Antimicrobial effects of three herbs (Brassica juncea, Forsythia suspensa, and Inula britannica) on membrane permeability and apoptosis in Salmonella.

AIMS: This study aimed synergistic effects of three herbs in Salmonella via increased membrane permeability and apoptosis. METHODS AND RESULTS: Using high-performance liquid chromatography, four types of phenylethyl glycosides and a lignan were detected in the herb mixture (Brassica juncea, Forsythia suspensa, and Inula britannica). During treatment with the herb mixture (1×, 2×, or 4× the MIC), viable cells decreased to 1·87 log CFU per ml (Salmonella Gallinarum) and 2·33 log CFU per ml (Salmonella Enteritidis) after 12 h of incubation according to inhibition of tricarboxylic acid cycle (P < 0·01). In addition, N-phenyl-1-naphthylamine uptake increased from 229·00 to 249·67 AU in S. Gallinarum and from 232·00 to 250·67 AU in S. Enteritidis (P < 0·05), whereas membrane potential decreased from 8855·00 to 3763·25 AU and from 8703·67 to 4300·38 AU, respectively. Apoptotic Salmonella cells were observed by confocal laser scanning microscopy and flow cytometry. Transmission electron microscopy observations with negative staining showed protein leakage from damaged Salmonella. CONCLUSIONS: These results showed the synergistic effect of the three herbs against avian pathogenic Salmonella induced by membrane damage and apoptosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Salmonella causes enormous economic losses in the poultry industry. These results indicated that potency of natural antimicrobial agents due to apoptosis in Salmonella.

Incidence of subsequent osteoporotic fractures after distal radius fractures and mortality of the subsequent distal radius fractures: a retrospective analysis of claims data of the Korea National Health Insurance Service.

A better understanding of the features of subsequent fractures after distal radius fracture (DRF) is important for the prevention of further osteoporotic fractures. This study found that the cumulative incidence of subsequent osteoporotic fractures in South Korea increased over time and that the mortality rates of subsequent DRFs were lower than those of first-time DRFs. INTRODUCTION: We examined the incidence of osteoporotic fractures following distal radius fractures (DRFs) and the mortality rate after subsequent DRFs using claims data from the Korea National Health Insurance (KNHI) Service. METHODS: We identified records for 41,417 patients with first-time DRFs in 2012. The occurrence of osteoporotic fractures of the spine, hip, wrist, and humerus at least 6 months after the index DRF was tracked through 2016. All fractures were identified by specific diagnosis and procedure codes. One-year mortality rates and standardized mortality ratios (SMRs) for initial and subsequent DRFs were calculated for all patients. RESULTS: The 4-year cumulative incidence of all subsequent osteoporotic fractures was 14.74% (6105/41,417; 9.47% in men, 15.9% in women). The number of associated subsequent fractures was 2850 for the spine (46.68%), 2271 for the wrist (37.2%), 708 for the hip (11.6%), and 276 for the humerus (4.52%). The cumulative mortality rate 1 year after the first-time and subsequent DRF was 1.47% and 0.71%, respectively, and the overall SMR was 1.48 (95% CI: 1.37-1.61) and 0.71 (95% CI: 0.42-1.21), respectively. CONCLUSION: The cumulative incidence of osteoporotic fractures following DRFs increased over the study period and was higher among women. The cumulative mortality rates and SMRs of subsequent DRFs were lower than those of first-time DRFs at the 1-year follow-up. Given the increasing incidence rate of DRFs, the incidence of subsequent osteoporotic fractures may also increase.

Inhibitory effects of herbal decoction Ojeoksan on proliferation and migration in vascular smooth muscle cells.

