Omega-3 fatty acids supplementation on major cardiovascular outcomes: an umbrella review of meta-analyses of observational studies and randomized controlled trials.

OBJECTIVE: Omega-3 fatty acids are commonly used as a lipid-lowering agent or dietary supplement for the purpose of prevention of cardiovascular diseases. However, even large-scale clinical trials have not shown significant results demonstrating clear clinical benefits in cardiovascular diseases. Thus, this umbrella review aims to summarize and evaluate the evidence of clinical effects of omega-3 fatty acids supplementation on cardiovascular outcomes through comprehensive analyses of previous randomized controlled trials (RCTs) or observational cohort studies. MATERIALS AND METHODS: We conducted relevant publication search in PubMed, Embase, and Cochrane Database of Systematic Reviews. We retrieved and analyzed 3,298 articles published until August 28th, 2019. RESULTS: We identified 29 relevant articles and analyzed 83 meta-analyses of RCTs or cohort studies therefrom. As a result, we identified 12 cardiovascular outcomes that are related to omega-3 fatty acids supplementation. Among them, total mortality from major cardiovascular causes (RR 0.92, 95% CI 0.86 to 0.98) had significant inverse associations, and moreover, statistical significances were maintained even in subgroup analysis of large-scale RCTs including more than 1,000 patients (RR 0.94, 95% CI 0.88 to 0.99). CONCLUSIONS: Our umbrella review study shows that omega-3 fatty acids supplementation have a clinical benefit in reducing mortality from cardiovascular causes. However, many studies still have shown conflicting results, and therefore, further studies will be needed to verify the clinical benefit of omega-3 supplementation.

Early life stress experience may blunt hypothalamic leptin signalling.

The aim of this study was to investigate whether neonatal maternal separation (MS) - chronic stress experience in early life - affects the anorectic efficacy of leptin in the offspring at adolescence. Sprague-Dawley pups were separated from the dam daily for 3 h during postnatal day 1-14 or left undisturbed as non-handled controls (NH). NH and MS male pups received an intraperitoneal leptin (100 µg/kg) or saline on postnatal day (PND) 28, and then food intake and body weight gain were recorded. The hypothalamic levels of leptin-signalling-related genes, phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein-tyrosine phosphatase 1B (PTP1B) were examined at 40 min after a single injection of leptin on PND 39 by immunohistochemistry and Western blot analysis. Leptin-induced suppressions in food intake and weight gain was observed in NH pups, but not in MS. Leptin increased pSTAT3 in the hypothalamic arcuate nucleus of NH pups, but not of MS. Interestingly, basal levels of the hypothalamic PTP1B and pSTAT3 were increased in MS pups compared with NH controls. The results suggest that neonatal MS experience may blunt the anorectic efficacy of leptin later in life, possibly in relation with increased expressions of PTP1B and/or pSTAT3 in the hypothalamus.

5,7-dihydroxy-3,4,6-trimethoxyflavone attenuates ischemic damage and apoptosis in mouse islets.

BACKGROUND: The transplantation of isolated pancreatic islets is a promising treatment for diabetes. 5,7-dihydroxy-3,4,6-trimethoxyflavone (Eupatilin), a pharmacologically active flavone derived from the Artemisia plant species, has been reported to have antioxidant and anti-inflammatory activities. This study examines the hypothesis that preoperative eupatilin treatment can attenuate ischemic damage and apoptosis before islet transplantation. METHODS: Islets isolated from Balb/c mice were randomly divided into 2 groups, and cultured in medium supplemented with or without eupatilin. In vitro islet viability and function were assessed. After treatment with a cytokine cocktail consisting of tumor necrosis factor (TNF)-α, interferon (INF)-γ, and interleukin (IL)-1ß, islet cell viability, function, and apoptotic status were determined. The glutathione (GSH) and nitrous oxide (NO) levels were also measured. Proteins related to apoptosis were analyzed using Western blotting. RESULTS: There was no difference in cell viability between the 2 groups. Islets cultured in the medium supplemented with eupatilin showed 1.4-fold higher glucose-induced insulin secretion than the islets cultured in the medium without eupatilin. After treatment with a cytokine cocktail, glucose-induced insulin release and the total insulin content of the islets were significantly improved in eupatilin-pretreated islets compared with islets not treated with eupatilin. Apoptosis was significantly decreased, and GSH levels were elevated in the eupatilin-pretreated group. Cytokine-only treated islets produced significantly higher levels of NO, iNOS, and caspase-3 than islets pretreated with eupatilin before cytokine treatment. CONCLUSIONS: These results suggest that preoperative eupatilin administration enhances islet function before transplantation and attenuates the cytokine-induced damage associated with NO production and apoptosis.

