic MASTER II and the Eclipse ASSR systems. The threshold differences and correlation with pure tone were measured and reliability was evaluated with Cronbach's α. In part I of the study, all subjects were included, in part II of the study, only mild hearing loss and normal hearing subjects were included. RESULTS: In part I, NB CE-Chirp ASSR revealed a significantly smaller difference in threshold than conventional ASSR, a better correlation and better reliability. However, lower frequencies of NB CE-Chirp tended to be less reliable than higher frequencies. In part II, NB CE-Chirp revealed smaller threshold differences than conventional ASSR. Both correlation scores and reliability values were generally lower in the part II results. CONCLUSION: NB CE-Chirp ASSR generally revealed more favorable outcomes. However, its reliability was reduced at lower frequencies and in patients with milder hearing loss.

Herbal Acupuncture for the Treatment of Obesity.

Obesity is the state of excessive body fat accumulation and is mainly caused by consuming more calories than are burned through physical activity. Herbal acupuncture (HA), also known as pharmacopuncture, has been increasingly used in clinics of Korean medical to alleviate obesity. This review analyzed four clinical studies and 16 animal studies on the effectiveness of HA as a treatment for obesity. Clinical evidence suggests that various kinds of HA might be beneficial for treating obesity; however, further investigations with well-designed, evidence-based, randomized clinical trials are needed. Animal studies support the idea that HA might be beneficial for the treatment of obesity and provide possible mechanisms, such as anti-inflammation, antioxidation, modulating lipid metabolism and so on, to explain the effect of HA on obesity. This review, based on the evidence collected, suggests that HA could have a beneficial effect for alleviating obesity by modulating inflammation, oxidative stress, lipid metabolism, leptin, and the insulin signal.

Susceptibility for ischemic stroke in Korean population is associated with polymorphisms of the interleukin-1 receptor antagonist and tumor necrosis factor-alpha genes, but not the interleukin-1beta gene.

Enhanced release of proinflammatory cytokines may contribute to the pathogenesis of ischemic stroke. Interleukin-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine, and tumor necrosis factor (TNF)-alpha and IL-1beta are proinflammatory cytokine. To determine the role of cytokines in genetic susceptibility to ischemic stroke, we genotyped ischemic stroke patients (n = 152) and the healthy control subjects (n = 165) for IL-1Ra, TNF-alpha and IL-1beta polymorphism by polymerase chain reaction-restriction fragment length polymorphism methods. The analysis shown the association of IL1RN*1, IL1RN*2 allele (IL1RN*1, OR=0.44, P = 0.0206 IL1RN*2, OR=2.90, P = 0.0141) and TNF1, TNF2 allele (TNF1, OR=2.16, P = 0.0225; TNF2, OR=2.16, P = 0.0225) to ischemic stroke. However, the genetic polymorphism of IL-1beta was not associated with ischemic stroke. Our results suggest that IL-1Ra and TNF-alpha gene polymorphism is associated with the susceptibility to ischemic stroke.

Inhibitory effect of aqueous extract from the gall of Rhus chinensis on alpha-glucosidase activity and postprandial blood glucose.

The present study examined the inhibitory effect of aqueous extract from the gall of Rhus chinensis (AEGRC) on alpha-glucosidase activity, an enzyme responsible for digestion of carbohydrate to monosaccharides in the process of intestinal absorption. AEGRC inhibited Bacillus alpha-glucosidase acitvity with an IC(50) of 0.9 micro g/ml. Its inhibition on alpha-glucosidase was determined to be noncompetitive and reversible when the enzyme-substrate mixture was simultaneously treated with AEGRC as an inhibitor. In addition, when it was orally administered to rats with sucrose (2g/kg), AEGRC (250-1000mg/kg) significantly suppressed the increase of blood glucose levels after sucrose loading in a dose dependent manner. These results suggest that AEGRC might exert anti-diabetic effect by suppressing carbohydrate absorption from intestine, and thereby reducing the postprandial increase of blood glucose.

Acupuncture for the treatment of urinary incontinence: A review of randomized controlled trials.

The aim of this study was to examine the effects of acupuncture on urinary incontinence and to discuss why these acupoints were selected. Seven databases were searched for any randomized controlled trials (RCTs) that investigated the use of acupuncture or acupressure as a treatment for urinary incontinence, and the Cochrane risk of bias tool was utilized to evaluate the risk of bias in each study. Four RCTs met all the inclusion criteria. The results from the selected RCTs failed to demonstrate any statistically significant improvements in urinary incontinence, although acupuncture or acupressure did exhibit favorable effects on overactive bladder symptoms and quality of life, in comparison with other conventional therapies. There have been limited results supporting acupuncture or acupressure as an effective treatment method for urinary incontinence; therefore, further RCTs are required to confirm the effectiveness of acupuncture or acupressure in the treatment of urinary incontinence.

Association between subclinical hypothyroidism and Sasang constitution in a Korean population.