The proliferation of vascular smooth muscle cells plays a crucial role in pathogenesis of cardiovascular disease. The principal objective of this study was to determine the effects of Ojeoksan (OJS) on human aortic smooth muscle cell (HASMC) proliferation induced by tumor necrosis factor α (TNF-aα). Thymidine incorporation after TNF-α treatment was increased and this effect was inhibited significantly by OJS treatment. HASMC proliferation and migration by kinetic live cell imaging were also reduced by treatment with OJS. TNF-α induced the expression of cyclins/cyclin-dependent kinases (CDKs) and reduced the expression of p21waf1/cip1/p27kip1. However, OJS also attenuated the expression of TNF-α-induced cell-cycle regulatory proteins. The results of Western blot analysis demonstrated that the TNF-α treated HASMC secreted gelatinases, probably including MMP-2/-9, which may be involved in the invasion and migration of HASMC. Additionally, OJS suppressed the mRNA expression levels of matrix metalloproteinase-2/-9 (MMP-2/-9) in a dose-dependent manner. OJS inhibited the production of TNF-α-induced hydrogen peroxide (H2O2) and the formation of DCF-sensitive intracellular reactive oxygen species (ROS). Further, OJS suppressed the nuclear translocation and phosphorylation of inhibitor of kappa B-α (IκB-α) of nuclear factor κB (NF-κB) under TNF-α conditions. Our results demonstrate that OJS exerts inhibitory effects on TNF-α-induced HASMC proliferation and migration, suggesting the involvement of the inhibition of both MMP-2 and MMP-9 expressions, and the downregulation of ROS/NF-κB signaling. Thus, herbal decoction OJS may be a possible therapeutic approach to the inhibition of cardiovascular disease including atherosclerosis.

Effects of ${\rm \small L}$-methionine on growth performance, carcass quality, feather traits, and small intestinal morphology of Pekin ducks compared with conventional ${\rm \small {DL}}$-methionine.

The research studied the effects of l-methionine (l-Met) on growth performance, carcass quality, feather traits, and small intestinal morphology of Pekin ducks compared with conventional dl-methionine (dl-Met). A total of 1080, 1-day-old male Pekin ducks were randomly allotted to 9 groups with 6 replicate pens of 20 birds each. During the starter phase (1 to 14 d), ducks were fed a basal diet (Met, 0.30%) or that supplemented with dl-Met or l-Met at 0.05, 0.10, 0.15, or 0.20% of feed. During the grower phase (15 to 35 d), ducks were fed a basal diet (Met, 0.24%) or that supplemented with dl-Met or l-Met at 0.04, 0.08, 0.12, or 0.16% of feed. Compared with ducks fed the basal diet, supplementation with either dl-Met or l-Met increased the body weight (BW) of ducks at days 14 and 35, increased average daily gain (ADG) and average daily feed intake (ADFI), decreased F:G at the starter phase, and increased ADG over the whole 35-d period (P < 0.05). The efficacy of l-Met compared to dl-Met was 140.1% for 14-d BW, 137.6% for ADG and 121.0% for F:G for days 1 to 14. Ducks fed diets supplemented with l-Met had greater proportion of leg muscle, higher than in ducks provided with dl-Met (P < 0.05). The breast muscle proportion was enhanced with dl-Met rather than l-Met supplementation (P < 0.01). The back feathers score and fourth primary wing feather length were increased with dl-Met or l-Met supplementation (P < 0.01), and there was increased efficacy of l-Met relative to dl-Met for back feathers score (153.1%). Dietary dl-Met or l-Met supplementation increased villus height of ileal mucosa of ducks at days 14 and 35 (P < 0.01). Overall, dietary l-Met or dl-Met supplementation affected the growth performance of ducks during the starter phase, and improved the feather traits and small intestinal morphology. The efficacy of l-Met to dl-Met ranged from 120 to 140% for growth performance of young ducks (1 to 14 d) and was 153% for the feather traits of ducks (35 d).

The effect of total sulfur amino acid levels on growth performance, egg quality, and bone metabolism in laying hens subjected to high environmental temperature.