Comparative analysis of the use of complementary and alternative medicine by Korean patients with androgenetic alopecia, atopic dermatitis and psoriasis.

BACKGROUND: Complementary and alternative medicine (CAM) is being increasingly used among Koreans with chronic dermatologic diseases, such as androgenetic alopecia (AGA), atopic dermatitis (AD) and psoriasis. OBJECTIVE: To quantify the usage of CAM in Korean patients with AGA, AD or psoriasis, and to offer valid information for the physicians frequently encountering such disorders. METHODS: Outpatients (n = 678) from three tertiary hospitals were investigated independently by constructed and self-directed questionnaire. RESULTS: Of the respondents, 62.1% (421/678) of the subjects reported current or previous use of CAM for their dermatologic conditions (AGA, 67.2%; AD, 68.9%; psoriasis, 46.6%). In AGA, topical applicants (50.2%) were most often used, followed by dietary therapy and health supplements. In AD, bath therapy (39.4%) was most often used, followed by oriental medicine and topical applicants. In psoriasis, oriental medicine (33.9%) was most frequently used, followed by bath therapy and health supplements. The proportion of patients who believed that CAM helped to improve their skin condition was relatively low (AGA, 16.1%; AD, 31.7%; psoriasis, 15.0%). LIMITATIONS: The results may not be applicable to other countries and generalized to general populations. CONCLUSION: These results indicate that CAM is widely used in Korean patients with chronic dermatological diseases despite their dissatisfactions. Thus, the advantages and disadvantages of CAM must be considered before its clinical practice.

Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: results of SMC NB-2004 study.

From January 2004 to December 2008, 50 consecutive patients with high-risk neuroblastoma were assigned to receive tandem HDCT (high-dose chemotherapy)/auto-SCT after nine cycles of induction chemotherapy. CEC (carboplatin + etoposide + cyclophosphamide) regimen and TM (thiotepa + melphalan)-TBI regimen (or TM regimen for stage 3 patients) were the first and second HDCT regimens. Local radiotherapy, differentiation therapy with 13-cis-retinoid acid and immunotherapy with interleukin-2 were given after tandem HDCT/auto-SCT. Of the 50 patients, 49 underwent a first HDCT/auto-SCT and 47 underwent a second HDCT/auto-SCT. The tumor relapsed or progressed in 14 patients, secondary malignancy developed in one patient and one patient died from chronic lung disease. Therefore, 34 patients remained event free with a median follow-up of 54.5 months (range, 14-94 months) from diagnosis. The probabilities of 5-year OS and EFS for all 50 patients were 77.0% (95% confidence interval (CI), 63.7-90.3) and 71.4% (95% CI, 58.7-84.1), respectively. However, all patients who remained event free for >3 years after tandem HDCT/auto-SCT experienced late adverse effects. Chemotherapeutic dose-escalation strategy using tandem HDCT/auto-SCT was very encouraging for survival. However, further studies incorporating newer treatment modalities are needed to reduce late adverse effects without jeopardizing the survival rate.

First Report of Powdery Mildew Caused by Erysiphe heraclei on Dill in Korea.

