Clinical outcomes of long-term inhaled combination therapies in patients with bronchiectasis and airflow obstruction.

BACKGROUND AND OBJECTIVES: Few studies have reported which inhaled combination therapy, either bronchodilators and/or inhaled corticosteroids (ICSs), is beneficial in patients with bronchiectasis and airflow obstruction. Our study compared the efficacy and safety among different inhaled combination therapies in patients with bronchiectasis and airflow obstruction. METHODS: Our retrospective study analyzed the patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity < 0.7 and radiologically confirmed bronchiectasis in chest computed tomography between January 2005 and December 2021. The eligible patients underwent baseline and follow-up spirometric assessments. The primary endpoint was the development of a moderate-to-severe exacerbation. The secondary endpoints were the change in the annual FEV1 and the adverse events. Subgroup analyses were performed according to the blood eosinophil count (BEC). RESULTS: Among 179 patients, the ICS/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA), ICS/LABA, and LABA/LAMA groups were comprised of 58 (32.4%), 52 (29.1%), and 69 (38.5%) patients, respectively. ICS/LABA/LAMA group had a higher severity of bronchiectasis and airflow obstruction, than other groups. In the subgroup with BEC ≥ 300/uL, the risk of moderate-to-severe exacerbation was lower in the ICS/LABA/LAMA group (adjusted HR = 0.137 [95% CI = 0.034-0.553]) and the ICS/LABA group (adjusted HR = 0.196 [95% CI = 0.045-0.861]) compared with the LABA/LAMA group. The annual FEV1 decline rate was significantly worsened in the ICS/LABA group compared to the LABA/LAMA group (adjusted ß-coefficient=-197 [95% CI=-307--87]) in the subgroup with BEC < 200/uL. CONCLUSION: In patients with bronchiectasis and airflow obstruction, the use of ICS/LABA/LAMA and ICS/LABA demonstrated a reduced risk of exacerbation compared to LABA/LAMA therapy in those with BEC ≥ 300/uL. Conversely, for those with BEC < 200/uL, the use of ICS/LABA was associated with an accelerated decline in FEV1 in comparison to LABA/LAMA therapy. Further assessment of BEC is necessary as a potential biomarker for the use of ICS in patients with bronchiectasis and airflow obstruction.

Cardiopulmonary Exercise Test With Comorbidity Index Before Allogeneic Hematopoietic Stem Cell Transplantation.

PURPOSE: To evaluate the role of the cardiopulmonary exercise test (CPET) with comorbidity index as a predictor of overall survival (OS) and non-relapse mortality (NRM) in patients with hematological malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We retrospectively analyzed consecutive adult patients with hematological malignancies who underwent HLA-matched donor-HSCT at Chungnam National University Hospital (Daejeon, South Korea) between January 2014 and December 2020. Maximal oxygen consumption (VO2max) was classified using the recommendations of the Mayo Clinic database. RESULTS: Of 72 patients, 38 (52.8%) had VO2max values lower than the 25th percentile (VO2max ≤ 25th) of an age- and sex-matched normal population. Patients with VO2max ≤ 25th had no significant differences both OS and NRM (30 month OS 29.8% vs 41%, P = .328; and 30 month NRM 16% vs 3.3%, P = .222), compared with other patients. VO2max ≤ 25th was assigned a weight of 1 when added to the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) to form a composite comorbidity/CPET index (HCT-CI/CPET). Patients with HCT-CI/CPET scores of 0 to 1 demonstrated significantly better OS and NRM than did patients with HCT-CI/CPET scores ≥2 [median OS not reached vs 6 months, P < .001 and 30 month NRM 7.4% vs 33.3%, P = .006]. An HCT-CI/CPET score ≥2 was the only adverse risk factor for NRM on multivariate analysis [hazard ratio (HR) of NRM 10.36 (95% CI 1.486-2.25, P = .018)]. CONCLUSION: The composite HCT-CI/CPET score can predict the survival and mortality of patients with hematological malignancies who undergo allogeneic HSCT.

Case Report: Acute Kidney Injury Due to Chronic Milk-Alkali Syndrome in a Patient With Colon Cancer.