This study evaluated the effects of total sulfur amino acid (TSAA) levels on performance, egg quality, and bone metabolism in laying hens subjected or not to high environmental temperature (HT). HyLine W36 layers (n = 144) were randomly distributed in a 2 × 3 factorial arrangement. Room temperature (control, CR: 21°C/24 h; and high temperature, HR: 32°C/8 h) and diets (70, 85, or 100% of TSAA) were the main factors, with 4 replicates of 6 birds (19 to 45 wk). The TSAA levels were obtained by adding L-Methionine (L-Met) to the basal diet (70% of TSAA) until 85 and 100% of TSAA were reached. At weeks 21, 34, and 45, growth performance, egg production, and egg quality traits were evaluated. At 45 wk, bones were evaluated for collagenous and non-collagenous proteins, bone volume, mineral content, and mineral density from total, cortical, trabecular, and medullary portions. When interactions were found, the increase of TSAA levels (85 and 100%) was able to counteract the negative effects of HT. In general, HT reduced egg production (P < 0.05) and did not significantly affect bone quality. The birds fed 70% of TSAA showed higher feed conversion, lower body weight, egg weight, and egg mass than birds fed 85 and 100% of TSAA in at least one phase. The birds fed 100% of TSAA showed higher egg production and egg mass than the other treatments at 21 wk of age. The cortical and trabecular bone mineral densities were higher for birds fed 100 than 70% of TSAA, whereas the medullary bone mineral content and density were higher for birds fed 70 than 100% of TSAA. In conclusion, HT had negative impact on performance, egg quality and no effect on bone development. The supplementation of L-Met until either 85 or 100% of TSAA levels were reached was enough to assure good performance, egg quality, and bone development in laying hens subjected or not to HT.

Current trends and future projections of hip fracture in South Korea using nationwide claims data.

UNLABELLED: Incidence of hip fracture increased in Korean populations over age 50 between 2008 and 2012, and the number of fractures was predicted to increase by 1.4 times by 2025. This is important information for public health planning. INTRODUCTION: The purposes of this study were to evaluate the trends in the incidence and mortality of hip fracture between 2008 and 2012 and predict the number of hip fractures in Korea through 2025 using nationwide claims data. METHODS: The data managed by the National Health Insurance Service were used to identify the hip fractures in patients aged >50 years between 2008 and 2012. Projections of hip fractures were conducted using the Poisson distribution from 2016 to 2025 in Korea. RESULTS: The incidence of hip fractures (per 100,000) increased by 14.1 % over the 5 years of the study, by 15.8 % in women and 10.9 % in men; the older age group showed a steep rise and shift in the incidence from 2008 to 2012. The cumulative mortality rates at 1 year after hip fractures were 17.2 % (3575/20,849) in 2008 and 16.0 % (4547/28,426) in 2012. Overall standardized mortality ratios (SMRs) for hip fracture were higher in men (11.93) than in women (11.22) and were higher than those in the general population in all age groups. In 2016, the total number of hip fractures was estimated to increase an overall of 1.4 times by 2025. CONCLUSIONS: The incidence of hip fracture continues to increase, and the related mortality is still high, although it has decreased over time. The socioeconomic burden of hip fracture is expected to increase in Korea along with the increased estimated number of fractures. Nationwide strategies should include attempts to reduce the future socioeconomic burdens of hip fractures.

Polysaccharides from Korean Citrus hallabong peels inhibit angiogenesis and breast cancer cell migration.

Although the peel of the hallabong (Citrus sphaerocarpa) fruit is rich in polysaccharides, which are valuable dietary ingredients for human health, it is normally wasted. The present study aimed to utilize the peel waste and identify properties it may have against breast cancer metastasis. Hallabong peel extract containing crude polysaccharides was fractionated by gel permeation chromatography to produce four different polysaccharide fractions (HBE-I, -II, -III, and -IV). The HBE polysaccharides significantly blocked tube formation of human umbilical vein vascular endothelial cells (HUVECs), at a concentration of 12.5 or 25 µg/mL. Tube formation appeared to be more sensitive to HBE-II than to other HBE polysaccharides. HBE-II also inhibited breast cancer cell migration, through downregulation of matrix metalloproteinase-9 (MMP-9) in MDA-MB-231 triple-negative breast cancer cells. Therefore, inhibition of tube formation and MMP-9-mediated migration observed in HUVEC and MDA-MB-231 cells, respectively, are likely to be important therapeutic targets in triple-negative breast cancer metastasis.

Differences in the risk factors of reflux esophagitis according to age in Korea.