Serum thyroid-stimulating hormone screening of asymptomatic individuals to diagnose subclinical hypothyroidism remains controversial. We evaluated the potential role of Sasang constitutional discrimination and ryodoraku testing as an alternative and complementary diagnostic tool for subclinical hypothyroidism. Among 1,105 potential subjects, 1,073 were included in this study. Of these, 134 subjects had subclinical hypothyroidism (SCH) and 939 were healthy (euthyroid; EU) control subjects. Blood parameters, including serum thyroid hormone levels, were measured. We classified the participants into the four Sasang constitutional types, Taeyang-type individuals, Taeeum-type individuals, Soyang-type individuals and Soeum-type individuals, and measured their ryodoraku scores (RS). The mean levels of free thyroxine (FT4), glucose, red blood cells and hematocrit in the SCH group were significantly lower compared to those in the EU group (p<0.0183, p=0.0006, p=0.0162 and p=0.0224, respectively). The mean FT4 level of the Soeum-type SCH patients was significantly lower compared to the Soeum-type EU patients (p=0.0423). The total RS was significantly higher in the Taeeum-type SCH patients (p=0.0253) and lower in the Soeum-type SCH patients (p=0.0094) compared to controls. Ryodoraku testing and Sasang constitutional discrimination have the potential to serve as alternative and complementary diagnostic tools for subclinical hypothyroidism.

An alternative therapy for graves' disease: clinical effects and mechanisms of an herbal remedy.

Graves' disease, the most common cause of hyperthyroidism, is an autoimmune disorder. Antithyroid drugs have been selected as the first-line treatment of Graves' disease in Korea, Japan, and European countries. However, antithyroid drugs such as methimazole (MMI) and prophylthiouracil (PTU) have limitations in clinical applications because of their side effects. In this study, we performed a clinical trial and in vitro study to investigate the clinical effects and action mechanism of Ahnjeonbaekho-tang (AJBHT), an herbal remedy for Graves' disease. In a clinical study of Graves' disease patients who had side effects from antithyroid drugs, we found that treatment by AJBHT resulted in a reduction of serum triiodothyronine (T3) and free thyroxine (FT4) levels and an increase in thyroid stimulating hormone (TSH) levels (T3: p<0.0001, FT4: p=0.0012, TSH: p=0.0370, respectively). In vitro, AJBHT significantly inhibits FRTL-5 cell proliferation, DNA synthesis, cyclic AMP production, T4 synthesis, and the expression of thyroglobulin (Tg) mRNA in comparison with the control. These results suggest that AJBHT might suppress T(4) synthesis by modulating adenosine 3',5'-cyclic monophosphate (cAMP) and Tg expression, and therefore, AJBHT could be an alternative therapy for Graves' disease patients who have side effects from antithyroid drugs.

Interaction between warfarin and Panax ginseng in ischemic stroke patients.

BACKGROUND: Today, the combined use of Oriental herbal medicines and Western biomedical medicines has been a prevalent yet controversial practice. Case reports and healthy volunteer trials have had conflicting results on the effect Panax ginseng has on warfarin's pharmacologic action, some reporting a reductive and others a potentiating influence. OBJECTIVE: This study investigated the interaction between warfarin and P. ginseng by observing the prothrombin time (PT) and the international normalized ratio (INR) in ischemic stroke patients who did not have a history of taking warfarin. DESIGN: Randomized, open-label, controlled study. SUBJECTS: Twenty-five (25) patients newly diagnosed with ischemic stroke by brain computed tomography or magnetic resonance imaging in the Korean Medical Hospital, Kyung Hee University (Seoul, Republic of Korea). INTERVENTION: Ischemic stroke patients were randomized into 2 groups: the ginseng group (n = 12), given both P. ginseng and warfarin, and the control group (n = 13), given only warfarin, both for 2 weeks. The warfarin dose was restricted to 2 mg in the first week and 5 mg in the second week. RESULTS: The peak values and the international normalized ratio (INR) and prothrombin time (PT) areas under the curve (AUC) in both groups significantly increased compared to those at baseline. However, there was no statistically significant difference in peak values and INR and PT AUC between groups in both the first and second weeks. CONCLUSIONS: This study suggests that coadministration of P. ginseng and warfarin in ischemic stroke patients does not influence the pharmacologic action of warfarin.

The inhibitory effects of aqueous extract of Magnolia officinalis on human mesangial cell proliferation by regulation of platelet-derived growth factor-BB and transforming growth factor-beta1 expression.

Mesangial cell (MC) proliferation, mediated by platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-beta1, and cyclin-dependent kinases (CDK), is the common feature of glomerulosclerosis. Magnolia officinalis, stem bark of Machilus thunbergii S., has multiple pharmacological effects. In this study, we investigated the influence of aqueous extract of Magnolia officinalis on MC proliferation, DNA synthesis, and expression of PDGF-BB, TGF-beta1, CDK1, CDK2, and CDK4 in fetal bovine serum (FBS)-activated human MC. Magnolia officinalis inhibited the MC proliferation, DNA synthesis, and the expression of PDGF-BB, CDK1, and CDK2 gene and CDK1, CDK2, and TGF-beta1 protein. These results suggest that the inhibitory effect of Magnolia officinalis on MC proliferation may be mediated by regulation of PDGF-BB and TGF-beta1expressions and by modulation of CDK1 and CDK2 expression.