BACKGROUND: Common causes of hypercalcemia include primary hyperparathyroidism and paraneoplastic syndrome of malignancy. Because of this, physicians can easily miss extrinsic causes of hypercalcemia such as milk-alkali syndrome in patients with cancer. We successfully treated a case of acute kidney injury due to severe hypercalcemia caused by milk-alkali syndrome due to long-term milk drinking in a patient with colon cancer. CASE DESCRIPTION: A 62-year-old man was referred to nephrology for hypercalcemia and azotemia that was found during preoperative evaluation for colon cancer surgery. The patient had experienced several months of dizziness and anorexia. We started hemodialysis because hypercalcemia and azotemia were not improved despite large amounts of hydration and diuretics. We suspected paraneoplastic syndrome because of concomitant colon cancer and low intact parathyroid hormone (PTH). Renal microcalcifications were observed on ultrasonography. Metastatic calcifications of the lung and stomach were present, but no malignant metastasis appeared on bone scans. There was no evidence of metastatic malignant lesions on chest or abdominal enhanced computed tomography. PTH-related peptide was not detected. Thus, other causes of hypercalcemia beyond malignancy were considered. On history-taking, the patient reported consuming 1,000 to 1,200 mL of milk daily for the prior 3 months. Hypercalcemia was due to chronic milk-alkali syndrome. We advised withdrawal of milk and nutritional pills. Hemodialysis was stopped after 2 weeks since azotemia and hypercalcemia were resolving. Acute kidney injury was improved, and mild hypercalcemia remained when he underwent hemicolectomy after 1 month. Thereafter, serum calcium and creatinine remained normal at discharge and follow-up for 1 year in the outpatient clinic. However, lung calcifications still remained on bone scan after 1 year. CONCLUSIONS: Chronic milk-alkali syndrome is a rare condition resulting from excessive calcium and alkali intake through various routes, like milk, nutritional supplements, and medicines for osteoporosis. Therefore, early management for hypercalcemia should include precise history taking including diet, previous diagnoses, and current medications.

What is the optimal antibiotic treatment strategy for carbapenem-resistant Acinetobacter baumannii (CRAB)? A multicentre study in Korea.

OBJECTIVES: The optimal treatment option for carbapenem-resistant Acinetobacter baumannii (CRAB) is still limited. This study investigated the efficacy of three or more antibiotic types and regimens for treatment of CRAB infection in high CRAB endemic areas. METHODS: A multicentre retrospective study was conducted to evaluate the efficacy of treatment types and regimens of CRAB infections in 10 tertiary hospitals in the Republic of Korea. The outcomes comprised 7-day and 28-day mortality, and clinical and microbiological responses at 7 days, 28 days, and the end of treatment. Nephrotoxicity and hepatotoxicity were evaluated as drug adverse reactions. RESULTS: A total of 282 patients were included in the study. Among the CRAB strains, the two most susceptible antibiotics were colistin (99.6%) and minocycline (80.4%). A combination of colistin and carbapenem significantly reduced 7-day mortality, and a sulbactam-containing regimen significantly reduced 28-day mortality. Colistin monotherapy was significantly associated with increased 7-day and 28-day mortality. A minocycline-containing regimen showed the best microbiological responses at 7 days, 28 days, and the end of treatment. Colistin and tigecycline were associated with increased nephrotoxicity and hepatotoxicity, respectively. Subgroup analysis of patients with pneumonia showed similar results to the overall CRAB infection. CONCLUSIONS: A combination of colistin and carbapenem and sulbactam-containing regimen may contribute improved mortality in CRAB infections. Colistin monotherapy should be considered cautiously in severe CRAB infections or CRAB pneumonia. A minocycline-containing regimen showed the best microbiological responses, and further studies may be needed to evaluate improved mortality.

Behaviors and Attitudes toward the Use of Complementary and Alternative Medicine among Korean Cancer Patients.

PURPOSE: A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea. MATERIALS AND METHODS: Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution. RESULTS: In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians. CONCLUSION: Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.

Distribution, accumulation, and potential risk of polybrominated diphenyl ethers in the marine environment receiving effluents from a sewage treatment plant.