The prevalence of gastroesophageal reflux disease in Korea has been believed to be low, but the incidence of gastroesophageal reflux disease in Korea is expected to increase because of the longer life expectancy and more ingestion of westernized food. The aim of this study was to report differences in the risk factors of reflux esophagitis (RE) according to age in Korea. We prospectively recruited the subjects who had RE among those who visited a health promotion center for upper gastrointestinal cancer surveillance at Hallym Medical Center (five institutions) between January 2008 and February 2009. The enrolled study participants comprised 742 subjects with RE and 1484 healthy controls. The independent risk factors of RE in young and adult group were male sex, smoking, coffee, body mass index ≥ 25, hiatal hernia, and Helicobacter pylori negativity. The risk factors of RE in elderly group were smoking, coffee, and hiatal hernia. The risk factors for RE according to age group were found to differ. In elderly group, Helicobacter pylori infection was not a significant protective factor contrary to young and adult groups.

The small molecule indirubin-3'-oxime activates Wnt/ß-catenin signaling and inhibits adipocyte differentiation and obesity.

OBJECTIVES: Activation of the Wnt/ß-catenin signaling pathway inhibits adipogenesis by maintaining preadipocytes in an undifferentiated state. We investigated the effect of indirubin-3'-oxime (I3O), which was screened as an activator of the Wnt/ß-catenin signaling, on inhibiting the preadipocyte differentiation in vitro and in vivo. METHODS: 3T3L1 preadipocytes were differentiated with 0, 4 or 20 µM of I3O. The I3O effect on adipocyte differentiation was observed by Oil-red-O staining. Activation of Wnt/ß-catenin signaling in I3O-treated 3T3L1 cells was shown using immunocytochemical and immunoblotting analyses for ß-catenin. The regulation of adipogenic markers was analyzed via real-time reverse transcription-PCR (RT-PCR) and immunoblotting analyses. For the in vivo study, mice were divided into five different dietary groups: chow diet, high-fat diet (HFD), HFD supplemented with I3O at 5, 25 and 100 mg kg(-1). After 8 weeks, adipose and liver tissues were excised from the mice and subject to morphometry, real-time RT-PCR, immunoblotting and histological or immunohistochemical analyses. In addition, adipokine and insulin concentrations in serum of the mice were accessed by enzyme-linked immunosorbent assay. RESULTS: Using a cell-based approach to screen a library of pharmacologically active small molecules, we identified I3O as a Wnt/ß-catenin pathway activator. I3O inhibited the differentiation of 3T3-L1 cells into mature adipocytes and decreased the expression of adipocyte markers, CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ, at both mRNA and protein levels. In vivo, I3O inhibited the development of obesity in HFD-fed mice by attenuating HFD-induced body weight gain and visceral fat accumulation without showing any significant toxicity. Factors associated with metabolic disorders such as hyperlipidemia and hyperglycemia were also improved by treatment of I3O. CONCLUSION: Activation of the Wnt/ß-catenin signaling pathway can be used as a therapeutic strategy for the treatment of obesity and metabolic syndrome and implicates I3O as a candidate anti-obesity agent.

Mycofumigation with Oxyporus latemarginatus EF069 for control of postharvest apple decay and Rhizoctonia root rot on moth orchid.

AIMS: To characterize the volatile antifungal compound produced by Oxyporus latemarginatus EF069 and to examine in vitro and in vivo fumigation activity of the fungus. METHODS AND RESULTS: An antifungal volatile-producing strain, O. latemarginatus EF069 inhibited the mycelial growth of Alternaria alternata, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium oxysporum f. sp. lycopersici, and Rhizoctonia solani by mycofumigation. An antifungal volatile compound was isolated from the hexane extract of wheat bran-rice hull cultures of O. latemarginatus EF069 by repeated silica gel column chromatography and identified as 5-pentyl-2-furaldehyde (PTF). The purified PTF inhibited mycelial growth of R. solani in a dose-dependent manner. The mycofumigation with solid cultures of EF069 also reduced effectively the development of postharvest apple decay caused by B. cinerea and Rhizoctonia root rot of moth orchid caused by R. solani. CONCLUSIONS: Oxyporus latemarginatus EF069 showed in vitro and in vivo fumigation activity against plant pathogenic fungi by producing 5-pentyl-2-furaldehyde. SIGNIFICANCE AND IMPACT OF THE STUDY: Oxyporus latemarginatus EF069 producing an antifungal volatile compound may be used as a biofumigant for the control of fungal plant diseases.

