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.

Breastfeeding and vitamin D.

The recent re-emergence of vitamin D deficiency (VDD) and rickets among breastfed infants without adequate sunlight exposure and vitamin D supplementation has been reported worldwide. Breastfed infants are particularly vulnerable to VDD because of the low vitamin D content of breast milk, restricted sunlight exposure, increased pollution, and limited natural dietary sources of vitamin D. The prevalence of VDD in breastfed infants differs vastly between studies and nations at 0.6%-91.1%. The recommended intake of vitamin D for lactating mothers to optimize their overall vitamin D status and, consequently, of their breast milk is 200-2,000 IU/day, indicating a lack of consensus. Some studies have suggested that maternal high-dose vitamin D supplementation (up to 6,400 IU/day) can be used as an alternate strategy to direct infant supplementation. However, concern persists about the safety of maternal high-dose vitamin D supplementation. Direct infant supplementation is the currently available option to support vitamin D status in breastfed infants. The recommended dose for vitamin D supplementation in breastfed infants according to various societies and organizations worldwide is 200-1,200 IU/day. Most international guidelines recommend that exclusively or partially breastfed infants be supplemented with 400 IU/day of vitamin D during their first year of life. However, domestic studies on the status and guidelines for vitamin D in breastfed infants are insufficient. This review summarizes the prevalence of VDD in breastfed infants, vitamin D content of breast milk, and current guidelines for vitamin D supplementation of lactating mothers and infants to prevent VDD in breastfed infants.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 2. Management of H1-Antihistamine-Refractory Chronic Urticaria.

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H1-antihistamines, even though the dose of H1-antihistamines is increased up to 4-fold. CSU that is not controlled with H1-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H1-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.

Radiologic findings as a determinant and no effect of macrolide resistance on clinical course of Mycoplasma pneumoniae pneumonia.

BACKGROUND: With the emergence of macrolide resistance, concerns about the efficacy of macrolides for the treatment of Mycoplasma pneumoniae (MP) pneumonia in children have been raised. This study aimed to determine the effect of macrolide resistance on the outcome of children who were hospitalized with MP pneumonia. METHODS: Between 2010 and 2015, we performed culture of MP from nasopharyngeal samples obtained from children who were hospitalized with pneumonia at five hospitals in Korea. Macrolide resistance was determined by the analysis of 23S rRNA gene transition and the minimal inhibitory concentrations of four macrolides. Medical records were reviewed to analyze the clinical response to treatment with macrolides. RESULTS: MP was detected in 116 (4.8%) of the 2436 children with pneumonia. MP pneumonia was prevalent in 2011 and 2015. Of the 116 patients with MP pneumonia, 82 (70.7%) were macrolide-resistant. There were no differences in the age distribution, total duration of fever, and chest x-ray patterns between the macrolide-susceptible and macrolide-resistant groups. After macrolide initiation, mean days to defervescence were longer in the macrolide-resistant group than in macrolide-susceptible group (5.7 days vs. 4.1 days, P = 0.021). However, logistic regression analysis revealed that the presence of extrapulmonary signs (P = 0.039), homogeneous lobar consolidation (P = 0.004), or parapneumonic effusion (P < 0.001) were associated with fever duration of ≥7 days after the initiation of macrolides, regardless of macrolide resistance. CONCLUSIONS: This study demonstrated that fever duration in MP pneumonia was determined by the radiologic findings of chest x-ray, not by the presence of macrolide resistance. The results highlight the need for future studies to assess therapeutic benefit from macrolides in the treatment of children with MP pneumonia.

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.

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.

Platycodon grandiflorum modifies adipokines and the glucose uptake in high-fat diet in mice and L6 muscle cells.

OBJECTIVES: Obesity and diabetes have become the most common human health problems worldwide. Obesity's contribution to type 2 diabetes might be due to dysregulation of adipokines and glucose uptake. METHODS: In this study, we performed in-vivo and in-vitro studies to evaluate the effects of Platycodon grandiflorum extract (PGE) on adipokines and glucose uptake. Before study, platycodin D concentrations were analysed by HPLC in PGE prepared in water, in 50% ethanol and in 80% ethanol, and we selected the 80% ethanol extract as the PGE for this study based on the HPLC results. KEY FINDINGS: We found that inclusion of PGE in the high-fat diet (HFD) markedly attenuated food intake, body weight, epididymal fat weight, adipocyte size and blood glucose levels by the oral glucose tolerance test in mice, and maintained serum levels of adiponectin, resistin, leptin, fructosamine and triglycerides. Gene expression analysis revealed that PGE up-regulated adiponectin, and down-regulated TNF-α and leptin in fat tissue. In L6 muscle cells in vitro, PGE increased insulin-stimulated glucose uptake. CONCLUSIONS: We conclude that PGE may improve obesity in mice fed an HFD and glucose uptake in L6 muscle cells by modifying adipokines, and could offer clinical benefits as a supplement to treat obesity and diabetes.