We investigated the effect of sewage treatment plant effluent on the distribution and accumulation of polybrominated diphenyl ethers (PBDEs) in the marine environment. PBDEs concentrations in seawater and surface sediments were within the ranges 1.58-6.94 ng/L and 2.18-307 ng/g dw, respectively. PBDE concentrations in sediments gradually decreased with increasing distance from inner bay including the sewage outfall. The contribution of effluent to PBDE distributions was very limited. The concentrations of PBDEs in sediment core decreased exponentially with increasing depth. PBDE concentrations in oysters were 4.7-37 ng/g lw. BDE-209 was the dominant congener in marine environmental samples receiving effluent. Estimated dietary exposures of PBDEs by seafood were 0.01-0.08 ng/kg body weight/day, which were more than six orders of magnitude lower than the reported levels of PBDEs with the no observable adverse effects. Hazard quotients demonstrated that, at present, PBDEs posed no potential risk to benthic organisms in the study area.

Identification of genotoxic compounds in crude oil using fractionation according to distillation, polarity and Kow.

We examined the degree of DNA damage caused by fractions of crude oil in accordance with the boiling points, polarity and log Kow. Relatively high DNA damage was observed in the aromatic fraction (290-330°C) and resin and polar fraction (350-400°C). The resin and polar fraction showed relatively high genotoxicity compared with the aliphatic and aromatic fraction at the 1-4 log Kow range. At the 6-7 log Kow range, the aromatic fraction showed relatively high DNA damage compared with the aliphatic and resin and polar fraction. In particular, every detailed fraction in accordance with the log Kow values (aliphatic and aromatic (310-320°C) and resins and polar fractions (370-380°C)) showed one or less than one DNA damage. However, the fractions before separation in accordance with log Kow values (aliphatic and aromatic (310-320°C) and resin and polar (370-380°C) fractions) showed high DNA damage. Thus, we confirm the synergistic action between the detailed compounds.

Is manipulative therapy clinically necessary for relief of neck pain? A systematic review and meta-analysis.

OBJECTIVE: To summarize and critically assess the effificacy of Eastern and Western manipulative therapies for the treatment of neck pain in adults. METHODS: A search of PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, EMBASE, etc. from their inception date to January 2014 with Chinese, Japanese, and Korean databases. Two reviewers independently selected randomized controlled trials (RCTs) with negative control or blank control, extracted data and assessed methodological quality. Meta-analysis and levels of evidence were performed by Revman5.1 and Grades of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Nineteen clinical trials with adequate randomization were included in this review, 11 of them had a low risk of bias. The primary outcome for short-term pain had no significant differences, however, the secondary outcome, only the Numerical Pain Rating Scale (NPRS) score of intermediate-term [n=916, pooled mean differences (MD) =-0.29, P=0.02], the Neck Disability Index (NDI) score of short-term (n=1,145, pooled MD=-2.10, P<0.01), and intermediate-term (n=987, pooled MD=-1.45, P=0.01) were signifificantly reduced with moderate quality evidence. However, it supported the minimally clinically important difference (MCID) of the Visual Analogue Scale and NPRS pain score to be 13 mm, while NDI was 3.5 points. The meta-analysis only suggested a trend in favor of manipulative therapy rather than clinical signifificance. CONCLUSIONS: The results do not support the existing evidences for the clinical value of Eastern or Western manipulative therapy for neck pain of short-term follow-up according to MCIDs. The limitations of our review related to blinding, allocation concealment and small sample size.

Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats.

The present study tested the hypothesis that Korean red ginseng (KRG) provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v) alcohol or an isocaloric amount of dextrin-maltose for the controls for 6 weeks: normal control (CON), alcohol control (ET), and ET treated with 125 or 250 mg/kg body weight/day of KRG (RGL or RGH, respectively). Compared with the CON group, the ET group exhibited a significant increase in triglycerides, total cholesterol and the presence of lipid droplets in the liver, and a decrease in fat mass, which were all attenuated by KRG supplementation in adose-dependent manner. The mitigation was accompanied by AMP-activated protein kinase (AMPK) signaling pathways in the liver and adipose tissue. In addition, suppression in the alcohol-induced changes of adipose adipokine mRNA expression was also observed in KRG supplementation group. These findings suggest that KRG may have the potential to ameliorate alcoholic fatty liver by suppressing inappropriate lysis of adipose tissue and preventing unnecessary de novo lipogenesis in the liver, which are mediated by AMPK signaling pathways. A mechanism for an interplay between the two organs is still needed to be examined with further assays.