Subthalamic lesion on MR imaging in a patient with nonketotic hyperglycemia-induced hemiballism.

SUMMARY: Hemiballism with corresponding striatal T1 hyperintensity on MR imaging has occasionally been reported in patients with nonketotic hyperglycemia. However, the subthalamic nucleus lesion, which is believed to be pathogenetically related to hemiballism, is rarely documented in a living patient with nonketotic hyperglycemia. We describe a patient with nonketotic hyperglycemia-induced hemiballism, whose responsible lesion (ie, the subthalamus) was demonstrated by MR imaging.

Kurarinol, tyrosinase inhibitor isolated from the root of Sophora flavescens.

It is well known that flavanones, sophoraflavanone G 1, kurarinone 2, and kurarinol 3, from the root of Sophora flavescens, have extremely strong tyrosinase inhibitory activity. This study delineates the principal pharmacological features of kurarinol 3 that lead to inhibition of the oxidation of l-tyrosine to melanin by mushroom tyrosinase (IC(50) of 100 nM). The inhibition kinetics analyses unveil that compounds 1 and 2 are noncompetitive inhibitors. However similar analysis shows kurarinol 3 to be a competitive inhibitor. Compounds 1 and 2 exhibited potent antibacterial activity with 10 microg/disk against Gram-positive bacteria, whereas kurarinol 3 did not ostend any antibacterial activity. Interestingly, kurarinol 3 inhibits production of melanin in S. bikiniensis without affecting the growth of microorganism. It is thus distinctly different from the other tyrosinase inhibitors 1 and 2. In addition, kurarinol 3 manifests relatively low cytotoxic activity (EC(50)>30 microM) compared to 1 and 2. To account for these observations, we conducted molecular modeling studies. These suggested that the lavandulyl group within 3 is instrumental in the interaction with the enzyme. More specifically, the terminal hydroxy function within the lavandulyl group is most important for optimal binding.

Bikaverin and fusaric acid from Fusarium oxysporum show antioomycete activity against Phytophthora infestans.

AIMS: To isolate and identify antioomycete substances from Fusarium oxysporum EF119 against Phytophthora infestans and to investigate their antimicrobial activities against various plant pathogenic bacteria, oomycetes and true fungi. METHODS AND RESULTS: Two antioomycete substances were isolated from liquid cultures of F. oxysporum EF119, which shows a potent disease control efficacy against tomato late blight caused by P. infestans. They were identified as bikaverin and fusaric acid by mass and nuclear magnetic resonance spectral analyses. They inhibited the mycelial growth of plant pathogenic oomycetes and fungi. Fusaric acid also effectively suppressed the cell growth of various plant pathogenic bacteria, but bikaverin was virtually inactive. Treatment with bikaverin at 300 microg ml(-1) suppressed the development of tomato late blight by 71%. Fusaric acid provided effective control against tomato late blight and wheat leaf rust over 67% at concentrations more than 100 microg ml(-1). CONCLUSIONS: Both bikaverin and fusaric acid showed in vitro and in vivo antioomycete activity against P. infestans. SIGNIFICANCE AND IMPACT OF THE STUDY: Fusarium oxysporum EF119 producing both bikaverin and fusaric acid may be used as a biocontrol agent against tomato late blight caused by P. infestans.

Effect of sun ginseng methanol extract on lipopolysaccharide-induced liver injury in rats.