Clinical characteristics and prevalence of vitamin D insufficiency in children less than two years of age.

PURPOSE: To evaluate the clinical characteristics of vitamin D deficiency and its association with iron deficiency anemia (IDA). METHODS: A total of 171 children aged less than two years underwent 25-hydroxyvitamin D(3) tests between January 2007 and July 2009. The study was classified into two groups: normal and vitamin D insufficiency, by their vitamin 25-hydroxyvitamin D(3) levels. RESULTS: In total, 120 children were in the normal group (mean age, body weight and heights 12.5±7.0, 9.3±0.9 kg and 76.8±1.1 cm), and 51 children in the vitamin D insufficiency group (9.9±5.4 months, 9.0±0.9 kg and 75.1±0.9 cm). Vitamin D insufficiency was most commonly diagnosed in the spring (44%). The proportion of complete breast-feeding was higher in the insufficiency (92%), and 25.5% of the children in the deficient group also experienced IDA compared that 12% of normal group. Ten children in the insufficiency group experienced bony changes. Six children received calcitriol medication in the normal group, in whom the mean vitamin 25-hydroxyvitamin D(3) level increased from 39.6±14.6 ng/mL (pre-medication) to 41.8±17.2 ng/mL (post-medication), and 13 in the insufficiency group, in whom the mean vitamin 25-hydroxyvitamin D(3) increased from 20.7±7.0 ng/mL to a mean post-treatment level of 43.7±23.8 ng/mL. CONCLUSION: This study demonstrated that approximately 30% of children aged ≤2 years experienced vitamin D insufficiency associated with subclinical rickets. Many children also experienced concurrent IDA. Guidelines for vitamin D supplement in such children must therefore be established.

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.

Development of a validated liquid chromatographic method for the quality control of Prunellae Spica: determination of triterpenic acids.

A simple and rapid reversed-phase HPLC-UV method was developed for the determination of triterpenic acids in the crude extract of Prunellae Spica. Five triterpenic acids were extracted and isolated from P. Spica as marker compounds for use in the quality control of herbal medicines. Various solvent extraction techniques were evaluated, and the greatest efficiency was observed with sonication in 100% ethanol. Elemental compositions of the five marker compounds were determined by high-resolution mass spectroscopy. The dynamic range of the HPLC-UV method depended on the specific analyte, and acceptable quantitation was obtained between 10 and 250 microgmL(-1) for oleanolic acid, between 10 and 300 microgmL(-1) for ursolic acid, between 3 and 75 microgmL(-1) for 2alpha,3alpha,24-trihydroxyolean-12en-28oic acid, between 5 and 100 microgmL(-1) for euscaphic acid, and between 5 and 100 microgmL(-1) for 2alpha,3alpha-dihydroxyurs-12en-28oic acid. The method was deemed satisfactory by inter- and intra-day validation and exhibited both high accuracy and precision (relative standard deviation <9.4%). Overall limits of quantitation and detection were approximately 0.5-2.5 microgmL(-1) at a signal-to-noise ratio (S/N) of 3 and were about 3.0-10.0 microgmL(-1) at a S/N of 10. In addition, principal component analysis (PCA) was performed on the analytical data of 15 different P. Spica samples in order to classify samples collected from different regions.

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.

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.

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.

Effect of Scutellariae radix extract on the high glucose-induced apoptosis in cultured vascular endothelial cells.

Endothelial cell apoptosis has been postulated as the initial trigger of the progression of microvascular disease in patients with diabetes mellitus. To investigate the role of Scutellariae radix extract, we examined its effect on the endothelial cell proliferation using the [3H]-thymidine incorporation method. Scutellariae radix extract significantly stimulated endothelial cell proliferation in a dose-dependent manner. We focused on the protective action of Scutellariae radix extract on the endothelial cell apoptosis induced by high glucose concentrations. Determination of endothelial cell apoptosis was performed using DNA gel electrophoresis, terminal deoxynuclotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and an ELISA kit. Exposure of vascular endothelial cell to high glucose (16.7 mM) for 72 h resulted in a significant increase in apoptosis, compared with the normal glucose concentrations (5.5 mM). Scutellariae radix extract inhibited high glucose-induced endothelial cell apoptosis. This result suggests that Scutellariae radix extract may contribute to antiapoptotic action against vascular endothelial cells, resulting in a beneficial effect in preventing diabetes-associated microvascular complications.