DNA damage caused by organic extracts of contaminated sediment, crude, and weathered oil and their fractions recovered up to 5 years after the 2007 Hebei Spirit oil spill off Korea.

We examined the degree of DNA damage caused by three fractions (F1, aliphatic hydrocarbons; F2, aromatic hydrocarbons; and F3, polar compounds) of the organic extract of sediments taken from Taean, Korea, following the Hebei Spirit oil spill. DNA damage was measured using the comet assay with blood cells of the striped beakfish (Oplegnathus fasciatus). DNA damage was also examined for fractions of crude oil (Iranian Heavy Crude Oil, IHC), weathered oil and six subfractions (F2.1-F2.6). The greatest DNA damage was found from the Sinduri dune region and DNA damage decreased to 40% weathered oil in F2 fraction compared with crude oil. The DNA damage of the sum of fractions was found higher than the organic extracts of sediments, suggesting antagonistic interactions between the genotoxic compounds. This study confirmed the persistence of potential genotoxicity in sediments of the severely affected regions as long as 5 years after the oil spill.

Stenotrophomonas maltophilia bloodstream infection in patients with hematologic malignancies: a retrospective study and in vitro activities of antimicrobial combinations.

BACKGROUND: Stenotrophomonas maltophilia causes serious infections in immunocompromised hosts. Here, we analyzed the clinical characteristics of S. maltophilia bloodstream infection (BSI) in patients with hematologic malignancies and evaluated in vitro synergistic effects of antimicrobial combinations. METHODS: We retrospectively reviewed all consecutive episodes of S. maltophilia BSIs in adult hematologic patients from June 2009 to May 2014, with in vitro susceptibility and synergy tests using high-throughput bioluminescence assay performed for available clinical isolates. RESULTS: Among 11,004 admissions during 5-year period, 31 cases were identified as S. maltophilia BSIs. The incidence rate of S. maltophilia BSI was 0.134 cases/1,000 patient-days. Overall and attributable mortality of S. maltophilia BSI was 64.5% and 38.7%, respectively. Severe neutropenia (adjusted hazard ratio [HR] 5.24, p =0.013), shock at the onset of BSI (adjusted HR 6.05, p <0.001), and pneumonia (adjusted HR 3.15, p =0.017) were independent risk factors for mortality. In vitro susceptibilities to ceftazidime, levofloxacin, ticarcillin-clavulanic acid (TIM) and trimethoprim-sulfamethoxazole (SXT) were 11.1%, 44.0%, 40.7%, and 88.9%, respectively. MIC50/MIC90 for moxifloxacin and tigecycline were 1/4 mg/L and 4/8 mg/L. The 50% and 90% fractional inhibitory concentrations (FIC(50)/FIC(90)) of clinical isolates against a combination of SXT and TIM were 0.500/0.750. For SXT plus levofloxacin or moxifloxacin, FIC(50)/FIC(90) were 0.625/1.000 and 0.625/0.625, respectively. CONCLUSION: S. maltophilia BSIs show high mortality, which is related to severe neutropenia, shock, and S. maltophilia pneumonia. Based upon drug susceptibility testing, the primary treatment of choice for S. maltophilia BSIs should be SXT in hematologic patients, rather than quinolones, with combination therapies including SXT serving as a feasible treatment option.

Impact of extended-spectrum ß-lactamase production on treatment outcomes of acute pyelonephritis caused by escherichia coli in patients without health care-associated risk factors.

Extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is increasingly identified as a cause of acute pyelonephritis (APN) among patients without recent health care contact, i.e., community-associated APN. This case-control study compared 75 cases of community-associated ESBL-EC APN (CA-ESBL) to 225 controls of community-associated non-ESBL-EC APN (CA-non-ESBL) to identify the risk factors for ESBL-EC acquisition and investigate the impact of ESBL on the treatment outcomes of community-associated APN (CA-APN) caused by E. coli at a Korean hospital during 2007 to 2013. The baseline characteristics were similar between the cases and controls; the risk factors for ESBL-EC were age (>55 years), antibiotic use within the previous year, and diabetes with recurrent APN. The severity of illness did not differ between CA-ESBL and CA-non-ESBL (Acute Physiology and Chronic Health Evaluation [APACHE] II scores [mean ± standard deviation], 7.7 ± 5.9 versus 6.4 ± 5.3; P = 0.071). The proportions of clinical (odds ratio [OR], 1.76; 95% confidence interval [CI], 0.57 to 5.38; P = 0.323) and microbiological (OR, 1.16; 95% CI, 0.51 to 2.65; P = 0.730) cures were similar, although the CA-ESBL APN patients were less likely to receive appropriate antibiotics within 48 h. A multivariable Cox proportional hazards analysis of the prognostic factors for CA-APN caused by E. coli showed that ESBL production was not a significant factor for clinical (hazard ratio [HR], 0.39; 95% CI, 0.12 to 1.30; P = 0.126) or microbiological (HR, 0.49; 95% CI, 0.21 to 1.12; P = 0.091) failure. The estimates did not change after incorporating weights calculated using propensity scores for acquiring ESBL-EC. Therefore, ESBL production did not negatively affect treatment outcomes among patients with community-associated E. coli APN.

Streptomyces panaciradicis sp. nov., a ß-glucosidase-producing bacterium isolated from ginseng rhizoplane.

A Gram-staining-positive actinobacterium, designated strain 1MR-8(T), was isolated from the rhizoplane of ginseng and its taxonomic status was determined using a polyphasic approach. The isolate formed long chains of spores that were straight, cylindrical and smooth-surfaced. Strain 1MR-8(T) grew at 10-37 °C (optimum 28 °C), whilst no growth was observed at 45 °C. The pH range for growth was 4.0-11.0 (optimum pH 6.0-8.0) and the NaCl range for growth was 0-7% (w/v) with optimum growth at 1% (w/v). Strain 1MR-8(T) had cell-wall peptidoglycans based on ll-diaminopimelic acid. Glucose, mannose and ribose were the whole-cell sugars. The predominant isoprenoid quinones were MK-9 (H4), MK-9 (H6) and MK-9 (H8) and the major fatty acids were anteiso-C(15:0), iso-C(15:0), anteiso-C(17:0) and iso-C(16:0). 16S rRNA gene sequencing studies showed that the novel strain was closely related to the type strains of Streptomyces caeruleatus GIMN4(T), Streptomyces curacoi NRRL B-2901(T), Streptomyces capoamus JCM 4734(T) and Streptomyces coeruleorubidus NBRC 12761(T) with similarities of 98.8%. However, DNA-DNA relatedness, as well as physiological and biochemical analyses, showed that strain 1MR-8(T) could be differentiated from its closest phylogenetic relatives. It is proposed that this strain should be classified as a representative of a novel species of the genus Streptomyces, with the suggested name Streptomyces panaciradicis sp. nov. The type strain is 1MR-8(T) ( = KACC 17632(T) = NBRC 109811(T)).

The efficacy of non-carbapenem antibiotics for the treatment of community-onset acute pyelonephritis due to extended-spectrum ß-lactamase-producing Escherichia coli.