Dill (Anethum graveolens L.) is a scented herb belonging to the family Apiaceae. The plant has a long and ancient history in many countries as a culinary and medicinal herb. In October 2008, plants showing typical symptoms of powdery mildew disease were found in polythene tunnels in Icheon, Korea. Symptoms first appeared as thin white colonies, which subsequently showed abundant growth on the leaves and stems. Most diseased plantings were unmarketable and shriveled without being harvested. The damage caused by powdery mildew infections on dill has reappeared every year, with confirmation of the causal agent made again in 2011. Voucher specimens were deposited in the Korea University Herbarium (KUS). Hyphae were septate, branched, and 4 to 7 µm wide. Appressoria on the mycelium were multilobed or moderately lobed. Conidiophores were unbranched, cylindrical, 80 to 140 × 8 to 10 µm, straight or slightly flexuous in foot cells, and produced conidia singly, followed by two to three cells. Conidia were oblong elliptical to oblong, 28 to 50 × 14 to 18 µm, lacked fibrosin bodies, and produced germ tubes on the subterminal position, with angular/rectangular wrinkling of the outer walls. Primary conidia were apically conical, basally subtruncate, and generally smaller than the secondary conidia. No chasmothecia were found but the above characteristics are consistent with Erysiphe heraclei DC. (1). To confirm the identity of the causal fungus, the complete internal transcribed spacer (ITS) region of rDNA from isolate KUS-F26425 was amplified with primers ITS5 and P3 as described by Takamatsu et al. (3) and directly sequenced. The resulting 630-bp sequence was deposited in GenBank (Accession No. JQ517297). Comparison with the sequences available in the GenBank database revealed that the isolate showed >99% sequence similarity with those of E. heraclei from Pleurospermum camtschaticum (GU173850) and Daucus carota (EU371725). Pathogenicity was confirmed through inoculation by gently pressing diseased leaves onto leaves of five healthy potted dill plants. Five noninoculated plants served as controls. Plants were maintained in a greenhouse at 22 ± 2°C. Inoculated plants developed signs and symptoms after 7 days, whereas the control plants remained healthy. The fungus present on the inoculated plants was morphologically identical to that originally observed on diseased plants. Powdery mildew caused by E. heraclei on dill has been known worldwide where the plant is cultivated (2). In East Asia, however, dill powdery mildew was known only from Taiwan (4). To our knowledge, this is the first report of powdery mildew infections by E. heraclei on dill in Korea. Since cultivation of dill was only recently started on a commercial scale in Korea, powdery mildew infections pose a serious threat to safe production of this herb, especially in organic farming where chemical control would be prohibited. References: (1) U. Braun. Beih. Nova Hedw. 89:1, 1987. (2) D. F. Farr and A. Y. Rossman. Fungal Databases, Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ January 28, 2012. (3) S. Takamatsu et al. Mycol. Res. 113:117, 2009. (4) J. G. Tsay. Trans. Mycol. Soc. Repub. China 5:1, 1990.

Immunological impact of Taekwondo competitions.

Immunological changes in elite adolescent female athletes during Taekwondo competitions were investigated on-field. 6 female athletes (16.7 ± 0.8 year-old) volunteered and performed 5 bouts of demonstration Taekwondo competitions simulating real tournaments in intensity, duration, and break-time intervals on the same day. Blood samples were taken before, after the competitions and during the recovery, respectively. Immunological changes and oxidative stress in peripheral blood mononuclear cells were evaluated by flow-cytometry. During the competitions, exercise intensity was 92.2 ± 3.8% (86.1~95.7) of the maximal heart rate. Blood lactate increased immediately after the competitions (p=0.0165) and decreased to baseline during recovery. Intracellular reactive oxygen species (ROS) in the peripheral blood increased continuously during recovery (p<0.05, respectively). Natural killer cells increased immediately after the competitions (p=0.0006), and decreased during recovery. B and T cells increased immediately after the competitions and remained elevated throughout recovery (p<0.05, respectively). CD4/CD8 ratio after the competitions was decreased (p=0.0091) and returned to baseline during recovery. These results suggest that the immunological function of the elite female adolescent athletes could be attenuated after Taekwondo competitions. Further large-scaled Taekwondo studies on immunologic and apoptotic changes related to oxidative stress should be performed for improving and protecting the health of adolescent athletes.

Management of bowel dysfunction in the community after spinal cord injury: a postal survey in the Republic of Korea.