Sun ginseng (SG) is heat-processed Panax ginseng C.A. Meyer steamed at 120 degrees C, which has ginsenoside-Rg(3), -Rk(1), and -Rg(5) as its main ginsenoside components. The effect of SG on lipopolysaccharide (LPS)-induced liver injury in rats was investigated in this study. Intravenous injection of LPS induced excessive nitric oxide (*NO) generation in serum and increased the hepatic mitochondrial thiobarbituric acid-reactive substance (TBA-RS) level. However, the elevated TBA-RS level was significantly lowered by 15 consecutive days of SG administrations. In addition, up-regulated hepatic inducible nitric oxide synthase and heme oxygenase 1 levels in LPS-treated control rats were significantly lowered and increased, respectively, by 100 mg/kg body weight/day of SG administration. These antioxidant effects were thought to be partially related to the deactivation of nuclear factor-kappaB by SG administration.

Therapeutic potential of heat-processed Panax ginseng with respect to oxidative tissue damage.

Panax ginseng has been reported to exhibit a wide range of pharmacological and physiological actions. A method of heat-processing to enhance the efficacy of ginseng is well established in South Korea based on a long history of ethnopharmacological evidence. We investigated the increase in free radical-scavenging activity of Panax ginseng as a result of heat-processing and its active compounds related to fortified antioxidant activity. In addition, the therapeutic potential of heat-processed ginseng (HPG) with respect to oxidative tissue damage was examined using rat models. Based upon chemical and biological activity tests, the free radical-scavenging active components such as less-polar ginsenosides and maltol in Panax ginseng significantly increased depending on the temperature of heat-processing. According to animal experiments related to oxidative tissue damage, HPG displayed hepatoprotective action by reducing the elevated thiobarbituric acid reactive substance (TBA-RS) level, as well as nuclear factor-kappa B (NF-kappaB) and inducible nitric oxide synthase (iNOS) protein expressions, while increasing heme oxygenase-1 in the lipopolysaccharide-treated rat liver, and HPG also displayed renal protective action by ameliorating physiological abnormalities and reducing elevated TBA-RS, advanced glycation endproduct (AGE) levels, NF-kappaB, cyclooxygenase-2, iNOS, 3-nitrotyrosine, N?-(carboxymethyl)lysine, and receptors for AGE protein expression in the diabetic rat kidney. Therefore, HPG clearly has a therapeutic potential with respect to oxidative tissue damage by inhibiting protein expression related to oxidative stress and AGEs, and further investigations of active compounds are underway. This investigation of specified bioactive constituents is important for the development of scientific ginseng-derived drugs as part of ethnomedicine.

Relationship between omega-3 fatty acids and plasma neuroactive steroids in alcoholism, depression and controls.

Deficiency in the long-chain omega-3 fatty acid, docosahexaenoic acid (DHA) has been associated with increased corticotropin releasing hormone and may contribute to hypothalamic pituitary axis (HPA) hyperactivity. Elevated levels of the neuroactive steroids, allopregnanolone (3alpha,5alpha-THP) and 3alpha,5alpha-tetrahydrodeoxycorticosterone (THDOC) appear to counter-regulate HPA hyperactivity. Plasma essential fatty acids and neurosteroids were assessed among 18 male healthy controls and among 34 male psychiatric patients with DSM-III alcoholism, depression, or both. Among all subjects, lower plasma DHA was correlated with higher plasma THDOC (r = -0.3, P < 0.05) and dihydroprogesterone (DHP) (r = -0.52, P < 0.05). Among psychiatric patients lower DHA was correlated with higher DHP (r = -0.60, P < 0.01), and among healthy controls lower plasma DHA was correlated with higher THDOC (r = -0.83, P < 0.01) and higher isopregnanolone (3beta,5alpha-THP) (r = -0.55, P < 0.05). In this pilot observational study, lower long-chain omega-3 essential fatty acid status was associated with higher neuroactive steroid concentrations, possibly indicating increased feedback inhibition of the HPA axis.

Effects of green tea consumption on inflammation, insulin resistance and pulse wave velocity in type 2 diabetes patients.

In this study, we examined the effects of green tea on inflammation and arterial stiffness in type 2 diabetes patients. As results, inflammatory markers, such as hsCRP and IL-6, were unchanged after green tea consumption, and neither were blood glucose, lipid profiles, insulin resistance, or serum adiponectin levels. Furthermore, tea consumption did not improve baPWV. These results suggest that the above-described mechanisms are unlikely to explain the cardiovascular risk reduction by tea consumption observed in epidemiological studies.