OBJECTIVE: Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli has become an important cause of community-onset urinary tract infections. We aimed to evaluate the efficacy of non-carbapenem antibiotics for acute pyelonephritis (APN) due to ESBL-producing E. coli. METHODS: We conducted a retrospective cohort study of patients with community-onset APN due to ESBL-producing E. coli at a single centre in Korea from 2007 to 2013. Outcomes included both microbiological and clinical failure. To adjust for non-random assignment of antibiotics, the propensity score method of inverse probability of treatment weighting and a multivariable analysis using Cox proportional hazards modelling were employed to estimate the efficacy of non-carbapenem antibiotics as compared with carbapenems. RESULTS: Of 152 eligible patients, 85 (55.9%) received carbapenems and 67 (44.1%) received non-carbapenems. Non-carbapenem antibiotics used in this cohort included aminoglycosides (n = 30), ß-lactam/ß-lactamase inhibitors (n = 13), fluoroquinolones (n = 12) and trimethoprim/sulfamethoxazole (n = 5). Microbiological failure was observed in 16 patients receiving carbapenems (16/83, 19.3%) versus 4 patients receiving non-carbapenem (4/67, 6.0%). After weighting, the risk of microbiological failure was similar between the two groups [weighted hazard ratio (HR) 0.99; 95% CI 0.31-3.19]. In a multivariable regression analysis combined with weights, the estimate did not change (weighted adjusted HR 0.96; 95% CI 0.41-2.27). The clinical failure rate was also similar in the two groups (weighted HR 1.05; 95% CI 0.24-4.62). CONCLUSIONS: These results suggest that non-carbapenem antibiotics were as effective as carbapenems as definitive therapy for treating community-onset APN caused by ESBL-producing E. coli if they are active in vitro.

Synthesis and anti-influenza virus activity of 4-oxo- or thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-ones.

A target-free approach was applied to discover anti-influenza viral compounds, where influenza infected Madin-Darby canine kidney cells were treated 7500 different small organic chemicals individually and reduction of virus-induced cytopathic effect was measured. One of the hit compounds was (Z)-1-((5-fluoro-1H-indol-3-yl)methylene)-6-methyl-4-thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-one (15a) with half-maximal effective concentrations of 17.4-21.1µM against influenza A/H1N1, A/H3N2 and B viruses without any cellular toxicity at 900µM. To investigate the structure-activity relationships, two dozens of the hit analogs were synthesized. Among them, 15g, 15j, 15q, 15s, 15t and 15x had anti-influenza viral activity comparable or superior to that of the initial hit. The anti-influenza viral compounds efficiently suppressed not only viral protein level of the infected cells but also production of viral progeny in the culture supernatants in a dose-dependent manner. Based on a mode-of-action study, they did not affect virus entry or RNA replication. Instead, they suppressed viral neuraminidase activity. This study is the first to demonstrate that dihydrofuropyridinones could serve as lead compounds for the discovery of alternative influenza virus inhibitors.

Moringa fruit inhibits LPS-induced NO/iNOS expression through suppressing the NF-κ B activation in RAW264.7 cells.

In this study, we evaluated the anti-inflammatory effects of moringa (Moringa oleifera Lam.), a natural biologically active substance, by determining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Extracts from different parts of moringa (root, leaf, and fruit) reduced LPS-induced nitric oxide (NO) release in a dose-dependent manner. The moringa fruit extract most effectively inhibited LPS-induced NO production and levels of inducible nitric oxide synthase (iNOS). The moringa fruit extract also was shown to suppress the production of inflammatory cytokines including IL-1ß, TNF-α, and IL-6. Furthermore, moringa fruit extract inhibited the cytoplasmic degradation of I κ B -α and the nuclear translocation of p65 proteins, resulting in lower levels of NF -κ B transactivation. Collectively, the results of this study demonstrate that moringa fruit extract reduces the levels of pro-inflammatory mediators including NO , IL-1ß, TNF-α, and IL-6 via the inhibition of NF -κ B activation in RAW264.7 cells. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of moringa fruit extract.

Subcutaneous phaeohyphomycosis caused by Exophiala equina, with susceptibility to eight antifungal drugs.

A case of subcutaneous phaeohyphomycosis caused by Exophiala equina is reported in a 75-year-old female, who showed subcutaneous abscesses on both forearms for 8 months. A lesion was initiated by inoculation with a spine from a tree. Histopathologically, suppurative granulomatous inflammation was present and short hyphal elements were observed. Upon culture greyish-black, velvety colonies of a black yeast were obtained after 3 weeks. The strain grew well at 25 °C, but poorly at 37 °C. After sequencing the internal transcribed spacer domain and the partial ß-tubulin gene, the fungus was identified as E. equina. The patient was successfully treated with fluconazole for 3 months.