STUDY DESIGN: A cross-sectional postal survey. OBJECTIVES: To describe defecation stimulation methods and their outcomes, and to investigate the impact of bowel dysfunction on the quality of life (QoL) in community-dwelling persons with spinal cord injury in South Korea. SETTING: Community-based, Korea. METHODS: A cross-sectional postal survey was conducted. Questionnaires were sent to 459 chronic spinal cord injury (SCI) patients who were registered as members of the Korean Spinal Cord Injury Association. Defecation stimulation methods and their outcomes, the impact of bowel dysfunction on the QoL were investigated. RESULTS: A total of 388 subjects (44.5±10.8 year of age; men, 76.0%; duration of time since the onset of SCI, 14.2±9.5 years) responded. Bowel-related general, social and home QoL deterioration was found in >60%. Suppositories (Supp) were most frequently used, followed by digital rectal stimulation (DRS). The mini enema (ME), which is exclusively used in Korea, was utilized in 18.8%. A defecation time of 30 min was more frequently reported in patients who stimulated defecation with Supp than in those who used DRS. CONCLUSIONS: The use of MEs and warm-water irrigations were newly identified in Korea. Bowel care-related factors that greatly deteriorate the QoL were fecal incontinence, time in one defecation >60 min, perianal skin problem, flatus incontinence and hemorrhoids. Alleviating these factors might help to improve the QoL. In particular, stimulation methods to reduce time for defecation might be recommended to persons with chronic SCI.

Short-acting nifedipine and risk of stroke in elderly hypertensive patients.

OBJECTIVES: Short-acting nifedipine is frequently prescribed in elderly hypertensive patients, despite warnings of possible harmful cardiovascular effects. We conducted a case-crossover study to estimate the risk of stroke episodes associated with use of short-acting nifedipine in elderly hypertensive patients. METHODS: We used the Korea Health Insurance Review & Assessment Service database. Cases included elderly hypertensive patients with hospitalization or emergency department visits for first stroke (International Classification of Diseases-10, I60-I64) between July 1, 2005, and June 30, 2006. Patients with prior stroke-related hospital admission or any visit related to TIA were excluded. Exposure to a short-acting nifedipine formulation was assessed within 7 days before the incident stroke episode (case period) and within a 7-day period preceding 60 days before the episode (control period). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by conditional logistic regression, with adjusting for antihypertensives, anticoagulants, antiplatelet agents, and pneumonia. RESULTS: A total of 16,069 stroke patients with a mean (±SD) age of 68.3 (±2.1) years were studied, of whom 8,573 (53.3%) were female. Short-acting nifedipine was prescribed at least once to 301 (1.9%) patients during the case period. An increased risk of stroke associated with use of short-acting nifedipine within 7 days (adjusted OR 2.56; 95% CI 1.96-3.37) was observed. Patients who were newly prescribed nifedipine within the recent 7 days showed an OR of 4.17 (95% CI 2.93-5.93) compared with nonusers. CONCLUSION: Use of short-acting nifedipine was associated with increased risk of stroke occurrence in elderly hypertensive patients.

Obesity of TallyHO/JngJ mouse is due to increased food intake with early development of leptin resistance.

TALLYHO/JngJ (TallyHo) mouse is a recently established animal model for type 2 diabetes mellitus (T2DM) with phenotypes of mild obesity and male-limited hyperglycemia. In this study, we investigated how obesity develops in TallyHo mice by measuring parameters of food intake and energy expenditure. At 4 weeks of age, TallyHo mice were heavier than control C57BL/6 mice with increased food intake but comparable energy expenditure parameters, such as body temperature, cold-induced thermogenesis, oxygen consumption rate (VO(2)) and spontaneous locomotor activity. Furthermore, pair-fed TallyHo mice, which were fed the same amount of food as C57BL/6 mice, showed similar patterns of body weight gain to C57BL/6 mice at all ages, implying that obesity in TallyHo mice may develop by increased food intake but not by decreased energy consumption. TallyHo mice appear to have hypothalamic leptin resistance at 4 weeks of age, as indicated by the increased expression of orexigenic neuropeptides in the hypothalamus and no alteration of food intake and neuropeptide expression upon intravenous leptin treatment. Leptin injection to TallyHo mice, however, increased the phosphorylation of STAT3 and Akt, an important signaling mediator of leptin, in a pattern similar to that in C57BL/6 mice. In conclusion, increased food intake is a crucial component in the development of obesity in TallyHo mice, in which central leptin resistance, possibly caused by uncoupling between activation of leptin signaling and neuropeptide expression, might be involved.

Preservation of rat aortic tissue transplant with green tea polyphenols.