Electrophysiologic and antiarrhythmic effects of the new class III antiarrhythmic drug KCB-328 in experimental canine atrial flutter.

BACKGROUND: The electrophysiologic and antiarrhythmic effects of a new class III antiarrhythmic drug (KCB-328), a delayed rectifier potassium current (IKr) blocker with minimal reverse use-dependent effect on atrial repolarization, were evaluated in the canine night atrial crush-injury model of atrial flutter (AFL). METHODS: Ten anesthetized, open-chest dogs, were studied after right atrial crush-injury. Atrial effective refractory period (ERP), conduction velocity (CV), wavelength, and dispersion of refractoriness were determined during programmed stimulation (S1S2 at S1S1 = 200, 300, 400, and 500 msec) at four sites via a mapping plaque sutured on the right atrial free wall. Right and left ventricular ERP were similarly measured at single sites. Electrophysiological parameters were determined at baseline and following sequential cumulative doses of KCB-328 (10, 30, 100, and 300 microg/kg). RESULTS: Sustained AFL was inducible in 7/10 dogs by rapid pacing following baseline electrophysiologic measurements. KCB-328 significantly prolonged sinus cycle length, but had no effect on PR interval, and prolonged QTc only at the highest dose level. KCB-328 significantly prolonged atrial ERP and wavelength and ventricular ERP, and significantly reduced dispersion of atrial refractoriness. KCB-328 significantly prolonged AFL cycle length, and increasing doses progressively terminated sustained AFL and prevented its reinduction by pacing. No adverse hemodynamic or ventricular proarrhythmic effects were observed. CONCLUSIONS: The electrophysiologic profile of KCB-328 in this canine model of AFL, particularly its lack of reverse use-dependent effect on atrial refractoriness, suggests that it may have significant antiarrhythmic potential in treatment of atrial arrhythmias.

Clinical and immunologic changes after allergen immunotherapy with Hop Japanese pollen.

BACKGROUND AND OBJECTIVE: Hop Japanese (Hop J) pollen has been reported as one of the major causative pollen allergens in the autumn season. There have been no published data regarding the clinical and immunologic effects of Hop J pollen immunotherapy in sensitized patients. In this study, we evaluated clinical and immunologic effects of Hop J immunotherapy. PATIENTS AND METHODS: Pollens were collected in our area, and "Depo-Hop J" was prepared in the laboratory of Allergopharma (Reinbek, Germany). Fifteen asthmatic patients who had Hop J immunotherapy for > 1 year were enrolled. Their clinical parameters, such as asthma symptom scores, were monitored. Skin reactivity to Hop J and degree of airway hyperresponsiveness to methacholine were measured before and 1 year after the immunotherapy. Sera were collected before the immunotherapy, at the end of initial therapy, and 1 year after the therapy. Serum total IgE levels were compared by radioimmunoassay. Serum-specific IgE, IgG1, and IgG4 levels to Hop J were compared by ELISA. To evaluate the changes of cellular mechanisms, soluble CD30 (sCD30), soluble interleukin (IL)-2 receptor (sIL-2R), soluble CD23 (sCD23), and IL-10 levels were measured by ELISA. RESULTS: Specific IgG1 and IgG4 levels began to increase at the end of the initial therapy (P < 0.05) with significant decreases in symptom scores (P < 0.05), whereas total and specific IgE levels showed variable responses during the immunotherapy with no statistical significance (P > 0.05). Serum sIL-2R and sCD30 levels decreased significantly (P < 0.05) 1 year after immunotherapy. No significant changes were noted in sCD23, IL-10, skin reactivity to Hop J, or airway responsiveness to methacholine (P > 0.05). CONCLUSIONS: We are certain that Hop J allergen immunotherapy, if carried out properly according to suitable indications, can favorably influence asthma. Thus, an increase in specific IgG4 and IgG1 antibodies and reduction of a possible Th2 lymphocyte marker (sCD30) may be associated with symptomatic improvements.