Temporal and geographical trends in the genotoxic effects of marine sediments after accidental oil spill on the blood cells of striped beakperch (Oplegnathus fasciatus).

To determine the impact of genetic toxicity caused by the Hebei Spirit oil spill on December 7, 2007, we measured DNA damage in the blood cells of striped beakperch in vitro after exposure to extracts from sediments in the Taean area. The objective of this study was to investigate temporal changes of toxic effects caused by residual PAHs in the sediments up to 18 months after an oil spill. In conclusion, DNA damage had reduced over this 18-month period; that is, the sediments recovered quickly from the oil pollution. In addition, statistically significant correlations between PAHs and DNA damage were observed. Because the comet assay is sensitive to DNA damage induced by genotoxic substances from the polluted sediments, the comet assay can be considered a useful tool as a biomarker in investigating genetic toxicity in environmental monitoring and elucidating the recovery of oil pollution after oil spill as well.

A prospective evaluation of adult men with iron-deficiency anemia in Korea.

OBJECTIVE: Iron-deficiency anemia (IDA) is the most common nutritional deficiency worldwide. However, the information concerning various causes of IDA in adult men is still insufficient. The aim of our study was to evaluate adult men with IDA. METHODS: We prospectively studied 206 adult men with IDA. All subjects had a direct history taken and underwent a physical examination. Esophagogastroduodenoscopy was performed in most patients, and colonoscopy was conducted if no lesion causing IDA was found or the fecal occult blood test was positive. RESULTS: The history of prior gastrectomy and blood-letting cupping therapy that probably had caused IDA were reported in 24 (11.7%) and 11 (5.3%) patients, respectively. In terms of potential causes of IDA, 68 (33.0%) patients were found to have upper gastrointestinal disorders (34 peptic ulcers, 17 erosive gastritis, 16 gastric cancers, and one gastrointestinal stromal tumor). Colonoscopy showed 42 (20.4%) clinically relevant lesions that probably caused IDA: colon cancer (five patients), colon polyps (14 patients), ulcerative colitis (one patient), and hemorrhoids (22 patients). One small bowel tumor was detected at small bowel series. Concerning malignant lesions that were responsible for IDA, 22 malignant lesions were found in patients of 50 years or older, accounting for 16.8% (22 of 131 patients), while only one (1.3%) early gastric cancer was found in the younger patients. CONCLUSION: This study demonstrated that gastrointestinal blood loss is the main cause of IDA in adult men, and that there is a high rate of malignancy in men older than 50 years, emphasizing the need for a complete, rigorous gastrointestinal examination in this group of patients. Considering blood-letting cupping therapy, there is a need to consider culture-specific procedures as a possible cause of IDA.

Enhanced hypothalamic leptin signaling in mice lacking dopamine D2 receptors.

The dopamine D(2) receptor (D2R) plays a critical role in diverse neurophysiological functions. D2R knock-out mice (D2R(-/-)) show reduced food intake and body weight while displaying an increased basal energy expenditure level, compared with their wild type littermates. Thus, these mice show a lean phenotype. D2R(-/-) mice displayed increased leptin sensitivity, and leptin injection induced increased phosphorylation of the hypothalamic signal transducer and activator of transcription 3 (STAT3) in D2R(-/-) mice relative to wild type littermates. Using double immunofluorescence histochemistry, we have demonstrated that D2Rs are present in leptin-sensitive STAT3-positive cells in the arcuate nucleus of the hypothalamus and that leptin injection induces STAT3 phosphorylation in hypothalamic neurons expressing D2Rs. Stimulation of D2R by the D2R agonist quinpirole suppressed the leptin-induced STAT3 phosphorylation and nuclear trans-localization of phospho-STAT3 in the hypothalamus of wild type mice. However, this regulation was not detected in the D2R(-/-) mice. Treatment of D2R agonist and antagonist could modulate the leptin-induced food intake and body weight changes in wild type mice but not in D2R(-/-) mice. Together, our findings suggest that the interaction between the dopaminergic system and leptin signaling in hypothalamus is important in control of energy homeostasis.