Green tea polyphenols have recently attracted medical attention as bioactive agents with anticancer, antimicrobial, and antiviral effects. We discovered their new usage as preservative agents for tissue transplants. We preserved rat aortas in a DMEM solution containing polyphenols extracted from green tea leaves. The preserved aortas retained original structures and mechanical strength, and were devoid of any undesirable cell secretions for over a month under physiological conditions. In addition, aortas from Lewis rats preserved for a month and transplanted to allogenic ACI rats completely avoided rejection by the host, suggesting that the polyphenols have immunosuppressive actions on the aortic tissues. From these results, we conclude that polyphenol treatment of aortic tissue transplant can maintain its viability for extended periods of time either before or after transplantation, and the method can be applicable to other transplantation situations.

Comparative effect of seeds of Rhynchosia volubilis and soybean on MG-63 human osteoblastic cell proliferation and estrogenicity.

The seeds of Rhynchosia volubilis (SRV) (Leguminosae) and soybean have been used in oriental folk medicine to prevent postmenopausal osteoporosis. Their beneficial effects are caused by a high content of isoflavone, which function as partial agonists or antagonists of estrogen. To compare the estrogenic effects of SRV and soybean on the MG-63 osteoblastic cell proliferation, 70% methanol extracts of SRV or soybean were treated on MG-63 cells. Although biphasic over a concentration range of 0.001 mg/ml-0.1 mg/ml, both SRV and soybean extracts increased MG-63 cell proliferation. However SRV was more effective at increasing the cell proliferation that paralleled with the greater estrogenic effects as determined by estrogen receptor alpha (ERalpha) expression, an estrogenic response element (ERE)-luciferase activity and the selective expression of insulin-like growth factor-I (IGF-I). SRV-induced IGF-I expression resulted from increases in the mRNA levels. Despite the increased expression of ERbeta, ERE activity and IGF-I expression by soybean were lower than those by SRV. Furthermore, the comparable estrogenic effects between SRV and the combined treatment of genistein and daidzein standards at 0.5 x 10(-8) M, which is a concentration of these two isoflavones similar to that of SRV at 0.001 mg/ml, demonstrate that the greater estrogenicity of SRV for MG-63 cell proliferation is mediated by the synergism of low levels of isoflavones for the selective expression of IGF-I.

The treatment of tuberculosis in South Korea.

South Korea's complex system of tuberculosis control has never been fully described. The prevalence of tuberculosis has dropped dramatically since 1965, partly because of farsighted governmental policy that provided low-cost, accessible tuberculosis treatment to the entire population. Within the tuberculosis control system, public and private sector entities provide a wide variety of treatment options. The National Tuberculosis Program focuses on improving cure rates for new cases, while the private sector has taken more of a role in the treatment of drug-resistant tuberculosis and other types of complicated cases. There has been a decrease in drug-resistant tuberculosis since 1980 for multiple reasons, including increased cure rates from the introduction of rifampin-based regimens, improved nutrition and living standards, and the treatment of drug-resistant cases in the private sector. Multidrug-resistant tuberculosis, however, still poses a significant threat to public health. The limited outcomes data that exist in South Korea for multidrug-resistant tuberculosis treatment suggest that cure rates are low and failure and abandonment rates are high. New public health measures are needed to improve the control of multidrug-resistant tuberculosis.

Effects of hwangryunjihwang-tang on in vitro ertilization and ovulation in mice fed a high-fat diet.

It has been generally accepted that hwangryunjihwang-tang (h-tang) is a useful prescription for treating polydipsia and to prevent obesity induced by a high-fat diet. The aim of this study was to clarify whether h-tang improved reproductive dysfunction caused by obesity in mice. Mice were fed a high density protein and lipid diet for 4 weeks, followed by administration of h-tang at 480 mg/kg body weight per day for 4 days. Thereafter, changes of body weight, ovulation rate, in vitro and in vivo fertilization, embryonic development and implantation rate were measured. H-tang markedly reduced the body weight of obese mice fed a high-fat diet, but not mice fed a normal diet. H-tang significantly improved ovulation rates, in vitro and in vivo fertilization rates and embryonic development. These results indicate pharmacological reversal of reproductive dysfunction caused by obesity, perhaps by adjusting internal secretions and metabolic functions.

Molecular characterization of a cDNA encoding putative calcium binding protein, HvCaBP1, induced during kernel development in barley (Hordeum vulgare L.).

Seed development is known to involve complex physiological and molecular events. In order to gain information on the molecular events that occur in the grains of barley during kernel development, we conducted suppression subtractive hybridization (SSH) using grains of barley cv. Karl at 14 days after fertilization (DAF) as the tester and grains at 5 DAF as the driver. We isolated an SSH clone that showed homology with a specific calcium binding protein in rice called EFA27. Screening the cDNA library, we identified two clones as a calcium binding protein. These clones, each carrying one calcium-binding EF-hand motif, were designated HvCaBP1 (Hordeum vulgare Calcium Binding Protein 1). HvCaBP1 possesses an N-terminal region with a conserved single Ca(2+)-binding EF-hand motif and one transmembrane helix. Northern hybridization showed that the highest expression occurred in grains and that expression increased in kernels at 8 DAF. As shown in situ hybridization, the HvCaBP1 gene was highly expressed in the embryo and tissues of the endosperm near the embryo and was detected in the vascular tissues of the glume in the kernel at 8 DAF. Accumulation of HvCaBP1 mRNAs subsequently increased in vegetative tissues for up to 48 h after abscisic acid (ABA) treatment. Transcripts of HvCaBP1 mRNAs may be regulated by endogenous ABA in the grains during kernel development.

Hepatitis B and C virus prevalence in a rural area of South Korea: the role of acupuncture.

A cross-sectional study evaluated the prevalence of and the risk factors for hepatitis C and B viruses among 700 adults above the age of 40 years in a rural area of South Korea. Seropositivity for hepatitis C virus antibody (11.0%, 95% confidence interval: 8.7-13.6) was higher than that for hepatitis B surface antigen (4.4%, 95% confidence interval: 3.0-6.2). Anti-hepatitis C virus seropositivity was associated with a history of repeated acupuncture (odds ratio=2.1, 95% confidence interval: 1.1-4.0), and blood transfusion (odds ratio=5.5, 95% confidence interval: 1.6-19.3) before 1992 when hepatitis C virus screening in blood donors became mandatory. Hepatitis C virus 2a was the most prevalent genotype, followed by 1b. Hepatitis C virus risk attributable to acupuncture was 38% (9% for men and 55% for women). Safer acupuncture practice has become a priority for hepatitis C virus prevention in South Korea.

A controlled clinical study of serosa-invasive gastric carcinoma patients who underwent surgery plus intraperitoneal hyperthermo-chemo-perfusion (IHCP).

BACKGROUND: Despite recent advances in the treatment of advanced gastric carcinomas, no satisfactory outcomes are available because of micrometastases and free-floating carcinoma cells already existing in the peritoneal cavity. From 1990, we started using intraperitoneal hyperthermo-chemo-perfusion (IHCP) to prevent and to treat peritoneal metastasis after surgical resection of stomach cancer. METHOD: We analyzed 103 serosa-invasive gastric carcinoma patients who underwent surgical resection between 1990 and 1995. Fifty-two patients who received surgery plus IHCP were compared with 51 patients who underwent surgery only, as controls. IHCP was administered for 2 h with an automatic IHCP device (closed-circuit system) just after surgical resection, with the patient under hypothermic general anesthesia (32.4 degrees C-34.0 degrees C). As perfusate, we used 1.5% peritoneal dialysis solution mixed with 10 micrograms/ml of mitomycin-C (MMC), warmed at an inflow temperature of over 44 degrees C. RESULTS: The overall 5-year survival rate (5-YSR) of the 103 patients was 29.97%. The 5-YSR was higher in the IHCP group than in the control group, at 32.7% and 27.1%, respectively, but this difference was not significant. However, in the 65 serosa-invasive gastric carcinoma patients (excluding those in stage IV) the 5-YSR was significantly higher (P = 0.0379) in the IHCP group than in the control group, at 58.6% and 44.4%, respectively. On multivariate analysis of all 103 patients, depth of tumor invasion and lymph node metastasis were significant factors for survival, whereas significant factors on univariate analysis, such as combined operation, distant metastasis, and peritoneal metastasis, were not significant. The most common recurrence patterns were loco-regional in the IHCP group and peritoneal in the control group. CONCLUSION: Complete cytoreductive surgery plus IHCP is effective to prevent and to treat peritoneal metastasis, and it should lead to long-term survival for serosa-invasive gastric carcinoma patients. However, there are some limitations for the treatment of peritoneal metastasis in stage IV patients with distant metastases.

Aqueous extract isolated from Platycodon grandiflorum elicits the release of nitric oxide and tumor necrosis factor-alpha from murine macrophages.

Herbal medicines are increasingly being utilized to treat a wide variety of disease processes. Aqueous extract from the root of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK), is reported to have antitumor and immunomodulatory activities; however, the mechanism underlying its therapeutic effect is not known. In the present study we examined the effects of CK on the release of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), and on the gene expression of iNOS and TNF-alpha in mouse macrophages. CK elicited a dose-dependent increase in NO and TNF-alpha production in cultured macrophages. CK significantly affected secretion at concentrations of more than 5 micrograms/ml, and its maximum effect was at concentration of 100 micrograms/ml. Reverse transcription polymerase chain reaction showed that increases in NO and TNF-alpha secretion were due to an increase in inducible NO synthase mRNA and TNF-alpha mRNA, respectively. Transient expression assays with NF-kappa B binding sites linked to the luciferase gene revealed that CK-induced increase of inducible NO synthase mRNA and TNF-alpha mRNA were mediated by the NF-kappa B transcription factor complex. These results demonstrate that CK stimulates NO and TNF-alpha release and is able to upregulate iNOS and TNF-alpha expression through NF-kappa B transactivation and this may be a mechanism whereby this herbal medicine elicits its therapeutic effects.

Augmentation of macrophage functions by an aqueous extract isolated from Platycodon grandiflorum.

Platycodon grandiflorum has been claimed to have a wide range of health benefits, which include immunostimulation and antitumor activity. The associated biological mechanisms are unclear; however, of the wide diversity of effects, it is believed that their activities may be exerted through several potent effector cells such as macrophages. Therefore, the effects of an aqueous extract from the root of P. grandiflorum (Changkil: CK) on mouse peritoneal macrophage function were investigated. It was found that CK stimulated macrophage proliferation, spreading ability, phagocytosis, cytostatic activity, and nitric oxide production in a dose-dependent manner, and that the production of cytokines such as TNF-alpha, IL-1beta and IL-6 were similarly increased. CK significantly affected secretion at concentrations greater than 10 microg/ml; its maximal effects were at the concentration of 100 microg/ml. Reverse transcription-polymerase chain reaction showed that CK increased the appropriate cytokine mRNAs. These results suggest that CK is a potent enhancer of macrophage function.

Anti-fibrotic effects of a hot-water extract from Salvia miltiorrhiza roots on liver fibrosis induced by biliary obstruction in rats.

The anti-fibrotic effects of a hot-water extract form the traditional Chinese medicinal herb Salvia miltiorrhiza (Labiatae) on liver fibrosis induced by biliary obstruction was studied in rats. Liver fibrosis was induced in male Sprague-Dawley rats by bile duct ligation and scission (BDL). After surgery, the hot-water extract of S. miltiorrhiza roots (100 mg kg(-1), p.o.) was administered daily for 28 days. The concentrations of aspartate transaminase, alanine transaminase, alkaline phosphatase, total bilirubin and total cholesterol in serum and hydroxyproline and malondialdehyde contents in liver were significantly increased in BDL rats. Treatment with the extract of S. miltiorrhiza significantly reduced (P < 0.01) the serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and total cholesterol concentrations in BDL rats. The liver hydroxyproline content in BDL rats treated with extract was also reduced to 68% of that in BDL control rats (P < 0.01). The liver malondialdehyde content in BDL rats treated with the extract was also reduced to 47% of that in BDL control rats (P < 0.01). The morphological characteristics of fibrotic livers were improved in BDL rats treated with extract. Immunohistochemical examination of fibrotic liver showed that the extract of S. miltiorrhiza markedly reduced protein expression of alpha-smooth muscle cell-like actin, which indicates that hepatic stellate cell activation was inhibited during liver fibrosis development. The results indicate that the hot-water extract of S. miltiorrhiza roots inhibits fibrosis and lipid peroxidation in rats with liver fibrosis induced by biliary obstruction.